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Sample records for gross alpha activities

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

    Science.gov (United States)

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

    2014-12-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Thakur, P., E-mail: pthakur@cemrc.org [Carlsbad Environmental Monitoring and Research Center, 1400 University Drive, Carlsbad, New Mexico 88220 (United States); Mulholland, G.P. [Carlsbad Environmental Monitoring and Research Center, 1400 University Drive, Carlsbad, New Mexico 88220 (United States)

    2011-09-15

    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-{alpha}/{beta}, 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 Simultaneous measurements of gross alpha and gross beta activities in the particulates from WIPP exhaust air were performed. > Ultra low level counter, PIC-MPC 9604-{alpha}/{beta} counter was used for the measurements. > Values of gross alpha activity concentrations ranged from Values of gross beta activity concentrations ranged from

  3. Monitoring gross alpha and beta activity in liquids by using ZnS(Ag) scintillation detectors

    Energy Technology Data Exchange (ETDEWEB)

    Stevanato, L.; Cester, D.; Filippi, D.; Lunardon, M.; Mistura, G.; Moretto, S.; Viesti, G. [Department of Physics and Astronomy ' Galileo Galilei' , University of Padova, (Italy); Badocco, D.; Pastore, P.; Romanini, F. [Department of Chemical Sciences, University of Padova, (Italy)

    2015-07-01

    In this work the possibility of monitoring gross alpha and beta activity in liquids using EJ-444 was investigated. Specific tests were carried out to determine the change of the detector properties in water tests. Possible protecting coating is also proposed and tested. Alpha/beta real-time monitoring in liquids is a goal of the EU project TAWARA{sub R}TM. (authors)

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

    Directory of Open Access Journals (Sweden)

    Sas Daniel

    2016-01-01

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

  5. 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)

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    Çakal Gaye Özgür

    2015-09-01

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

  8. 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.

  9. A rapid method for the simultaneous determination of gross alpha and beta activities in water samples using a low background liquid scintillation counter

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez-Cabeza, J.A.; Pujol, Ll. [Universitat Autonoma de Barcelona, Bellaterra (Spain)

    1995-05-01

    The radiological examination of water requires a rapid screening technique that permits the determination of the gross alpha and beta activities of each sample in order to decide if further radiological analyses are necessary. In this work, the use of a low background liquid scintillation system (Quantulus 1220) is proposed to simultaneously determine the gross activities in water samples. Liquid scintillation is compared to more conventional techniques used in most monitoring laboratories. In order to determine the best counting configuration of the system, pulse shape discrimination was optimized for 6 scintillant/vial combinations. It was concluded that the best counting configuration was obtained with the scintillation cocktail Optiphase Hisafe 3 in Zinsser low diffusion vials. The detection limits achieved were 0.012 Bq L{sup -1} and 0.14 Bq L{sup {minus}1} for gross alpha and beta activity respectively, after a 1:10 concentration process by simple evaporation and for a counting time of only 360 min. The proposed technique is rapid, gives spectral information, and is adequate to determine gross activities according to the World Health Organization (WMO) guideline values.

  10. Determination of gross alpha, 224Ra, 226Ra, and 228Ra activities in drinking water using a single sample preparation procedure.

    Science.gov (United States)

    Parsa, Bahman; Obed, Reynaldo N; Nemeth, William K; Suozzo, Gail P

    2005-12-01

    The current federal and New Jersey State regulations have greatly increased the number of gross alpha and radium tests for public and private drinking water supplies. The determination of radium isotopes in water generally involves lengthy and complicated processes. In this study, a new approach is presented for the determination of gross alpha, 224Ra, 226Ra, and 228Ra activities in water samples. The method includes a single sample preparation procedure followed by alpha counting and gamma-ray spectroscopy. The sample preparation technique incorporates an EPA-approved co-precipitation methodology for gross alpha determination with a few alterations and improvements. Using 3-L aliquots of sample, spiked with 133Ba tracer, the alpha-emitting radionuclides are isolated by a BaSO4 and Fe(OH)3 co-precipitation scheme. First the gross alpha-particle activity of the sample is measured with a low-background gas-flow proportional counter, followed by radium isotopes assay by gamma-ray spectroscopy, using the same prepared sample. Gamma-ray determination of 133Ba tracer is used to assess the radium chemical recovery. The 224Ra, 226Ra, and 228Ra activities in the sample are measured through their gamma-ray-emitting decay products, 212Pb, 214Pb/214Bi, and 228Ac, respectively. In cases where 224Ra determination is required, the gamma-ray counting should be performed within 2-4 d from sample collection. To measure 226Ra activity in the sample, the gamma-ray spectroscopy can be repeated 21 d after sample preparation to ensure that 226Ra and its progeny have reached the equilibrium state. At this point, the 228Ac equilibration with parent 228Ra is already established. Analysis of aliquots of de-ionized water spiked with NIST-traceable 230Th, 224Ra, 226Ra, and 228Ra standards demonstrated the accuracy and precision of this method. Various performance evaluation samples were also assayed for gross alpha as well as radium isotope activity determination using this procedure and the

  11. Gross alpha determination in radioactive wastes from nuclear power plants using the track registration technique

    Energy Technology Data Exchange (ETDEWEB)

    Suarez-Navarro, M.J. [Universidad Politecnica de Madrid (UPM) E.T.S.I de Caminos, Canales y Puertos, Profesor Aranguren, s/n, 28040 Madrid (Spain)]. E-mail: he04@caminos.upm.es; Pujol, Ll. [Centro de Estudios y Experimentacion de Obras Publicas (CEDEX), Alfonso XII, 3, 28014 Madrid (Spain); Gonzalez-Gonzalez, J.A. [Universidad Politecnica de Madrid (UPM) E.T.S.I de Caminos, Canales y Puertos, Profesor Aranguren, s/n, 28040 Madrid (Spain)

    2007-03-15

    Low and intermediate level nuclear wastes (ion-exchange resins and evaporator concentrates) essentially contain beta and gamma emitters, with very few alpha emitters. Several techniques may be used to determine gross alpha activity but, in this case, solid-state nuclear track detectors (SSNTDs) are a suitable technique for gross alpha determination because track detectors are not sensitive to beta and gamma emitters. Also, this technique is simple and inexpensive. In this paper, we studied the parameters (background, efficiency and self-absorption) that could affect the gross alpha determination using SSNTDs for both sample preparation methods, the 'dry method' with tensioactives and the 'wet method'. For the 'dry method', a self-absorption curve for {sup 241}Am standard was prepared using a set of varying thickness of sodium salt and for two different tensioactives: Tween{sup (R)}20 and Teg. The results showed that, below 1mg/cm{sup 2}, the self-absorption factor can be considered similar for both tensioactives and equal to unity. Several detectors for gross alpha determination were compared and we found that the most suitable techniques were ZnS(Ag) solid scintillator and track detectors. Both detectors were used to compare radioactive waste samples. Finally, the proposed methods ('dry method' with Teg tensioactive and 'wet method') using track detectors were tested by analysing the gross alpha activity of several radioactive wastes.

  12. The implications of particle energy and acidic media on gross alpha and gross beta determination using liquid scintillation

    Energy Technology Data Exchange (ETDEWEB)

    Zapata-Garcia, D. [Laboratori de Radiologia Ambiental (LRA), Departament de Quimica Analitica, Universitat de Barcelona, Marti i Franques, 1-11 Planta 3, E-08028 Barcelona (Spain); Llaurado, M., E-mail: montse.llaurado@ub.edu [Laboratori de Radiologia Ambiental (LRA), Departament de Quimica Analitica, Universitat de Barcelona, Marti i Franques, 1-11 Planta 3, E-08028 Barcelona (Spain); Rauret, G. [Laboratori de Radiologia Ambiental (LRA), Departament de Quimica Analitica, Universitat de Barcelona, Marti i Franques, 1-11 Planta 3, E-08028 Barcelona (Spain)

    2012-04-15

    The interaction of humans with radioactivity present in the environment from natural and artificial sources necessitates an evaluation of its risk on human health. Gross alpha and gross beta activities can provide a rapid evaluation of the radioactive content of a sample and can be simultaneously determined by using liquid scintillation counters. However, calibration of the liquid scintillation counter is required and is affected by many factors, such as particle energy and the acidity of the media. This study investigates what effect the particle energy used for calibration has on misclassification and how to account for this misclassification in routine measurements. The variability in measurement produced by the final pH, as well as any acids used in sample treatment, was also studied. These results showed that the most commonly used acid for these types of analyses, HNO{sub 3}, produced a high amount of misclassifications at very low pH. The results improved when HCl was used to adjust the sample to low pH. - Highlights: Black-Right-Pointing-Pointer We study the effect of alpha and beta energies on PSA optimisation. Black-Right-Pointing-Pointer The optimum PSA shifts to higher values as the alpha energy increases. Beta energies do not affect it. Black-Right-Pointing-Pointer We study the effect of pH on the simultaneous determination of gross alpha/beta activities. Black-Right-Pointing-Pointer HNO{sub 3} produces a high amount of misclassification at very low pH. Black-Right-Pointing-Pointer The results improve when HCl is used to adjust the sample to low pH.

  13. Gross alpha and beta radioactivity concentration in water, soil and sediment of the Bendimahi River and Van Lake (Turkey).

    Science.gov (United States)

    Selçuk Zorer, Ozlem; Ceylan, Hasan; Doğru, Mahmut

    2009-01-01

    The concentrations of the natural radioactivity in water, soil and sediment samples collected from Bendimahi River which originates near the Tendürek Mountain (Van, Turkey), its tributaries and Van Lake (Turkey) were measured. The gross-alpha and gross-beta radioactivity concentrations were investigated in May and August in 2005. Determination of the gross-alpha and gross-beta radioactivity of river water, soil and sediment samples was obtained by using gas-flow proportional counter, PIC-MPC 9604-alpha/beta counter. In water samples, the obtained results show that in May; gross-alpha and gross-beta activity concentrations varied between 0.063-0.782 and 0.021-0.816 Bq l(-1) and in August the values were 0.009-0.037 and 0.081-3.116 Bq l(-1), respectively. The gross-alpha and gross-beta activity concentrations in soil samples ranged from 0.800 to 4.277 Bq g(-1) and 0.951 to 11.773 Bq g(-1) in May and 0.686 to 4.713 Bq g(-1) and 0.073 to 9.524 Bq g(-1) in August, respectively. Concentrations ranging from 0.782 to 4.596 Bq g(-1) and from 0.482 to 10.372 Bq g(-1) in May and from 0.580 to 5.824 Bq g(-1) and from 0.303 to 9.702 Bq g(-1) in August for gross-alpha and gross-beta radioactivity were observed in sediments, respectively.

  14. Evaluation of different parameters affecting the liquid scintillation spectrometry measurement of gross alpha and beta index in water samples

    Energy Technology Data Exchange (ETDEWEB)

    Palomo, M. [Unitat de Radioquimica Ambiental i Sanitaria, Universitat Rovira i Virgili, Tarragona (Spain); Villa, M. [Centro de Investigacion, Tecnologia e Innovacion. Servicio Radioisotopos. Universidad de Sevilla (Spain); Casacuberta, N. [Institut de Ciencia i Tecnologia Ambientals-Departament de Fisica, Universitat Autonoma de Barcelona. Spain (Spain); Penalver, A.; Borrull, F. [Unitat de Radioquimica Ambiental i Sanitaria, Universitat Rovira i Virgili, Tarragona (Spain); Aguilar, C., E-mail: carme.aguilar@urv.cat [Unitat de Radioquimica Ambiental i Sanitaria, Universitat Rovira i Virgili, Tarragona (Spain)

    2011-09-15

    Liquid scintillation spectrometry is a fast competitive technique for the simultaneous evaluation of gross alpha and beta indexes. However, the implementation of this technique should not be considered as straightforward, and the pre-concentration methods to decrease the detection limit together with quenching and alpha, and beta crossover corrections should be carefully chosen according to the needs of the laboratory. Both aspects are being approached in this work as to find an easy and robust method for alpha/beta measurement in water samples, taking into account the quenching and alpha/beta crossover interferences effects. Results showed that most of the pre-concentration methods increased the quenching in the measurement, although HNO{sub 3} 0.05 M points to be the best solution for pre-concentration and re-dissolution of the sample as converges into low quenching and maximum recovery. Subsequently, in the measurement of water samples with different conductivities, the analysis of the raw counts to obtain gross alpha and beta indexes was carried out using different approaches to implement quenching and interference corrections. If quenching and salt content in the sample are relatively low, interference and quenching-efficiency corrections do not improve the accuracy of the results within the usual precision assumed for a result of gross alpha and beta index (25%). Special attention must be paid when corrections are applied to high quenched or saline samples and when alpha and beta activities values are different in several orders of magnitude. - Highlights: > Developed method for simultaneously quantifying gross alpha and gross beta indexes based on LSC was as accurate and precise as the results obtained from methods based on gas proportional counting and ZnS alpha counting. > Alpha/beta crossover and/or quenching corrections were applied and the results obtained did not improve accuracy within 25% dispersion, a widespread acceptance limit for gross alpha and

  15. The natural radioactivity in water by gross alpha and beta measurements

    Energy Technology Data Exchange (ETDEWEB)

    Bonotto, D.M. [Departamento de Petrologia e Metalogenia, Universidade Estadual Paulista (UNESP), Av. 24-A No. 1515, C.P. 178, CEP 13506-900, Rio Claro, SP (Brazil)], E-mail: danielbonotto@yahoo.com.br; Bueno, T.O.; Tessari, B.W.; Silva, A. [Departamento de Petrologia e Metalogenia, Universidade Estadual Paulista (UNESP), Av. 24-A No. 1515, C.P. 178, CEP 13506-900, Rio Claro, SP (Brazil)

    2009-01-15

    An alternative method for evaluating gross alpha and beta radioactivity in water was developed by performing alpha counting using a surface barrier detector and gamma- ray spectrometry using a NaI(Tl) scintillation detector. Several experiments were realized under controlled conditions in the laboratory with the aim of establishing adequate calibration of the systems utilized for performing activity concentration measurements in water samples of variable salinity. Groundwater samples collected at several spas in Sao Paulo and Minas Gerais States in Brazil were submitted to the developed technique in order to assure its applicability in waters characterized by different Total Dissolved Solids content. The values obtained were compatible with the previous knowledge of the radioactivity of the studied water sources, thus indicating the reliability and usefulness of the method for generating information on investigations focusing environmental aspects and/or the evaluation of the drinking water quality in terms of radiological aspects.

  16. A measurement of $\\alpha_{s}$ (M$_{Z}^{2}$) from the Gross Llewellyn Smith sum rule

    CERN Document Server

    Harris, D A; Auchincloss, P S; De Barbaro, P; Bazarko, A O; Bernstein, R H; Bodek, A; Bolton, T; Budd, H; Conrad, J; Drucker, R B; Johnson, R A; Kim, J H; King, B J; Kinnel, T; Koizumi, G; Koutsoliotas, S; Lamm, M J; Lefmann, W C; Marsh, W; McFarland, K S; McNulty, C; Mishra, S R; Naples, D; Nienaber, P; Nussbaum, M; Oreglia, M J; Perera, L; Quintas, P Z; Romosan, A; Sakumoto, W K; Schumm, B A; Sciulli, F J; Seligman, W G; Shaevitz, M H; Smith, W H; Spentzouris, P; Steiner, R; Stern, E G; Vakili, M; Yang, U K

    1995-01-01

    The Gross Llewellyn Smith sum rule has been measured at different values of four-momentum transfer squared (Q^{2}) by combining the precise CCFR neutrino data with data from other deep-inelastic scattering experiments at lower values of Q^{2}. A comparison with the {\\cal O}(\\alpha^{3}_{s}) predictions of perturbative QCD yields a determination of \\alpha_{s} and its dependence on Q^{2} in the range 1\\,GeV^2 < Q^{2} < 20 \\,GeV^{2}. Low \\qsq\\ tests have greater sensitivity to \\alfs(\\mztwo) than high \\qsq\\ tests, since at low Q^2, \\alpha_s is large and changing rapidly.

  17. 210Po in Nevada groundwater and its relation to gross alpha radioactivity

    Science.gov (United States)

    Seiler, R.L.

    2011-01-01

    Polonium-210 (210Po) is a highly toxic alpha emitter that is rarely found in groundwater at activities exceeding 1 pCi/L. 210Po activities in 63 domestic and public-supply wells in Lahontan Valley in Churchill County in northern Nevada, United States, ranged from 0.01 ± 0.005 to 178 ± 16 pCi/L with a median activity of 2.88 pCi/L. Wells with high 210Po activities had low dissolved oxygen concentrations (less than 0.1 mg/L) and commonly had pH greater than 9. Lead-210 activities are low and aqueous 210Po is unsupported by 210Pb, indicating that the 210Po is mobilized from aquifer sediments. The only significant contributors to alpha particle activity in Lahontan Valley groundwater are 234/238U, 222Rn, and 210Po. Radon-222 activities were below 1000 pCi/L and were uncorrelated with 210Po activity. The only applicable drinking water standard for 210Po in the United States is the adjusted gross alpha radioactivity (GAR) standard of 15 pCi/L. 210Po was not volatile in a Nevada well, but volatile 210Po has been reported in a Florida well. Additional information on the volatility of 210Po is needed because GAR is an inappropriate method to screen for volatile radionuclides. About 25% of the samples had 210Po activities that exceed the level associated with a lifetime total cancer risk of 1× 10−4 (1.1 pCi/L) without exceeding the GAR standard. In cases where the 72-h GAR exceeds the uranium activity by more than 5 to 10 pCi/L, an analysis to rule out the presence of 210Po may be justified to protect human health even though the maximum contaminant level for adjusted GAR is not exceeded.

  18. Activity level of gross α and gross β in airborne aerosol samples around the Qinshan NPP

    Institute of Scientific and Technical Information of China (English)

    CHEN Bin; YE Jida; CHEN Qianyuan; WU Xiaofei; SONG Weili; WANG Hongfeng

    2007-01-01

    The monitoring results of gross α and gross β activity from 2001 to 2005 for environmental airborne aerosol samples around the Qinshan NPP base are presented in this paper. A total of 170 aerosol samples were collected from monitoring sites of Caichenmen village, Qinlian village, Xiajiawan village and Yangliucun village around the Qinshan NPP base. The measured specific activity of gross α and gross β are in the range of 0.02 ~ 0.38 mBq/m3 and 0.10 ~ 1.81 mBq/m3, respectively, with an average of 0.11 mBq/m3 and 0.45mBq/m3, respectively. They are lower than the average of 0.15 mBq/m3 and 0.52mBq/m3, of reference site at Hangzhou City. It is indicated that the specific activity of gross α and gross β for environmental aerosol samples around the Qinshan NPP base had not been increased in normal operating conditions of the NPP.

  19. Interpreting EEG alpha activity.

    Science.gov (United States)

    Bazanova, O M; Vernon, D

    2014-07-01

    Exploring EEG alpha oscillations has generated considerable interest, in particular with regards to the role they play in cognitive, psychomotor, psycho-emotional and physiological aspects of human life. However, there is no clearly agreed upon definition of what constitutes 'alpha activity' or which of the many indices should be used to characterize it. To address these issues this review attempts to delineate EEG alpha-activity, its physical, molecular and morphological nature, and examine the following indices: (1) the individual alpha peak frequency; (2) activation magnitude, as measured by alpha amplitude suppression across the individual alpha bandwidth in response to eyes opening, and (3) alpha "auto-rhythmicity" indices: which include intra-spindle amplitude variability, spindle length and steepness. Throughout, the article offers a number of suggestions regarding the mechanism(s) of alpha activity related to inter and intra-individual variability. In addition, it provides some insights into the various psychophysiological indices of alpha activity and highlights their role in optimal functioning and behavior.

  20. Determination of natural radioactivity by gross alpha and beta measurements in ground water samples.

    Science.gov (United States)

    Turhan, S; Ozçitak, E; Taşkin, H; Varinlioğlu, A

    2013-06-01

    In this study, the activity concentrations of the gross α and β in ground water samples collected from the different drilled wells in Nevşehir province were measured to assess annual effective dose due to the ingestion of the water samples. Nevşehir province is one of the major cities of Cappadocia Region which is a popular tourist destination as it has many areas with unique geological, historic, and cultural features. Sampling and measurements were carried out in the autumn of 2011 and the spring of 2012. The values of the activity concentrations of the gross α and β measured in the water samples ranged from 80 to 380 mBq L(-1) with a mean of 192 mBq L(-1) and 120-3470 mBq L(-1) with a mean of 579 mBq L(-1) respectively. All values of the gross α were lower than the limit value of 500 mBq L(-1) while two ground water samples were found to have gross β activity concentrations of greater than 1000 mBq L(-1). Therefore two water samples were the subject of further radioisotope-specific analysis. The obtained result indicated that the elevated activity concentrations of the gross β in these water samples are dominated by (40)K activity. Annual effective doses ranged from 0.04 to 0.20 mSv y(-1).

  1. Methods and Data Used to Investigate Polonium-210 as a Source of Excess Gross-Alpha Radioactivity in Ground Water, Churchill County, Nevada

    Science.gov (United States)

    Seiler, Ralph L.

    2007-01-01

    Ground water is the major source of drinking water in the Carson River Basin, California and Nevada. Previous studies have shown that uranium and gross-alpha radioactivities in ground water can be greater than U.S. Environmental Protection Agency Maximum Contaminant Levels, particularly in the Carson Desert, Churchill County, Nevada. Studies also have shown that the primary source of the gross-alpha radioactivity and alpha-emitting radionuclides in ground water is the dissolution of uranium-rich granitic rocks and basin-fill sediments that have their origins in the Sierra Nevada. However, ground water sampled from some wells in the Carson Desert had gross-alpha radioactivities greater than could be accounted for by the decay of dissolved uranium. The occurrence of polonium-210 (Po-210) was hypothesized to explain the higher than expected gross-alpha radioactivities. This report documents and describes the study design, field and analytical methods, and data used to determine whether Po-210 is the source of excess gross-alpha radioactivity in ground water underlying the Carson Desert in and around Fallon, Nevada. Specifically, this report presents: 1) gross alpha and uranium radioactivities for 100 wells sampled from June to September 2001; and 2) pH, dissolved oxygen, specific conductance, and Po-210 radioactivity for 25 wells sampled in April and June 2007. Results of quality-control samples for the 2007 dataset are also presented.

  2. Gross-beta activity in ground water: natural sources and artifacts of sampling and laboratory analysis

    Science.gov (United States)

    Welch, Alan H.

    1995-01-01

    Gross-beta activity has been used as an indicator of beta-emitting isotopes in water since at least the early 1950s. Originally designed for detection of radioactive releases from nuclear facilities and weapons tests, analysis of gross-beta activity is widely used in studies of naturally occurring radioactivity in ground water. Analyses of about 800 samples from 5 ground-water regions of the United States provide a basis for evaluating the utility of this measurement. The data suggest that measured gross-beta activities are due to (1) long-lived radionuclides in ground water, and (2) ingrowth of beta-emitting radionuclides during holding times between collection of samples and laboratory measurements.Although40K and228Ra appear to be the primary sources of beta activity in ground water, the sum of40K plus228Ra appears to be less than the measured gross-beta activity in most ground-water samples. The difference between the contribution from these radionuclides and gross-beta activity is most pronounced in ground water with gross-beta activities > 10 pCi/L, where these 2 radionuclides account for less than one-half the measured ross-beta activity. One exception is groundwater from the Coastal Plain of New Jersey, where40K plus228Ra generally contribute most of the gross-beta activity. In contrast,40K and228Ra generally contribute most of beta activity in ground water with gross-beta activities measure all beta activity in ground water. Although3H contributes beta activity to some ground water, it is driven from the sample before counting and therefore is not detected by gross-beta measurements. Beta-emitting radionuclides with half-lives shorter than a few days can decay to low values between sampling and counting. Although little is known about concentrations of most short-lived beta-emitting radionuclides in environmental ground water (water unaffected by direct releases from nuclear facilities and weapons tests), their activities are expected to be low.Ingrowth of

  3. Evaluation of gross radioactivity in foodstuffs

    Energy Technology Data Exchange (ETDEWEB)

    Zorer, Oezlem Selcuk; Oeter, Cigdem [Yuzuncu Yil Univ., Van (Turkey). Dept. of Chemistry

    2015-05-15

    The paper presents the results of radiological investigations of food products sampled in the summer and fall of 2011 and 2012 in different parts of Van, Turkey. Gross radioactivity measurements in food products were evaluated. Food items were divided into eight groups: (1) water, (2) fish, (3) cheese products, (4) fruits, (5) vegetables, (6) herbs, (7) walnut and (8) rock salt. The levels of the gross alpha and gross beta radioactivity in all food samples varied widely ranging from 0.070 to 10.885 Bq/g and from 0.132 to 48.285 Bq/g on dry mass basis, respectively. In one sample, gross alpha and gross beta activity concentrations were found to be relatively high according to the other samples and in all samples, the gross alpha radioactivity was measured lower than the gross beta radioactivity. The gross α and gross β activities were measured by using α/β counter of the multi-detector low background system (PIC MPC-9604).

  4. Gross β activity level of fallout in the environment around Qinshan Nuclear Power Plant

    Institute of Scientific and Technical Information of China (English)

    YE Ji-Da; CHEN Bin; WU Zong-Mei

    2005-01-01

    This paper presents the measurement results of gross β activities in fallout samples collected from the environment around Qinshan Nuclear Power Plant (NPP) during 1993-2002. The gross β activity of 191 samples collected at five monitoring spots were (0.11~3.64) Bq · m-2 · d-1, with an average of (0.91 ±0.49) Bq · m-2 · d-1. This value was lower than (1.02±0.35) Bq·m-2·d-1 , the average of the samples collected at the reference spot in Hangzhou.It indicated that no obvious rise in the gross β activity level of fallout was observed in ambience of Qinshan NPP.

  5. Determination of gross-β and γ-ray activity concentrations of human tooth

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Hayun Ja [Dept. of Dental Hygene, Daegu Health College, Daegu (Korea, Republic of); Kang, Hyun Kyung [Dept. of Dental Hygene, Silla University, Daegu (Korea, Republic of); Kim, Sung Hwan [Dept. of Radiological Science, Cheongju University, Cheongju (Korea, Republic of)

    2014-12-15

    The γ-ray concentration and grossactivity by age group were measured in the teeth of males and females of the domestic residents. They were divided into 7 age groups from 10s to the age of 70s. The grossactivity concentration was measured by using the Tennelec XLB measuring instrument filled with P10 gas (argon 90%, methane 10%). The γ-ray was measured through the γ-ray spectroscopic analytical method by using the high purity germanium (HPGe) radiation detector. The range of grossactivity concentration was measured 0.089 to 0.32 Bq/kg in females and 0.13 to 0.26 Bq/kg in males. From the γ-ray spectroscopic analysis of the teeth, the natural radioactive isotopes of '4{sup 0}K, {sup 208}Tl, {sup 228}Ac and {sup 234}Th were detected and their measured γ-ray activity concentrations were found to be 20.7, 21.9, 3.88 and 5.24 Bq/kg, respectively.

  6. Measurement of {ital {alpha}}{sub {ital s}}({ital Q}{sup 2}) from the Gross{endash}Llewellyn Smith Sum Rule

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, R.A.; Vakili, M. [University of Cincinnati, Cincinnati, Ohio 45221 (United States); Kim, J.H.; Arroyo, C.G.; Bazarko, A.O.; Conrad, J.; King, B.J.; Lefmann, W.C.; McNulty, C.; Mishra, S.R.; Quintas, P.Z.; Romosan, A.; Schellman, H.; Sciulli, F.J.; Seligman, W.G.; Shaevitz, M.H.; Spentzouris, P.; Stern, E.G. [Columbia University, New York, New York 10027 (United States); Bernstein, R.H.; Lamm, M.J.; Marsh, W.; McFarland, K.S.; Yu, J. [Fermi National Accelerator Laboratory, Batavia, Illinois 60510 (United States); Bolton, T.; Naples, D. [Kansas State University, Manhattan, Kansas 66506 (United States); de Barbaro, L. [Northwestern University, Evanston, Illinois 60208 (United States); Harris, D.A.; de Barbaro, P.; Bodek, A.; Budd, H.; Sakumoto, W.K.; Yang, U.K. [University of Rochester, Rochester, New York 14627 (United States); Kinnel, T.; Smith, W.H. [University of Wisconsin, Madison, Wisconsin 53706 (United States)

    1998-10-01

    We extract a set of values for the Gross{endash}Llewellyn Smith sum rule at different values of 4-momentum transfer squared (Q{sup 2} ), by combining revised CCFR neutrino data with data from other neutrino deep-inelastic scattering experiments for 1{lt}Q{sup 2}{lt}15 GeV{sup 2}/c{sup 2} . A comparison with the order {alpha}{sup 3}{sub s} theoretical predictions yields a determination of {alpha}{sub s} at the scale of the Z -boson mass of 0.114{plus_minus}{sup 0.009}{sub 0.012} . This measurement provides a new and useful test of perturbative QCD at low Q{sup 2} , because of the low uncertainties in the higher order calculations. {copyright} {ital 1998} {ital The American Physical Society }

  7. 探讨串道现象对饮用水中的总放射性测量结果的影响%Influence of crosstalk phenomenon on the measurement of gross alpha and gross beta radioactivity in drinking water

    Institute of Scientific and Technical Information of China (English)

    格日勒满达呼; 哈日巴拉; 许潇; 申娜; 赛文嘎; 白桂林; 王成国

    2014-01-01

    目的 研究串道现象对饮用水中的总放射性测量结果的影响程度.方法 采用不同标准物质、不同的厚度、不同面积进行总放射性测量试验.结果 用241 Am粉测试的串道因子数随质量增加无明显变化,铀粉则随质量增加而增加.仪器测试通道不同,串道因子数也不同.总α对总β的串道影响很明显,反过来串道因子数很小,可忽略.串道因子数受样品盘面积的影响不明显.结论 做饮用水中总放射性检测使用α-β同时测量模式时,总β放射性活度受α串道影响,可以通过粉末标准物质进行修正,减小对测量结果的影响.%Objective To study the influence of crosstalk phenomenon on the measurement of gross radioactivity in drinking water.Methods The gross activity in different standard materials with different thickness and area was measured using national standard method.Results There was no obvious change in crosstalk factor with the increase of 241Am powder amount in the measurement,whereas the larger amount of uranium used might lead to larger crosstalk factor.The different measurement channels resulted in different crosstalk factors.The influence of beta radioactivity on alpha radioactivity measurement was significant.On the contrary,the alpha-to-beta crosstalk factor was negligible.The area of sample plate imposed no significant influence on crosstalk factor.Conclusions The gross beta activity can be corrected to decrease the influence of alpha radioactivity using powder standard samples,when simultaneous alpha and beta counting mode is applied in measurement grass radioactivity in drinking water.

  8. Peroxisome Proliferator-Activated Receptor Alpha Target Genes

    OpenAIRE

    Maryam Rakhshandehroo; Bianca Knoch; Michael Müller; Sander Kersten

    2010-01-01

    The peroxisome proliferator-activated receptor alpha (PPAR alpha) is a ligand-activated transcription factor involved in the regulation of a variety of processes, ranging from inflammation and immunity to nutrient metabolism and energy homeostasis. PPAR alpha serves as a molecular target for hypolipidemic fibrates drugs which bind the receptor with high affinity. Furthermore, PPAR alpha binds and is activated by numerous fatty acids and fatty acid-derived compounds. PPAR alpha governs biologi...

  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. Relationship between time use in physical activity and gross motor performance of preschool children.

    Science.gov (United States)

    Lin, Ling-Yi; Cherng, Rong-Ju; Chen, Yung-Jung

    2017-02-01

    Participation in physical activity is an important health concern for children in most Western communities, but little is known about Asian children's participation. The purpose of this study was to extend the current knowledge on how much time preschool children in Taiwan spend on physical activity, to examine its relationship with gross motor performance and to provide information on the establishment of physical activity guidelines for preschool children in Taiwan. Two hundred and sixty-four children between 36 and 71 months old were recruited from a university medical centre and from preschools in Taiwan. The primary outcomes were measured using the Movement Assessment Battery for Children-Second Edition and the modified Preschool-aged Children's Physical Activity Questionnaire. 89.8% of our participants did not meet the recommendations from the National Association for Sport and Physical Education for time spent in physical activities. Participants spent an average of 155 minutes/week in low intensity physical activity. Children with motor difficulties tended to spend less time on physical activity than did typically developing children. The mother's level of education and whether the child was overweight or obese correlated with how much time the children spent on physical activity. We conclude that paediatric occupational therapists should explain to parents the relationship between physical activity and motor development and advocate for developmentally positive physical activities for preschool children. Physical activity guidelines for Taiwanese preschoolers should be established immediately. © 2016 Occupational Therapy Australia.

  11. Determination of total alpha and beta activities on vegetable samples by LSC; Determinacao de atividades alfa total e beta total em amostras vegetais por LSC

    Energy Technology Data Exchange (ETDEWEB)

    Nogueira, Regina Apolinaria; Santos, Eliane Eugenia dos; Bakker, Alexandre Pereira [Centro Regional de Ciencias Nucleares do Centro-Oeste (CRCN-CO/CNEN-GO), Abadia de Goias, GO (Brazil); Vavassori, Giullia [Centro Regional de Ciencias Nucleares do Centro-Oeste (CRCN-CO/CNEN-GO), Abadia de Goias, GO (Brazil); Pontificia Universidade Catolica de Goias (PUC-GO), Goiania, GO (Brazil). Dept. de Engenharia, Engenharia Ambiental; Mingote, Raquel Maia [Centro Regional de Ciencias Nucleares do Centro-Oeste (CRCN-CO/CNEN-GO), Abadia de Goias, GO (Brazil); Universidade Federal de Minas Gerais (DEN/UFMG), Belo Horizonte, MG (Brazil)

    2011-07-01

    Gross alpha and beta analyses are screening techniques used for environmental radioactivity monitoring. The present study proposes to determine the gross alpha and beta activities in vegetable samples by using LSC - liquid scintillation spectrometry. The procedure was applied to vegetable foods. After ashing vegetable samples in a muffle furnace, 100 mg of ash were added to gel mixture of scintillation cocktails, Water - Instagel - Ultima Gold AB (6:10:4) ml, in polyethylene vial. Am-241 standard solution and a KCl (K-40) solution were used to determine the counting configuration, alpha/beta efficiencies and spillover

  12. [Individual alpha activity of electroencephalogram and nonverbal creativity].

    Science.gov (United States)

    Bazanova, O M; Aftanas, L I

    2007-01-01

    The main objective of present correlational investigation was to clarify relationships between nonverbal creativity indices and individual electroencephalogram alpha activity indices: individual alpha peak frequency, alpha band width, magnitude of alpha desynchronization and alpha spindle indices such as duration, amplitude, variability and skewness. The EEG was recorded in 98 healthy male right-handed subjects. Scores of nonverbal creativity (i. e., fluency, originality, and flexibility) were assessed using the Torrance test of nonverbal performance. The study showed that fluency in creative performance was associated with individual alpha peak frequency and alpha spindles duration, whereas originality and plasticity--with individual alpha band width and spindle amplitude variability. The findings also show that both highest and lowest individual alpha peak frequency indices are associated with enhanced scores of originality. It is suggested that individual alpha activity indices could be presented as individual predictors of fluency, plasticity and originality of nonverbal creativity.

  13. Peroxisome Proliferator-Activated Receptor Alpha Target Genes

    NARCIS (Netherlands)

    Rakhshandehroo, M.; Knoch, B.; Müller, M.R.; Kersten, A.H.

    2010-01-01

    The peroxisome proliferator-activated receptor alpha (PPAR alpha) is a ligand-activated transcription factor involved in the regulation of a variety of processes, ranging from inflammation and immunity to nutrient metabolism and energy homeostasis. PPAR alpha serves as a molecular target for hypolip

  14. Peroxisome Proliferator-Activated Receptor Alpha Target Genes

    NARCIS (Netherlands)

    Rakhshandehroo, M.; Knoch, B.; Müller, M.R.; Kersten, A.H.

    2010-01-01

    The peroxisome proliferator-activated receptor alpha (PPAR alpha) is a ligand-activated transcription factor involved in the regulation of a variety of processes, ranging from inflammation and immunity to nutrient metabolism and energy homeostasis. PPAR alpha serves as a molecular target for

  15. Do collaborative practical tests encourage student-centered active learning of gross anatomy?

    Science.gov (United States)

    Green, Rodney A; Cates, Tanya; White, Lloyd; Farchione, Davide

    2016-05-06

    Benefits of collaborative testing have been identified in many disciplines. This study sought to determine whether collaborative practical tests encouraged active learning of anatomy. A gross anatomy course included a collaborative component in four practical tests. Two hundred and seven students initially completed the test as individuals and then worked as a team to complete the same test again immediately afterwards. The relationship between mean individual, team, and difference (between team and individual) test scores to overall performance on the final examination (representing overall learning in the course) was examined using regression analysis. The overall mark in the course increased by 9% with a decreased failure rate. There was a strong relationship between individual score and final examination mark (P learning occurring during the collaborative testing and that weaker students gained the benefit from team marks without significant active learning taking place. This negative outcome may be due to insufficient encouragement of the active learning strategies that were expected to occur during the collaborative testing process. An improved understanding of the efficacy of collaborative assessment could be achieved through the inclusion of questionnaire based data to allow a better interpretation of learning outcomes. Anat Sci Educ 9: 231-237. © 2015 American Association of Anatomists. © 2015 American Association of Anatomists.

  16. 76 FR 28754 - Agency Information Collection Activities: Notice of Intent To Renew Collection 3038-0026, Gross...

    Science.gov (United States)

    2011-05-18

    ... From the Federal Register Online via the Government Publishing Office COMMODITY FUTURES TRADING COMMISSION Agency Information Collection Activities: Notice of Intent To Renew Collection 3038-0026, Gross Collection of Exchange-Set Margins for Omnibus Accounts AGENCY: Commodity Futures Trading Commission....

  17. Interplay of drought and tropical cyclone activity in SE U.S. gross primary productivity

    Science.gov (United States)

    Lowman, Lauren E. L.; Barros, Ana P.

    2016-06-01

    Tropical cyclones (TCs), often associated with massive flooding and landslides in the Southeast U.S. (SE U.S.), provide a significant input of freshwater to the hydrologic system, and their timing and trajectory significantly impact drought severity and persistence. This manuscript investigates the sensitivity of gross primary productivity (GPP) in the SE U.S. to TC activity using the 1-D column implementation of the Duke Coupled Hydrology Model with Vegetation (DCHM-V) including coupled water and energy cycles and a biochemical representation of photosynthesis. Decadal-scale simulations of water, energy, and carbon fluxes were conducted at high temporal (30 min) and spatial (4 km) resolution over the period 2002-2012. At local scales, model results without calibration compare well against AmeriFlux tower data. At regional scales, differences between the DCHM-V estimates and the Moderate Resolution Imaging Spectroradiometer GPP product reflect the spatial organization of soil hydraulic properties and soil moisture dynamics by physiographic region, highlighting the links between the water and carbon cycles. To isolate the contribution of TC precipitation to SE U.S. productivity, control forcing simulations are contrasted with simulations where periods of TC activity in the atmospheric forcing data were replaced with climatology. During wet years, TC activity impacts productivity in 40-50% of the SE U.S. domain and explains a regional GPP increase of 3-5 Mg C/m2 that is 9% of the warm season total. In dry years, 23-34% of the domain exhibits a smaller positive response that corresponds to 4-8% of the seasonal carbon uptake, depending on TC timing and trajectory.

  18. The activity of granulocyte alpha-amylase in acute appendicitis.

    Science.gov (United States)

    Zakrzewska, I; Gajda, R

    1994-01-01

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

  19. 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.

  20. 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.......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....

  1. Distribution of alpha-amylase activity in selected broiler tissues.

    Science.gov (United States)

    Rodeheaver, D P; Wyatt, R D

    1986-02-01

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

  2. Antibacterial activity of citreamicin-alpha (LL-E 19085 alpha) against gram-positive cocci.

    Science.gov (United States)

    Qadri, S M; Saldin, H; Ueno, Y; al-Ballaa, S R

    1992-01-01

    In vitro antibacterial activity of 429 clinical isolates of gram-positive cocci was tested against citreamicin-alpha (LL-E 19085-alpha) by the agar dilution method. The microorganisms consisted of 313 isolates of staphylococci and 116 strains of streptococci. In vitro activity of citreamicin-alpha was compared with ampicillin, augmentin, cephalothin, erythromycin and vancomycin. MICs of citreamicin-alpha for staphylococci ranged between 0.12-4.0 micrograms/ml and 0.03-0.12 micrograms/ml for Streptococcus pyogenes. Enterococci, however, were relatively more resistant, requiring 2.0 micrograms/ml of this drug to inhibit 64% of the 62 isolates tested. In vitro activity of this antibacterial agent was far superior to that of ampicillin, augmentin, cephalothin and erythromycin, but equal to or slightly inferior to that of vancomycin.

  3. 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.

  4. Effect of task-oriented training and high-variability practice on gross motor performance and activities of daily living in children with spastic diplegia

    National Research Council Canada - National Science Library

    Kwon, Hae-Yeon; Ahn, So-Yoon

    2016-01-01

    [Purpose] This study investigates how a task-oriented training and high-variability practice program can affect the gross motor performance and activities of daily living for children with spastic diplegia...

  5. Alpha-mannosidase activity in goats fed with Sida carpinifolia.

    Science.gov (United States)

    Bedin, Marisete; Moleta Colodel, Edson; Viapiana, Marli; Matte, Ursula; Driemeier, David; Giugliani, Roberto

    2010-03-01

    Human alpha-mannosidosis results from alpha-mannosidase deficiency and progressive accumulation of mannose-rich oligosaccharides in lysosomes. Two days before Saanen goats were fed with Sida carpinifolia, alpha-mannosidase activity in leukocytes was 128+/-28 nmoles4-MU/h/mgprotein (first trial) and 104+/-6 nmoles4-MU/h/mgprotein (second trial). At day 5, after the introduction of S. carpinifolia diet, the alpha-mannosidase activity in leukocytes was significantly increased, both in the first (288+/-13 nmoles4-MU/h/mgprotein) and in the second trial (303+/-45 nmoles4-MU/h/mgprotein), and it returned to normal levels 2 days after the withdrawal of the plant from the diet (114+/-7 nmoles4-MU/h/mgprotein in first trial, and 108+/-25 nmoles4-MU/h/mgprotein in the second one). Plasma alpha-mannosidase activity decreased significantly 4 days after animal exposure to the S. carpinifolia diet (769+/-167 nmoles4-MU/h/ml) and returned to normal values 10 days after the withdrawal of the plant from the diet (1289+/-163 nmoles4-MU/h/ml). Thin-layer chromatography showed an abnormal excretion of oligosaccharides in urine as of day 2 after diet exposure, which persisted until one day after the withdrawal of the plant. Animals presented neurological clinical signs beginning at day 37 (in the first trial) and at day 25 (in the second trial) after being fed with the plant. The results obtained herein suggest that oligosaccharides observed in urine are a result of a decrease in alpha-mannosidase activity in plasma. S. carpinifolia seems to have other compounds that act on alpha-mannosidase enzyme in leukocytes in a competitive manner with swainsonine. The increase in alpha-mannosidase enzyme in leukocytes could be attributed to one of these compounds present in S. carpinifolia. Copyright 2009 Elsevier GmbH. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Maëlle Lempereur

    2016-01-01

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

  7. Adsorption behavior of alpha -cypermethrin on cork and activated carbon.

    Science.gov (United States)

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

    2007-08-01

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

  8. Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST-RA database

    DEFF Research Database (Denmark)

    Sokka, T; Kautiainen, H; Pincus, T

    2009-01-01

    OBJECTIVE: To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country. METHODS: The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) cohort includes clinical......-related variables were analysed according to GDP per capita, including 14 "high GDP" countries with GDP per capita greater than US$24,000 and 11 "low GDP" countries with GDP per capita less than US$11,000. RESULTS: Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly...... associated with GDP (r = -0.78, 95% CI -0.56 to -0.90, r(2) = 61%). Disease activity levels differed substantially between "high GDP" and "low GDP" countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents...

  9. Hydrolytic activity of alpha-amylase in anaerobic digested sludge.

    Science.gov (United States)

    Higuchi, Y; Ohashi, A; Imachi, H; Harada, H

    2005-01-01

    Hydrolysis is usually considered to be a rate-limiting step in anaerobic digestion. For improving anaerobic solid waste treatments, it is essential to elucidate the mechanism of hydrolysis. In this study, alpha-amylase, one of the hydrolytic enzymes, was investigated for the elucidation of more precise mechanism of hydrolysis. Alpha-amylase activity of solid starch-degrading bacteria (SDB) was estimated through batch experiments with several different substrates and with distinction between cell-bound and cell-free alpha-amylase. Monitoring of newly isolated strains of SDB was done by fluorescence in situ hybridization. Results indicated that cell-bound alpha-amylase is chiefly responsible for the hydrolysis in the digested sludge, providing very useful information that the contact between microbial cells and solids is significantly important. The activity of alpha-amylase of the digested sludge remained quite low when not required, but increased as they recognized appropriate substrates. Several-fold higher activity was obtained for starch or maltose as compared to glucose only.

  10. 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.

  11. 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

  12. Gross motor control

    Science.gov (United States)

    Gross motor control is the ability to make large, general movements (such as waving an arm or lifting a leg). ... Gross motor control is a milestone in the development of an infant. Infants develop gross motor control before they develop ...

  13. Somatosensory Anticipatory Alpha Activity Increases to Suppress Distracting Input

    Science.gov (United States)

    Haegens, Saskia; Luther, Lisa; Jensen, Ole

    2012-01-01

    Effective processing of sensory input in daily life requires attentional selection and amplification of relevant input and, just as importantly, attenuation of irrelevant information. It has been proposed that top-down modulation of oscillatory alpha band activity (8-14 Hz) serves to allocate resources to various regions, depending on task…

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

    DEFF Research Database (Denmark)

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

    1998-01-01

    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...... 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...

  15. 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

    -terminal His-tag and the p85alpha regulatory domain in Sf9 insect cells. The complex consisting of p110alpha and p85alpha was purified by nickel affinity chromatography. The authors established an adenosine triphosphate (ATP) depletion assay to measure the activity of p110alpha/p85alpha. The assay...

  16. alpha-MSH enhances activity-based anorexia.

    Science.gov (United States)

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

    2005-10-01

    Activity-based anorexia (ABA) is considered an animal model of anorexia nervosa (AN). In ABA, scheduled feeding in combination with voluntary access to running wheels, results in hyperactivity, hypophagia, body weight loss and activation of the HPA axis. Since stimulation of the melanocortin (MC) system has similar effects, this system is a candidate system involved in ABA. Here it is shown that chronic alpha-MSH treatment enhances ABA by increasing running wheel activity (RWA), decreasing food intake and increasing HPA axis activation.

  17. Surface activity and radiation field measurements of the TMI-2 reactor building gross decontamination experiment

    Energy Technology Data Exchange (ETDEWEB)

    McIsaac, C V

    1983-10-01

    Surface samples were collected from concrete and metal surfaces within the Three Mile Island Unit 2 Reactor Building on December 15 and 17, 1981 and again on March 25 and 26, 1982. The Reactor Building was decontaminated by hydrolasing during the period between these dates. The collected samples were analyzed for radionuclide concentration at the Idaho National Engineering Laboratory. The sampling equipment and procedures, and the analysis methods and results are discussed. The measured mean surface concentrations of /sup 137/Cs and /sup 90/Sr on the 305-ft elevation floor before decontamination were, respectively, 3.6 +- 0.9 and 0.17 +- 0.04 ..mu..Ci/cm/sup 2/. Their mean concentrations on the 347-ft elevation floor were about the same. On both elevations, walls were found to be considerably less contaminated than floors. The fractions of the core inventories of /sup 137/Cs, /sup 90/Sr, and /sup 129/I deposited on Reactor Building surfaces prior to decontamination were calculated using their mean concentrations on various types of surfaces. The calculated values for these three nuclides are 3.5 +- 0.4 E-4, 2.4 +- 0.8 E-5, and 5.7 +- 0.5 E-4, respectively. The decontamination operations reduced the /sup 137/Cs surface activity on the 305- and 347-ft elevations by factors of 20 and 13, respectively. The /sup 90/Sr surface activity reduction was the same for both floors, that being a factor of 30. On the whole, decontamination of vertical surfaces was not achieved. Beta and gamma exposure rates that were measured during surface sampling were examined to determine the degree to which they correlated with measured surface activities. The data were fit with power functions of the form y = ax/sup b/. As might be expected, the beta exposure rates showed the best correlation. Of the data sets fit with the power function, the set of December 1981 beta exposure exhibited the least scatter. The coefficient of determination for this set was calculated to be 0.915.

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

    Directory of Open Access Journals (Sweden)

    Freya M Mowat

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

  19. Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST–RA database

    Science.gov (United States)

    Sokka, T; Kautiainen, H; Pincus, T; Toloza, S; da Rocha Castelar Pinheiro, G; Lazovskis, J; Hetland, M L; Peets, T; Immonen, K; Maillefert, J F; Drosos, A A; Alten, R; Pohl, C; Rojkovich, B; Bresnihan, B; Minnock, P; Cazzato, M; Bombardieri, S; Rexhepi, S; Rexhepi, M; Andersone, D; Stropuviene, S; Huisman, M; Sierakowski, S; Karateev, D; Skakic, V; Naranjo, A; Baecklund, E; Henrohn, D; Gogus, F; Badsha, H; Mofti, A; Taylor, P; McClinton, C; Yazici, Y

    2009-01-01

    Objective: To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country. Methods: The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST–RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 “high GDP” countries with GDP per capita greater than US$24 000 and 11 “low GDP” countries with GDP per capita less than US$11 000. Results: Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r  =  −0.78, 95% CI −0.56 to −0.90, r2  =  61%). Disease activity levels differed substantially between “high GDP” and “low GDP” countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents. Conclusions: The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in “low GDP” than in “high GDP” countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries. PMID:19643759

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

    African Journals Online (AJOL)

    Changes in the composition of the pulp, alpha-amylase activity and titratable acidity during the controlled rotting of egusi fruits ( Colocynthis citrullus l.) ... The alpha-amylase activity which was not detectable at 0 hour reached a ... Article Metrics.

  1. Activity of alpha-amylase inhibitors from Phaseolus coccineus on digestive alpha-amylases of the coffee berry borer.

    Science.gov (United States)

    Valencia-Jiménez, Arnubio; Arboleda Valencia, Jorge W; Grossi-De-Sá, Maria Fátima

    2008-04-09

    Seeds of scarlet runner bean ( Phaseolus coccineus L.) were analyzed for alpha-amylase inhibitor (alpha-AI) activity. Through the use of polyclonal antibodies raised against pure alpha-AI-1 from common bean ( Phaseolus vulgaris L.), typical alpha-AlphaIota polypeptides (Mr 14-18 kDa) as well as a large polypeptide of Mr 32000 Da, usually referred to as "amylase inhibitor like", were detected. The inhibitor activity present in four accessions of P. coccineus was examined, both in semiquantitative zymograms allowing the separation of different isoforms and in quantitative assays against human salivary amylase, porcine pancreatic amylase, and coffee berry borer, Hypothenemus hampei Ferrari (Coleoptera: Scolytidae) amylase. Differential inhibition curves lead to the suggestion that the gene encoding one of the inhibitors in P. coccineus (in accession G35590) would be a good candidate for genetic engineering of coffee resistance toward the coffee berry borer. An in vitro proteolytic digestion treatment of pure alpha-AlphaIota-1 resulted in a rapid loss of the inhibitory activity, seriously affecting its natural capacity to interact with mammalian alpha-amylases.

  2. [Mechanisms of gross saponins of Tribulus terrestris via activating PKCepsilon against myocardial apoptosis induced by oxidative stress].

    Science.gov (United States)

    Wang, Si-Si; Ji, Ying-Shi; Li, Hong; Yang, Shi-Jie

    2009-02-01

    This study is to observe the effect of gross saponins of Tribulus terrestris (GSTT) on protein kinase Cepsilon (PKCepsilon) and apoptosis-associated protein in the apoptosis of cultured cardiocyte apoptosis induced by hydrogen peroxide (H2O2), and to explore the mechanisms of GSTT against myocardial apoptosis. Primary cardiocytes were isolated and cultured. Myocardial apoptosis was induced by H2O2 and analyzed with flow cytometry. Protein content of phospho-PKCepsilon, Bcl-2, and Bax were detected with Western blotting analysis. Cleaved caspase-3 protein content was determined with immunocytochemical technique. After the pretreatment of 100 mg x L(-1) GSTT, compared with H2O2 group, GSTT could not only decrease the apoptotic percentage in cardiocytes damaged by H2O2 (P < 0.01), but also reduce protein contents of Bax and cleaved caspase-3 (P < 0.01), and increase protein content of phospho-PKCepsilon and Bcl-2 significantly (P < 0.01). PKC inhibitor chelerythrine (Che) could prevent partly the effect of GSTT against myocardial apoptosis (P < 0.05 and P < 0.01). Mechanisms of GSTT against myocardial apoptosis might be associated with inhibition of mitochondrial apoptosis pathway after PKCepsilon activation.

  3. Activating STAT3 Alpha for Promoting Healing of Neurons

    Science.gov (United States)

    Conway, Greg

    2008-01-01

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

  4. T cells activate the tumor necrosis factor-alpha system during hemodialysis, resulting in tachyphylaxis

    NARCIS (Netherlands)

    van Riemsdijk, I C; Baan, C C; Loonen, E H; Knoop, C J; Navarro Betonico, G; Niesters, H G; Zietse, R; Weimar, W

    2001-01-01

    BACKGROUND: The immunosuppressive state of hemodialysis (HD) patients is accompanied by activation of antigen-presenting cell-derived cytokines, for example, tumor necrosis factor-alpha (TNF-alpha), which are required for T-cell activation. To test whether an activated TNF-alpha system results in im

  5. 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,

  6. Ultraviolet-mediated antimycotic activity of alpha-terthienyl on Microsporum cookei.

    Science.gov (United States)

    Mares, D; Fasulo, M P; Bruni, A

    1990-01-01

    Alpha-terthienyl (alpha-T) in the presence of UV-A irradiation reduced the growth rate of Microsporum cookei. In the dark, alpha-T accumulated in small diffuse vacuoles within the hyphae. After UV-A treatment, alpha-T caused damage to the membranes of the nucleus, mitochondria and endoplasmic reticulum. Plasmolytic and autolytic changes occurred resulting in plasma membrane breakage and cell wall aberrations. UV-A activated alpha-T would appear to target membrane proteins.

  7. NM Gross Receipts Baseline

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — This layer represents boundaries for New Mexico's gross receipts tax districts as identified on the "Gross Receipts Tax Rate Schedule" published by the Taxation and...

  8. Gross National Happiness

    DEFF Research Database (Denmark)

    Giri, Krishna Prasad; Kjær-Rasmussen, Lone Krogh

    This paper investigates practices related to the ideology of infusing Gross National Happiness (GNH) into school curriculum, the effectiveness of the meditation and mind training and the implication of GNH for school environment. It also explores how GNH ambience has been managed and practiced...... of Gross National Happiness and Educating for Gross National happiness....

  9. Role of G{alpha}12 and G{alpha}13 as Novel Switches for the Activity of Nrf2, a Key Antioxidative Transcription Factor

    OpenAIRE

    2007-01-01

    G{alpha}12 and G{alpha}13 function as molecular regulators responding to extracellular stimuli. NF-E2-related factor 2 (Nrf2) is involved in a protective adaptive response to oxidative stress. This study investigated the regulation of Nrf2 by G{alpha}12 and G{alpha}13. A deficiency of G{alpha}12, but not of G{alpha}13, enhanced Nrf2 activity and target gene transactivation in embryo fibroblasts. In mice, G{alpha}12 knockout activated Nrf2 and thereby facilitated heme catabolism to bilirubin a...

  10. [Alpha-glucosidase inhibitory activity of Aeschynanthus maculatus].

    Science.gov (United States)

    Tian, Pu-yu; Kang, Wen-yi

    2012-10-01

    To study the inhibitory activity of Aeschynanthus maculatus on alpha-glucosidase. The inhibilitory model of in vitro alpha-glucosidase was established. Active extracts of A. maculatus were isolated and identified bymultiple chromatographic methods, and their molecular structures were identifiied by spectral techniques. Seven coumpounts were isolated from A. maculatus and isolated as lupeol(1), stigmasterol(2), ursolic acid(3), stigmast-5,22(E)-diene-3beta-ol(4), beta-daucosterol(5), 3-hydroxy-12-taraxasten-28-oic-acid(6) and oleanic acid(7). Compounds 1 (IC50 25.41 mg x L(-1)),3(IC0 4.42 mg L(-1)),4(IC50 11.50 mg x L(-1)),6(IC50 14.17 mg x L(-1)) and 7(IC50 2.88 mg x L(-1)) had higher inhibitory activities than that of acarbose (IC50 1103.01 mg x L(-1)) as the positive control drug. Compound 1-7 were isolated from this plant for the first time. Compound 6 was isolated from Gesneriaceae family for the first time. Compound 7 was isolated from Aeschynanthus genus for the first time.

  11. Functional analysis of alpha-DOX2, an active alpha-dioxygenase critical for normal development in tomato plants.

    Science.gov (United States)

    Bannenberg, Gerard; Martínez, Marta; Rodríguez, María José; López, Miguel Angel; Ponce de León, Inés; Hamberg, Mats; Castresana, Carmen

    2009-11-01

    Plant alpha-dioxygenases initiate the synthesis of oxylipins by catalyzing the incorporation of molecular oxygen at the alpha-methylene carbon atom of fatty acids. Previously, alpha-DOX1 has been shown to display alpha-dioxygenase activity and to be implicated in plant defense. In this study, we investigated the function of a second alpha-dioxygenase isoform, alpha-DOX2, in tomato (Solanum lycopersicum) and Arabidopsis (Arabidopsis thaliana). Recombinant Slalpha-DOX2 and Atalpha-DOX2 proteins catalyzed the conversion of a wide range of fatty acids into 2(R)-hydroperoxy derivatives. Expression of Slalpha-DOX2 and Atalpha-DOX2 was found in seedlings and increased during senescence induced by detachment of leaves. In contrast, microbial infection, earlier known to increase the expression of alpha-DOX1, did not alter the expression of Slalpha-DOX2 or Atalpha-DOX2. The tomato mutant divaricata, characterized by early dwarfing and anthocyanin accumulation, carries a mutation at the Slalpha-DOX2 locus and was chosen for functional studies of alpha-DOX2. Transcriptional changes in such mutants showed the up-regulation of genes playing roles in lipid and phenylpropanoid metabolism, the latter being in consonance with the anthocyanin accumulation. Transgenic expression of Atalpha-DOX2 and Slalpha-DOX2 in divaricata partially complemented the compromised phenotype in mature plants and fully complemented it in seedlings, thus indicating the functional exchangeability between alpha-DOX2 from tomato and Arabidopsis. However, deletion of Atalpha-DOX2 in Arabidopsis plants did not provoke any visible phenotypic alteration indicating that the relative importance of alpha-DOX2 in plant physiology is species specific.

  12. Peroxisome proliferator-activated receptor alpha target genes.

    Science.gov (United States)

    Rakhshandehroo, Maryam; Knoch, Bianca; Müller, Michael; Kersten, Sander

    2010-01-01

    The peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcription factor involved in the regulation of a variety of processes, ranging from inflammation and immunity to nutrient metabolism and energy homeostasis. PPARα serves as a molecular target for hypolipidemic fibrates drugs which bind the receptor with high affinity. Furthermore, PPARα binds and is activated by numerous fatty acids and fatty acid-derived compounds. PPARα governs biological processes by altering the expression of a large number of target genes. Accordingly, the specific role of PPARα is directly related to the biological function of its target genes. Here, we present an overview of the involvement of PPARα in lipid metabolism and other pathways through a detailed analysis of the different known or putative PPARα target genes. The emphasis is on gene regulation by PPARα in liver although many of the results likely apply to other organs and tissues as well.

  13. Peroxisome Proliferator-Activated Receptor Alpha Target Genes

    Directory of Open Access Journals (Sweden)

    Maryam Rakhshandehroo

    2010-01-01

    Full Text Available The peroxisome proliferator-activated receptor alpha (PPARα is a ligand-activated transcription factor involved in the regulation of a variety of processes, ranging from inflammation and immunity to nutrient metabolism and energy homeostasis. PPARα serves as a molecular target for hypolipidemic fibrates drugs which bind the receptor with high affinity. Furthermore, PPARα binds and is activated by numerous fatty acids and fatty acid-derived compounds. PPARα governs biological processes by altering the expression of a large number of target genes. Accordingly, the specific role of PPARα is directly related to the biological function of its target genes. Here, we present an overview of the involvement of PPARα in lipid metabolism and other pathways through a detailed analysis of the different known or putative PPARα target genes. The emphasis is on gene regulation by PPARα in liver although many of the results likely apply to other organs and tissues as well.

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

    DEFF Research Database (Denmark)

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

    1995-01-01

    with the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate, a direct activator of protein kinase C, induced a rapid, transient increase in RPTP alpha activity due to a 2- to 3-fold increase in substrate affinity. A transient increase in RPTP alpha serine phosphorylation was concomitant with the enhanced activity....... Tryptic phosphopeptide mapping of RPTP alpha demonstrated that phosphorylation of three tryptic peptides was enhanced in response to phorbol ester. In vitro dephosphorylation of RPTP alpha from phorbol ester-treated cells reduced RPTP alpha activity to prestimulation levels, indicating that enhanced...

  15. 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.

  16. 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

    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...... 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...

  17. VLDL hydrolysis by LPL activates PPAR-alpha through generation of unbound fatty acids.

    Science.gov (United States)

    Ruby, Maxwell A; Goldenson, Benjamin; Orasanu, Gabriela; Johnston, Thomas P; Plutzky, Jorge; Krauss, Ronald M

    2010-08-01

    Recent evidence suggests that lipoproteins serve as circulating reservoirs of peroxisomal proliferator activated receptor (PPAR) ligands that are accessible through lipolysis. The present study was conducted to determine the biochemical basis of PPAR-alpha activation by lipolysis products and their contribution to PPAR-alpha function in vivo. PPAR-alpha activation was measured in bovine aortic endothelial cells following treatment with human plasma, VLDL lipolysis products, or oleic acid. While plasma failed to activate PPAR-alpha, oleic acid performed similarly to VLDL lipolysis products. Therefore, fatty acids are likely to be the PPAR-alpha ligands generated by VLDL lipolysis. Indeed, unbound fatty acid concentration determined PPAR-alpha activation regardless of fatty acid source, with PPAR-alpha activation occurring only at unbound fatty acid concentrations that are unachievable under physiological conditions without lipase action. In mice, a synthetic lipase inhibitor (poloxamer-407) attenuated fasting-induced changes in expression of PPAR-alpha target genes. Apolipoprotein CIII (apoCIII), an endogenous inhibitor of lipoprotein and hepatic lipase, regulated access to the lipoprotein pool of PPAR-alpha ligands, because addition of exogenous apoCIII inhibited, and removal of endogenous apoCIII potentiated, lipolytic PPAR-alpha activation. These data suggest that the PPAR-alpha response is generated by unbound fatty acids released locally by lipase activity and not by circulating plasma fatty acids.

  18. Does a physiotherapy programme of gross motor training influence motor function and activities of daily living in children presenting with developmental coordination disorder?

    Directory of Open Access Journals (Sweden)

    Sonill S. Maharaj

    2016-02-01

    Full Text Available Background: Children with developmental coordination disorder (DCD lack motor coordination and have difficulty performing motor skills and activities of daily living. Research shows these children do not outgrow their motor difficulties and without intervention do not improve. Physiotherapy is relevant for these children, but due to limited clinical protocols for DCD the aim of this study was to determine the effect of a gross motor training programme for 6–12-year-old children with DCD.Methods: This randomised pre-test, post-test study recruited 64 children with scores of 15th percentile or below using the Movement Assessment Battery for Children (M-ABC. The children were divided equally into an intervention group receiving 8 weeks of gross motor training for core stability, strengthening exercises, balance and coordination with task-specific activities for 30 min per week, while the control group continued with general therapy and activities of daily living. The M-ABC and Developmental Coordination Disorder Questionnaire (DCDQ were used to assess each child before and after 8 weeks.Results: Sixty children completed the study, with 43 males and 17 females (mean age 10.02 years, SD = 2.10. There were no adverse reactions to the programme and M-ABC scores for the intervention programme improved by 6.46%, ball skills (3.54% and balance (4.80% compared with the control (0.17% and (0.15%, respectively. There were significant (p < 0.05 improvements in DCDQ scores, but teachers allocated lower scores than parents.Conclusion: This study supports 8 weeks of gross motor training which can be a beneficial intervention for physiotherapists to improve gross motor function for DCD.Keywords: Developmental, co-ordination, skills, motor

  19. Effects of alpha-AMPK knockout on exercise-induced gene activation in mouse skeletal muscle.

    Science.gov (United States)

    Jørgensen, Sebastian B; Wojtaszewski, Jørgen F P; Viollet, Benoit; Andreelli, Fabrizio; Birk, Jesper B; Hellsten, Ylva; Schjerling, Peter; Vaulont, Sophie; Neufer, P Darrell; Richter, Erik A; Pilegaard, Henriette

    2005-07-01

    We tested the hypothesis that 5'AMP-activated protein kinase (AMPK) plays an important role in regulating the acute, exercise-induced activation of metabolic genes in skeletal muscle, which were dissected from whole-body alpha2- and alpha1-AMPK knockout (KO) and wild-type (WT) mice at rest, after treadmill running (90 min), and in recovery. Running increased alpha1-AMPK kinase activity, phosphorylation (P) of AMPK, and acetyl-CoA carboxylase (ACC)beta in alpha2-WT and alpha2-KO muscles and increased alpha2-AMPK kinase activity in alpha2-WT. In alpha2-KO muscles, AMPK-P and ACCbeta-P were markedly lower compared with alpha2-WT. However, in alpha1-WT and alpha1-KO muscles, AMPK-P and ACCbeta-P levels were identical at rest and increased similarly during exercise in the two genotypes. The alpha2-KO decreased peroxisome-proliferator-activated receptor gamma coactivator (PGC)-1alpha, uncoupling protein-3 (UCP3), and hexokinase II (HKII) transcription at rest but did not affect exercise-induced transcription. Exercise increased the mRNA content of PGC-1alpha, Forkhead box class O (FOXO)1, HKII, and pyruvate dehydrogenase kinase 4 (PDK4) similarly in alpha2-WT and alpha2-KO mice, whereas glucose transporter GLUT 4, carnitine palmitoyltransferase 1 (CPTI), lipoprotein lipase, and UCP3 mRNA were unchanged by exercise in both genotypes. CPTI mRNA was lower in alpha2-KO muscles than in alpha2-WT muscles at all time-points. In alpha1-WT and alpha1-KO muscles, running increased the mRNA content of PGC-1alpha and FOXO1 similarly. The alpha2-KO was associated with lower muscle adenosine 5'-triphosphate content, and the inosine monophosphate content increased substantially at the end of exercise only in alpha2-KO muscles. In addition, subcutaneous injection of 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) increased the mRNA content of PGC-1alpha, HKII, FOXO1, PDK4, and UCP3, and alpha2-KO abolished the AICAR-induced increases in PGC-1alpha and HKII mRNA. In

  20. 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...

  1. Automated docking of {alpha}-(1,4)- and {alpha}-(1,6)-linked glucosyl trisaccharides in the glucoamylase active site

    Energy Technology Data Exchange (ETDEWEB)

    Countinho, P.M.; Reilly, P.J. [Iowa State Univ., Ames, IA (United States). Dept. of Chemical Engineering; Dowd, M.K. [Dept. of Agriculture, New Orleans, LA (United States). Southern Regional Research Center

    1998-06-01

    Low-energy conformers of five {alpha}-(1,4)- and {alpha}-(1,6)-linked glucosyl trisaccharides were flexibly docked into the glucoamylase active site using AutoDock 2.2. To ensure that all significant conformational space was searched, the starting trisaccharide conformers for docking were all possible combinations of the corresponding disaccharide low-energy conformers. All docked trisaccharides occupied subsites {minus}1 and +1 in very similar modes to those of corresponding nonreducing-end disaccharides. For linear substrates, full binding at subsite +2 occurred only when the substrate reducing end was {alpha}-(1,4)-linked, with hydrogen-bonding with the hydroxy-methyl group being the only polar interaction there. Given the absence of other important interactions at this subsite, multiple substrate conformations are allowed. For the one docked branched substrate, steric hindrance in the {alpha}-(1,6)-glycosidic oxygen suggests that the active-site residues have to change position for hydrolysis to occur. Subsite +1 of the glucoamylase active site allows flexibility in binding but, at least in Aspergillus glucoamylases, subsite +2 selectively binds substrates {alpha}-(1,4)-linked between subsites +1 and +2. Enzyme engineering to limit substrate flexibility at subsite +2 could improve glucoamylase industrial properties.

  2. Glutathione transferase classes alpha, pi, and mu: GSH activation mechanism.

    Science.gov (United States)

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

    2010-10-14

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

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

    Directory of Open Access Journals (Sweden)

    Shogo eHaraguchi

    2011-08-01

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

  4. Contribution of mucosal maltase-glucoamylase activities to mouse small intestinal starch alpha-glucogenesis.

    Science.gov (United States)

    Quezada-Calvillo, Roberto; Robayo-Torres, Claudia C; Opekun, Antone R; Sen, Partha; Ao, Zihua; Hamaker, Bruce R; Quaroni, Andrea; Brayer, Gary D; Wattler, Sigrid; Nehls, Michael C; Sterchi, Erwin E; Nichols, Buford L

    2007-07-01

    Digestion of starch requires activities provided by 6 interactive small intestinal enzymes. Two of these are luminal endo-glucosidases named alpha-amylases. Four are exo-glucosidases bound to the luminal surface of enterocytes. These mucosal activities were identified as 4 different maltases. Two maltase activities were associated with sucrase-isomaltase. Two remaining maltases, lacking other identifying activities, were named maltase-glucoamylase. These 4 activities are better described as alpha-glucosidases because they digest all linear starch oligosaccharides to glucose. Because confusion persists about the relative roles of these 6 enzymes, we ablated maltase-glucoamylase gene expression by homologous recombination in Sv/129 mice. We assayed the alpha-glucogenic activities of the jejunal mucosa with and without added recombinant pancreatic alpha-amylase, using a range of food starch substrates. Compared with wild-type mucosa, null mucosa or alpha-amylase alone had little alpha-glucogenic activity. alpha-Amylase amplified wild-type and null mucosal alpha-glucogenesis. alpha-Amylase amplification was most potent against amylose and model resistant starches but was inactive against its final product limit-dextrin and its constituent glucosides. Both sucrase-isomaltase and maltase-glucoamylase were active with limit-dextrin substrate. These mucosal assays were corroborated by a 13C-limit-dextrin breath test. In conclusion, the global effect of maltase-glucoamylase ablation was a slowing of rates of mucosal alpha-glucogenesis. Maltase-glucoamylase determined rates of digestion of starch in normal mice and alpha-amylase served as an amplifier for mucosal starch digestion. Acarbose inhibition was most potent against maltase-glucoamylase activities of the wild-type mouse. The consortium of 6 interactive enzymes appears to be a mechanism for adaptation of alpha-glucogenesis to a wide range of food starches.

  5. Mediating effects of the ICF domain of function and the gross motor function measure on the ICF domains of activity, and participation in children with cerebral palsy.

    Science.gov (United States)

    Lee, Byoung-Hee; Kim, Yu-Mi; Jeong, Goo-Churl

    2015-10-01

    [Purpose] This study aimed to evaluate the mediating effect of gross motor function, measured using the Gross Motor Function Measure (GMFM) and of general function, measured using the International Classification of Functioning, Disability and Health-Child and Youth Check List (ICF-CY), on the ICF domains of activity and participation in children with cerebral palsy (CP). [Subjects] Ninety-five children with CP, from Seoul, Korea, participated in the study. [Methods] The GMFM was administered in its entirety to patients without orthoses or mobility aids. The ICF-CY was used to evaluate the degree of disability and health of subjects. [Results] GMFM score and ICF-CY function were negatively correlated to ICF-CY activity and participation. ICF-CY partially mediated the effects of the GMFM on activity and participation. [Conclusion] When establishing a treatment plan for a child with CP, limitations in activity and participation, as described by the ICF-CY, should be considered in addition to the child's physical abilities and development. In addition, the treatment plan should focus on increasing the child's activity and participation level, as well as his/her physical level.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-09-07

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

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

    Science.gov (United States)

    Deiber, Marie-Pierre; Sallard, Etienne; Ludwig, Catherine; Ghezzi, Catherine; Barral, Jérôme; Ibañez, Vicente

    2012-01-01

    Alpha-band activity (8-13 Hz) is not only suppressed by sensory stimulation and movements, but also modulated by attention, working memory and mental tasks, and could 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 (TF) 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 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 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.

  8. 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. 

  9. 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

    Agonists and positive allosteric modulators of the alpha(7) nicotinic acetylcholine receptor (nAChR) are currently being developed for the treatment of cognitive disturbances in patients with schizophrenia or Alzheimer's disease. This review describes the neurobiological properties of the alpha n......AChR and the cognitive effects of alpha(7) nAChR activation, focusing on the translational aspects in the development of these drugs. The functional properties and anatomical localization of the alpha(7) nAChR makes it well suited to modulate cognitive function. Accordingly, systemic administration of alpha(7) n......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...

  10. 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.

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

    Science.gov (United States)

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

    2015-01-01

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

    Science.gov (United States)

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

    2015-01-01

    Background & Aim Alpha-amylase in both blood and saliva has been used as a diagnostic parameter. While studies examining alpha-amylase activity in saliva have shown that it is sensitive to physiological and psychological challenge of the adrenergic system, no challenge studies have attempted to elucidate the role of the adrenergic system in alpha-amylase activity in blood. We set out to examine the impact of psychological and pharmacological challenge on alpha-amylase in blood in two separate studies. Methods 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 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. Conclusions 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. PMID:26110636

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

    CERN Document Server

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

    2006-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Isabella Irrcher

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

  15. Study of alpha one antitrypsin activity in lepra reaction.

    Science.gov (United States)

    Sengupta, S R; Dhole, T N; Jahagirdar, V L; Yemul, V L; Chawhan, R N

    1983-04-01

    In our earlier study (Yemul et, al, 1983) we have reported elevation of serum alpha one antitrypsin levels in patients of lepromatous leprosy and lepra reaction. In this study estimation of serum alpha one antitrypsin levels in fifty lepra reaction patients (8 of type 1 and 42 of type II) and fifty age and sex matched healthy controls is described. Alpha one antitrypsin levels were elevated in lepra reaction patients (type I--mean value of 332 mg% and S.D. +/- 118.8 and type II--mean value of 450 mg% and S.D. +/- 73.7) when compared with the healthy controls (mean value of 285 mg% and S.D. +/- 66.05). The increase in levels in type II lepra reaction patients was statistically significant. The results are discussed to correlate the increased levels of alpha one antitrypsin and the high bacterial load leading to the release of various proteases in type II lepra reaction.

  16. 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

    Highlights: {yields} PPAR{alpha} activation increased mRNA expression levels of fatty acid oxidation-related genes in human intestinal epithelial Caco-2 cells. {yields} PPAR{alpha} activation also increased oxygen consumption rate and CO{sub 2} production and decreased secretion of triglyceride and ApoB from Caco-2 cells. {yields} Orally administration of bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and CO{sub 2} production in small intestinal epithelial cells. {yields} Treatment with bezafibrate decreased postprandial serum concentration of triglyceride after oral injection of olive oil in mice. {yields} It suggested that intestinal lipid metabolism regulated by PPAR{alpha} activation suppresses postprandial lipidemia. -- Abstract: Activation of peroxisome proliferator-activated receptor (PPAR)-{alpha} which regulates lipid metabolism in peripheral tissues such as the liver and skeletal muscle, decreases circulating lipid levels, thus improving hyperlipidemia under fasting conditions. Recently, postprandial serum lipid levels have been found to correlate more closely to cardiovascular diseases than fasting levels, although fasting hyperlipidemia is considered an important risk of cardiovascular diseases. However, the effect of PPAR{alpha} activation on postprandial lipidemia has not been clarified. In this study, we examined the effects of PPAR{alpha} activation in enterocytes on lipid secretion and postprandial lipidemia. In Caco-2 enterocytes, bezafibrate, a potent PPAR{alpha} agonist, increased mRNA expression levels of fatty acid oxidation-related genes, such as acyl-CoA oxidase, carnitine palmitoyl transferase, and acyl-CoA synthase, and oxygen consumption rate (OCR) and suppressed secretion levels of both triglycerides and apolipoprotein B into the basolateral side. In vivo experiments revealed that feeding high-fat-diet containing bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and

  17. Loovkirjutamist õpetab Philip Gross

    Index Scriptorium Estoniae

    2011-01-01

    T.S. Elioti luulepreemia laureaat Philip Gross on Tallinna Ülikooli talvekooli rahvusvahelise kursuse "Poetry: A Conversation between Words and Silence" läbiviija. Oma seminarides keskendub ta lisaks loovkirjutamisele ka loova lugemise vajadusele

  18. Gross Sales Tax Collections

    Data.gov (United States)

    City of Jackson, Mississippi — This data is captured directly from the MS Department of Revenue and specific to the City of Jackson. It is compiled from Gross Sales Tax reported by taxpayers each...

  19. PGC-1alpha activates CYP7A1 and bile acid biosynthesis.

    Science.gov (United States)

    Shin, Dong-Ju; Campos, Jose A; Gil, Gregorio; Osborne, Timothy F

    2003-12-12

    Cholesterol 7-alpha-hydroxylase (CYP7A1) is the key enzyme that commits cholesterol to the neutral bile acid biosynthesis pathway and is highly regulated. In the current studies, we have uncovered a role for the transcriptional co-activator PGC-1alpha in CYP7A1 gene transcription. PGC-1alpha plays a vital role in adaptive thermogenesis in brown adipose tissue and stimulates genes important to mitochondrial function and oxidative metabolism. It is also involved in the activation of hepatic gluconeogenesic gene expression during fasting. Because the mRNA for CYP7A1 was also induced in mouse liver by fasting, we reasoned that PGC-1alpha might be an important co-activator for CYP7A1. Here we show that PGC-1alpha and CYP7A1 are also co-induced in livers of mice in response to streptozotocin induced diabetes. Additionally, infection of cultured HepG2 cells with a recombinant adenovirus expressing PGC-1alpha directly activates CYP7A1 gene expression and increases bile acid biosynthesis as well. Furthermore, we show that PGC-1alpha activates the CYP7A1 promoter directly in transient transfection assays in cultured cells. Thus, PGC-1alpha is a key activator of CYP7A1 and bile acid biosynthesis and is likely responsible for the fasting and diabetes dependent induction of CYP7A1. PGC-1alpha has already been shown to be a critical activator of several other oxidative processes including adaptive thermogenesis and fatty acid oxidation. Our studies provide further evidence of the fundamental role played by PGC-1alpha in oxidative metabolism and define PGC-1alpha as a link between diabetes and bile acid metabolism.

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

    Science.gov (United States)

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

    2008-02-01

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

  1. Tumor cell alpha-N-acetylgalactosaminidase activity and its involvement in GcMAF-related macrophage activation.

    Science.gov (United States)

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

    2002-05-01

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

  2. 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

    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......-adrenergic stimulation induced expression of LXRalpha, ADD1/SREBP1c and PGC1alpha in cells with a brown-like adipose phenotype. We demonstrate that ADD1/SREBP1c is a powerful inducer of PGC1alpha expression via a conserved E box in the proximal promoter and that beta-adrenergic stimulation led to recruitment of ADD1...

  3. 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...

  4. Interferon-alpha (Intron A) upregulates urokinase-type plasminogen activator receptor gene expression.

    Science.gov (United States)

    Wu, Shanshan; Murrell, George A C; Wang, Yao

    2002-07-01

    The regulation of urokinase plasminogen activator receptor (uPAR) gene expression by interferon-alpha (IFN-alpha, or Intron A) and interferon-gamma (IFN-gamma) was studied in a HCT116 colon cancer cell line. uPAR mRNA levels were increased in a dose- and time-dependent manner in cells stimulated with IFN-alpha or IFN-gamma. uPAR protein levels reflected IFN-alpha and IFN-gamma induction of uPAR mRNA production. Cycloheximide, a protein synthesis inhibitor, also induced uPAR mRNA accumulation either alone or in combination with IFN-alpha or IFN-gamma, suggesting that the effect on uPAR mRNA levels activated by IFN-alpha or IFN-gamma does not require de novo protein synthesis. Both sodium butyrate and amiloride inhibited the uPAR mRNA levels induced by IFN-alpha or IFN-gamma. These results may provide useful information for the treatment of patients receiving IFN-alpha or IFN-gamma.

  5. Comparison of alpha-amylase and protease activities of a zoophytophagous and two phytozoophagous Heteroptera.

    Science.gov (United States)

    Zeng, F; Cohen, A C

    2000-05-01

    To better understand the nature of facultative phytophagy in the zoophytophagous Geocoris punctipes (Say), and facultative zoophagy in phytozoophagous Lygus hesperus (Knight) and Lygus lineolaris (Palisot de Beauvois), we compared the activities of both the starch digesting enzyme alpha-amylase and of general proteases in these species. The alpha-amylases and proteases were demonstrated in L. hesperus, L. lineolaris and G. punctipes. The presence of alpha-amylase in the salivary gland complexes of G. punctipes indicates a disposition of this species toward utilization of nutrients that can be derived only from plants, either directly from ingestion of plant macromolecules or from second-hand ingestion of plant material from the digestive system of their prey. The alpha-amylase activity in G. punctipes was much less than those of phytozoophagous L. hesperus and L. lineolaris. The relative importance of amylolytic activity and proteolytic activity is also discussed.

  6. New alkoxycarbonylalkyloxychalcones and their alpha, beta-dibromo derivatives of potential antimicrobial activity.

    Science.gov (United States)

    Szajda, M; Kedzia, B

    1989-03-01

    New ortho, meta- and para-substituted alkoxycarbonylalkyloxychalcones and their alpha, beta-dibromo derivatives have been synthesized. It can be demonstrated that some of these compounds show antimicrobial activity.

  7. On-Going Frontal Alpha Rhythms Are Dominant in Passive State and Desynchronize in Active State in Adult Gray Mouse Lemurs

    Science.gov (United States)

    Rahman, Anisur; Lamberty, Yves; Bordet, Regis; Richardson, Jill C.; Forloni, Gianluigi; Drinkenburg, Wilhelmus; Lopez, Susanna; Aujard, Fabienne; Babiloni, Claudio; Pifferi, Fabien

    2015-01-01

    The gray mouse lemur (Microcebus murinus) is considered a useful primate model for translational research. In the framework of IMI PharmaCog project (Grant Agreement n°115009, www.pharmacog.org), we tested the hypothesis that spectral electroencephalographic (EEG) markers of motor and locomotor activity in gray mouse lemurs reflect typical movement-related desynchronization of alpha rhythms (about 8–12 Hz) in humans. To this aim, EEG (bipolar electrodes in frontal cortex) and electromyographic (EMG; bipolar electrodes sutured in neck muscles) data were recorded in 13 male adult (about 3 years) lemurs. Artifact-free EEG segments during active state (gross movements, exploratory movements or locomotor activity) and awake passive state (no sleep) were selected on the basis of instrumental measures of animal behavior, and were used as an input for EEG power density analysis. Results showed a clear peak of EEG power density at alpha range (7–9 Hz) during passive state. During active state, there was a reduction in alpha power density (8–12 Hz) and an increase of power density at slow frequencies (1–4 Hz). Relative EMG activity was related to EEG power density at 2–4 Hz (positive correlation) and at 8–12 Hz (negative correlation). These results suggest for the first time that the primate gray mouse lemurs and humans may share basic neurophysiologic mechanisms of synchronization of frontal alpha rhythms in awake passive state and their desynchronization during motor and locomotor activity. These EEG markers may be an ideal experimental model for translational basic (motor science) and applied (pharmacological and non-pharmacological interventions) research in Neurophysiology. PMID:26618512

  8. 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.

  9. Interaction of iodine with 2-hydroxypropyl-alpha-cyclodextrin and its bactericidal activity.

    Science.gov (United States)

    Tomono, K; Goto, H; Suzuki, T; Ueda, H; Nagai, T; Watanabe, J

    2002-11-01

    To obtain an effective iodine solution, the use of 2-hydroxypropyl-alpha-cyclodextrin (2-HP-alpha-CD) as solubilizer was examined in comparison with alpha-cyclodextrin (alpha-CD), beta-cyclodextrin (beta-CD), potassium iodide (KI), and polyvinylpyrrolidone (PVP). The stability constants for inclusion of iodine with cyclodextrin and KI were ascertained by the solubility method. The apparent stability constants increased in the following order: KI stabilization ability. The largest volatile depression effect was exhibited by 2HP-alpha-CD. The measurement of the minimum inhibitory concentration (MC) using Escherichia coli NIH-J-2 and Staphylococcus aureus FDA209P suggested that the bactericidal activity of the iodine/2-HP-alpha-CD system was the same as that of the iodine/alpha-CD, iodine/beta-CD, and iodine/PVP systems. The present results suggest that the combination of 2-HP-alpha-CD and iodine is useful for a stable and effective iodine solution.

  10. 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.

  11. 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.

  12. Exercise induces transient transcriptional activation of the PGC-1alpha gene in human skeletal muscle.

    Science.gov (United States)

    Pilegaard, Henriette; Saltin, Bengt; Neufer, P Darrell

    2003-02-01

    Endurance exercise training induces mitochondrial biogenesis in skeletal muscle. The peroxisome proliferator activated receptor co-activator 1alpha (PGC-1alpha) has recently been identified as a nuclear factor critical for coordinating the activation of genes required for mitochondrial biogenesis in cell culture and rodent skeletal muscle. To determine whether PGC-1alpha transcription is regulated by acute exercise and exercise training in human skeletal muscle, seven male subjects performed 4 weeks of one-legged knee extensor exercise training. At the end of training, subjects completed 3 h of two-legged knee extensor exercise. Biopsies were obtained from the vastus lateralis muscle of both the untrained and trained legs before exercise and after 0, 2, 6 and 24 h of recovery. Time to exhaustion (2 min maximum resistance), as well as hexokinase II (HKII), citrate synthase and 3-hydroxyacyl-CoA dehydrogenase mRNA, were higher in the trained than the untrained leg prior to exercise. Exercise induced a marked transient increase (P 40-fold) and mRNA content (7- to 10-fold), peaking within 2 h after exercise. Activation of PGC-1alpha was greater in the trained leg despite the lower relative workload. Interestingly, exercise did not affect nuclear respiratory factor 1 (NRF-1) mRNA, a gene induced by PGC-1alpha in cell culture. HKII, mitochondrial transcription factor A, peroxisome proliferator activated receptor alpha, and calcineurin Aalpha and Abeta mRNA were elevated (approximately 2- to 6-fold; P < 0.05) at 6 h of recovery in the untrained leg but did not change in the trained leg. The present data demonstrate that exercise induces a dramatic transient increase in PGC-1alpha transcription and mRNA content in human skeletal muscle. Consistent with its role as a transcriptional coactivator, these findings suggest that PGC-1alpha may coordinate the activation of metabolic genes in human muscle in response to exercise.

  13. 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.

  14. The topography of alpha-band activity tracks the content of spatial working memory.

    Science.gov (United States)

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

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1978-01-01

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

  16. Children and adults minimise activated muscle volume by selecting gait parameters that balance gross mechanical power and work demands.

    Science.gov (United States)

    Hubel, Tatjana Y; Usherwood, James R

    2015-09-01

    Terrestrial locomotion on legs is energetically expensive. Compared with cycling, or with locomotion in swimming or flying animals, walking and running are highly uneconomical. Legged gaits that minimise mechanical work have previously been identified and broadly match walking and running at appropriate speeds. Furthermore, the 'cost of muscle force' approaches are effective in relating locomotion kinetics to metabolic cost. However, few accounts have been made for why animals deviate from either work-minimising or muscle-force-minimising strategies. Also, there is no current mechanistic account for the scaling of locomotion kinetics with animal size and speed. Here, we report measurements of ground reaction forces in walking children and adult humans, and their stance durations during running. We find that many aspects of gait kinetics and kinematics scale with speed and size in a manner that is consistent with minimising muscle activation required for the more demanding between mechanical work and power: spreading the duration of muscle action reduces activation requirements for power, at the cost of greater work demands. Mechanical work is relatively more demanding for larger bipeds--adult humans--accounting for their symmetrical M-shaped vertical force traces in walking, and relatively brief stance durations in running compared with smaller bipeds--children. The gaits of small children, and the greater deviation of their mechanics from work-minimising strategies, may be understood as appropriate for their scale, not merely as immature, incompletely developed and energetically sub-optimal versions of adult gaits.

  17. 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

    Targeted alpha therapy (TAT) a promising treatment for small, residual, and micrometastatic diseases has questionable efficacy against malignant lesions larger than the α-particle range, and likely requires favorable intratumoral activity distribution. Here, we characterized and quantified...

  18. Formation of Raman Scattering Wings around H alpha, H beta and Pa alpha in Active Galactic Nuclei

    CERN Document Server

    Chang, Seok-Jun; Di Mille, Francesco; Angeloni, Rodolfo; Palma, Tali; Lee, Hee-Won

    2015-01-01

    Powered by a supermassive black hole with an accretion disk, the spectra of active galactic nuclei (AGNs) are characterized by prominent emission lines including Balmer lines. The unification schemes of AGNs require the existence of a thick molecular torus that may hide the broad emission line region from the view of observers near the equatorial direction. In this configuration, one may expect that the far UV radiation from the central engine can be Raman scattered by neutral hydrogen to reappear around Balmer and Paschen emission lines which can be identified with broad wings. We produce H$\\alpha$, H$\\beta$ and Pa$\\alpha$ wings using a Monte Carlo technique to investigate their properties. The neutral scattering region is assumed to be a cylindrical torus specified by the inner and outer radii and the height. While the covering factor of the scattering region affects the overall strengths of the wings, the wing widths are primarily dependent on the neutral hydrogen column density $N_{\\rm HI}$ being roughly ...

  19. Direct screening of libraries of yeast clones for alpha-amylase activity on raw starch hydrolysis.

    Science.gov (United States)

    Wong, Dominic W S; Batt, Sarah B; Lee, Charles C; Robertson, George H

    2003-10-01

    High-throughput screening for high-activity barley alpha-amylase mutants expressed in Saccharomyces cerevisiae is hampered by the interference of reducing agents, particularly the glucose used in yeast growth media. The present investigation employed colorimetric and chemiluminescent detection systems that enable direct and rapid screening of activities on raw starch substrate. Active clones could be separated into two groups, based on high total activity or high specific activity.

  20. Interleukin-1 alpha has antiallodynic and antihyperalgesic activities in a rat neuropathic pain model.

    Science.gov (United States)

    Mika, Joanna; Korostynski, Michal; Kaminska, Dorota; Wawrzczak-Bargiela, Agnieszka; Osikowicz, Maria; Makuch, Wioletta; Przewlocki, Ryszard; Przewlocka, Barbara

    2008-09-15

    Nerve injury and the consequent release of interleukins (ILs) are processes implicated in pain transmission. To study the potential role of IL-1 in the pathogenesis of allodynia and hyperalgesia, IL-1alpha and comparative IL-1beta, IL-6, and IL-10 mRNA levels were quantified using competitive RT-PCR of the lumbar spinal cord and dorsal root ganglia (DRG; L5-L6) three and seven days after chronic constriction injury (CCI) in rats. Microglial and astroglial activation in the ipsilateral spinal cord and DRG were observed after injury. In naive and CCI-exposed rats, IL-1alpha mRNA and protein were not detected in the spinal cord. IL-1beta and IL-6 mRNAs were strongly ipsilaterally elevated on day seven after CCI. In the ipsilateral DRG, IL-1alpha, IL-6, and IL-10 mRNA levels were increased on days three and seven; IL-1beta was elevated only on day seven. Western blot analysis revealed both the presence of IL-1alpha proteins (45 and 31 kDa) in the DRG and the down-regulation of these proteins after CCI. Intrathecal administration of IL-1alpha (50-500 ng) in naive rats did not influence nociceptive transmission, but IL-1beta (50-500 ng) induced hyperalgesia. In rats exposed to CCI, an IL-1alpha or IL-1 receptor antagonist dose-dependently attenuated symptoms of neuropathic pain; however, no effect of IL-1beta was observed. In sum, the first days after CCI showed a high abundance of IL-1alpha in the DRG. Together with the antiallodynic and antihyperalgesic effects observed after IL-1alpha administration, this finding indicates an important role for IL-1alpha in the development of neuropathic pain symptoms.

  1. Structure-function relationships in the receptor for urokinase-type plasminogen activator. Comparison to other members of the Ly-6 family and snake venom alpha-neurotoxins

    DEFF Research Database (Denmark)

    Ploug, M; Ellis, V

    1994-01-01

    Plasminogen activation is regulated by the interaction between urokinase-type plasminogen activator (uPA) and its specific glycolipid-anchored cell surface receptor (uPAR). uPAR is composed of three homologous domains and is the only multi-domain member of the Ly-6 family of glycolipid-anchored m......Plasminogen activation is regulated by the interaction between urokinase-type plasminogen activator (uPA) and its specific glycolipid-anchored cell surface receptor (uPAR). uPAR is composed of three homologous domains and is the only multi-domain member of the Ly-6 family of glycolipid......-anchored membrane proteins. Recent evidence has highlighted similarities between the individual domains of uPAR and the large family of secreted, single domain snake venom alpha-neurotoxins, suggesting that uPAR may adopt the same gross folding pattern as these structurally well characterized proteins. Structural...... aspects of the binding between alpha-neurotoxins and the acetylcholine receptor may have a major influence on future studies of the interaction between uPA and uPAR....

  2. Chloroquine modulates HIV-1-induced plasmacytoid dendritic cell alpha interferon: implication for T-cell activation.

    Science.gov (United States)

    Martinson, Jeffrey A; Montoya, Carlos J; Usuga, Xiomara; Ronquillo, Rollie; Landay, Alan L; Desai, Seema N

    2010-02-01

    Plasmacytoid dendritic cells (pDC) contribute to antiviral immunity mainly through recognition of microbial products and viruses via intracellular Toll-like receptor 7 (TLR7) or TLR9, resulting in the production of type I interferons (IFNs). Although interferons reduce the viral burden in the acute phase of infection, their role in the chronic phase is unclear. The presence of elevated plasma IFN-alpha levels in advanced HIV disease and its association with microbial translocation in chronic HIV infection lead us to hypothesize that IFN-alpha could contribute to immune activation. Blocking of IFN-alpha production using chloroquine, an endosomal inhibitor, was tested in a novel in vitro model system with the aim of characterizing the effects of chloroquine on HIV-1-mediated TLR signaling, IFN-alpha production, and T-cell activation. Our results indicate that chloroquine blocks TLR-mediated activation of pDC and MyD88 signaling, as shown by decreases in the levels of the downstream signaling molecules IRAK-4 and IRF-7 and by inhibition of IFN-alpha synthesis. Chloroquine decreased CD8 T-cell activation induced by aldrithiol-2-treated HIV-1 in peripheral blood mononuclear cell cultures. In addition to blocking pDC activation, chloroquine also blocked negative modulators of the T-cell response, such as indoleamine 2,3-dioxygenase (IDO) and programmed death ligand 1 (PDL-1). Our results indicate that TLR stimulation and production of IFN-alpha by pDC contribute to immune activation and that blocking of these pathways using chloroquine may interfere with events contributing to HIV pathogenesis. Our results suggests that a safe, well-tolerated drug such as chloroquine can be proposed as an adjuvant therapeutic candidate along with highly active antiretroviral therapy to control immune activation in HIV-1 infection.

  3. The association of fatigue, comorbidity burden, disease activity, disability and gross domestic product in patients with rheumatoid arthritis. Results from 34 countries participating in the Quest-RA program

    DEFF Research Database (Denmark)

    Grøn, Kathrine Lederballe; Ørnbjerg, Lykke Midtbøll; Hetland, Merete Lund

    2014-01-01

    OBJECTIVES: The aim is to assess the prevalence of comorbidities and to further analyse to which degree fatigue can be explained by comorbidity burden, disease activity, disability and gross domestic product (GDP) in patients with rheumatoid arthritis (RA). METHODS: Nine thousands eight hundred s...

  4. Comparative study between the effect of the peroxisome proliferator activated receptor-alpha ligands fenofibrate and n-3 polyunsaturated fatty acids on activation of 5'-AMP-activated protein kinase-alpha1 in high-fat fed rats.

    Science.gov (United States)

    Motawi, Tarek M Kamal; Hashem, Reem M; Rashed, Laila A; El-Razek, Sabry M Abd

    2009-10-01

    Obesity is a risk factor for type 2 diabetes mellitus. It results from an energy imbalance in which energy intake exceeds energy expenditure. The cellular fuel gauge 5'-AMP-activated protein kinase (AMPK) is a heterotrimeric protein consisting of one catalytic subunit (alpha) and two non-catalytic subunits (beta and gamma), and approximately equal levels of alpha1 and alpha2 complexes are present in the liver. AMPK regulates metabolic pathways in response to metabolic stress and in particular ATP depletion to switch on energy-producing catabolic pathways such as beta-oxidation of fatty acids and switch off energy-depleting processes such as synthesis of fatty acid and cholesterol. A high-fat diet alters AMPK-alpha1 gene expression in the liver and skeletal muscle of rats and results in body weight gain and hyperglycaemia. The aim of this study was to investigate and compare the potential effects of peroxisome proliferator-activated receptor (PPAR)-alpha agonists fenofibrate and n-3 polyunsaturated fatty acids (PUFAs) in modulation of AMPK-alpha1 activity in liver and skeletal muscle of high-fat diet fed rats. Reverse transcription-polymerase chain reaction was used for determination of AMPK-alpha1 in liver and soleus muscle and both PPAR-alpha and CPT-1 in hepatic tissues. Serum, total cholesterol, triacylglycerol, fatty acid and fasting blood glucose were determined colorimetrically. Both PPAR-alpha agonists, fenofibrate and n-3 PUFA, increased the mRNA expression of AMPK-alpha1 activity in liver and skeletal muscle of obese diabetic rats. Fenofibrate was superior in its activation of hepatic mRNA expression of AMPK-alpha 1 to exert more lipolytic effect and body weight reduction, as estimated through the decrease of triacylglycerol output and serum levels of fatty acid on the one hand and the increase in CPT-1 mRNA expression, the key enzyme in beta-oxidation of fatty acid, on the other hand. n-3 PUFA activated AMPK-alpha1 mRNA expression in skeletal muscle much

  5. Genome-wide analysis of PPAR Alpha activation in murine small intestine

    NARCIS (Netherlands)

    Bünger, M.; Bosch, van den H.M.; Meijde, van der J.; Kersten, A.H.; Hooiveld, G.J.E.J.; Müller, M.R.

    2007-01-01

    The peroxisome proliferator-activated receptor alpha (PPAR) is a fatty acid-activated transcription factor that governs a variety of biological processes. Little is known about the role of PPAR in the small intestine. Since this organ is frequently exposed to high levels of PPAR ligands via the

  6. Examination of Ligand-Dependent Coactivator Recruitment by Peroxisome Proliferator-Activated Receptor-alpha (PPARalpha).

    Science.gov (United States)

    Tien, Eric S; Hannon, Daniel B; Thompson, Jerry T; Vanden Heuvel, John P

    2006-01-01

    The ligand-dependent recruitment of coactivators to peroxisome proliferator-activated receptor-alpha (PPARalpha) was examined. PPAR-binding protein (PBP), PPARgamma coactivator-1alpha (PGC-1alpha), steroid receptor coactivator-1 (SRC-1), and CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2) affected PPARalpha activity in the presence of Wy-14,643. The effects on PPARalpha activity in light of increased or decreased expression of these coactivators were qualitatively different depending on the ligand examined. Diminished expression of PGC-1alpha, SRC-1, or PBP by RNAi plasmids affected natural or synthetic agonist activity whereas only Wy-14,643 was affected by decreased PGC-1alpha. The interaction of PPARalpha with an LXXLL-containing peptide library showed ligand-specific patterns, indicative of differences in conformational change. The association of coactivators to PPARalpha occurs predominantly via the carboxyl-terminus and mutating (456)LHPLL to (456)LHPAA resulted in a dominant-negative construct. This research confirms that coactivator recruitment to PPARalpha is ligand-dependent and that selective receptor modulators (SRMs) of this important protein are likely.

  7. 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.

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

    CERN Document Server

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

    2016-01-01

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

  9. alpha-MSH enhances activity-based anorexia

    NARCIS (Netherlands)

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

    2005-01-01

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

  10. alpha-MSH enhances activity-based anorexia

    NARCIS (Netherlands)

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

    2005-01-01

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

  11. 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

  12. 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 measuremen

  13. Gene program-specific regulation of PGC-1{alpha} activity

    DEFF Research Database (Denmark)

    Schmidt, Søren F; Mandrup, Susanne

    2011-01-01

    Peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1 α (PGC-1α) activation coordinates induction of the hepatic fasting response through coactivation of numerous transcription factors and gene programs. In the June 15, 2011, issue of Genes & Development, Lustig and colleagues (pp...

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Differential neural activation of vascular alpha-adrenoceptors in oral tissues of cats.

    Science.gov (United States)

    Koss, Michael C

    2002-04-05

    The aim of this study was to determine the relative contribution of alpha(1)- and alpha(2)-adrenoceptors involved in sympathetic-evoked vasoconstrictor responses in tissues perfused by the lingual arterial circulation in pentobarbital anesthetized cats. Blood flow in the lingual artery was measured by ultrasonic flowmetry. Laser-Doppler flowmetry was utilized to measure oral tissue vasoconstrictor responses in the maxillary gingiva and from the surface of the tongue. Electrical stimulation of the preganglionic superior cervical sympathetic nerve resulted in frequency-dependent blood flow decreases at all three sites. These responses were stable over time and were uniformly antagonized by administration of phentolamine (0.3 - 3.0 mg kg(-1)). The selective alpha(1)-adrenoceptor antagonist, prazosin (10 - 300 microg kg(-1)), attenuated vasoconstriction in the lingual artery and gingiva, but was ineffective in blocking vasoconstriction in the tongue. Subsequent administration of rauwolscine (300 microg kg(-1)) antagonized remaining vasoconstrictor responses. In contrast, rauwolscine (10 - 300 microg kg(-1)), given alone, blocked evoked vasoconstriction in the tongue, and was without effect on gingival or lingual artery vasoconstrictor responses. Subsequent administration of prazosin (300 microg kg(-1)) largely antagonized remaining neurally elicited responses. These results suggest that neural vasoconstrictor responses in some regional vascular beds in the cat oral cavity are mediated by both alpha(1)- and alpha(2)-adrenoceptors. In contrast, tongue surface vasoconstrictor responses to sympathetic nerve activation appear to be mediated primarily by alpha(2)-adrenoceptors.

  19. 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....

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

    African Journals Online (AJOL)

    Methods: Extracts were prepared using hexane, chloroform, ethyl acetate, acetone (AE), methanol, ... screening has revealed moderate antiglucosidase and antioxidant activities in the ... glucosidase inhibitor in vivo and in vitro has been.

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

  2. 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......SIE-oligonucleotide probe, IL-2 and IL-15 activated the slowly migrating isoform, Stat3alpha. In contrast, minimal or no activation of Stat3beta was observed, suggesting that IL-2 and IL-15 predominantly activate Stat3alpha in human CD4(+) T cells. In this way, diversity in the expression and activation of Stat3 proteins...... may provide additional means of regulating cytokine-induced T cell responses....

  3. 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...

  4. 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

  5. The Escherichia coli RNA polymerase alpha subunit and transcriptional activation by bacteriophage lambda CII protein.

    Science.gov (United States)

    Gabig, M; Obuchowski, M; Ciesielska, A; Latała, B; Wegrzyn, A; Thomas, M S; Wegrzyn, G

    1998-01-01

    Bacteriophage lambda is not able to lysogenise the Escherichia coli rpoA341 mutant. This mutation causes a single amino acid substitution Lys271Glu in the C-terminal domain of the RNA polymerase alpha subunit (alphaCTD). Our previous studies indicated that the impaired lysogenisation of the rpoA341 host is due to a defect in transcriptional activation by the phage CII protein and suggested a role for alphaCTD in this process. Here we used a series of truncation and point mutants in the rpoA gene placed on a plasmid to investigate the process of transcriptional activation by the cII gene product. Our results indicate that amino-acid residues 265, 268 and 271 in the a subunit may play an important role in the CII-mediated activation of the pE promoter (most probably residue 271) or may be involved in putative interactions between alphaCTD and an UP-like element near pE (most probably residues 265 and 268). Measurement of the activity of pE-lacZ, pI-lacZ and p(aQ)-lacZ fusions in the rpoA+ and rpoA341 hosts demonstrated that the mechanism of activation of these CII-dependent promoters may be in each case different.

  6. Gross decontamination experiment report

    Energy Technology Data Exchange (ETDEWEB)

    Mason, R.; Kinney, K.; Dettorre, J.; Gilbert, V.

    1983-07-01

    A Gross Decontamination Experiment was conducted on various levels and surfaces of the TMI - Unit 2 reactor building in March 1982. The polar crane, D-rings, missile shields, refueling canals, refueling bridges, equipment, and elevations 305' and 347'-6'' were flushed with low pressure water. Additionally, floor surfaces on elevation 305' and floor surfaces and major pieces of equipment on elevation 347'-6'' were sprayed with high pressure water. Selective surfaces were decontaminated with a mechanical scrubber and chemicals. Strippable coating was tested and evaluated on equipment and floor surfaces. The effectiveness, efficiency, and safety of several decontamination techniques were established for the large, complex decontamination effort. Various decontamination equipment was evaluated and its effectiveness was documented. Decontamination training and procedures were documented and evaluated, as were the support system and organization for the experiment.

  7. AP-2{alpha} suppresses skeletal myoblast proliferation and represses fibroblast growth factor receptor 1 promoter activity

    Energy Technology Data Exchange (ETDEWEB)

    Mitchell, Darrion L. [Department of Cell Biology and Anatomy, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064 (United States); DiMario, Joseph X., E-mail: joseph.dimario@rosalindfranklin.edu [Department of Cell Biology and Anatomy, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064 (United States)

    2010-01-15

    Skeletal muscle development is partly characterized by myoblast proliferation and subsequent differentiation into postmitotic muscle fibers. Developmental regulation of expression of the fibroblast growth factor receptor 1 (FGFR1) gene is required for normal myoblast proliferation and muscle formation. As a result, FGFR1 promoter activity is controlled by multiple transcriptional regulatory proteins during both proliferation and differentiation of myogenic cells. The transcription factor AP-2{alpha} is present in nuclei of skeletal muscle cells and suppresses myoblast proliferation in vitro. Since FGFR1 gene expression is tightly linked to myoblast proliferation versus differentiation, the FGFR1 promoter was examined for candidate AP-2{alpha} binding sites. Mutagenesis studies indicated that a candidate binding site located at - 1035 bp functioned as a repressor cis-regulatory element. Furthermore, mutation of this site alleviated AP-2{alpha}-mediated repression of FGFR1 promoter activity. Chromatin immunoprecipitation studies demonstrated that AP-2{alpha} interacted with the FGFR1 promoter in both proliferating myoblasts and differentiated myotubes. In total, these results indicate that AP-2{alpha} is a transcriptional repressor of FGFR1 gene expression during skeletal myogenesis.

  8. DHEA metabolites activate estrogen receptors alpha and beta

    Science.gov (United States)

    Michael Miller, Kristy K.; Al-Rayyan, Numan; Ivanova, Margarita M.; Mattingly, Kathleen A.; Ripp, Sharon L.; Klinge, Carolyn M.; Prough, Russell A.

    2012-01-01

    Dehydroepiandrosterone (DHEA) levels were reported to associate with increased breast cancer risk in postmenopausal women, but some carcinogen-induced rat mammary tumor studies question this claim. The purpose of this study was to determine how DHEA and its metabolites affect estrogen receptors α or β (ERα or ERβ) -regulated gene transcription and cell proliferation. In transiently transfected HEK-293 cells, androstenediol, DHEA, and DHEA-S activated ERα. In ERβ transfected HepG2 cells, androstenedione, DHEA, androstenediol, and 7-oxo DHEA stimulated reporter activity. ER antagonists ICI 182,780 (fulvestrant) and 4-hydroxytamoxifen, general P450 inhibitor miconazole, and aromatase inhibitor exemestane inhibited activation by DHEA or metabolites in transfected cells. ERβ-selective antagonist R,R-THC (R,R-cis-diethyl tetrahydrochrysene) inhibited DHEA and DHEA metabolite transcriptional activity in ERβ-transfected cells. Expression of endogenous estrogen-regulated genes: pS2, progesterone receptor, cathepsin D1, and nuclear respiratory factor-1 was increased by DHEA and its metabolites in an ER-subtype, gene, and cell-specific manner. DHEA metabolites, but not DHEA, competed with 17β-estradiol for ERα and ERβ binding and stimulated MCF-7 cell proliferation, demonstrating that DHEA metabolites interact directly with ERα and ERβ in vitro, modulating estrogen target genes in vivo. PMID:23123738

  9. Detection of alpha- and beta-hemolytic-like activity from Campylobacter jejuni.

    OpenAIRE

    Misawa, N; Hirayama, K.; Itoh, K.; Takahashi, E.

    1995-01-01

    Alpha-hemolytic-like activity from Campylobacter jejuni was clearly apparent when the medium pH ranged from 6.0 to 6.5, but the hemolytic zones disappeared when the pH of the medium increased. Beta-hemolytic-like activity just beneath the bacterial growth appeared after prolonged incubation. The hemolytic activity was not influenced by the species of blood.

  10. DHEA metabolites activate estrogen receptors alpha and beta

    OpenAIRE

    Michael Miller, Kristy K.; AL-RAYYAN, NUMAN; Ivanova, Margarita M.; Mattingly, Kathleen A.; Ripp, Sharon L.; Klinge, Carolyn M; Prough, Russell A.

    2012-01-01

    Dehydroepiandrosterone (DHEA) levels were reported to associate with increased breast cancer risk in postmenopausal women, but some carcinogen-induced rat mammary tumor studies question this claim. The purpose of this study was to determine how DHEA and its metabolites affect estrogen receptors α or β (ERα or ERβ) -regulated gene transcription and cell proliferation. In transiently transfected HEK-293 cells, androstenediol, DHEA, and DHEA-S activated ERα. In ERβ transfected HepG2 cells, andro...

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

    Directory of Open Access Journals (Sweden)

    Stephen eWhitmarsh

    2011-10-01

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

  12. Melatonin inhibits both ER alpha activation and breast cancer cell proliferation induced by a metalloestrogen, cadmium.

    Science.gov (United States)

    Martínez-Campa, C; Alonso-González, C; Mediavilla, M D; Cos, S; González, A; Ramos, S; Sánchez-Barceló, E J

    2006-05-01

    Cadmium (Cd) is a heavy metal affecting human health both through environmental and occupational exposure. There is evidence that Cd accumulates in several organs and is carcinogenic to humans. In vivo, Cd mimics the effect of estrogens in the uterus and mammary gland. In estrogen-responsive breast cancer cell lines, Cd stimulates proliferation and can also activate the estrogen receptor independent of estradiol. The ability of this metalloestrogen to increase gene expression in MCF7 cells is blocked by anti-estrogens suggesting that the activity of these compounds is mediated by ER alpha. The aims of this work were to test whether melatonin inhibits Cd-induced proliferation in MCF7 cells, and also to study whether melatonin specifically inhibits Cd-induced ER alpha transactivation. We show that melatonin prevents the Cd-induced growth of synchronized MCF7 breast cancer cells. In transient transfection experiments, we prove that both ER alpha- and ER beta-mediated transcription are stimulated by Cd. Melatonin is a specific inhibitor of Cd-induced ER alpha-mediated transcription in both estrogen response elements (ERE)- and AP1-containing promoters, whereas ER beta-mediated transcription is not inhibited by the pineal indole. Moreover, the mutant ER alpha-(K302G, K303G), unable to bind calmodulin, is activated by Cd but becomes insensitive to melatonin treatment. These results proved that melatonin inhibits MCF7 cell growth induced by Cd and abolishes the stimulatory effect of the heavy metal in cells expressing ER alpha at both ERE-luc and AP1-luc sites. We can infer from these experiments that melatonin regulates Cd-induced transcription in both ERE- and AP1 pathways. These results also reinforce the hypothesis of the anti-estrogenic properties of melatonin as a valuable tool in breast cancer therapies.

  13. Receptor density is key to the alpha2/beta interferon differential activities.

    Science.gov (United States)

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

    2009-09-01

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

  14. 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...

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

    NARCIS (Netherlands)

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

    2003-01-01

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

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

    NARCIS (Netherlands)

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

    2003-01-01

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

  17. N-methyl-D-aspartate antagonist activity of alpha- and beta-sulfallorphans.

    Science.gov (United States)

    Shukla, V K; Lemaire, S

    1997-01-01

    Resolved equatorial (alpha) and axial (beta) forms of S-allylmorphinans, alpha-sulfallorphan and beta-sulfallorphan, were tested for their ability to compete with the binding of phencyclidine and sigma receptor ligands to mouse brain membranes and to antagonize N-methyl-D-aspartate (NMDA)-induced convulsions in mice. alpha- and beta-sulfallorphans displayed distinct binding affinities for phencyclidine and sigma sites, inhibiting the binding of [3H]-(5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten++ +-5, 10-imine ([3H]MK-801) with Ki values of 2.32 and 0.13 microM and that of [3H](+)-pentazocine with Ki values of 1.97 and 1.61 microM, respectively. Intracerebroventricular administration of these compounds in mice caused dose-dependent inhibitions of NMDA-induced convulsions, but did not affect convulsions induced by (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), kainic acid and bicuculline. alpha- and beta-sulfallorphans blocked the convulsive activity of NMDA (1 nmol/mouse; intracerebroventricular) with ED50 values of 0.48 and 0.015 nmol/mouse, as compared with 0.55, 0.039 and 0.013 nmol/mouse for dextrorphan, MK-801 and (+/-)3-(2-carboxypiperazine-4yl)propyl-1-proprionic acid, respectively. The structurally related compound, dextrallorphan, significantly but less potently blocked NMDA-induced convulsions (ED60, 2.68 nmol/mouse). At the protective doses, alpha- and beta-sulfallorphans markedly reduced NMDA- and AMPA-induced mortality without inducing locomotion and falling behavior. These results indicate that alpha- and beta-sulfallorphans are potent and selective NMDA antagonists devoid of motor side effects at protective doses.

  18. Communications: Comparison of activation barriers for the Johari-Goldstein and alpha relaxations and its implications.

    Science.gov (United States)

    Goldstein, Martin

    2010-01-28

    The range of activation barrier heights for the Johari-Goldstein (JG) relaxation in glasses is shown to overlap the range for the main (alpha) relaxation, but to be on the average somewhat lower. This suggests the JG relaxation, like the alpha, involve transitions between megabasins in the energy landscape, and that the original conjecture by Johari and this author that the JG relaxation is an intrabasin one cannot be correct. A further possibility is that there is a closer connection of the JG relaxation to the phenomenon of dynamic heterogeneity in supercooled liquids than so far assumed.

  19. $Ly \\alpha$ Fluorescent Excitation of FeII in Active Galactic Nuclei

    CERN Document Server

    Sigut, T A A; Pradhan, Anil K.

    1998-01-01

    We have calculated FeII emission line strengths for Active Galactic Nuclei Broad-Line Regions using precise radiative transfer and Iron Project atomic data. We improve the treatment of all previously considered excitation mechanisms for the FeII emission, continuum fluorescence, collisional excitation, fluorescence by self-overlap among the iron lines, and fluorescent excitation by Lyman-alpha. We demonstrate that Lyman-alpha fluorescence is of fundamental importance in determining the strength of the FeII emission. In addition to enhancing the ultraviolet and optical FeII flux, Lyman-alpha fluorescence also results in significant near-infrared FeII emission in the 8500-9500 Angstrom wavelength range. New observations are suggested to probe this effect in strong FeII emitting quasars.

  20. Mindfulness-of-breathing exercise modulates EEG alpha activity during cognitive performance.

    Science.gov (United States)

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

    2016-09-01

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

  1. BOREAS HYD-8 Gross Precipitation Data

    Science.gov (United States)

    Fernandes, Richard; Hall, Forrest G. (Editor); Knapp, David E. (Editor); Smith, David E. (Technical Monitor)

    2000-01-01

    The Boreal Ecosystem-Atmosphere Study (BOREAS) Hydrology (HYD)-08 team made measurements of surface hydrological processes at the Southern Study Area-Old Black Spruce (SSA-OBS) Tower Flux site to support its research into point hydrological processes and the spatial variation of these processes. Data collected may be useful in characterizing canopy interception, drip, throughfall, moss interception, drainage, evaporation, and capacity during the growing season at daily temporal resolution. This particular data set contains the gross precipitation measurements for July to August 1996. Gross precipitation is the precipitation that falls that is not intercepted by tree canopies. These data are stored in ASCII text files. The HYD-08 gross precipitation data are available from the Earth Observing System Data and Information System (EOSDIS) Oak Ridge National Laboratory (ORNL) Distributed Active Archive Center (DAAC). The data files are available on a CD-ROM (see document number 20010000884).

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

    Directory of Open Access Journals (Sweden)

    Liang Qin

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

  3. 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.

  4. 5 Alpha-reductase inhibitory and antiandrogenic activities of novel steroids in hamster seminal vesicles.

    Science.gov (United States)

    Cabeza, Marisa; Bratoeff, Eugene; Flores, Eugenio; Ramírez, Elena; Calleros, Jorge; Montes, Diana; Quiroz, Alexandra; Heuze, Ivonne

    2002-11-01

    The pharmacological activity of several 16-bromosubstituted trienediones 4 and 5, 16-methyl substituted dienediones 6 and 7 and the 16-methyl substituted trienedione 8 was determined on gonadectomized hamster seminal vesicles by measuring the in vitro conversion of testosterone (T) to dihydrotestosterone (DHT) as 5alpha-reductase inhibitors and also the ability of these steroids to bind to the androgen receptor. Steroids 6 and 7 when injected together with T decreased the weight of the seminal vesicles thus showing an antiandrogenic effect. Compounds 5 and 6 reduced substantially the conversion of T to DHT and therefore can be considered good inhibitors for the enzyme 5alpha-reductase; however both steroids failed to form a complex with the androgen receptor. On the other hand compound 7 which showed a very small inhibitory activity for the enzyme 5alpha-reductase, exhibited a very high affinity for the androgen receptor and thus can be considered an effective antiandrogen. This compound also reduced substantially the weight of the seminal vesicles. Steroids 4 and 8 did not reduce the weight of the seminal vesicles and exhibited a low affinity for the androgen receptor; 8 showed a weak 5alpha-reductase inhibitory activity, whereas 4 exhibited a weak androgenic effect.

  5. Binding of Tris to Bacillus licheniformis alpha-amylase can affect its starch hydrolysis activity.

    Science.gov (United States)

    Ghalanbor, Zahra; Ghaemi, Nasser; Marashi, Sayed-Amir; Amanlou, Massoud; Habibi-Rezaei, Mehran; Khajeh, Khosro; Ranjbar, Bijan

    2008-01-01

    Bacillus licheniformis alpha-amylase (BLA) is routinely used as a model thermostable amylase in biochemical studies. Its starch hydrolysis activity has recently been studied in Tris buffer. Here, we address the question that whether the application of Tris buffer may influence the results of BLA activity analyses. Based on the inhibition studies and docking simulations, we suggest that Tris molecule is a competitive inhibitor of starch-hydrolyzing activity of BLA, and it has a high tendency to bind the enzyme active site. Hence, it is critically important to consider such effect when interpreting the results of activity studies of this enzyme in Tris buffer.

  6. Roles of tumor necrosis factor alpha on sperm acrosin activity and acrosome reaction

    Institute of Scientific and Technical Information of China (English)

    Shu-LingBian; Guo-YiLiu; Hai-XiaWen; Shu-ZhenWang; JiangNi; WeiZhang; HuiSi

    2004-01-01

    Aim: To study the roles of tumor necrosis factor alpha (TNF-a)on the sperm acrosin activity and acrosome reaction. Methods:The sperm acrosin activity was tested by the method of BAEE/ADH Unity and the acrosome reaction by the Triple-stain technique. Results: TNF-a decreased the sperm acrosin activityand acrosome reaction (P<0.01, P<0.01, respectively);

  7. Activity Concentration Monitoring for Alpha Radioactive Aerosol in CRARL after Reprocessing Experiments

    Institute of Scientific and Technical Information of China (English)

    WANG; Xiang-li; LIU; Ning; WANG; Xiao-rong; BAI; Yang; JIAO; Xiao-yan; XU; Xin; MA; Hao-ran

    2015-01-01

    The activity concentration for alpha radioactive aerosol in CRARL after reprocessing experiments was analyzed.Through the decay method of activity concentration monitoring,the processed result shows the background is 3.05×10-3 s-1,σ(0)=2.25×10-3,LC=2.33×10-3 Bq/m3,LD=4.66×10-3 Bq/m3.The result indicated

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

    Energy Technology Data Exchange (ETDEWEB)

    Mason, C.F.V.; Allander, K.S.; Bounds, J.A.; Garner, S.E. [Los Alamos National Lab., NM (United States); Walter, K.J. [Brown and Root Environmental, Albuquerque, NM (United States)

    1994-03-01

    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.

  9. Icodextrin metabolism and alpha-amylase activity in nonuremic rats undergoing chronic peritoneal dialysis.

    Science.gov (United States)

    García-López, Elvia; Pawlaczyk, Krzysztof; Anderstam, Björn; Qureshi, A Rashid; Kuzlan-Pawlaczyk, Malgorzata; Heimbürger, Olof; Werynski, Andrzej; Lindholm, Bengt

    2007-01-01

    To study the metabolism of icodextrin and alpha-amylase activity following daily exposure to dialysis solutions containing either glucose or icodextrin as osmotic agent in rats. Male Wistar rats with implanted peritoneal catheters were infused twice daily for 3 weeks with 20 mL 7.5% icodextrin-based peritoneal dialysis fluid (IPDF; ICO group, n = 12) or 3.86% glucose-based peritoneal dialysis fluid (GLU group, n = 11). A 4-hour dwell study using 30 mL IPDF was performed on day 10 (D1) and day 21 (D2) in both the ICO and the GLU groups. Radiolabeled serum albumin (RISA) was used as a macromolecular volume marker. Dialysate samples were collected at 3, 15, 30, 60, 90, 120, and 240 minutes. Blood samples were drawn before the start and at the end of the dwell. During all dwell studies, the dialysate concentrations of total icodextrin decreased due to decrease in high molecular weight (MW) fractions, whereas there was a marked increase in icodextrin low MW metabolites. alpha-Amylase activity increased in dialysate and decreased in plasma. About 60% of the total icodextrin was absorbed from the peritoneal cavity during the 4-hour dwells. Low MW icodextrin metabolites were present in the dialysate already at 3 minutes, and maltose (G2), maltotriose (G3), maltotetraose (G4), and maltopentaose (G5) increased progressively, reaching maximum concentrations at 60 minutes. Maltohexaose (G6) and maltoheptaose (G7) were also detected already at 3 minutes but did not change significantly during the dwells. During the two 4-hour dwell studies (D1 and D2), the concentrations of total icodextrin and icodextrin metabolites and alpha-amylase activity in dialysate did not differ between the ICO and GLU groups, during either D1 or D2. No icodextrin metabolites were detected in plasma at the end of the dwells. alpha-Amylase activity in the dialysate increased six- to eightfold whereas plasma alpha-amylase activity decreased by 21% - 26% during the two 4-hour dwells in both the ICO and

  10. Chemical modification of an alpha 3-fucosyltransferase; definition of amino acid residues essential for enzyme activity.

    Science.gov (United States)

    Britten, C J; Bird, M I

    1997-02-11

    The biosynthesis of the carbohydrate antigen sialyl Lewis X (sLe(x)) is dependent on the activity of an alpha 3-fucosyltransferase (EC 2.4.1.152, GDP-fucose:Gal beta (1-4)GlcNAc-R alpha (1-3)fucosyltransferase). This enzyme catalyses the transfer of fucose from GDP-beta-fucose to the 3-OH of N-acetylglucosamine present in lactosamine acceptors. In this report, we have investigated the amino acids essential for the activity of a recombinant alpha 3-fucosyltransferase (FucT-VI) through chemical modification of the enzyme with group-selective reagents. FucT-VI activity was found to be particularly sensitive to the histidine-selective reagent diethylpyrocarbonate and the cysteine reagent N-ethylmaleimide, with IC50 values of less than 200 microM. Reagents selective for arginine and lysine had no effect on enzyme activity. The inclusion of GDP-beta-fucose during preincubation with NEM reduces the rate of inactivation whereas inclusion of an acceptor saccharide for the enzyme, Gal beta (1-4)GlcNAc, had no effect. No protective effect with either GDP-beta-fucose or Gal beta (1-4)GlcNAc was observed on treatment of the enzyme with diethylpyrocarbonate. These data suggest that in addition to an NEM-reactive cysteine in, or adjacent to, the substrate-binding site of the enzyme, FucT-VI possesses histidine residue(s) that are essential for enzyme activity.

  11. The influence of the calibration standard and the chemical composition of the water samples residue in the counting efficiency of proportional detectors for gross alpha and beta counting. Application on the radiologic control of the IPEN-CNEN/SP; A influencia do padrao de calibracao e da composicao do residuo de amostras de agua na eficiencia de contadores proporcionais para contagem alfa e beta total. Aplicacao no controle radiologico do IPEN-CNEN/SP

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Cecilia Martins

    2003-07-01

    In this work the efficiency calibration curves of thin-window and low background gas-flow proportional counters were determined for calibration standards with different energies and different absorber thicknesses. For the gross alpha counting we have used {sup 241}Am and natural uranium standards and for the gross beta counting we have used {sup 90}Sr/{sup 90}Y and {sup 137}Cs standards in residue thicknesses ranging from 0 to approximately 18 mg/cm{sup 2}. These sample thicknesses were increased with a previously determined salted solution prepared simulating the chemical composition of the underground water of IPEN The counting efficiency for alpha emitters ranged from 0,273 +- 0,038 for a weightless residue to only 0,015 +- 0,002 in a planchet containing 15 mg/cm{sup 2} of residue for {sup 241}Am standard. For natural uranium standard the efficiency ranged from 0,322 +- 0,030 for a weightless residue to 0,023 +- 0,003 in a planchet containing 14,5 mg/cm{sup 2} of residue. The counting efficiency for beta emitters ranged from 0,430 +- 0,036 for a weightless residue to 0,247 +- 0,020 in a planchet containing 17 mg/cm{sup 2} of residue for {sup 137}Cs standard. For {sup 90}Sr/{sup 90}Y standard the efficiency ranged from 0,489 +- 0,041 for a weightless residue to 0,323 +- 0,026 in a planchet containing 18 mg/cm{sup 2} of residue. Results make evident the counting efficiency variation with the alpha or beta emitters energies and the thickness of the water samples residue. So, the calibration standard, the thickness and the chemical composition of the residue must always be considered in the gross alpha and beta radioactivity determination in water samples. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    Warburton, W.K.

    2005-07-22

    analyzing the preamplifier signals with a digital signal 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{sup 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{sup 2} electrode into 4 square segments, each 625 cm{sup 2} and demonstrating that signal noise on individual channels reduced as expected. Because the Phase II counter with a 1 m{sup 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

  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 A

  14. 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.

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

    CERN Document Server

    Llama, J

    2015-01-01

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

  16. Expression of feline interferon-alpha subtypes in Esherichia coli, and their antiviral activity and animal species specificity.

    Science.gov (United States)

    Taira, Osamu; Suzuki, Makoto; Takeuchi, Yuko; Aramaki, Yoshitaka; Sakurai, Itsuki; Watanabe, Takao; Motokawa, Kenji; Arai, Setsuo; Sato, Hisaaki; Maehara, Nobutoshi

    2005-05-01

    Two kinds of FeIFN-alpha consisting of 166 amino acids (aa) and 171 aa were expressed in Escherichia coli, and the purified proteins were tested for antiviral activity on homologous and heterologous animal cells. Crude FeIFN induced in feline cells revealed antiviral activity on both homologous and heterologous animal cells. In contrast, both types of recombinant FeIFN-alpha revealed antiviral activity only on the feline cells. All of the FeIFN-alpha subtypes showed high activity to vesicular stomatitis virus, and the three species of feline viruses belonging to different families.

  17. Comparison of the activities of various alginates to induce TNF-alpha secretion in RAW264.7 cells.

    Science.gov (United States)

    Kurachi, Maki; Nakashima, Takuji; Miyajima, Chihiro; Iwamoto, Yoshiko; Muramatsu, Tsuyoshi; Yamaguchi, Kenichi; Oda, Tatsuya

    2005-08-01

    We compared the abilities of alginate polymers having different molecular sizes and compositions to induce the secretion of tumor necrosis factor (TNF)-alpha in RAW264.7 cells. The molecular sizes and alpha-L-guluronate/beta-D-mannuronate (M/G) ratios of highly purified alginate polymers used in this study were 9000-38 000 and 1.50-3.17, respectively. Among the alginates tested, I-S, which had the highest molecular weight, showed the most potent TNF-alpha-inducing activity. The M/G ratio also seemed to influence this activity, and, among alginates with similar molecular sizes, alginates with a higher M/G ratio tended to show higher activity. Interestingly, the enzymatic depolymerization of I-S with bacterial alginate lyase resulted in a dramatic increase in the TNF-alpha-inducing activity. Such an effect of enzymatic digestion was also observed in a relatively low-molecular-weight alginate (ULV-3), which originally had very low TNF-alpha-inducing activity. Furthermore, the inhibition profiles of the TNF-alpha-inducing activity of enzymatically digested I-S shown by three specific mitogen-activated protein (MAP) kinase inhibitors differed from those of intact I-S. These results suggest that the underlying mechanism of the TNF-alpha-inducing activity of enzymatically depolymerized alginate oligomers is not necessarily the same as that of original alginate polymer.

  18. Antioxidant alpha-lipoic acid inhibits osteoclast differentiation by reducing nuclear factor-kappaB DNA binding and prevents in vivo bone resorption induced by receptor activator of nuclear factor-kappaB ligand and tumor necrosis factor-alpha.

    Science.gov (United States)

    Kim, Hyon Jong; Chang, Eun-Ju; Kim, Hyun-Man; Lee, Seung Bok; Kim, Hyun-Duck; Su Kim, Ghi; Kim, Hong-Hee

    2006-05-01

    The relationship between oxidative stress and bone mineral density or osteoporosis has recently been reported. As bone loss occurring in osteoporosis and inflammatory diseases is primarily due to increases in osteoclast number, reactive oxygen species (ROS) may be relevant to osteoclast differentiation, which requires receptor activator of nuclear factor-kappaB ligand (RANKL). Tumor necrosis factor-alpha (TNF-alpha) frequently present in inflammatory conditions has a profound synergy with RANKL in osteoclastogenesis. In this study, we investigated the effects of alpha-lipoic acid (alpha-LA), a strong antioxidant clinically used for some time, on osteoclast differentiation and bone resorption. At concentrations showing no growth inhibition, alpha-LA potently suppressed osteoclastogenesis from bone marrow-derived precursor cells driven either by a high-dose RANKL alone or by a low-dose RANKL plus TNF-alpha (RANKL/TNF-alpha). alpha-LA abolished ROS elevation by RANKL or RANKL/TNF-alpha and inhibited NF-kappaB activation in osteoclast precursor cells. Specifically, alpha-LA reduced DNA binding of NF-kappaB but did not inhibit IKK activation. Furthermore, alpha-LA greatly suppressed in vivo bone loss induced by RANKL or TNF-alpha in a calvarial remodeling model. Therefore, our data provide evidence that ROS plays an important role in osteoclast differentiation through NF-kappaB regulation and the antioxidant alpha-lipoic acid has a therapeutic potential for bone erosive diseases.

  19. Iron K$\\alpha$ emission in type-I and type-II Active Galactic Nuclei

    CERN Document Server

    Ricci, Claudio; Paltani, Stephane; Ichikawa, Kohei; Gandhi, Poshak; Awaki, Hisamitsu

    2014-01-01

    The narrow Fe K$\\alpha$ line is one of the main signatures of the reprocessing of X-ray radiation from the material surrounding supermassive black holes, and it has been found to be omnipresent in the X-ray spectra of active galactic nuclei (AGN). In this work we study the characteristics of the narrow Fe K$\\alpha$ line in different types of AGN. Using the results of a large Suzaku study we find that Seyfert 2s have on average lower Fe K$\\alpha$ luminosities than Seyfert 1s for the same 10-50 keV continuum luminosity. Simulating dummy Sy1s and Sy2s populations using physical torus models of X-ray reflected emission, we find that this difference can be explained by means of different average inclination angles with respect to the torus, as predicted by the unified model. Alternative explanations include differences in the intensities of Compton humps or in the photon index distributions. We show that the ratio between the flux of the broad and narrow Fe K$\\alpha$ line in the 6.35-6.45 keV range depends on the ...

  20. Structural Basis for Iloprost as a Dual Peroxisome Proliferator-activated Receptor [alpha/delta] Agonist

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Lihua; Lin, Shengchen; Rong, Hui; Zheng, Songyang; Jin, Shikan; Wang, Rui; Li, Yong (Pitt); (Xiamen)

    2012-03-15

    Iloprost is a prostacyclin analog that has been used to treat many vascular conditions. Peroxisome proliferator-activated receptors (PPARs) are ligand-regulated transcription factors with various important biological effects such as metabolic and cardiovascular physiology. Here, we report the crystal structures of the PPAR{alpha} ligand-binding domain and PPAR{delta} ligand-binding domain bound to iloprost, thus providing unambiguous evidence for the direct interaction between iloprost and PPARs and a structural basis for the recognition of PPAR{alpha}/{delta} by this prostacyclin analog. In addition to conserved contacts for all PPAR{alpha} ligands, iloprost also initiates several specific interactions with PPARs using its unique structural groups. Structural and functional studies of receptor-ligand interactions reveal strong functional correlations of the iloprost-PPAR{alpha}/{delta} interactions as well as the molecular basis of PPAR subtype selectivity toward iloprost ligand. As such, the structural mechanism may provide a more rational template for designing novel compounds targeting PPARs with more favorable pharmacologic impact based on existing iloprost drugs.

  1. 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.

  2. Comparison of starch hydrolysis activity and thermal stability of two Bacillus licheniformis alpha-amylases and insights into engineering alpha-amylase variants active under acidic conditions.

    Science.gov (United States)

    Lee, Seunjae; Oneda, Hiroshi; Minoda, Masashi; Tanaka, Akiyoshi; Inouye, Kuniyo

    2006-06-01

    Bacillus licheniformis alpha-amylase (BLA) is widely used in various procedures of starch degradation in the food industry, and a BLA species with improved activity at higher temperature and under acidic conditions is desirable. Two BLA species, designated as PA and MA, have been isolated from the wild-type B. licheniformis strain and a mutant strain, respectively. In this study, their starch-hydrolysis activity and thermal stability were examined. MA showed higher activity than PA, especially at acidic pH (pH 5.0-5.5), and even after 1 h of treatment at 90 degrees C. MA was active in the range of pH 4.0-8.0, which is much wider than that (pH 4.5-7.5) of PA. It was shown that the proton dissociation constants on the acidic and alkaline sides (pKa1 and pKa2) were shifted to more acidic and basic values, respectively, by the mutation of PA to MA. The activation energy and thermodynamic parameters for their thermal inactivation indicate that MA is more thermally stable and catalytically active than PA, suggesting that MA could be useful for glucose-production process coupled with reactions catalyzed by beta-amylase.

  3. 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

  4. Fine structure of histograms of alpha-activity measurements depends on direction of alpha particles flow and the Earth rotation: experiments with collimators

    CERN Document Server

    Shnoll, S E; Berulis, I I; Udaltsova, N V; Rubinstein, I A; Shnoll, Simon E.; Zenchenko, Konstantin I.; Berulis, Iosas I.; Udaltsova, Natalia V.; Rubinstein, Ilia A.

    2004-01-01

    The fine structure of histograms of measurements of 239Pu alpha-activity varies periodically, and the period of these variations is equal to sidereal day (1436 minutes). The periodicity is not observed in the experiments with collimator that restricts the alpha particles flow to be oriented to the Polar Star. Based on this study and other independent data, such as measurements conducted by the Arctic expedition, and similarity of the histograms in processes observed at different locations at the same local time, the conclusion was made, that the fine structure of statistical distributions of the observed processes depends on the celestial sphere.

  5. 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.

  6. Human salivary alpha-amylase Trp58 situated at subsite -2 is critical for enzyme activity.

    Science.gov (United States)

    Ramasubbu, Narayanan; Ragunath, Chandran; Mishra, Prasunkumar J; Thomas, Leonard M; Gyémánt, Gyöngyi; Kandra, Lili

    2004-06-01

    The nonreducing end of the substrate-binding site of human salivary alpha-amylase contains two residues Trp58 and Trp59, which belong to beta2-alpha2 loop of the catalytic (beta/alpha)(8) barrel. While Trp59 stacks onto the substrate, the exact role of Trp58 is unknown. To investigate its role in enzyme activity the residue Trp58 was mutated to Ala, Leu or Tyr. Kinetic analysis of the wild-type and mutant enzymes was carried out with starch and oligosaccharides as substrates. All three mutants exhibited a reduction in specific activity (150-180-fold lower than the wild type) with starch as substrate. With oligosaccharides as substrates, a reduction in k(cat), an increase in K(m) and distinct differences in the cleavage pattern were observed for the mutants W58A and W58L compared with the wild type. Glucose was the smallest product generated by these two mutants in the hydrolysis oligosaccharides; in contrast, wild-type enzyme generated maltose as the smallest product. The production of glucose by W58L was confirmed from both reducing and nonreducing ends of CNP-labeled oligosaccharide substrates. The mutant W58L exhibited lower binding affinity at subsites -2, -3 and +2 and showed an increase in transglycosylation activity compared with the wild type. The lowered affinity at subsites -2 and -3 due to the mutation was also inferred from the electron density at these subsites in the structure of W58A in complex with acarbose-derived pseudooligosaccharide. Collectively, these results suggest that the residue Trp58 plays a critical role in substrate binding and hydrolytic activity of human salivary alpha-amylase.

  7. Structural determinants of glutathione transferases with azathioprine activity identified by DNA shuffling of alpha class members.

    Science.gov (United States)

    Kurtovic, Sanela; Modén, Olof; Shokeer, Abeer; Mannervik, Bengt

    2008-02-01

    A library of alpha class glutathione transferases (GSTs), composed of chimeric enzymes derived from human (A1-1, A2-2 and A3-3), bovine (A1-1) and rat (A2-2 and A3-3) cDNA sequences was constructed by the method of DNA shuffling. The GST variants were screened in bacterial lysates for activity with the immunosuppressive agent azathioprine, a prodrug that is transformed into its active form, 6-mercaptopurine, by reaction with the tripeptide glutathione catalyzed by GSTs. Important structural determinants for activity with azathioprine were recognized by means of primary structure analysis and activities of purified enzymes chosen from the screening. The amino acid sequences could be divided into 23 exchangeable segments on the basis of the primary structures of 45 chosen clones. Segments 2, 20, 21, and 22 were identified as primary determinants of the azathioprine activity representing two of the regions forming the substrate-binding H-site. Segments 21 and 22 are situated in the C-terminal helix characterizing alpha class GSTs, which is instrumental in their catalytic function. The study demonstrates the power of DNA shuffling in identifying segments of primary structure that are important for catalytic activity with a targeted substrate. GSTs in combination with azathioprine have potential as selectable markers for use in gene therapy. Knowledge of activity-determining segments in the structure is valuable in the protein engineering of glutathione transferase for enhanced or suppressed activity.

  8. Sight restoration after congenital blindness does not reinstate alpha oscillatory activity in humans.

    Science.gov (United States)

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

    2016-01-01

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

  9. Involvement of vacuolar sequestration and active transport in tolerance of Saccharomyces cerevisiae to hop iso-alpha-acids.

    Science.gov (United States)

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

    2010-01-01

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

  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. 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.…

  12. New evidence of similarity between human and plant steroid metabolism: 5alpha-reductase activity in Solanum malacoxylon.

    Science.gov (United States)

    Rosati, Fabiana; Danza, Giovanna; Guarna, Antonio; Cini, Nicoletta; Racchi, Milvia Luisa; Serio, Mario

    2003-01-01

    The physiological role of steroid hormones in humans is well known, and the metabolic pathway and mechanisms of action are almost completely elucidated. The role of plant steroid hormones, brassinosteroids, is less known, but an increasing amount of data on brassinosteroid biosynthesis is showing unexpected similarities between human and plant steroid metabolic pathways. Here we focus our attention on the enzyme 5alpha-reductase (5alphaR) for which a plant ortholog of the mammalian system, DET2, was recently described in Arabidopsis thaliana. We demonstrate that campestenone, the natural substrate of DET2, is reduced to 5alpha-campestanone by both human 5alphaR isozymes but with different affinities. Solanum malacoxylon, which is a calcinogenic plant very active in the biosynthesis of vitamin D-like molecules and sterols, was used to study 5alphaR activity. Leaves and calli were chosen as examples of differentiated and undifferentiated tissues, respectively. Two separate 5alphaR activities were found in calli and leaves of Solanum using campestenone as substrate. The use of progesterone allowed the detection of both activities in calli. Support for the existence of two 5alphaR isozymes in S. malacoxylon was provided by the differential actions of inhibitors of the human 5alphaR in calli and leaves. The evidence for the presence of two isozymes in different plant tissues extends the analogies between plant and mammalian steroid metabolic pathways.

  13. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha activation of CYP7A1 during food restriction and diabetes is still inhibited by small heterodimer partner.

    Science.gov (United States)

    Shin, Dong-Ju; Osborne, Timothy F

    2008-05-30

    Cholesterol 7alpha-hydroxylase (CYP7A1) catalyzes the rate-limiting step in the classic pathway of hepatic bile acid biosynthesis from cholesterol. During fasting and in type I diabetes, elevated levels of peroxisome proliferator-activated receptor gamma-coactivator-1alpha (PGC-1alpha) induce expression of the Cyp7A1 gene and overexpression of PGC-1alpha in hepatoma cells stimulates bile acid synthesis. Using Ad-PGC-1alpha-RNA interference to induce acute disruption of PGC-1alpha in mice, here we show that PGC-1alpha is necessary for fasting-mediated induction of CYP7A1. Co-immunoprecipitation and promoter activation studies reveal that the induction of CYP7A1 is mediated by direct interaction between PGC-1alpha and the AF2 domain of liver receptor homolog-1 (LRH-1). In contrast, the very similar PGC-1beta could not substitute for PGC-1alpha. We also show that transactivation of PGC-1alpha and LRH-1 is repressed by the small heterodimer partner (SHP). Treatment of mice with GW4064, a synthetic agonist for farnesoid X receptor, induced SHP expression and decreased both the recruitment of PGC-1alpha to the Cyp7A1 promoter and the fasting-induced expression of CYP7A1 mRNA. These data suggest that PGC-1alpha is an important co-activator for LRH-1 and that SHP targets the interaction between LRH-1 and PGC-1alpha to inhibit CYP7A1 expression. Overall, these studies provide further evidence for the important role of PGC-1alpha in bile acid homeostasis and suggest that pharmacological targeting of farnesoid X receptor in vivo can be used to reverse the increase in CYP7A1 associated with adverse metabolic conditions.

  14. 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.

  15. Activation of antilipolytic alpha(2)-adrenergic receptors by epinephrine during exercise in human adipose tissue.

    Science.gov (United States)

    Stich, V; de Glisezinski, I; Crampes, F; Suljkovicova, H; Galitzky, J; Riviere, D; Hejnova, J; Lafontan, M; Berlan, M

    1999-10-01

    The involvement of the antilipolytic alpha(2)-adrenergic pathway and the specific role of epinephrine in the control of lipolysis during exercise in adipose tissue (AT) were investigated in healthy male subjects (age: 24.1 +/- 2.2 yr; body mass index: 23.0 +/- 1.6). An in vitro study carried out on isolated adipocytes showed that the weak lipolytic effect of epinephrine was potentiated after blockade of alpha(2)-adrenergic receptor (AR) by an alpha(2)-AR antagonist and reached that of isoproterenol, a beta-AR agonist. The effect of the nonselective alpha(2)-AR antagonist phentolamine on the response of the extracellular glycerol concentration (EGC) in AT during two successive bouts of aerobic exercise (50% maximum O(2) uptake, 60 min duration) was evaluated using the microdialysis method. The metabolic responses measured in perfused probes with Ringer solution were compared with those obtained in perfused probes with Ringer plus 0.1 mmol/l phentolamine. Plasma norepinephrine level was not different during the two exercise bouts, whereas that of epinephrine was 2.5-fold higher during the second exercise. EGC in AT was twofold higher in the second compared with the first exercise, and the same response pattern was found for plasma glycerol. The exercise-induced increase in EGC was higher in the probe perfused with phentolamine compared with the control probe in both bouts of exercise. However, the potentiating effect of phentolamine on EGC was significant during the second exercise bout but did not reach a significant level during the first. These results suggest that epinephrine is involved in the control of lipid mobilization through activation of antilipolytic alpha(2)-AR in human subcutaneous AT during exercise.

  16. 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.

  17. Enhancement of gene transfer activity mediated by mannosylated dendrimer/alpha-cyclodextrin conjugate (generation 3, G3).

    Science.gov (United States)

    Arima, Hidetoshi; Chihara, Yuko; Arizono, Masayo; Yamashita, Shogo; Wada, Koki; Hirayama, Fumitoshi; Uekama, Kaneto

    2006-11-01

    To enhance gene transfer activity of dendrimers, we prepared its conjugate (generation 3, G3) with alpha-cyclodextrin bearing mannose (Man-alpha-CDE conjugates) with various degrees of substitution of the mannose moiety (DSM5, 10, 13, 20) and compared their cytotoxicity and gene transfer activity, and elucidated the enhancing mechanism for the activity. Of the various carriers used here, Man-alpha-CDE conjugate (G3, DSM10) provided the highest gene transfer activity in NR8383, A549, NIH3T3 and HepG2 cells, being independent of the expression of mannose receptors. Gene transfer activity of Man-alpha-CDE conjugate (G3, DSM10) was not decreased by the addition of 10% serum in A549 cells. Cytotoxicity of the polyplex with Man-alpha-CDE conjugates (G3, DSM10) was not observed in A549 and NIH3T3 cells up to the charge ratio of 200/1 (carrier/pDNA). The gel mobility and particle size of polyplex with Man-alpha-CDE conjugate (G3, DSM10) were relevant to those with alpha-CDE conjugate (G3), but zeta-potential, DNase I stability, pDNA condensation of the former polyplex were somewhat different from those of the latter one. Cellular association of polyplex with Man-alpha-CDE conjugate (G3, DSM10) was almost comparable to that with dendrimer (G3) complex and alpha-CDE conjugate (G3). The addition of mannan and mannose attenuated gene transfer activity of Man-alpha-CDE conjugate (G3, DSM10) in A549 cells. Alexa-pDNA complex with TRITC-Man-alpha-CDE conjugate (G3, DSM10), but not the complex with TRITC-alpha-CDE conjugate (G3), was found to translocate to nucleus at 24 h after incubation in A549 cells. HVJ-E vector including mannan, but neither the vector alone nor the vector including dextran, suppressed the nuclear localization of TRITC-Man-alpha-CDE conjugate (G3, DSM10) to a striking degree after 24 h incubation in A549 cells. These results suggest that Man-alpha-CDE conjugate (G3, DSM10) has less cytotoxicity and prominent gene transfer activity through not only its serum

  18. Activity of cytisine and its brominated isosteres on recombinant human alpha7, alpha4beta2 and alpha4beta4 nicotinic acetylcholine receptors.

    Science.gov (United States)

    Houlihan, L M; Slater, Y; Guerra, D L; Peng, J H; Kuo, Y P; Lukas, R J; Cassels, B K; Bermudez, I

    2001-09-01

    Effects of cytisine (cy), 3-bromocytisine (3-Br-cy), 5-bromocytisine (5-Br-cy) and 3,5-dibromocytisine (3,5-diBr-cy) on human (h) alpha7-, alpha4beta2- and alpha4beta4 nicotinic acetylcholine (nACh) receptors, expressed in Xenopus oocytes and cell lines, have been investigated. Cy and its bromo-isosteres fully inhibited binding of both [alpha-(125)I]bungarotoxin ([alpha-(125)I]BgTx) to halpha7- and [(3)H]cy to halpha4beta2- or halpha4beta4-nACh receptors. 3-Br-cy was the most potent inhibitor of both [alpha-(125)I]BgTx and [(3)H]cy binding. Cy was less potent than 3-Br-cy, but 5-Br-cy and 3,5-diBr-cy were the least potent inhibitors. Cy and 3-Br-cy were potent full agonists at halpha7-nACh receptors but behaved as partial agonists at halpha4beta2- and halpha4beta4-nACh receptors. 5-Br-cy and 3,5-diBr-cy had low potency and were partial agonists at halpha7- and halpha4beta4-nACh receptors, but they elicited no responses on halpha4beta2-nACh receptors. Cy and 3-Br-cy produced dual dose-response curves (DRC) at both halpha4beta2- and halpha4beta4-nACh receptors, but ACh produced dual DRC only at halpha4beta2-nACh receptors. Low concentrations of cy, 3-Br-cy and 5-Br-cy enhanced ACh responses of oocytes expressing halpha4beta2-nACh receptors, but at high concentrations they inhibited the responses. In contrast, 3,5-diBr-cy only inhibited, in a competitive manner, ACh responses of halpha4beta2-nACh receptors. It is concluded that bromination of the pyridone ring of cy produces marked changes in effects of cy that are manifest as nACh receptor subtype-specific differences in binding affinities and in functional potencies and efficacies.

  19. Gross job flows and firms

    OpenAIRE

    Scott Schuh; Robert K. Triest

    1999-01-01

    This paper extends the work of Dunne, Roberts, and Samuelson [3] and Davis, Haltiwanger, and Schuh [2] on gross job flows among manufacturing plants. Gross job creation, destruction, and reallocation have been shown to be important in understanding the birth, growth, and death of plants, and the relation of plant life cycles to the business cycle. However, little is known about job flows between firms or how job flows among plants occur within firms (corporate restructuring). We use informati...

  20. Activation of the Drosophila MLK by ceramide reveals TNF-alpha and ceramide as agonists of mammalian MLK3.

    Science.gov (United States)

    Sathyanarayana, Pradeep; Barthwal, Manoj K; Kundu, Chanakya N; Lane, Mary Ellen; Bergmann, Andreas; Tzivion, Guri; Rana, Ajay

    2002-12-01

    Mixed lineage kinases (MLKs) are MAPKKK members that activate JNK and reportedly lead to cell death. However, the agonist(s) that regulate MLK activity remain unknown. Here, we demonstrate ceramide as the activator of Drosophila MLK (dMLK) and identify ceramide and TNF-alpha as agonists of mammalian MLK3. dMLK and MLK3 are activated by a ceramide analog and bacterial sphingomyelinase in vivo, whereas a low nanomolar concentration of natural ceramide activates them in vitro. Specific inhibition of dMLK and MLK3 significantly attenuates activation of JNK by ceramide in vivo without affecting ceramide-induced p38 or ERK activation. In addition, TNF-alpha also activates MLK3 and evidently leads to JNK activation in vivo. Thus, the ceramide serves as a common agonist of dMLK and MLK3, and MLK3 contributes to JNK activation induced by TNF-alpha.

  1. Neohesperidin dihydrochalcone: presentation of a small molecule activator of mammalian alpha-amylase as an allosteric effector.

    Science.gov (United States)

    Kashani-Amin, Elaheh; Larijani, Bagher; Ebrahim-Habibi, Azadeh

    2013-03-18

    Flavonoids and their precursor trans-chalcone have been reported as inhibitors of mammalian alpha-amylase. With regard to this background, neohesperidin dihydrochalcone (NHDC) effect was investigated toward porcine pancreatic alpha-amylase (PPA), and found to be an activator of the enzyme. The maximal activation (up to threefold) was found to occur at 4.8mM of NHDC, which could be considered to have a high activation profile, with regard to the alpha and beta parameters (alpha<1activator of the enzyme and based on the results obtained from modeling tools, it is suggested to interact with PPA at a hydrophilic site located at the N-terminal, far from the active site of the enzyme.

  2. 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

    , 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...... in patients with schizophrenia. In addition, PCP increased the basal mRNA expression in the PFC of the activity-regulated cytoskeleton-associated protein (Arc), a molecule involved in synaptic plasticity. These molecular changes produced by PCP were accompanied by a behavioral impairment as determined...... 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...

  3. About the effectiveness of spectrometry in alpha-activity monitoring of industrial air-borne particles

    Energy Technology Data Exchange (ETDEWEB)

    Domnikov, V.N.; Saltykov, L.S.; Slusarenko, L.I.; Shevchenko, S.V. E-mail: shevsv@i.kiev.ua

    2001-10-01

    The maximum-likelihood method (MLM) is applied for the analysis of the background compensation problem when using alpha-spectrometry to measure the transuranium radionuclide (TRU) content in thick aerosol samples. It is shown, that the uncertainty of the measurement results has a rather small dependence on the digit capacity of the analog to digital converter (ADC). For the total TRU alpha-activity measurement a 7-bit conversion in the energy range up to 9-10 MeV is sufficient to evaluate the background parameters in the energy region of interest (ROI). Background compensation is also made by subtraction of the estimated total background from the sum of counts measured in the ROI.

  4. Effect of salivary gland adenocarcinoma cell-derived alpha-N-acetylgalactosaminidase on the bioactivity of macrophage activating factor.

    Science.gov (United States)

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

    2004-03-01

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

  5. 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

  6. Structural and Biochemical Basis for the Binding Selectivity of Peroxisome Proliferator-activated Receptor [gamma] to PGC-1[alpha

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yong; Kovach, Amanda; Suino-Powell, Kelly; Martynowski, Dariusz; Xu, H. Eric (Pitt); (Van Andel)

    2008-07-23

    The functional interaction between the peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) and its coactivator PGC-1{alpha} is crucial for the normal physiology of PPAR{gamma} and its pharmacological response to antidiabetic treatment with rosiglitazone. Here we report the crystal structure of the PPAR{gamma} ligand-binding domain bound to rosiglitazone and to a large PGC-1{alpha} fragment that contains two LXXLL-related motifs. The structure reveals critical contacts mediated through the first LXXLL motif of PGC-1{alpha} and the PPAR{gamma} coactivator binding site. Through a combination of biochemical and structural studies, we demonstrate that the first LXXLL motif is the most potent among all nuclear receptor coactivator motifs tested, and only this motif of the two LXXLL-related motifs in PGC-1{alpha} is capable of binding to PPAR{gamma}. Our studies reveal that the strong interaction of PGC-1{alpha} and PPAR{gamma} is mediated through both hydrophobic and specific polar interactions. Mutations within the context of the full-length PGC-1{alpha} indicate that the first PGC-1{alpha} motif is necessary and sufficient for PGC-1{alpha} to coactivate PPAR{gamma} in the presence or absence of rosiglitazone. These results provide a molecular basis for specific recruitment and functional interplay between PPAR{gamma} and PGC-1{alpha} in glucose homeostasis and adipocyte differentiation.

  7. Protein kinase A and mitogen-activated protein kinase pathways mediate cAMP induction of alpha-epithelial Na+ channels (alpha-ENaC).

    Science.gov (United States)

    Mustafa, Shamimunisa B; Castro, Robert; Falck, Alison J; Petershack, Jean A; Henson, Barbara M; Mendoza, Yvonne M; Choudary, Ahsan; Seidner, Steven R

    2008-04-01

    A major mechanism for Na+ transport across epithelia occurs through epithelial Na+ channels (ENaC). ENaC is a multimeric channel consisting of three subunits (alpha, beta, and gamma). The alpha-subunit is critical for ENaC function. In specific culture conditions, the rat submandibular gland epithelial cell line (SMG-C6) demonstrates minimal Na+ transport properties and exposure to dibutyryl cAMP (DbcAMP) for up to 48 h caused an elevation of alpha-ENaC mRNA and protein expression and amiloride-sensitive short-circuit current (I(SC)). Here we examined the early signaling pathways evoked by DbcAMP which contribute to the eventual increase in Na+ transport is present. Treatment with either of the protein kinase A (PKA) inhibitors KT5720 or H-89 followed by exposure to 1 mM DbcAMP for 24 h markedly attenuated DbcAMP-induced alpha-ENaC protein formation and I(SC). Exposure of SMG-C6 cells to 1 mM DbcAMP induced a rapid, transient phosphorylation of the cAMP response element binding protein (CREB). This response was attenuated in the presence of either KT5720 or H-89. Dominant-negative CREB decreased DbcAMP-induced alpha-ENaC expression. Suppression of the extracellular signal-regulated protein kinase (ERK 1,2) with PD98059 or the p38 mitogen-activated protein kinase (MAPK) pathway with SB203580 reduced DbcAMP-induced alpha-ENaC protein levels in SMG-C6 cells. DbcAMP-induced phosphorylation of CREB was markedly attenuated by PD98059 or SB203580. DbcAMP-induced activation of the either the p38 or the ERK 1,2 MAPK pathways was abolished by either of the PKA inhibitors, H-89 or KT5720. Cross talk between these signaling pathways induced by DbcAMP via the activation of CREB appears to contribute to increased levels of alpha-ENaC observed after 24 h of treatment in SMG-C6 epithelial cells.

  8. Enzymic synthesis of alpha- and beta-D-glucosides of 1-deoxynojirimycin and their glycosidase inhibitory activities.

    Science.gov (United States)

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

    1994-05-20

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

  9. 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.

  10. Inhibitory Activities of Phenolic Compounds Isolated from Adina rubella Leaves Against 5[alpha]-Reductase Associated with Benign Prostatic Hypertrophy

    National Research Council Canada - National Science Library

    Jun Yin; Jun Hyeok Heo; Yoon Jeong Hwang; Thi Tam Le; Min Won Lee

    2016-01-01

    .... The current study evaluated the anti-oxidative and anti-inflammatory activities and 5[alpha]-reductase inhibition of isolated compounds of AR leaves to find a potential therapeutic agent for benign prostatic hypertrophy...

  11. Effect of novel benzoylphenylurea derivatives on DNA polymerase alpha activity using the synthesome-based in vitro model system.

    Science.gov (United States)

    Abdel-Aziz, Waleed; Hickey, Robert; Edelman, Martin; Malkas, Linda

    2003-11-01

    Six benzoylphenylurea (BPU) derivatives have been synthesized in Japan and extensively evaluated by the U.S. National Cancer Institute. They demonstrated potent antitumor activity in vitro against several cancer cell lines as well as in vivo against several tumor models. One of these agents, NSC639829, has now entered clinical trials. Studies have shown that these compounds are effective inhibitors of in vitro tubulin polymerization. The parent compound, NSC624548 (HO-221), has been shown to inhibit calf thymus DNA polymerase alpha activity. In this study we examined the effects of four BPU derivatives (NSC624548, NSC639828, NSC639829, and NSC654259) on the activity of the synthesome-associated DNA polymerase alpha, Escherichia coli DNA polymerase I, and calf thymus DNA polymerase alpha. Among the compounds tested, only NSC624548 and NSC639828 inhibited the activities of E. coli DNA polymerase I and calf thymus DNA polymerase alpha. Excess DNA polymerase I or DNA polymerase alpha dramatically reduced the inhibition produced by these compounds. NSC624548 and NSC639828 also showed inhibitory effects of the synthesome-associated DNA polymerase alpha similar to that produced upon using the purified E. coli and calf thymus enzymes. All of the four compounds did not show inhibitory effect on DNA polymerase delta. The similar pattern of inhibition these compounds exert on both the purified calf thymus and the synthesome-associated DNA polymerase alpha offers further support for the validity of the DNA synthesome as a novel in vitro model system for studying anticancer drug action.

  12. Anti-inflammatory activity of Pistacia lentiscus essential oil: involvement of IL-6 and TNF-alpha.

    Science.gov (United States)

    Maxia, Andrea; Sanna, Cinzia; Frau, Maria Assunta; Piras, Alessandra; Karchuli, Manvendra Singh; Kasture, Veena

    2011-10-01

    The topical anti-inflammatory activity of essential oil of Pistacia lentiscus L. was studied using carrageenan induced rat paw edema and cotton pellet induced granuloma. The effect on serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in rats inserted with cotton pellet was also investigated. On topical application, the oil exhibited a significant decrease in paw edema. The oil also inhibited cotton pellet-induced granuloma, and reduced serum TNF-alpha and IL-6. It can be concluded that the essential oil of Pistacia lentiscus reduces leukocyte migration to the damaged tissue and exhibits anti-inflammatory activity.

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

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  14. Activation of alpha(2)-adrenergic receptors impairs exercise-induced lipolysis in SCAT of obese subjects.

    Science.gov (United States)

    Stich, V; De Glisezinski, I; Crampes, F; Hejnova, J; Cottet-Emard, J M; Galitzky, J; Lafontan, M; Rivière, D; Berlan, M

    2000-08-01

    With the use of the microdialysis method, exercise-induced lipolysis was investigated in subcutaneous adipose tissue (SCAT) in obese subjects and compared with lean ones, and the effect of blockade of alpha(2)-adrenergic receptors (ARs) on lipolysis during exercise was explored. Changes in extracellular glycerol concentrations and blood flow were measured in SCAT in a control microdialysis probe at rest and during 60-min exercise bouts (50% of heart rate reserve) and in a probe supplemented with the alpha(2)-AR antagonist phentolamine. At rest and during exercise, plasma norepinephrine and epinephrine concentrations were not different in obese compared with lean men. In the basal state, plasma and extracellular glycerol concentrations were higher, whereas blood flow was lower in SCAT of obese subjects. During exercise, the increase of plasma glycerol was higher in obese subjects (115 +/- 35 vs. 65 +/- 21 micromol/l). Oppositely, the exercise-induced increase in extracellular glycerol concentrations in SCAT was five- to sixfold lower in obese than in lean subjects (50 +/- 14 vs. 318 +/- 53 micromol/l). The exercise-induced increase in extracellular glycerol concentration was not significantly modified by phentolamine infusion in lean subjects but was strongly enhanced in the obese subjects and reached the concentrations found in lean sujects (297 +/- 46 micromol/l). These findings demonstrate that the physiological stimulation of SCAT adipocyte alpha(2)-ARs during exercice-induced sympathetic nervous system activation contributes to the blunted lipolysis noted in obese men.

  15. Activation measurement of the 3He(alpha,gamma)7Be cross section at low energy

    CERN Document Server

    Bemmerer, D; Costantini, H; Formicola, A; Gyürky, G; Bonetti, R; Broggini, C; Corvisiero, P; Elekes, Z; Fülöp, Z; Gervino, G; Guglielmetti, A; Gustavino, C; Imbriani, G; Junker, M; Laubenstein, M; Lemut, A; Limata, B; Lozza, V; Marta, M; Menegazzo, R; Prati, P; Roca, V; Rolfs, C; Alvarez, C R; Somorjai, E; Straniero, O; Strieder, F; Terrasi, F; Trautvetter, H P; Gyurky, Gy.; Fulop, Zs.

    2006-01-01

    The nuclear physics input from the 3He(alpha,gamma)7Be cross section is a major uncertainty in the fluxes of 7Be and 8B neutrinos from the Sun predicted by solar models and in the 7Li abundance obtained in big-bang nucleosynthesis calculations. The present work reports on a new precision experiment using the activation technique at energies directly relevant to big-bang nucleosynthesis. Previously such low energies had been reached experimentally only by the prompt-gamma technique and with inferior precision. Using a windowless gas target, high beam intensity and low background gamma-counting facilities, the 3He(alpha,gamma)7Be cross section has been determined at 127, 148 and 169 keV center-of-mass energy with a total uncertainty of 4%. The sources of systematic uncertainty are discussed in detail. The present data can be used in big-bang nucleosynthesis calculations and to constrain the extrapolation of the 3He(alpha,gamma)7Be astrophysical S-factor to solar energies.

  16. Anterior asymetrical alpha activity predicts Iowa gambling performance: distinctly but reversed.

    Science.gov (United States)

    Schutter, Dennis J L G; de Haan, Edward H F; van Honk, Jack

    2004-01-01

    Animal research indicates that the prefrontal cortex (PFC) plays a crucial role in decision making. In concordance, deficits in decision making have been observed in human patients with damage to the PFC. Contemporary accounts of decision making suggest that emotion guides the process of decision making by ways of providing for reward-punishment contingencies. A task capable of assessing the influence of reward and punishment on decision making is the Iowa gambling task. In this task decisions become motivated by inherent punishment and reward schedules. Insensitivity for punishment together with a strong reward dependency results in risk taking, which is in the gambling task the disadvantageous strategy. Interestingly, the processing of punishment and reward is argued to be lateralized over the right and left PFC, respectively. Here we investigated whether more relative left compared to right-sided frontal brain activity (left-sided dominance) quantified as reduced alpha (8-12 Hz) activity in the electroencephalogram (EEG) would lead to a more risky, disadvantageous pattern of decision making. Contrary to what was expected, relatively more right compared to left frontal brain activity was strongly associated with the disadvantageous strategy. The results are discussed in terms of recent theoretical accounts which argue that the functional interpretation of baseline frontal alpha activity depends on the mental operation involved and does not necessarily imply inactivity.

  17. Tat-APE1/ref-1 protein inhibits TNF-alpha-induced endothelial cell activation.

    Science.gov (United States)

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

    2008-03-28

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

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

    Science.gov (United States)

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

    2000-02-01

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

  19. Ablation of AMP-activated protein kinase alpha1 and alpha2 from mouse pancreatic beta cells and RIP2.Cre neurons suppresses insulin release in vivo.

    Science.gov (United States)

    Sun, G; Tarasov, A I; McGinty, J; McDonald, A; da Silva Xavier, G; Gorman, T; Marley, A; French, P M; Parker, H; Gribble, F; Reimann, F; Prendiville, O; Carzaniga, R; Viollet, B; Leclerc, I; Rutter, G A

    2010-05-01

    AMP-activated protein kinase (AMPK) is an evolutionarily conserved enzyme and a target of glucose-lowering agents, including metformin. However, the precise role or roles of the enzyme in controlling insulin secretion remain uncertain. The catalytic alpha1 and alpha2 subunits of AMPK were ablated selectively in mouse pancreatic beta cells and hypothalamic neurons by breeding Ampkalpha1 [also known as Prkaa1]-knockout mice, bearing floxed Ampkalpha2 [also known as Prkaa2] alleles (Ampkalpha1 ( -/- ),alpha2( fl/fl ),), with mice expressing Cre recombinase under the rat insulin promoter (RIP2). RIP2 was used to express constitutively activated AMPK selectively in beta cells in transgenic mice. Food intake, body weight and urinary catecholamines were measured using metabolic cages. Glucose and insulin tolerance were determined after intraperitoneal injection. Beta cell mass and morphology were analysed by optical projection tomography and confocal immunofluorescence microscopy, respectively. Granule docking, insulin secretion, membrane potential and intracellular free Ca(2+) were measured with standard techniques. Trigenic Ampkalpha1 ( -/- ),alpha2( fl/fl ) expressing Cre recombinase and lacking both AMPKalpha subunits in the beta cell, displayed normal body weight and increased insulin sensitivity, but were profoundly insulin-deficient. Secreted catecholamine levels were unchanged. Total beta cell mass was unaltered, while mean islet and beta cell volume were reduced. AMPK-deficient beta cells displayed normal glucose-induced changes in membrane potential and intracellular free Ca(2+), while granule docking and insulin secretion were enhanced. Conversely, betaAMPK transgenic mice were glucose-intolerant and displayed defective insulin secretion. Inhibition of AMPK activity within the beta cell is necessary, but not sufficient for stimulation of insulin secretion by glucose to occur. AMPK activation in extrapancreatic RIP2.Cre-expressing cells might also influence

  20. FEATURES OF THE ALPHA ACTIVITY OF THE BRAIN ON THE BACKGROUND OF MEDITATIVEPSYCHOLOGICAL TRAINING

    Directory of Open Access Journals (Sweden)

    A. S. Yanina

    2016-01-01

    Full Text Available The aim of the study was to identify the characteristics of the alpha activity of the brain on the background of meditative psychological training, depending on experience and qualifications.Materials and methods. Examined 30 volunteers of 25-45 years old, 12 men and 18 women. Depending on the experience of meditative practices, the participants were divided into three groups: a group with no experience of meditation (beginners, group practicing Kundalini yoga in General classes (1-3 times a week – average level, and a group of professionals (yoga teachers, practicing for at least three years and having a daily practice. All participants did not had neurological and psychiatric diseases, and had no dependence on alcohol or drugs and was relatively healthy. A study was conducted of the electrical activity of the brain at rest, during and after the meditative psychological training. As a result we acquired data for the frontal, Central, occipital and temporal leads.Results. Identified a number of changes of EEG parameters in the application of meditation techniques, which depended on the experience and qualifications of the subjects. Changes of alpha activity occur in all areas of the brain with the development of meditation techniques, whereas newcomers have changes mainly in the frontal region. The index of alpha-rhythm at rest is higher in groups with experience of meditation practice. The given material allows to recommend psychological training (meditation techniques of Kundalini yoga to reduce the level of fatigue and correction of psycho-emotional excitation. 

  1. Sulfate- and sialic acid-containing glycolipids inhibit DNA polymerase alpha activity.

    Science.gov (United States)

    Simbulan, C M; Taki, T; Tamiya-Koizumi, K; Suzuki, M; Savoysky, E; Shoji, M; Yoshida, S

    1994-03-16

    The effects of various glycolipids on the activity of immunoaffinity-purified calf thymus DNA polymerase alpha were studied in vitro. Preincubation with sialic acid-containing glycolipids, such as sialosylparagloboside (SPG), GM3, GM1, and GD1a, and sulfatide (cerebroside sulfate ester, CSE) dose-dependently inhibited the activity of DNA polymerase alpha, while other glycolipids, as well as free sphingosine and ceramide did not. About 50% inhibition was achieved by preincubating the enzyme with 2.5 microM of CSE, 50 microM of SPG or GM3, and 80 microM of GM1. Inhibition was noncompetitive with both the DNA template and the substrate dTTP, as well as with the other dNTPs. Since the inhibition was largely reversed by the addition of 0.05% Nonidet P40, these glycolipids may interact with the hydrophobic region of the enzyme protein. Apparently, the sulfate moiety in CSE and the sialic acid moiety in gangliosides were essential for the inhibition since neither neutral glycolipids (i.e., glucosylceramide, galactosylceramide, lactosylceramide) nor asialo-gangliosides (GA1 and GA2) showed any inhibitory effect. Furthermore, the ceramide backbone was also found to be necessary for maximal inhibition since the inhibition was largely abolished by substituting the lipid backbone with cholesterol. Increasing the number of sialic acid moieties per molecule further enhanced the inhibition, while elongating the sugar chain diminished it. It was clearly shown that the N-acetyl residue of the sialic acid moiety is particularly essential for inhibition by both SPG and GM3 because the loss of this residue or substitution with a glycolyl residue completely negated their inhibitory effect on DNA polymerase alpha activity.

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

    CERN Document Server

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

    2016-01-01

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

  3. On a question of Gross

    Science.gov (United States)

    Banerjee, Abhijit

    2007-03-01

    Using the notion of weighted sharing of sets we prove two uniqueness theorems which improve the results proved by Fang and Qiu [H. Qiu, M. Fang, A unicity theorem for meromorphic functions, Bull. Malaysian Math. Sci. Soc. 25 (2002) 31-38], Lahiri and Banerjee [I. Lahiri, A. Banerjee, Uniqueness of meromorphic functions with deficient poles, Kyungpook Math. J. 44 (2004) 575-584] and Yi and Lin [H.X. Yi, W.C. Lin, Uniqueness theorems concerning a question of Gross, Proc. Japan Acad. Ser. A 80 (2004) 136-140] and thus provide an answer to the question of Gross [F. Gross, Factorization of meromorphic functions and some open problems, in: Proc. Conf. Univ. Kentucky, Lexington, KY, 1976, in: Lecture Notes in Math., vol. 599, Springer, Berlin, 1977, pp. 51-69], under a weaker hypothesis.

  4. A Tumor-Penetrating Peptide Modification Enhances the Antitumor Activity of Thymosin Alpha 1

    OpenAIRE

    Xingzhen Lao; Meng Liu; Jiao Chen; Heng Zheng

    2013-01-01

    A serious limitation of numerous antitumor drugs is the incapacity to penetrate solid tumors. However, addition of an RGD fragment to peptide drugs might solve this problem. In this study, we explored whether the introduction of a permeability-enhancing sequence, such as iRGD (CRGDK/RGPD/EC) fragments, would enhance the activity of thymosin alpha 1 (Tα1). The modified Tα1 (Tα1-iRGD) was successfully expressed and purified, and the in vitro assay showed that Tα1-iRGD presented a similar activi...

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

    OpenAIRE

    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...

  6. Detection of alpha particle contamination on ultra low activity-grade integrated circuits

    Directory of Open Access Journals (Sweden)

    Fernandes Ana C.

    2016-01-01

    Full Text Available We propose to apply the superheated droplet detector (SDD technology to the measurement of alpha-particle emissivity on integrated circuits of ultra-low activity grade (< 1α/khcm2 for high reliability applications. This work is based on the SDDs employed within our team to the direct search for dark matter. We describe the modifications in the dark matter SDDs with respect to fabrication, signal analysis and characterization, in order to obtain a device with the adequate detection sensitivity and background noise.

  7. 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.

  8. 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.

  9. Pore-forming activity of alpha-toxin is essential for clostridium septicum-mediated myonecrosis.

    Science.gov (United States)

    Kennedy, Catherine L; Lyras, Dena; Cordner, Leanne M; Melton-Witt, Jody; Emmins, John J; Tweten, Rodney K; Rood, Julian I

    2009-03-01

    Clostridium septicum alpha-toxin is a beta-barrel pore-forming cytolysin that is functionally similar to aerolysin. Residues important in receptor binding, oligomerization, and pore formation have been identified; however, little is known about the activity of the toxin in an infection, although it is essential for disease. We have now shown that deletion of a small portion of the transmembrane domain, so that the toxin is no longer able to form pores, completely abrogates its ability to contribute to disease, as does replacement of the sole cysteine residue with leucine. However, although previous biochemical and cytotoxicity assays clearly indicated that mutations in residues important in oligomerization, binding, and prepore conversion greatly reduced activity or rendered the toxin inactive, once the mutated toxins were overexpressed by the natural host in the context of an infection it was found they were able to cause disease in a mouse model of myonecrosis. These results highlight the importance of testing the activity of virulence determinants in the normal host background and in an infectious disease context and provide unequivocal evidence that it is the ability of alpha-toxin to form a pore that confers its toxicity in vivo.

  10. X-ray structures associated with disappearing H-alpha filaments in active regions

    Science.gov (United States)

    Kahler, S. W.

    1980-01-01

    The paper examines the relationship between active region disappearing H-alpha filaments and the associated coronal X-ray structures observed both before the disappearance event and afterwards. The events chosen for the study were selected from a list of active region X-ray transients observed in the images from the X-ray telescope on Skylab and from a list compiled by Webb (1976) of sudden disappearances of filaments during the Skylab period. Results indicate no distinction between the disappearing and the remaining active region filaments in terms of their pre-event associated X-ray emission features. However, X-ray brightenings were associated in a nearly one-to-one correspondence with disappearing portions of the filaments.

  11. Determination of thorium concentrations and activity ratios in silicate rocks by alpha spectrometry.

    Science.gov (United States)

    dos Santos, R N; Marques, L S; Nicolai, S H A; Ribeiro, F B

    2004-01-01

    A detailed radiochemical procedure for alpha spectrometry measurements of thorium concentrations and of 230Th/232Th activity ratios in silicates is presented. The Th behaviour, during each step of the chemical process, was investigated by using a 234Th tracer, which is a gamma-ray emitter. The described chemical processing provides relatively high thorium yields, which varied between 56% and 88%, in the analysis of GB-1 (granite) and BB-1 (basalt) Brazilian geological standards. Also, the application of the established radiochemical method allowed a determination of both Th concentrations and activity ratios with high reproducibility, on the order of 2%. The estimation of the concentration result accuracy is also about 2%, which was calculated by using published data obtained from neutron activation analysis as reference values.

  12. 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

  13. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-01-08

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

  15. 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.

  16. Determination of total alpha and beta activity in water for human consumption by LSC(Liquid Scintillation Counter); Determinacao de atividades alfa e beta total em agua para consumo humano por LSC (Contador de Cintilacao Liquida))

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-07-01

    The Ordinance Brazilian of Ministry of Health (MS 2914/2011) establishes the standards for quality of water intended for human consumption, being limits values of 5.0 Bq/L for gross alpha, and 1.0 Bq/L for gross beta radioactivity. The liquid scintillation spectrometry (LSC) technique has been presented as an alternative to conventional procedure using gas flow proportional counter. The present work shows a review of the methods for determination of gross alpha and gross beta in water by using LSC. Between the factors that influence the accuracy and repeatability of the analytical results we can highlight: thermal preconcentration, type of the acid and calibration standard. A procedure was established and carried out to samples of the National Program of Intercomparison of Radionuclides in Environmental Samples for evaluation of its performance. The gross alpha and gross beta analysis in samples of the public water supplies in the Metropolitan Region of Goiania, state of Goias was carried out. The results are consistent with the guideline values form the Ministry of Health concerning radioactivity. (author)

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

    Science.gov (United States)

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

    2016-09-01

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

  18. The TF1-ATPase and ATPase activities of assembled alpha 3 beta 3 gamma, alpha 3 beta 3 gamma delta, and alpha 3 beta 3 gamma epsilon complexes are stimulated by low and inhibited by high concentrations of rhodamine 6G whereas the dye only inhibits the alpha 3 beta 3, and alpha 3 beta 3 delta complexes.

    Science.gov (United States)

    Paik, S R; Yokoyama, K; Yoshida, M; Ohta, T; Kagawa, Y; Allison, W S

    1993-12-01

    The ATPase activity of the F1-ATPase from the thermophilic bacterium PS3 is stimulated at concentrations of rhodamine 6G up to about 10 microM where 70% stimulation is observed at 36 degrees C. Half maximal stimulation is observed at about 3 microM dye. At rhodamine 6G concentrations greater than 10 microM, ATPase activity declines with 50% inhibition observed at about 75 microM dye. The ATPase activities of the alpha 3 beta 3 gamma and alpha 3 beta 3 gamma delta complexes assembled from isolated subunits of TF1 expressed in E. coli deleted of the unc operon respond to increasing concentrations of rhodamine 6G nearly identically to the response of TF1. In contrast, the ATPase activities of the alpha 3 beta 3 and alpha 3 beta 3 delta complexes are only inhibited by rhodamine 6G with 50% inhibition observed, respectively, at 35 and 75 microM dye at 36 degrees C. The ATPase activity of TF1 is stimulated up to 4-fold by the neutral detergent, LDAO. In the presence of stimulating concentrations of LDAO, the ATPase activity of TF1 is no longer stimulated by rhodamine 6G, but rather, it is inhibited with 50% inhibition observed at about 30 microM dye at 30 degrees C. One interpretation of these results is that binding of rhodamine 6G to a high-affinity site on TF1 stimulates ATPase activity and unmasks a low-affinity, inhibitory site for the dye which is also exposed by LDAO.

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

    Directory of Open Access Journals (Sweden)

    Jan eKubanek

    2015-07-01

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

  20. Oxytocin- and aluminium fluoride-induced phospholipase C activity and prostaglandin F2 alpha secretion during the ovine luteolytic period.

    Science.gov (United States)

    Graf, G A; Burns, P D; Silvia, W J

    1998-03-01

    A series of studies was conducted to characterize changes in components of the cell signalling cascade that mediates oxytocin-induced prostaglandin F2 alpha (PGF2 alpha) synthesis at the onset of luteolysis in sheep. In the first experiment, caruncular tissue was dissected from 20 ewes on days 12-15 of the oestrous cycle, and incubated for the measurement of phospholipase C (PLC) activity or secretion of PGF2 alpha. Activation of GTP-binding proteins with aluminium fluoride stimulated both inositol phosphate accumulation and PGF2 alpha secretion on all days examined. However, oxytocin did not stimulate PLC activity or PGF2 alpha accumulation until day 13. While the ability of oxytocin to stimulate PLC activity increased after day 13, oxytocin-induced PGF2 alpha secretion declined slightly from day 13 to 15, suggesting that cell signalling components downstream from PLC modulate the response to oxytocin after day 13. Oxytocin failed to stimulate PGF2 alpha synthesis on day 14 after oestrus. Secretion of endogenous luteal oxytocin may have rendered uterine tissues collected on day 14 refractory to oxytocin in vitro. Therefore, a second study was conducted in ovariectomized, steroid replaced ewes. Ovarian steroids were administered to mimic endogenous changes in progesterone and oestradiol. The temporal patterns of PGF2 alpha synthesis in response to oxytocin and pharmacological agents were similar to uterine tissues from cyclic ewes in the first experiment; however, the magnitude of the response was less. These data suggest that oxytocin receptors are absent or are not coupled to PLC until day 13 after oestrus.

  1. PDH-E1alpha dephosphorylation and activation in human skeletal muscle during exercise: effect of intralipid infusion.

    Science.gov (United States)

    Pilegaard, Henriette; Birk, Jesper B; Sacchetti, Massimo; Mourtzakis, Marina; Hardie, D Graham; Stewart, Greg; Neufer, P Darrell; Saltin, Bengt; van Hall, Gerrit; Wojtaszewski, Jorgen F P

    2006-11-01

    To investigate pyruvate dehydrogenase (PDH)-E1alpha subunit phosphorylation and whether free fatty acids (FFAs) regulate PDH activity, seven subjects completed two trials: saline (control) and intralipid/heparin (intralipid). Each infusion trial consisted of a 4-h rest followed by a 3-h two-legged knee 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-E1alpha 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-E1alpha phosphorylation and PDHa activity exists. Short-term elevation in plasma FFA at rest increases PDH-E1alpha phosphorylation, but exercise overrules this effect of FFA on PDH-E1alpha phosphorylation leading to even greater dephosphorylation during exercise with intralipid infusion than with saline.

  2. 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)

  3. The Protective Effect of Alpha 7 Nicotinic Acetylcholine Receptor Activation on Critical Illness and Its Mechanism

    Science.gov (United States)

    REN, Chao; TONG, Ya-lin; LI, Jun-cong; LU, Zhong-qiu; YAO, Yong-ming

    2017-01-01

    Critical illnesses and injuries are recognized as major threats to human health, and they are usually accompanied by uncontrolled inflammation and dysfunction of immune response. The alpha 7 nicotinic acetylcholine receptor (α7nAchR), which is a primary receptor of cholinergic anti-inflammatory pathway (CAP), exhibits great benefits for critical ill conditions. It is composed of 5 identical α7 subunits that form a central pore with high permeability for calcium. This putative structure is closely associated with its functional states. Activated α7nAChR exhibits extensive anti-inflammatory and immune modulatory reactions, including lowered pro-inflammatory cytokines levels, decreased expressions of chemokines as well as adhesion molecules, and altered differentiation and activation of immune cells, which are important in maintaining immune homeostasis. Well understanding of the effects and mechanisms of α7nAChR will be of great value in exploring effective targets for treating critical diseases. PMID:28123345

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

    Institute of Scientific and Technical Information of China (English)

    陆小军; 何林锋; 徐一鹤; 曹振; 孙训; 唐方东

    2014-01-01

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

  5. 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.

  6. Chaperone-like activity of alpha-cyclodextrin via hydrophobic nanocavity to protect native structure of ADH.

    Science.gov (United States)

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

    2010-01-26

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

  7. Molecular Mechanism of Peroxisome Proliferator-Activated Receptor alpha Activation by WY14643: a New Mode of Ligand Recognition and Receptor Stabilization

    NARCIS (Netherlands)

    Bernardes, Amanda; Telles de Souza, Paulo C; Muniz, João R C; Ricci, Clarisse G; Ayers, Stephen D; Parekh, Nili M; Godoy, André S; Trivella, Daniela B B; Reinach, Peter; Webb, Paul; Skaf, Munir S; Polikarpov, Igor

    2013-01-01

    Peroxisome proliferator-activated receptors (PPARs) are members of a superfamily of nuclear transcription factors. They are involved in mediating numerous physiological effects in humans, including glucose and lipid metabolism. PPAR alpha ligands effectively treat dyslipidemia and have significant

  8. Comparison of alpha-amylase activity in larval stages of flour beetles, Tribolium confusum (Coleoptera: Tenebionidae).

    Science.gov (United States)

    Bandani, A R; Balvasi, A

    2006-01-01

    Flour beetles attack stored grain products such as flour, cereals, meal, dried pet food, dried flowers and even dried museum specimens and other foods in the house. Stored-product insects cause tremendous losses by lowering weight, germination rate, nutritional value and grain grade. These beetles are of the most important pests of stored products in the home and grocery stores. The adult female may live for as long as two years, depositing 300 to 400 eggs. The life cycle requires one to four months when temperatures are favorable. Several methods could be used to control this insect including synthetic insecticides, biological control, physical control and transgenic plant carrying gene of interest. Chemical controls are discouraged due to pesticide residue in the commodities and resistance in insects. The study of insect digestive enzymes seems to make sense in the realization that the gut is the major interface between the insect and its environment. Hence, an understanding of digestive enzyme function is essential when developing methods of insect control such as the use of enzyme inhibitors and transgenic plants to control insect pests. Therefore, the aim of the current study was to get a good understanding from enzyme composition of different larval stages of the insect and finally characterize amylase which is the key enzyme in digestive system of this insect. For alpha-amylase study whole larvae were homogenized in 0.02 M phosphate buffer at pH 7.2. The homogenates were separately transferred to a 1.5 ml of centrifuge tubes and centrifuged at 15000xg for 20 min at 4degrees C. The supernatants were used as enzyme source in assays. alpha-Amylase activity was assayed by the dinitrosalicylic acid (DNS) procedure using 1% soluble starch (Merck) as substrate. The results show that enzyme activity (OD) in the first, second, third and fourth larval stages were 0.5, 1.15, 1.35 and 1.362, respectively. There are significant differences in amylase activity in

  9. Directed evolution of a bacterial alpha-amylase: toward enhanced pH-performance and higher specific activity.

    Science.gov (United States)

    Bessler, Cornelius; Schmitt, Jutta; Maurer, Karl-Heinz; Schmid, Rolf D

    2003-10-01

    alpha-Amylases, in particular, microbial alpha-amylases, are widely used in industrial processes such as starch liquefaction and pulp processes, and more recently in detergency. Due to the need for alpha-amylases with high specific activity and activity at alkaline pH, which are critical parameters, for example, for the use in detergents, we have enhanced the alpha-amylase from Bacillus amyloliquefaciens (BAA). The genes coding for the wild-type BAA and the mutants BAA S201N and BAA N297D were subjected to error-prone PCR and gene shuffling. For the screening of mutants we developed a novel, reliable assay suitable for high throughput screening based on the Phadebas assay. One mutant (BAA 42) has an optimal activity at pH 7, corresponding to a shift of one pH unit compared to the wild type. BAA 42 is active over a broader pH range than the wild type, resulting in a 5-fold higher activity at pH 10. In addition, the activity in periplasmic extracts and the specific activity increased 4- and 1.5-fold, respectively. Another mutant (BAA 29) possesses a wild-type-like pH profile but possesses a 40-fold higher activity in periplasmic extracts and a 9-fold higher specific activity. The comparison of the amino acid sequences of these two mutants with other homologous microbial alpha-amylases revealed the mutation of the highly conserved residues W194R, S197P, and A230V. In addition, three further mutations were found K406R, N414S, and E356D, the latter being present in other bacterial alpha-amylases.

  10. 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....

  11. Functional activities of receptors for tumor necrosis factor-alpha on human vascular endothelial cells.

    NARCIS (Netherlands)

    Paleolog, E.M.; Delasalle, S.A.; Buurman, W.A.; Feldmann, M.

    1994-01-01

    Tumor necrosis factor-alpha (TNF-alpha) plays a critical role in the control of endothelial cell function and hence in regulating traffic of circulating cells into tissues in vivo. Stimulation of endothelial cells in vitro by TNF-alpha increases the surface expression of leukocyte adhesion molecules

  12. 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...

  13. 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.

  14. Sensitization of voltage activated calcium channel currents for capsaicin in nociceptive neurons by tumor-necrosis-factor-alpha.

    Science.gov (United States)

    Hagenacker, T; Czeschik, J C; Schäfers, M; Büsselberg, D

    2010-01-15

    It is known that application of tumor-necrosis-factor-alpha (TNF-alpha) sensitizes neuronal calcium channels for heat stimuli in rat models of neuropathic pain. This study examines whether TNF-alpha modulates the capsaicin-induced effects after transient receptor potential vanilloid (TRPV)-1 receptor activation on voltage activated calcium channel currents (I(Ca(V))). TRPV-1 receptors are activated by heat and play an important role in the pathogenesis of thermal hyperalgesia in neuropathic pain syndromes, while voltage activated channels are essential for transmission of neuronal signals. Eliciting I(Ca(V)) in DRG neurons of rats by a depolarization from the resting potential to 0 mV, TNF-alpha (100 ng/ml) reduces I(Ca(V)) by 16.9+/-2.2%, while capsaicin (0.1 microM) decreases currents by 27+/-4.3%. Pre-application of TNF-alpha (100 ng/ml) for 24h results in a sensitization of I(Ca(V)) to capsaicin (0.1 microM) with a reduction of 42.8+/-4.4% mediated by TRPV-1. While L-type (36.6+/-5.2%) and P/Q-type currents (35.6+/-4.1%) are also sensitized by TRPV-1 activation, N-type channel currents are most sensitive (74.5+/-7.3%). The capsaicin-induced shift towards the hyperpolarizing voltage range does not occur when TNF-alpha is applied. Summarizing, TNF-alpha sensitizes nociceptive neurons for capsaicin.

  15. Generation of antitumor active neutral medium-sized alpha-glycan in apple vinegar fermentation.

    Science.gov (United States)

    Abe, Kaoru; Kushibiki, Toshisada; Matsue, Hajime; Furukawa, Ken-Ichi; Motomura, Shigeru

    2007-09-01

    The physiologically active substances in apple vinegar have not yet been chemically characterized. We studied the biological functions of apple vinegar produced from crushed apples, and found that the constituent neutral medium-sized alpha-glycan (NMalphaG) acts as an antitumor agent against experimental mouse tumors. NMalphaG is a homoglycan composed of glucose having a molecular weight of about 10,000 and a branched structure bearing alpha (1-4,6) linkages. In this study, we clarified the origin of NMalphaG in apple vinegar by examination of its content in alcohol and acetic acid fermentation products sequentially. We found that NMalphaG appeared in acetic acid fermentation, but not in alcohol fermentation. Furthermore we investigated NMalphaG origin using acetic acid fermentation from alcohol fortifiied apple without alcohol fermentation and from raw material with varying amounts of pomace. The results indicate that NMalphaG originated in the apple fruit body and that its production requires both fermentation processes.

  16. 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.

  17. 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)

  18. 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.

  19. Peroxisome proliferator-activated receptor alpha improves pancreatic adaptation to insulin resistance in obese mice and reduces lipotoxicity in human islets

    NARCIS (Netherlands)

    Lalloyer, Fanny; Vandewalle, Brigitte; Percevault, Frederic; Torpier, Gerard; Kerr-Conte, Julie; Oosterveer, Maaike; Paumelle, Rejane; Fruchart, Jean-Charles; Kuipers, Folkert; Pattou, Francois; Fievet, Catherine; Staels, Bart

    Peroxisome proliferator-activated receptor (PPAR) alpha is a transcription factor controlling lipid and glucose homeostasis. PPAR alpha-deficient (-/-) mice are protected from high-fat diet-induced insulin resistance. However, the impact of PPAR alpha in the pathophysiological setting of

  20. Megakaryocytic cells synthesize and platelets secrete alpha5-laminins, and the endothelial laminin isoform laminin 10 (alpha5beta1gamma1) strongly promotes adhesion but not activation of platelets.

    Science.gov (United States)

    Nigatu, Ayele; Sime, Wondossen; Gorfu, Gezahegn; Geberhiwot, Tarekegn; Andurén, Ingegerd; Ingerpuu, Sulev; Doi, Masayuki; Tryggvason, Karl; Hjemdahl, Paul; Patarroyo, Manuel

    2006-01-01

    Following vascular injury, basement membrane (BM) components of the blood vessels are exposed to circulating cells and may contribute to hemostasis and/or thrombosis. Laminins 8 (LN-8) (alpha4beta1gamma1) and 10 (LN-10) (alpha5beta1gamma1) are major laminin isoforms of the endothelial BM, and LN-8 is also secreted by activated platelets. In the present study, we demonstrate synthesis of alpha5-laminins LN-10 and LN-11 (alpha5beta2gamma1) by megakaryocytic cells, and intracellular expression of these laminin isoforms in blood platelets. In contrast to platelet LN alpha4 chain that had an apparent molecular weight of 180 kDa and associated mostly to LNbeta1 chain, platelet LNalpha5 consisted of 300/350 kDa polypeptides and associated mainly to LNbeta2. Both alpha4- and alpha5-laminins were secreted by platelets following stimulation. When compared to recombinant human (rh) LN-8, rhLN-10 was much more adhesive to platelets, though adhesion to both proteins was largely mediated via alpha6beta1 integrin. In spite of their adhesive properties, rhLN-8 and rhLN-10 induced neither P-selectin expression nor cell aggregation, two signs of platelet activation. This study demonstrates synthesis/expression of heterotrimeric alpha5-laminins in hematopoietic/blood cells, and provides evidence for the adhesive, but not activating, role of endothelial laminin isoforms in platelet biology.

  1. Substance P induces tumor necrosis factor-alpha release from human skin via mitogen-activated protein kinase.

    Science.gov (United States)

    Okabe, T; Hide, M; Koro, O; Yamamoto, S

    2000-06-16

    Substance P plays an important role in neurogenic inflammation with granulocyte infiltration. To investigate cytokines involved in the substance P-induced inflammation and the mechanism of cell activation, we studied the release of TNF (tumor necrosis factor)-alpha and histamine from human skin slices in response to substance P and antigen. Substance P induced the release of histamine and TNF-alpha in a dose-dependent manner at concentrations from 0.8 to 100 microM. PD 098059 (2'-amino-3'-methoxyflavone) selectively inhibited the release of TNF-alpha, but not the release of histamine induced by either substance P or antigen. SB 203580 ([4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-++ +imida zole]) slightly inhibited TNF-alpha release induced by antigen, but not that induced by substance P, and slightly enhanced histamine release induced by either stimulation. The release of TNF-alpha in response to either stimulation was inhibited by 1 nM-1 microM dexamethasone, but histamine release was not affected. These results suggest that substance P, in addition to antigen, induced TNF-alpha release from human skin by a mitogen-activated protein (MAP) kinase, predominantly extracellular signaling-regulated protein kinase (ERK)-dependent, and dexamethasone-sensitive pathway, which is separate from that for histamine release from mast cells.

  2. Alpha- and Beta-Cyclodextrin Inclusion Complexes with 5-Fluorouracil: Characterization and Cytotoxic Activity Evaluation

    Directory of Open Access Journals (Sweden)

    Cristina Di Donato

    2016-12-01

    Full Text Available Cyclodextrins are natural macrocyclic oligosaccharides able to form inclusion complexes with a wide variety of guests, affecting their physicochemical and pharmaceutical properties. In order to obtain an improvement of the bioavailability and solubility of 5-fluorouracil, a pyrimidine analogue used as chemotherapeutic agent in the treatment of the colon, liver, and stomac cancers, the drug was complexed with alpha- and beta-cyclodextrin. The inclusion complexes were prepared in the solid state by kneading method and characterized by Fourier transform-infrared (FT-IR spectroscopy and X-ray powder diffractometry. In solution, the 1:1 stoichiometry for all the inclusion complexes was established by the Job plot method and the binding constants were determined at different pHs by UV-VIS titration. Furthermore, the cytotoxic activity of 5-fluorouracil and its complexation products were evaluated using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay on MCF-7 (breast cancer cell line, Hep G2 (hepatocyte carcinoma cell line, Caco-2 (colon adenocarcinoma cell line, and A-549 (alveolar basal epithelial carcinoma cell line. The results showed that both inclusion complexes increased the 5-fluorouracil capability of inhibiting cell growth. In particular, 5-fluorouracil complexed with beta-cyclodextrin had the highest cytotoxic activity on MCF-7; with alpha-cyclodextrin the highest cytotoxic activity was observed on A-549. The IC50 values were equal to 31 and 73 µM at 72 h, respectively. Our results underline the possibility of using these inclusion complexes in pharmaceutical formulations for improving 5-fluorouracil therapeutic efficacy.

  3. Peroxisome proliferator-activated receptor alpha controls hepatic heme biosynthesis through ALAS1.

    Science.gov (United States)

    Degenhardt, Tatjana; Väisänen, Sami; Rakhshandehroo, Maryam; Kersten, Sander; Carlberg, Carsten

    2009-05-01

    Heme is an essential prosthetic group of proteins involved in oxygen transport, energy metabolism and nitric oxide production. ALAS1 (5-aminolevulinate synthase) is the rate-limiting enzyme in heme synthesis in the liver and is highly regulated to adapt to the metabolic demand of the hepatocyte. In the present study, we describe human hepatic ALAS1 as a new direct target for the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha). In primary human hepatocytes and in HepG2 cells, PPARalpha agonists induced an increase in ALAS1 mRNA levels, which was abolished by PPARalpha silencing. These effects are mediated by two functional PPAR binding sites at positions -9 and -2.3 kb relative to the ALAS1 transcription start site. PPARalpha ligand treatment also up-regulated the mRNA levels of the genes ALAD (5-aminolevulinate dehydratase), UROS (uroporphyrinogen III synthase), UROD (uroporphyrinogen decarboxylase), CPOX (coproporphyrinogen oxidase) and PPOX (protoporphyrinogen oxidase) encoding for enzymes controlling further steps in heme biosynthesis. In HepG2 cells treated with PPARalpha agonists and in mouse liver upon fasting, the association of PPARalpha, its partner retinoid X receptor, PPARgamma co-activator 1alpha and activated RNA polymerase II with the transcription start site region of all six genes was increased, leading to higher levels of the metabolite heme. In conclusion, these data strongly support a role of PPARalpha in the regulation of human ALAS1 and of five additional genes of the pathway, consequently leading to increased heme synthesis.

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

    Energy Technology Data Exchange (ETDEWEB)

    Martinez, Oscar A [ORNL

    2016-01-01

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

  5. Soil to plant transfer of alpha activity in potato plants: impact of phosphate fertilizers.

    Science.gov (United States)

    Chauhan, Rishi Pal; Kumar, Amit

    2015-01-01

    Radionuclides in the phosphate fertilizers belonging to (232)Th and (238)U and (40) K are the major contributors to the outdoor terrestrial natural radiation. These radionuclides are transferred from fertilizer to food through soil. Present work deals with the alpha activity in the different parts of the potato (Solanum Tuberosum) plants grown under controlled pots experiment using different amounts of phosphate fertilizers and urea. Alpha activities have been measured by track etch technique using the solid-state nuclear track detectors (LR-115). Translocation factor for the fruit (edible Part) varied from 0.13 (for DAP) to 0.73 (for PF) with an average of 0.40 ± 0.26 for the plant grown with 20 g of fertilizers. Translocation factors increased with the increase in amount of fertilizers having value 0.51 ± 0.31 for the plant grown with 50 g of fertilizers. The translocation factor for the lower and the upper part of leaves varied from 0.44 to 0.67 and 0.22 to 0.83 with an average value 0.55 ± 0.15 and 0.45 ± 0.23 respectively. The transfer factor (TF's) for the potato plants varied from 1.5 × 10(-2) to 1.03 × 10(-1) for root, from 1.3 × 10(-2) to 1.23 × 10(-1) for stem, from 2.1 × 10(-3) to 4.5 × 10(-2) for fruit and from 5.4 × 10(-3) to 5.8 × 10(-3) for lower part of the leaves after 105 days of the plantation. The results revealed that the alpha activity in the potato plants was higher in case of the plants grown with the use of phosphate fertilizers than with other fertilizers.

  6. Activated AMPK inhibits PPAR-{alpha} and PPAR-{gamma} transcriptional activity in hepatoma cells.

    Science.gov (United States)

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

    2011-10-01

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

  7. Activation of podocytes by mesangial-derived TNF-alpha: glomerulo-podocytic communication in IgA nephropathy.

    Science.gov (United States)

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

    2008-04-01

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

  8. Application of neural network method to detect type of uranium contamination by estimation of activity ratio in environmental alpha spectra.

    Science.gov (United States)

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

    2016-01-01

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

  9. 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 ...

  10. Synthesis and biological activities of octyl 2,3-di-O-sulfo-alpha-L-fucopyranosyl-(1-->3)-2-O-sulfo-alpha-L-fucopyranosyl-(1-->4)-2,3-di-O-sulfo-alpha-L-fucopyranosyl-(1-->3)-2-O-sulfo-alpha-L-fucopyranosyl-(1-->4)-2,3-di-O-sulfo-beta-L-fucopyranoside.

    Science.gov (United States)

    Hua, Yuxia; Du, Yuguo; Yu, Gangli; Chu, Shidong

    2004-08-23

    Octyl 2,3-di-O-sulfo-alpha-L-fucopyranosyl-(1-->3)-2-O-sulfo-alpha-L-fucopyranosyl-(1-->4)-2,3-di-O-sulfo-alpha-L-fucopyranosyl-(1-->3)-2-O-sulfo-alpha-L-fucopyranosyl-(1-->4)-2,3-di-O-sulfo-beta-L-fucopyranoside, a fucosyl pentasaccharide with a regular structure resembling the repeating unit of a natural sulfated fucan, was chemically synthesized using a convergent '2+3' strategy. Regioselective 3-O-silylation of beta-thiofucopyranoside and AgOTf-catalyzed glycosylation of the protected glycosyl trichloroacetimidate facilitated a one-pot trisaccharide synthesis. The synthesized target compound showed good antitumor activity in vivo, and promising anticoagulant activity in vitro.

  11. 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

    and the CCN-derived single hygroscopicity parameter kappa for different experimental conditions: varying precursor concentrations (10-40 ppb), different OH sources (photolysis of HONO either with or without the addition of NO or ozonolysis of tetramethylethylene), and exposure to light. Oxygenation......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...... was described by the contribution of the aerosol mass spectrometer (AMS) mass fragment m/z 44 to the total organic signal (f(44)) and the oxygen to carbon molar ratio (O/C), likewise determined with AMS. CCN activity, described by the hygroscopicity parameter kappa, was determined with a CCN counter...

  12. Alpha-hydroxybutyrate dehydrogenase activity in sex-linked muscular dystrophy.

    Science.gov (United States)

    Johnston, H A; Wilkinson, J H; Withycombe, W A; Raymond, S

    1966-05-01

    In two families with severe sex-linked muscular dystrophy, high levels of alpha-hydroxybutyrate dehydrogenase (HBD), lactate dehydrogenase (LD), aspartate transaminase (AspT), aldolase, and creatine phosphokinase (CPK) were found in the sera of three young affected males. In both families the mother had a raised level of HBD activity. Four sisters of the three affected boys had raised serum enzyme levels, and they are regarded as presumptive carriers of the disease. Biopsy specimens of dystrophic muscle had LD and HBD contents which were significantly lower than those of control specimens, while the HBD/LD ratios were markedly greater. Muscle from two unaffected members of the same family also exhibited high ratios, indicating the presence of the electrophoretically fast LD isoenzymes, and this was confirmed by acrylamide-gel electrophoresis.

  13. 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

    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. PMID:27611371

  14. Supine posture inhibits cortical activity: Evidence from Delta and Alpha EEG bands.

    Science.gov (United States)

    Spironelli, Chiara; Busenello, Jessica; Angrilli, Alessandro

    2016-08-01

    Past studies have shown consistent evidence that body position significantly affects brain activity, revealing that both head-down and horizontal bed-rest are associated with cortical inhibition and altered perceptual and cognitive processing. The present study investigates the effects of body position on spontaneous, open-eyes, resting-state EEG cortical activity in 32 young women randomly assigned to one of two conditions, seated position (SP) or horizontal bed rest (BR). A between-group repeated-measure experimental design was used, EEG recordings were made from 38 scalp locations, and low-frequency (delta and alpha) amplitudes of the two groups were compared in four different conditions: when both groups (a) were seated (T0), (b) assumed two different body positions (seated vs. supine conditions, immediate [T1] and 120min later [T2]), and (c) were seated again (T3). Overall, the results showed no a priori between-group differences (T0) before experimental manipulation. As expected, delta amplitude, an index of cortical inhibition in awake resting participants, was significantly increased in group BR, revealing both rapid (T1) and mid-term (T2) inhibitory effects of supine or horizontal positions. Instead, the alpha band was highly sensitive to postural transitions, perhaps due to baroreceptor intervention and, unlike the delta band, underwent habituation and decreased after a 2-h bed rest. These results indicate clear-cut differences at rest between the seated and supine positions, thus supporting the view that the role of body position in the differences found between brain metabolic methods (fMRI and PET) in which participants lie horizontally, and EEG-MEG-TMS techniques with participants in a seated position, has been largely underestimated so far.

  15. Cyclin C regulates adipogenesis by stimulating transcriptional activity of CCAAT/enhancer binding protein alpha.

    Science.gov (United States)

    Song, Ziyi; Xiaoli, Alus M; Zhang, Quanwei; Zhang, Yi; Yang, Ellen S T; Wang, Sven; Chang, Rui; Zhang, Zhengdong D; Yang, Gongshe; Strich, Randy; Pessin, Jeffrey E; Yang, Fajun

    2017-03-28

    Brown adipose tissue (BAT) is important for maintaining energy homeostasis and adaptive thermogenesis in rodents and humans. As disorders arising from dysregulated energy metabolism, such as obesity and metabolic diseases, have increased, so has interest in the molecular mechanisms in adipocyte biology. Using a functional screen, we identified cyclin C (CycC), a conserved subunit of the Mediator complex, as a novel regulator for brown adipocyte formation. siRNA-mediated CycC knockdown (KD) in brown preadipocytes impaired the early transcriptional program of differentiation, and genetic knockout (KO) of CycC completely blocked the differentiation process. RNA-seq analyses of CycC-KD revealed a critical role of CycC in activating genes co-regulated by peroxisome proliferator activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha (C/EBPα). Overexpression of PPARγ2 or addition of the PPARγ ligand rosiglitazone rescued the defects in CycC-KO brown preadipocytes, and efficiently activated the PPARγ-responsive promoters in both wild-type (WT) and CycC-KO cells, suggesting that CycC is not essential for PPARγ transcriptional activity. In contrast, CycC-KO significantly reduced C/EBPα-dependent gene expression. Unlike for PPARγ, overexpression of C/EBPα could not induce C/EBPα target gene expression in CycC-KO cells or rescue the CycC-KO defects in brown adipogenesis, suggesting that CycC is essential for C/EBPα-mediated gene activation. CycC physically interacted with C/EBPα and this interaction was required for C/EBPα transactivation domain activity. Consistent with the role of C/EBPα in white adipogenesis, CycC-KD also inhibited differentiation of 3T3-L1 cells into white adipocytes. Together, these data indicate that CycC activates adipogenesis by stimulating the transcriptional activity of C/EBPα.

  16. Differential effects of defined chemical modifications on antigenic and pharmacological activities of scorpion alpha and beta toxins.

    Science.gov (United States)

    el Ayeb, M; Darbon, H; Bahraoui, E M; Vargas, O; Rochat, H

    1986-03-03

    Specific chemical modifications of scorpion alpha and beta toxins have been used to study the involvement of particular residues in both the pharmacological and the antigenic sites of these toxins. Modification by 1,2-cyclohexanedione of arginine-27 of a beta toxin, Centruroides suffusus suffusus toxin II, drastically decrease the antigenic activity without any influence on the pharmacological activity. Conversely, modification by the same reagent of arginine-2 of an alpha toxin, Androctonus australis Hector toxin III, led to a 100-times less pharmacologically potent derivative and did not induce a significant loss of antigenic activity. Excision of the N-terminal pentapeptide of another alpha toxin, Buthus occitanus mardochei toxin III, by pepsin digestion led to a non-toxic derivative retaining full antigenic activity. Thus, the N-terminal part of the conserved hydrophobic surface of the toxin is highly implicated in the pharmacological activity, whereas the region of arginine-27, located in the alpha helix situated on the back surface, opposite the conserved hydrophobic region, is fully implicated in the antigenic activity and is far from the pharmacological site. These results are good arguments in favor of the idea that in scorpion toxins the surfaces implicated in the pharmacological and the antigenic activities do not overlap. Since the antigenic sites are present in highly variable sequence the development of an efficient polyvalent serotherapy is questionable.

  17. 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.

  18. 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.

  19. [Chemical constituents from Psoralea corylifolia and their antioxidant alpha-glucosidase inhibitory and antimicrobial activities].

    Science.gov (United States)

    Wang, Tian-Xiao; Yin, Zhen-Hua; Zhang, Wei; Peng, Tao; Kang, Wen-Yi

    2013-07-01

    Twelve compounds were isolated from Psoralea corylifolia and their structures were identified as isopsoralen (1), psoralen (2), 8-methoxypsoralen (3), psoralidin (4), corylin (5), bavachin (6), daidzein (7), corylifolinin (8), bavachinin (9), neobavaisoflavone (10), daidzin (11) and astragalin (12). The results showed that psoralidin had the activity of scavenging DPPH free radicals activity (IC50 43.85 mg x L(-1)). Psoralidin (IC50 1.32 mg x L(-1))c, oryfolin (IC50 4.97 mg x L(-1)), daidzin (IC50 10.47 mg x S(-1)), daidzein (IC50 34.22 mg) x L(-1)) and astragalin (IC50 31.27 mg x L(-1)) had the activity of scavenging ABTS free radical. Psoralidin (IC50 40.74 mg x L(-1)), coryfolin (IC50 45.73 mg x L(-1)) and daidzein (IC50 49.44 mg x L(-1)) had alpha-glucosidase inhibitory activity. Corylifolinin and neobavaisoflavone had significantly effect of inhibiting SA, MRSA and ESBLs-SA (MIC 0. 781 3, 1.562, 5, 0.781 25 microg x disc(-1) and 6.25, 6.25, 6.25 microg x disc(-1).

  20. 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.

  1. 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.

  2. Activation of peroxisome proliferator-activated receptor alpha in rat spinal cord after peripheral noxious stimulation.

    Science.gov (United States)

    Benani, A; Heurtaux, T; Netter, P; Minn, A

    2004-10-07

    Following recurrent noxious stimulation, both functional modification and structural reorganization such as activation of the arachidonate cascade or axon sprouting occur in the central nervous system (CNS). It has been recently proposed that these alterations observed during chronic pain state were supported by an intensification of the lipid metabolism. In this regard, it has been shown that mRNA coding for several fatty acid metabolizing enzymes are up-regulated in the rat lumbar spinal cord in response to persistent nociception induced by a peripheral inflammation. As peroxisome proliferators-activated receptor (PPAR) could mediate such effects, we therefore investigated the activation of this transcription factor in the rat spinal cord following subcutaneous injection of complete Freund's adjuvant (CFA) into a hind paw. In this study, we compared the DNA-binding activity of nuclear proteins extracted from healthy and inflamed rats toward a PPAR response element. Using electrophoretic mobility-shift assay (EMSA), we found that only the PPARalpha isoform was activated in the rat spinal cord after CFA injection. This activation occurred rapidly, as early as 30 min post-CFA injection, and was persistent up to 10 h, reaching a maximum at 6h after CFA injection. In view of the consequences of PPARalpha activation in other tissues, these results suggest that fatty acid utilization is enhanced in the CNS during chronic pain state. Although the physiopathological relevance of PPARalpha activation during hyperalgesia needs further investigation, we provided here a new player in the molecular modeling of pain pathways.

  3. NM Gross Receipts July - December 2012

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — This layer represents boundaries for New Mexico's gross receipts tax districts as identified on the "Gross Receipts Tax Rate Schedule" published by the Taxation and...

  4. NM Gross Receipts January - June 2014

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — This layer represents boundaries for New Mexico's gross receipts tax districts as identified on the "Gross Receipts Tax Rate Schedule" published by the Taxation and...

  5. NM Gross Receipts January - June 2012

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — This layer represents boundaries for New Mexico's gross receipts tax districts as identified on the "Gross Receipts Tax Rate Schedule" published by the Taxation and...

  6. NM Gross Receipts January - June 2013

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — This layer represents boundaries for New Mexico's gross receipts tax districts as identified on the "Gross Receipts Tax Rate Schedule" published by the Taxation and...

  7. NM Gross Receipts January - June 2011

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — This layer represents boundaries for New Mexico's gross receipts tax districts as identified on the "Gross Receipts Tax Rate Schedule" published by the Taxation and...

  8. NM Gross Receipts July - December 2013

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — This layer represents boundaries for New Mexico's gross receipts tax districts as identified on the "Gross Receipts Tax Rate Schedule" published by the Taxation and...

  9. Effects of metals on {alpha}-amylase activity in the digestive gland of the green mussel, Perna viridis L.

    Energy Technology Data Exchange (ETDEWEB)

    Yan, T.; Teo, L.H.; Sin, Y.M. [National Univ. of Singapore (Singapore)

    1996-04-01

    A number of digestive enzymes in the green mussel, Perna viridis L., have been reported, and {alpha}-amylase is believed to have a higher activity than the others. Small plankton, on which the green mussel feeds, may supply plenty of starch and glycogen. They may be an important source of nutrients for the green mussel and the ability of the latter to make good use of them depends mainly on the activities of amylase. The effect of heavy metals on amylase activity is also important as the ability of the mussel`s digestive gland to accumulate these metals is well known. High concentrations of heavy metals, especially lead, have been observed in the water around Singapore. The in vitro inhibition of some metals on the activities of digestive enzymes from the green mussel has been observed, but kinetic properties of the inhibition and the in vivo inhibition of the heavy metals on digestive enzymes are little understood. In the present study, in vitro inhibition of four metals (Pb, Cd, Zn and Hg) on the activity of {alpha}-amylase from the digestive gland of the green mussel will be compared. Their effects on the K{sub M} and V{sub max} values of {alpha}-amylase will also be compared. Finally, lead is either added to the food or water, to see how it affects the activity of {alpha}-amylase and how this effect acts in combination with starvation. 12 refs., 3 figs., 3 tabs.

  10. Activity of nAChRs containing alpha9 subunits modulates synapse stabilization via bidirectional signaling programs.

    Science.gov (United States)

    Murthy, Vidya; Taranda, Julián; Elgoyhen, A Belén; Vetter, Douglas E

    2009-12-01

    Although the synaptogenic program for cholinergic synapses of the neuromuscular junction is well known, little is known of the identity or dynamic expression patterns of proteins involved in non-neuromuscular nicotinic synapse development. We have previously demonstrated abnormal presynaptic terminal morphology following loss of nicotinic acetylcholine receptor (nAChR) alpha9 subunit expression in adult cochleae. However, the molecular mechanisms underlying these changes have remained obscure. To better understand synapse formation and the role of cholinergic activity in the synaptogenesis of the inner ear, we exploit the nAChR alpha9 subunit null mouse. In this mouse, functional acetylcholine (ACh) neurotransmission to the hair cells is completely silenced. Results demonstrate a premature, effusive innervation to the synaptic pole of the outer hair cells in alpha9 null mice coinciding with delayed expression of cell adhesion proteins during the period of effusive contact. Collapse of the ectopic innervation coincides with an age-related hyperexpression pattern in the null mice. In addition, we document changes in expression of presynaptic vesicle recycling/trafficking machinery in the alpha9 null mice that suggests a bidirectional information flow between the target of the neural innervation (the hair cells) and the presynaptic terminal that is modified by hair cell nAChR activity. Loss of nAChR activity may alter transcriptional activity, as CREB binding protein expression is decreased coincident with the increased expression of N-Cadherin in the adult alpha9 null mice. Finally, by using mice expressing the nondesensitizing alpha9 L9'T point mutant nAChR subunit, we show that increased nAChR activity drives synaptic hyperinnervation.

  11. Alpha self-absorption in monazite dusts.

    Science.gov (United States)

    Terry, K W

    1995-10-01

    Measurements have been made of the self-absorption effects in monazite of alpha particles of the 232Th decay series. Samples of six size fractions of monazite were deposited on filters at different dust concentrations and then the gross alpha activity determined. Self-absorption effects were negligible in monazite particles up to 8 microns diameter provided dust concentrations were less than 1 mg cm-2. Significant self-absorption effects occurred for both larger particle sizes and higher dust loadings. As reported AMAD values in the mineral sands industry range up to 15 microns, which is equivalent to an actual mean size of 8 microns diameter monazite particle, minimal self-absorption occurs in samples collected in air monitoring programs conducted in the industry provided that dust concentrations on the filters are less than 1 mg cm-2.

  12. Persistent HIF-1alpha activation in gut ischemia/reperfusion injury: potential role of bacteria and lipopolysaccharide.

    Science.gov (United States)

    Koury, Jadd; Deitch, Edwin A; Homma, Hiroshi; Abungu, Billy; Gangurde, Pranoti; Condon, Michael R; Lu, Qi; Xu, Da-Zhong; Feinman, Rena

    2004-09-01

    -dependent manner in IEC-6 cells indicated that the induction of HIF-1 by exposure to P. aeruginosa is not dependent on bacterial viability. In conclusion, these results suggest that HIF-1alpha activation is an early reperfusion-independent event in models of gut ischemia-reperfusion and that this HIF-1alpha response is potentiated by the presence of P. aeruginosa or lipopolysaccharide.

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

    Science.gov (United States)

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

    2016-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Marco Emanuele

    2016-05-01

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

  15. A tumor-penetrating peptide modification enhances the antitumor activity of thymosin alpha 1.

    Directory of Open Access Journals (Sweden)

    Xingzhen Lao

    Full Text Available A serious limitation of numerous antitumor drugs is the incapacity to penetrate solid tumors. However, addition of an RGD fragment to peptide drugs might solve this problem. In this study, we explored whether the introduction of a permeability-enhancing sequence, such as iRGD (CRGDK/RGPD/EC fragments, would enhance the activity of thymosin alpha 1 (Tα1. The modified Tα1 (Tα1-iRGD was successfully expressed and purified, and the in vitro assay showed that Tα1-iRGD presented a similar activity as Tα1 in promoting proliferation of mouse splenocytes. Meanwhile, cell adhesion analysis revealed that Tα1-iRGD exhibited more specific and greater binding with tumor cells compared with Tα1. Furthermore, the iRGD fragment evidently enhanced the basal ability of Tα1 to inhibit proliferation of cancer cells in vitro, particularly of mouse melanoma cell line B16F10 and human lung cancer cell line H460. Our findings indicated that the addition of an iRGD fragment increased the anti-proliferative activity of Tα1 against cancer cells by improving the ability of Tα1 to penetrate the tumor cells. This study highlighted the important roles of an iRGD sequence in the therapeutic strategy of Tα1-iRGD. Thus, Tα1-iRGD could be a novel drug candidate for cancer treatment.

  16. A tumor-penetrating peptide modification enhances the antitumor activity of thymosin alpha 1.

    Science.gov (United States)

    Lao, Xingzhen; Liu, Meng; Chen, Jiao; Zheng, Heng

    2013-01-01

    A serious limitation of numerous antitumor drugs is the incapacity to penetrate solid tumors. However, addition of an RGD fragment to peptide drugs might solve this problem. In this study, we explored whether the introduction of a permeability-enhancing sequence, such as iRGD (CRGDK/RGPD/EC) fragments, would enhance the activity of thymosin alpha 1 (Tα1). The modified Tα1 (Tα1-iRGD) was successfully expressed and purified, and the in vitro assay showed that Tα1-iRGD presented a similar activity as Tα1 in promoting proliferation of mouse splenocytes. Meanwhile, cell adhesion analysis revealed that Tα1-iRGD exhibited more specific and greater binding with tumor cells compared with Tα1. Furthermore, the iRGD fragment evidently enhanced the basal ability of Tα1 to inhibit proliferation of cancer cells in vitro, particularly of mouse melanoma cell line B16F10 and human lung cancer cell line H460. Our findings indicated that the addition of an iRGD fragment increased the anti-proliferative activity of Tα1 against cancer cells by improving the ability of Tα1 to penetrate the tumor cells. This study highlighted the important roles of an iRGD sequence in the therapeutic strategy of Tα1-iRGD. Thus, Tα1-iRGD could be a novel drug candidate for cancer treatment.

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

    Science.gov (United States)

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

    1988-10-01

    DL-alpha-Difluoromethylarginine (DFMA) is an enzyme-activated irreversible inhibitor of arginine decarboxylase (ADC) in vitro. DFMA has also been shown to inhibit ADC activities in a variety of plants and bacteria in vivo. However, we questioned the specificity of this inhibitor for ADC in tobacco ovary tissues, since ornithine decarboxylase (ODC) activity was strongly inhibited as well. We now show that [3,4-3H]DFMA is metabolized to DL-alpha-difluoromethyl[3,4-3H]ornithine [( 3,4-3H]DFMO), the analogous mechanism-based inhibitor of ODC, by tobacco tissues in vivo. Both tobacco and mammalian (mouse, bovine) arginases (EC 3.5.3.1) hydrolyse DFMA to DFMO in vitro, suggesting a role for this enzyme in mediating the indirect inhibition of ODC by DFMA in tobacco. These results suggest that DFMA may have other effects, in addition to the inhibition of ADC, in tissues containing high arginase activities. The recent development of potent agmatine-based ADC inhibitors should permit selective inhibition of ADC, rather than ODC, in such tissues, since agmatine is not a substrate for arginase.

  18. 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.

  19. 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.

  20. 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.

  1. 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

    Detailed experimental data from patch clamp experiments on pancreatic alpha-cells in intact mouse islets are used to model the electrical activity associated with glucagon secretion. Our model incorporates L- and T-type Ca2+ currents, delayed rectifying and A-type K+ currents, a voltage-gated Na......+ 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...

  2. 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

    Due to the cognitive-enhancing properties of alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) agonists, they have attracted interest for the treatment of cognitive disturbances in schizophrenia. Schizophrenia typically presents in late adolescence or early adulthood. It is therefore important...... to study whether alpha7 nAChR stimulation activates brain regions involved in cognition in juvenile as well as adult individuals. Here, we compared the effects of the novel and selective alpha7 nAChR agonist 2-methyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole (A-582941) in the juvenile...... 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...

  3. alpha-MSH tripeptide analogs activate the melanocortin 1 receptor and reduce UV-induced DNA damage in human melanocytes.

    Science.gov (United States)

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

    2009-10-01

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

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

    Science.gov (United States)

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

    2004-04-30

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

  5. Comparison of the LUNA 3He(alpha,gamma)7Be activation results with earlier measurements and model calculations

    CERN Document Server

    Gyurky, Gy; Confortola, F; Costantini, H; Formicola, A; Bonetti, R; Broggini, C; Corvisiero, P; Elekes, Z; Fülöp, Z; Gervino, G; Guglielmetti, A; Gustavino, C; Imbriani, G; Junker, M; Laubenstein, M; Lemut, A; Limata, B; Lozza, V; Marta, M; Menegazzo, R; Prati, P; Roca, V; Rolfs, C; Alvarez, C Rossi; Somorjai, E; Straniero, O; Strieder, F; Terrasi, F; Trautvetter, H P

    2007-01-01

    Recently, the LUNA collaboration has carried out a high precision measurement on the 3He(alpha,gamma)7Be reaction cross section with both activation and on-line gamma-detection methods at unprecedented low energies. In this paper the results obtained with the activation method are summarized. The results are compared with previous activation experiments and the zero energy extrapolated astrophysical S factor is determined using different theoretical models.

  6. 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

    2015-10-01

    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.

  7. Synthesis and evaluation of phytotoxic activity of {alpha}-Santonin derivatives; Sintese e avaliacao da atividade fitotoxica de derivados da {alpha}-Santonina

    Energy Technology Data Exchange (ETDEWEB)

    Alvarenga, Elson S.; Barbosa, Luiz C.A.; Saliba, William A.; Arantes, Francisco F.P.; Demuner, Antonio J. [Universidade Federal de Vicosa (UFV), MG (Brazil). Dept. de Quimica]. E-mail: elson@ufv.br; Silva, Antonio A. [Universidade Federal de Vicosa (UFV), MG (Brazil). Dept. de Fitotecnia

    2009-07-01

    Mixtures of {alpha}-Santonin and various solvents were irradiated by either high or low pressure mercury lamps. The photochemical reactions afforded lumisantonin (11) (76% in acetonitrile), (3 S,3a S,9{beta}S)-3,6,6-trimethyl-3,3a,4,5-tetrahydronafto[1,2-b]furan-2,7({eta}6,9{beta}{eta}) dione (12) (100% in acetonitrile), 10{alpha}-acetoxy-3-oxo-1,7{alpha}H{eta},6,11{alpha}a{eta}-guaia-4-en-6,12-oli= de (8) (26% in acetic acid), 10{alpha}-hydroxy-3-oxo-1,7{alpha}a{eta},6,11{alpha}{eta}-guaia-4-en-6,12-olid= e (10) (32%) and (E)-3-((3 S,3a S,7{alpha}S)-3-methyl-2-oxo-6-(propan-2-ylidene)hexahydrobenzofuran- 7 - (7{alpha}{eta})-ylidene)propanoic acid (9) (44%) (in water/ acetic acid 1:1, v/v). Lactone 12 was also prepared by irradiation of lumisantonin in diethyl ether. Lactones 8 and 10 were converted, respectively, into the 10 {alpha}-acetoxy-3{alpha}-hydroxy-1,7{alpha}H,6,11{alpha}H-guaia-4-en-6,12-olid= e (13) (87%) and 3a,10a-dihydroxy-1,7{alpha}H,6,11{alpha}H-guaia-4-en-6,12-olide (14) (75%) by sodium borohydride reduction. The effects of the compounds on the development of radicle of Sorghum bicolor and Cucumis sativus were evaluated. (author)

  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 inh

  9. Gross anatomy of network security

    Science.gov (United States)

    Siu, Thomas J.

    2002-01-01

    Information security involves many branches of effort, including information assurance, host level security, physical security, and network security. Computer network security methods and implementations are given a top-down description to permit a medically focused audience to anchor this information to their daily practice. The depth of detail of network functionality and security measures, like that of the study of human anatomy, can be highly involved. Presented at the level of major gross anatomical systems, this paper will focus on network backbone implementation and perimeter defenses, then diagnostic tools, and finally the user practices (the human element). Physical security measures, though significant, have been defined as beyond the scope of this presentation.

  10. 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

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

  11. 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.

  12. [Neurophysiological manifestations of the monotony state in the human-operators with different alpha-activity hemispheric asymmetry].

    Science.gov (United States)

    Lebedeva, N N; Karimova, E D

    2014-01-01

    This paper presents the monotony state investigation of the human-operator while simulator driving by using a combination of psychophysiological testing, registration of an electrocardiogram and electroencephalogram (EEG). The appearance of specific EEG-pattern (power ascension of the theta-, alpha- and beta-rhythms) during operator activity due to the monotony state progression was revealed. We found out the reduction in health, decrease activity, the increase of the situational anxiety, and the reaction time after 90 minutes of the monotonous activity. The signs of drowsiness were detected at the rest with closed eyes after operator activity. Moreover, these negative manifestations of the monotony state were observed mainly in subjects with domination of the alpha-activity in the left hemisphere.

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  14. The Reflecting Brain: Reflection Competence in an Educational Setting Is Associated with Increased Electroencephalogram Activity in the Alpha Band

    Science.gov (United States)

    Rominger, Christian; Reitinger, Johannes; Seyfried, Clemens; Schneckenleitner, Eva; Fink, Andreas

    2017-01-01

    Teachers' ability to critically reflect classroom situations in relation to their own actions constitutes an important prerequisite to improve teaching performance and professional behavior. This study investigated electroencephalogram activity in the alpha band during a reflection task before and after training in a sample of preservice teachers.…

  15. Region-specific modulations in oscillatory alpha activity serve to facilitate processing in the visual and auditory modalities

    NARCIS (Netherlands)

    Mazaheri, Ali; van Schouwenburg, Martine R; Dimitrijevic, Andrew; Denys, D.; Cools, Roshan; Jensen, Ole

    2014-01-01

    There have been a number of studies suggesting that oscillatory alpha activity (~10 Hz) plays a pivotal role in attention by gating information flow to relevant sensory regions. The vast majority of these studies have looked at shifts of attention in the spatial domain and only in a single modality

  16. Cervical dilatation related to uterine electromyographic activity and endocrinological changes during prostaglandin F(2alpha)-induced parturition in cows.

    NARCIS (Netherlands)

    Breeveld-Dwarkasingh, V.N.; Struijk, P.C.; Lotgering, F.K.; Eijskoot, F.; Kindahl, H.; Weijden, G.C. van der; Taverne, M.A.

    2003-01-01

    The temporal relationship between changes in cervical dilatation, uterine electromyographic (EMG) activity, and maternal plasma concentrations of estradiol 17beta (E(2)), progesterone (P(4)), and 13,14-dihydro-15-keto-prostaglandin-F(2alpha) (PGFM), was investigated in six parturient cows. Calving

  17. 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

    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...... 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...... models are not mimicked in healthy humans and schizophrenic patients, where attentional improvement predominates. This discrepancy may result from inherent differences in testing methods or from species differences in the level of expression of alpha(7) nAChRs in limbic brain regions, and may hamper...

  18. Insecticidal activity of alpha-cypermethrin against small banded pine weevil Pissodes castaneus (Coleoptera: Curculionidae in forest plantations and thickets

    Directory of Open Access Journals (Sweden)

    Prokocka Aleksandra

    2016-09-01

    Full Text Available Scots pine (Pinus sylvestris plantations and thickets damaged by biotic and abiotic factors are particularly attractive to small-banded pine weevil Pissodes castaneus, whose larvae excavate feeding tunnels in the stems of young trees, causing their death. There are no chemical methods that can be applied to protect forest plantations and thickets against this pest. Therefore, the studies were undertaken aimed at the assessment of the efficacy of alpha-cypermethrin used to reduce the numbers of this pest within restock areas. The scope of work included laboratory and field estimation of insecticidal activity of alpha-cypermethrin.

  19. Plasminogen activator inhibitor type 1 interacts with alpha3 subunit of proteasome and modulates its activity.

    Science.gov (United States)

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

    2011-02-25

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

  20. Analysis and Quantitation of NF-[kappa]B Nuclear Translocation in Tumor Necrosis Factor Alpha (TNF-[alpha]) Activated Vascular Endothelial Cells

    Science.gov (United States)

    Fuseler, John W.; Merrill, Dana M.; Rogers, Jennifer A.; Grisham, Matthew B.; Wolf, Robert E.

    2006-07-01

    Nuclear factor kappa B (NF-[kappa]B) is a heterodimeric transcription factor typically composed of p50 and p65 subunits and is a pleiotropic regulator of various inflammatory and immune responses. In quiescent cells, p50/p65 dimers are sequestered in the cytoplasm bound to its inhibitors, the I-[kappa]Bs, which prevent entry into the nucleus. Following cellular stimulation, the I-[kappa]Bs are rapidly degraded, activating NF-[kappa]B. The active form of NF-[kappa]B rapidly translocates into the nucleus, binding to consensus sequences in the promoter/enhancer region of various genes, promoting their transcription. In human vascular endothelial cells activated with tumor necrosis factor-alpha, the activation and translocation of NF-[kappa]B is rapid, reaching maximal nuclear localization by 30 min. In this study, the appearance of NF-[kappa]B (p65 subunit, p65-NF-[kappa]B) in the nucleus visualized by immunofluorescence and quantified by morphometric image analysis (integrated optical density, IOD) is compared to the appearance of activated p65-NF-[kappa]B protein in the nucleus determined biochemically. The appearance of p65-NF-[kappa]B in the nucleus measured by fluorescence image analysis and biochemically express a linear correlation (R2 = 0.9477). These data suggest that localization and relative protein concentrations of NF-[kappa]B can be reliably determined from IOD measurements of the immunofluorescent labeled protein.

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

    Directory of Open Access Journals (Sweden)

    Garner Warren

    2009-03-01

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

  2. The activity of cobalt and silicon in the Co - Si system with special focus on the {alpha} - Co solid solution

    Energy Technology Data Exchange (ETDEWEB)

    Lexa, D.; Kematick, R.J.; Myers, C.E. [Binghamton Univ. - SUNY, NY (United States). Dept. of Chemistry and Institute for Materials Research

    1997-08-01

    The activities of cobalt and silicon at 1463 K have been determined across the whole composition range in the Co - Si system, including the {alpha} - Co solid solution, for which no activity data were previously available. Simple and reactive Knudsen effusion mass spectroscopy employed in this work were shown to successfully overcome problems normally encountered in studying high-temperature solid binary systems, such as slow equilibration and low partial pressures of the components. The composition dependence of the cobalt activities within the {alpha} - Co solid solution phase was used to calculate the self-interaction coefficients of silicon in {alpha} - Co: ln {gamma}{sub Si} = 10.4 {+-} 0.2 and {epsilon}{sub Si}{sup (Si)} = 18.6 {+-} 0.8. The regular solution model was shown to be a fairly good description of the {alpha} - Co solid solution, with an energy parameter Z{sub CoSi} of -120 {+-} 5 kJ{center_dot}mol{sup -1}. The results compare well with literature data on similar systems, such as Fe - Si and Ni - Si.

  3. A Field-Based Testing Protocol for Assessing Gross Motor Skills in Preschool Children: The Children's Activity and Movement in Preschool Study Motor Skills Protocol

    Science.gov (United States)

    Williams, Harriet G.; Pfeiffer, Karin A.; Dowda, Marsha; Jeter, Chevy; Jones, Shaverra; Pate, Russell R.

    2009-01-01

    The purpose of this study was to develop a valid and reliable tool for use in assessing motor skills in preschool children in field-based settings. The development of the Children's Activity and Movement in Preschool Study Motor Skills Protocol included evidence of its reliability and validity for use in field-based environments as part of large…

  4. Overproduction and purification of biologically active native fungal alpha-sarcin in Escherichia coli.

    Science.gov (United States)

    Lacadena, J; Martínez del Pozo, A; Barbero, J L; Mancheño, J M; Gasset, M; Oñaderra, M; López-Otín, C; Ortega, S; García, J; Gavilanes, J G

    1994-05-03

    An efficient system was developed to produce, in Escherichia coli, large amounts of native alpha-sarcin (alpha Sar), a cytotoxin from the mold Aspergillus giganteus. The protein has been purified to homogeneity with a yield of 1.5 micrograms/ml of original culture. The constructed expression vector (pINPG alpha S) is based on the synthesis of a fusion protein between alpha Sar and a modified version of the OmpA signal peptide. This peptide seems to favour the postranslational processing of the fusion protein. The purified recombinant alpha-sarcin (re-alpha Sar) is structurally identical to the mature fungal protein according to the following criteria: N-terminal amino acid (aa) sequence, aa composition, electrophoretic mobility, chromatographic behaviour, immunoreactivity and spectroscopic features. Indeed, the recombinant protein recovered is completely functional, since it cleaves, in vitro, eukaryotic rRNA and it is able to interact with phospholipid vesicles with the same specificity as the native fungal alpha Sar.

  5. [Effect of triterpenoid glycosides on alpha- and beta-amylase activity and total protein content in wheat seedlings].

    Science.gov (United States)

    Davidiants, E S

    2011-01-01

    Influence of the aleanolic acid glycosides from Silphium perfoliatum L. (silphioside B, C, E and G) and their progenins on the amylase activity and total protein content in wheat seedlings was studied. Treatment of the Triticum aestivum L. seeds with 1-10 microM water solutions of mono- and diglycosides (mono- and bisdesmosines) elevated the alpha-amylase and total amylase activities in seedlings. Silphioside E containing three glucose moieties in its molecule did not change alpha-amylase activity, but it did if bis-triglycoside acetylated carbohydrate (as in silphioside C). Effects of 5-10 microM solutions of the active glycosides was comparable with that of exogenous gibberellin A3 and 6-benzylaminopurine.

  6. Activation of endogenous C-type retroviral genomes by internal alpha-irradiation of mice with /sup 224/Radium

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, J.; Erfle, V.; Mueller, W.A.

    1985-01-01

    Sensitive co-cultivation techniques were applied to study the radiation-induced activation of endogenous retroviral genomes in different mouse strains by the alpha-emitting radionuclide /sup 224/Radium. Activated infectious C-type retroviruses were detected in spleen, bone marrow and bone tissues of C57BL/6-, BALB/c- and NMRI mice. The titres of high-dose-irradiated animals were higher than those found in low-dose-irradiated animals. Infectious retrovirus could be detected with a dose of 13.2 rad (maximum dose rate 0.9 rad/day) in the skeleton, and a dose of 4.2 rad (maximum dose rate 0.3 rad/day) in the spleen. The virus activation pattern was different in the three mouse strains. These data indicate that activation of endogenous retroviral genomes by alpha-irradiation shows a dose-effect relationship and a dependence on the genetic background of the mouse.

  7. Hydroxy-alpha-sanshool activates TRPV1 and TRPA1 in sensory neurons.

    Science.gov (United States)

    Koo, Jae Yeon; Jang, Yongwoo; Cho, Hawon; Lee, Chang-Hun; Jang, Kyoung Hwa; Chang, Yong Ha; Shin, Jongheon; Oh, Uhtaek

    2007-09-01

    Sanshools are major active ingredients of Zanthoxylum piperitum and are used as food additives in East Asia. Sanshools cause irritant, tingling and sometimes paresthetic sensations on the tongue. However, the molecular mechanism underlying the pungent or tingling sensation induced by sanshools is not known. Because many transient receptor potential (TRP) channels are responsible for the sensations induced by various spices and food additives, we expressed 17 TRP channels in human embryonic kidney (HEK) cells and investigated their activation by hydroxy-alpha-sanshool (HalphaSS) or hydroxy-beta-sanshool (HbetaSS) isolated from Zanthoxylum piperitum. It was found that HalphaSS, but not HbetaSS, depolarized sensory neurons with concomitant firing of action potentials and evoked inward currents. Among 17 TRP channels expressed in HEK cells, HalphaSS caused Ca(2+) influx in cells transfected with TRPV1 or TRPA1, and evoked robust inward currents in cells transfected with TRPV1 or TRPA1. In primary cultured sensory neurons, HalphaSS induced inward currents and Ca(2+) influx in a capsazepine-dependent manner. Moreover, HalphaSS-induced currents and Ca(2+) influx were greatly diminished in TRPV1(-/-) mice. HalphaSS evoked licking behavior when injected into a single hind paw of wild-type mice, but this was much reduced in TRPV1-deficient mice. These results indicate that TRPV1 and TRPA1 are molecular targets of HalphaSS in sensory neurons. We conclude that the activations of TRPV1 and TRPA1 by HalphaSS explain its unique pungent, tingling sensation.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-10-23

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

  9. Na/H exchanger regulatory factors control parathyroid hormone receptor signaling by facilitating differential activation of G(alpha) protein subunits.

    Science.gov (United States)

    Wang, Bin; Ardura, Juan A; Romero, Guillermo; Yang, Yanmei; Hall, Randy A; Friedman, Peter A

    2010-08-27

    The Na/H exchanger regulatory factors, NHERF1 and NHERF2, are adapter proteins involved in targeting and assembly of protein complexes. The parathyroid hormone receptor (PTHR) interacts with both NHERF1 and NHERF2. The NHERF proteins toggle PTHR signaling from predominantly activation of adenylyl cyclase in the absence of NHERF to principally stimulation of phospholipase C when the NHERF proteins are expressed. We hypothesized that this signaling switch occurs at the level of the G protein. We measured G protein activation by [(35)S]GTPgammaS binding and G(alpha) subtype-specific immunoprecipitation using three different cellular models of PTHR signaling. These studies revealed that PTHR interactions with NHERF1 enhance receptor-mediated stimulation of G(alpha)(q) but have no effect on stimulation of G(alpha)(i) or G(alpha)(s). In contrast, PTHR associations with NHERF2 enhance receptor-mediated stimulation of both G(alpha)(q) and G(alpha)(i) but decrease stimulation of G(alpha)(s). Consistent with these functional data, NHERF2 formed cellular complexes with both G(alpha)(q) and G(alpha)(i), whereas NHERF1 was found to interact only with G(alpha)(q). These findings demonstrate that NHERF interactions regulate PTHR signaling at the level of G proteins and that NHERF1 and NHERF2 exhibit isotype-specific effects on G protein activation.

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

    Science.gov (United States)

    Miller, Lee M.

    2016-01-01

    Abstract 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 while suppressing irrelevant. In this electroencephalography study using healthy human volunteers, we examined whether modulations in alpha power also occur after the onset of a bilaterally presented target and distractor. Spatial attention was manipulated through spatial cues and feature-based attention through adjusting the color-similarity of distractors to the target. Consistent with previous studies, we found that informative spatial cues induced a relative decrease of pretarget alpha power at occipital electrodes contralateral to the expected target location. Interestingly, this pattern reemerged relatively late (300–750 ms) after stimulus onset, suggesting that lateralized alpha reflects not only preparatory attention, but also ongoing attentive stimulus processing. Uninformative cues (i.e., conveying no information about the spatial location of the target) resulted in an interaction between spatial attention and feature-based attention in post-target alpha lateralization. When the target was paired with a low-similarity distractor, post-target alpha was lateralized (500–900 ms). Crucially, the lateralization was absent when target selection was ambiguous because the distractor was highly similar to the target. Instead, during this condition, midfrontal theta was increased, indicative of reactive conflict resolution. Behaviorally, the degree of alpha lateralization was negatively correlated with the reaction time distraction cost induced by target–distractor similarity. These results suggest a pivotal role for poststimulus alpha lateralization in protecting sensory processing of target information. PMID:27822505

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

    Science.gov (United States)

    Payghami, Nasrin; Jamili, Shahla; Rustaiyan, Abdolhossein; Saeidnia, Soodabeh; Nikan, Marjan; Gohari, Ahmad Reza

    2014-01-01

    Sargassum species (phaeophyceae) are economically important brown algae in southern parts of Iran. Sargassum is mainly harvested as a row material in alginate production industries and is a source of plant foods or plant bio-stimulants even a component of animal foods. In this study, Sargassum glaucescens, collected from the seashore of Chabahar, was employed for phytochemical and biological evaluations. For that purpose, the dried algae was extracted by methanol and subjected to different chromatographic separation methods. Six sterols, fucosterol (1), 24(S)-hydroxy-24-vinylcholesterol (2), 24(R)-hydroxy-24-vinylcholesterol (3), stigmasterol (4), β-sitosterol (5) and cholesterol (6) were identified by spectroscopic methods including (1)H-NMR, (13)C-NMR and mass spectroscopy. In vitro alpha-amylase inhibitory test was performed on the methanolic extract and the results revealed a potent inhibition (IC50 = 8.9 ± 2.4 mg/mL) of the enzyme compared to acarbose as a positive control. Various biological activities and distribution of sterols in Sargassum genus have been critically reviewed here. The results concluded that these algae are a good candidate for further anti-diabetic investigations in animals and human.

  12. beta-Naphthoflavone protects from peritonitis by reducing TNF-alpha-induced endothelial cell activation.

    Science.gov (United States)

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

    2015-12-01

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

  13. Diffusion of Active Particles With Stochastic Torques Modeled as $\\alpha$-Stable Noise

    CERN Document Server

    Noetel, Joerg; Schimansky-Geier, Lutz

    2016-01-01

    We investigate the stochastic dynamics of an active particle moving at a constant speed under the influence of a fluctuating torque. In our model the angular velocity is generated by a constant torque and random fluctuations described as a L\\'evy-stable noise. Two situations are investigated. First, we study white L\\'evy noise where the constant speed and the angular noise generate a persistent motion characterized by the persistence time $\\tau_D$. At this time scale the crossover from ballistic to normal diffusive behavior is observed. The corresponding diffusion coefficient can be obtained analytically for the whole class of symmetric $\\alpha$-stable noises. As typical for models with noise-driven angular dynamics, the diffusion coefficient depends non-monotonously on the angular noise intensity. As second example, we study angular noise as described by an Ornstein-Uhlenbeck process with correlation time $\\tau_c$ driven by the Cauchy white noise. We discuss the asymptotic diffusive properties of this model ...

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

    Science.gov (United States)

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

    2010-05-01

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

  15. 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

  16. About the effectiveness of the ABPD methods in air-borne alpha-activity monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Shevchenko, S.V. [SSC ' Technocentre' Ministry of Emergency of Ukraine, Kiev (Ukraine)]. E-mail: shevsv@i.kiev.ua; Saltykov, L.S. [Institute of Nuclear Researches of NAS of Ukraine, Kiev (Ukraine); Slusarenko, L.I. [Institute of Nuclear Researches of NAS of Ukraine, Kiev (Ukraine)

    2006-01-01

    A modified version of the alpha-beta-pseudo-coincidence-difference (ABPD-M) method is proposed with a view to suppressing natural background radiation when measuring the transuranium radionuclide (TRU) content in aerosol samples. It is shown that complementing the traditional 'pseudo-coincidence' method with a treatment of (comparatively) fast beta-alpha coincidences provides a means to significantly improve the suppression of background fluctuations and the accuracy of measurement results in comparison with the traditional method.

  17. Mechanisms of transcriptional activation of the mouse claudin-5 promoter by estrogen receptor alpha and beta.

    Science.gov (United States)

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

    2014-07-01

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

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

    Science.gov (United States)

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

    2000-01-01

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

  19. A single gene directs synthesis of a precursor protein with beta- and alpha-amylase activities in Bacillus polymyxa.

    Science.gov (United States)

    Uozumi, N; Sakurai, K; Sasaki, T; Takekawa, S; Yamagata, H; Tsukagoshi, N; Udaka, S

    1989-01-01

    The Bacillus polymyxa amylase gene comprises 3,588 nucleotides. The mature amylase comprises 1,161 amino acids with a molecular weight of 127,314. The gene appeared to be divided into two portions by the direct-repeat sequence located at almost the middle of the gene. The 5' region upstream of the direct-repeat sequence was shown to be responsible for the synthesis of beta-amylase. The 3' region downstream of the direct-repeat sequence contained four sequences homologous with those in other alpha-amylases, such as Taka-amylase A. The 48-kilodalton (kDa) amylase isolated from B. polymyxa was proven to have alpha-amylase activity. The amino acid sequences of the peptides generated from the 48-kDa amylase showed complete agreement with the predicted amino acid sequence of the C-terminal portion. The B. polymyxa amylase gene was therefore concluded to contain in-phase beta- and alpha-amylase-coding sequences in the 5' and 3' regions, respectively. A precursor protein, a 130-kDa amylase, directed by a plasmid, pYN520, carrying the entire amylase gene, had both beta- and alpha-amylase activities. This represents the first report of a single protein precursor in procaryotes that gives rise to two enzymes. Images PMID:2464578

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-10-14

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

  1. The inhibition of P338 lymphocytic leukemia DNA polymerase alpha activity by cis-diamminedichloroplatinum(II) and related derivatives.

    Science.gov (United States)

    Oswald, C B; Hall, I H

    1989-01-01

    Cis-platinum derivatives were observed to inhibit the activity of DNA polymerase alpha of P388 lymphocytic leukemia cells. A 600g nuclear preparation of the polymerase alpha was inhibited by cis-diamminedichloroplatinum(II) [cDDP], diamminemalonatoplatinum(II) [MAL], (1,2-diaminocyclohexane)-dichloroplatinum(II) [DACH-Pt-CL2], and (1,2-diaminocyclohexane)malonato-platinum(II) [DACH-Pt-MAL]. cDDP was a more potent inhibitor of the enzyme activity which was positively correlated with the observed inhibition of DNA synthesis of P388 cells in vivo and in vitro. The inhibition of the 600g preparation by cDDP could be partially reversed by the addition of exogenous ctDNA, but 35% inhibition was not retreivable by adding new template. Isolation of the P388 DNA polymerase alpha enzyme by DEAE column chromatography led to an enzyme with 100 fold purification, which was sensitive to N-ethyl maleimide at 0.1 mM concentration. cDDP inhibited the activity of this enzyme in a dose dependent manner. However, MAL, DACH-Pt-Cl2 and DACH-Pt-MAL afforded no inhibition, nor did the latter two derivatives bind to the enzyme. cDDP inhibition of the activity of purified enzyme was partially reversed by the addition of exogenous ctDNA and by the addition of dGTP, whereas addition of other d(NTP)s had no effect on the recovery of the enzyme activity. These studies suggest that cDDP inhibits DNA polymerase alpha activity and that the inhibition is not the sole mechanism of the action of the drug in suppression of DNA synthesis and cell death. Preliminary studies suggest that the drug may bind to the apoprotein of the enzyme in a competitive manner with dGTP.

  2. The inhibition of the human cholesterol 7alpha-hydroxylase gene (CYP7A1) promoter by fibrates in cultured cells is mediated via the liver x receptor alpha and peroxisome proliferator-activated receptor alpha heterodimer.

    Science.gov (United States)

    Gbaguidi, G Franck; Agellon, Luis B

    2004-01-01

    In previous work, we showed that the binding of the liver x receptor alpha:peroxisome proliferator-activated receptor alpha (LXRalpha:PPARalpha) heterodimer to the murine Cyp7a1 gene promoter antagonizes the stimulatory effect of their respective ligands. In this study, we determined if LXRalpha:PPARalpha can also regulate human CYP7A1 gene promoter activity. Co-expression of LXRalpha and PPARalpha in McArdle RH7777 hepatoma cells decreased the activity of the human CYP7A1 gene promoter in response to fibrates and 25-hydroxycholesterol. In vitro, the human CYP7A1 Site I bound LXRalpha:PPARalpha, although with substantially less affinity compared with the murine Cyp7a1 Site I. The binding of LXRalpha:PPARalpha to human CYP7A1 Site I was increased in the presence of either LXRalpha or PPARalpha ligands. In HepG2 hepatoblastoma cells, fibrates and 25-hydroxycholesterol inhibited the expression of the endogenous CYP7A1 gene as well as the human CYP7A1 gene promoter when co-transfected with plasmids encoding LXRalpha and PPARalpha. However, a derivative of the human CYP7A1 gene promoter that contains a mutant form of Site I that does not bind LXRalpha:PPARalpha was not inhibited by WY 14,643 or 25-hydroxycholesterol in both McArdle RH7777 and HepG2 cells. The ligand-dependent recruitment of LXRalpha:PPARalpha heterodimer onto the human CYP7A1 Site I can explain the inhibition of the human CYP7A1 gene promoter in response to fibrates and 25-hydroxycholesterol.

  3. Effect of peroxisome proliferator-activated receptor-alpha ligands in the interaction between adipocytes and macrophages in obese adipose tissue.

    Science.gov (United States)

    Toyoda, Takuya; Kamei, Yasutomi; Kato, Hirotsugu; Sugita, Satoshi; Takeya, Motohiro; Suganami, Takayoshi; Ogawa, Yoshihiro

    2008-06-01

    This study was designed to examine the effect of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) ligands on the inflammatory changes induced by the interaction between adipocytes and macrophages in obese adipose tissue. PPAR-alpha ligands (Wy-14,643 and fenofibrate) were added to 3T3-L1 adipocytes, RAW264 macrophages, or co-culture of 3T3-L1 adipocytes and RAW264 macrophages in vitro, and monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) mRNA expression and secretion were examined. PPAR-alpha ligands were administered to genetically obese ob/ob mice for 2 weeks. Moreover, the effect of PPAR-alpha ligands was also evaluated in the adipose tissue explants and peritoneal macrophages obtained from PPAR-alpha-deficient mice. In the co-culture of 3T3-L1 adipocytes and RAW264 macrophages, PPAR-alpha ligands reduced MCP-1 and TNF-alpha mRNA expression and secretion in vitro relative to vehicle-treated group. The anti-inflammatory effect of Wy-14,643 was observed in adipocytes treated with macrophage-conditioned media or mouse recombinant TNF-alpha and in macrophages treated with adipocyte-conditioned media or palmitate. Systemic administration of PPAR-alpha ligands inhibited the inflammatory changes in adipose tissue from ob/ob mice. Wy-14,643 also exerted an anti-inflammatory effect in the adipose tissue explants but not in peritoneal macrophages obtained from PPAR-alpha-deficient mice. This study provides evidence for the anti-inflammatory effect of PPAR-alpha ligands in the interaction between adipocytes and macrophages in obese adipose tissue, thereby improving the dysregulation of adipocytokine production and obesity-related metabolic syndrome.

  4. 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.

  5. A novel role for mixed-lineage kinase-like mitogen-activated protein triple kinase alpha in neoplastic cell transformation and tumor development.

    Science.gov (United States)

    Cho, Yong-Yeon; Bode, Ann M; Mizuno, Hideya; Choi, Bu Young; Choi, Hong Seok; Dong, Zigang

    2004-06-01

    Previously, no member of the mixed-lineage kinase (MLK) protein family was known to function as an oncogene. Here, we demonstrate that MLK-like mitogen-activated protein triple kinase (MLTK)-alpha, a member of the MLK family, induced neoplastic cell transformation and tumorigenesis in athymic nude mice. Introduction of small interference RNA (siRNA)-MLTK-alpha into MLTK-alpha-overexpressing cells dramatically suppressed cell transformation. Nuclear accumulation of the pHisG-MLTK-alpha fusion protein was observed after epidermal growth factor or 12-O-tetradecanoylphorbol-13-acetate treatment. Phosphorylation of downstream mitogen-activated protein kinase-targeted transcription factors including c-Myc, Elk-1, c-Jun, and activating transcription factor (ATF) 2 was also differentially enhanced in MLTK-alpha-overexpressing cells exposed to epidermal growth factor or 12-O-tetradecanoylphorbol-13-acetate stimulation compared with cells expressing mock vector or siRNA-MLTK-alpha. Very importantly, MLTK-alpha-overexpressing cells formed fibrosarcomas when injected s.c. into athymic nude mice, whereas almost no tumor formation was observed in mice that received injections of mock or siRNA-MLTK-alpha stably transfected cells. These results are the first to indicate that MLTK-alpha plays a key role in neoplastic cell transformation and cancer development.

  6. Effects of clonidine and alpha-adrenoceptor antagonists on motor activity in DSP4-treated mice II: interactions with apomorphine.

    Science.gov (United States)

    Fredriksson, A; Archer, T

    2000-04-01

    Adult mice were administered either the noradrenaline (NA) neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) or distilled water (control), 10-12 days before motor activity testing, and 6 h before testing all the mice were administered reserpine (10 mg/kg), the monoamine-depleting agent. The interactive effects of (I) clonidine, the alpha(2)-adrenoceptor agonist, with the dopamine (DA) agonist, apomorphine, and the alpha(2)-antagonist, yohimbine, and (II) with either yohimbine or the alpha(1)-antagonist, prazosin, upon motor behaviour in activity test chambers were studied in reserpinized DSP4-treated and control mice. It was shown that apomorphine (3 mg/kg) increased locomotor and total activity in both reserpinized DSP4-treated and control mice but the effect was attenuated in the DSP4 mice. Co-administration of clonidine (3 mg/kg) with apomorphine potentiated the effects of apomorphine on motor activity and this effect was enhanced markedly by DSP4 pretreatment. Yohimbine (10 mg/kg) antagonized the motor activity-stimulating effects of apomorphine in both DSP4-treated and control mice. Co-administration of clonidine with apomorphine, following yohimbine, restored motor activity levels to those obtained in the absence of yohimbine and this effect upon locomotor activity was enhanced by DSP4 pretreatment. The effects of clonidine on motor activity were enhanced by NA-denervation. Prazzosin (3 mg/kg) enhanced the locomotor activity of both reserpinized DSP4-treated and control mice after the initial 30-min period but was not affected by DSP4 treatment. Analysis of post-decapitation convulsions (PDCs) indicated loss of the reflex by DSP4 pretreatment. Reserpine pretreatment abolished the initial, exploratory phase (30 min) of motor activity. These results demonstrate interactions between NA and DA systems that may bear eventual relevance to neurologic disorders such as parkinsonism.

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

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    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.

  8. Phentolamine inhibits exocytosis of glucagon by Gi2 protein-dependent activation of calcineurin in rat pancreatic alpha -cells.

    Science.gov (United States)

    Høy, M; Bokvist, K; Xiao-Gang, W; Hansen, J; Juhl, K; Berggren, P O; Buschard, K; Gromada, J

    2001-01-12

    Capacitance measurements were used to investigate the molecular mechanisms by which imidazoline compounds inhibit glucagon release in rat pancreatic alpha-cells. The imidazoline compound phentolamine reversibly decreased depolarization-evoked exocytosis >80% without affecting the whole-cell Ca(2+) current. During intracellular application through the recording pipette, phentolamine produced a concentration-dependent decrease in the rate of exocytosis (IC(50) = 9.7 microm). Another imidazoline compound, RX871024, exhibited similar effects on exocytosis (IC(50) = 13 microm). These actions were dependent on activation of pertussis toxin-sensitive G(i2) proteins but were not associated with stimulation of ATP-sensitive K(+) channels or adenylate cyclase activity. The inhibitory effect of phentolamine on exocytosis resulted from activation of the protein phosphatase calcineurin and was abolished by cyclosporin A and deltamethrin. Exocytosis was not affected by intracellular application of specific alpha(2), I(1), and I(2) ligands. Phentolamine reduced glucagon release (IC(50) = 1.2 microm) from intact islets by 40%, an effect abolished by pertussis toxin, cyclosporin A, and deltamethrin. These data suggest that imidazoline compounds inhibit glucagon secretion via G(i2)-dependent activation of calcineurin in the pancreatic alpha-cell. The imidazoline binding site is likely to be localized intracellularly and probably closely associated with the secretory granules.

  9. The Impact of Investments and Gross Value Added upon Earnings

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    Larisa APARASCHIVEI

    2011-02-01

    Full Text Available In this paper we tried to capture the impact of investments and gross value added, but also the impact of the employment on the average wage. The analysis refers to the period 1998- 2008 and we are using data on the activities of the Romanian economy. The results of this study confirm the negative influence of the employment, being consistent with the theory. Also, the impact of investments and that of gross value added came out to be positive and significant.

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

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    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.

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

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    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.

  12. Activation of alpha chymotrypsin by three phase partitioning is accompanied by aggregation.

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    Gulam Mohmad Rather

    Full Text Available Precipitation of alpha chymotrypsin in the simultaneous presence of ammonium sulphate and t-butanol (three phase partitioning resulted in preparations which showed self aggregation of the enzyme molecules. Precipitation with increasing amounts of ammonium sulphate led to increasing size of aggregates. While light scattering estimated the hydrodynamic diameter of these aggregates in the range of 242-1124 nm; Nanoparticle tracking analysis (NTA gave the value as 130-462 nm. Scanning electron microscopy and gel filtration on Sephadex G-200 showed extensive aggregation in these preparations. Transmission electron microscopy showed that the aggregates had irregular shapes. All the aggregates had about 3× higher catalytic activity than the native enzyme. These aggregates did not differ in λ(max of fluorescence emission which was around 340 nm. However, all the aggregates showed higher fluorescence emission intensity. Far-UV and near-UV circular dichroism also showed no significant structural changes as compared to the native molecule. Interestingly, HPLC gel filtration (on a hydroxylated silica column gave 14 nm as the diameter for all preparations. Light scattering of preparations in the presence of 10% ethylene glycol also dissociated the aggregates to monomers of 14 nm. Both these results indicated that hydrophobic interactions were the driving force behind this aggregation. These results indicate: (1 Even without any major structural change, three phase partitioning led to protein molecules becoming highly prone to aggregation. (2 Different methods gave widely different estimates of sizes of aggregates. It was however possible to reconcile the data obtained with various approaches. (3 The nature of the gel filtration column is crucial and use of this technique for refolding and studying aggregation needs a rethink.

  13. Activation of alpha chymotrypsin by three phase partitioning is accompanied by aggregation.

    Science.gov (United States)

    Rather, Gulam Mohmad; Mukherjee, Joyeeta; Halling, Peter James; Gupta, Munishwar Nath

    2012-01-01

    Precipitation of alpha chymotrypsin in the simultaneous presence of ammonium sulphate and t-butanol (three phase partitioning) resulted in preparations which showed self aggregation of the enzyme molecules. Precipitation with increasing amounts of ammonium sulphate led to increasing size of aggregates. While light scattering estimated the hydrodynamic diameter of these aggregates in the range of 242-1124 nm; Nanoparticle tracking analysis (NTA) gave the value as 130-462 nm. Scanning electron microscopy and gel filtration on Sephadex G-200 showed extensive aggregation in these preparations. Transmission electron microscopy showed that the aggregates had irregular shapes. All the aggregates had about 3× higher catalytic activity than the native enzyme. These aggregates did not differ in λ(max) of fluorescence emission which was around 340 nm. However, all the aggregates showed higher fluorescence emission intensity. Far-UV and near-UV circular dichroism also showed no significant structural changes as compared to the native molecule. Interestingly, HPLC gel filtration (on a hydroxylated silica column) gave 14 nm as the diameter for all preparations. Light scattering of preparations in the presence of 10% ethylene glycol also dissociated the aggregates to monomers of 14 nm. Both these results indicated that hydrophobic interactions were the driving force behind this aggregation. These results indicate: (1) Even without any major structural change, three phase partitioning led to protein molecules becoming highly prone to aggregation. (2) Different methods gave widely different estimates of sizes of aggregates. It was however possible to reconcile the data obtained with various approaches. (3) The nature of the gel filtration column is crucial and use of this technique for refolding and studying aggregation needs a rethink.

  14. Activity of phospholipase C and release of prostaglandin F2 alpha by endometrial tissue from ovariectomized ewes receiving progesterone and estradiol.

    Science.gov (United States)

    Raw, R E; Silvia, W J

    1991-03-01

    Progesterone and estradiol interact to regulate secretion of prostaglandin (PG) F2 alpha from the ovine endometrium in response to oxytocin. Two experiments were conducted to determine if these effects were due to changes in activity of phospholipase C or in the second messenger responsive pathways that regulate production of PGF2 alpha. In both experiments, ovariectomized ewes were assigned to one of four treatment groups (control, estradiol, progesterone, progesterone and estradiol). Steroids were administered, in vivo, to mimic the changes that occur during the estrous cycle. On Day 16 of steroid treatment, endometrial tissue was collected and incubated, in vitro, to measure activity of phospholipase C and release of PGF2 alpha. Treatment with progesterone, in vivo, enhanced basal and oxytocin-induced activity of phospholipase C and release of PGF2 alpha, in vitro. Estradiol suppressed oxytocin-induced activity of phospholipase C, both in the presence and absence of progesterone. In contrast to its effects on phospholipase C, estradiol inhibited basal and oxytocin-induced release of PGF2 alpha when administered alone, but not when administered with progesterone. Steroids had similar effects on the release of PGF2 alpha induced by phorbol 12-myristate 13-acetate and A23187. It was concluded that progesterone and estradiol regulate endometrial release of PGF2 alpha by affecting both the activity of phospholipase C and its associated second messenger responsive pathways that may regulate production of PGF2 alpha.

  15. Accumulation of mutant alpha1-antitrypsin Z in the endoplasmic reticulum activates caspases-4 and -12, NFkappaB, and BAP31 but not the unfolded protein response.

    Science.gov (United States)

    Hidvegi, Tunda; Schmidt, Bela Z; Hale, Pamela; Perlmutter, David H

    2005-11-25

    In alpha(1)-antitrypsin (alpha1AT) deficiency, a polymerogenic mutant form of the secretory glycoprotein alpha1AT, alpha1ATZ, is retained in the endoplasmic reticulum (ER) of liver cells. It is not yet known how this results in liver injury in a subgroup of deficient individuals and how the remainder of deficient individuals escapes liver disease. One possible explanation is that the "susceptible" subgroup is unable to mount the appropriate protective cellular responses. Here we examined the effect of mutant alpha1ATZ on several potential protective signaling pathways by using cell lines with inducible expression of mutant alpha1AT as well as liver from transgenic mice with liver-specific inducible expression of mutant alpha1AT. The results show that ER retention of polymerogenic mutant alpha1ATZ does not result in an unfolded protein response (UPR). The UPR can be induced in the presence of alpha1ATZ by tunicamycin excluding the possibility that the pathway has been disabled. In striking contrast, ER retention of nonpolymerogenic alpha1AT mutants does induce the UPR. These results indicate that the machinery responsible for activation of the UPR can distinguish the physical characteristics of proteins that accumulate in the ER in such a way that it can respond to misfolded but not relatively ordered polymeric structures. Accumulation of mutant alpha1ATZ does activate specific signaling pathways, including caspase-12 in mouse, caspase-4 in human, NFkappaB, and BAP31, a profile that was distinct from that activated by nonpolymerogenic alpha1AT mutants.

  16. Activating mutations of the Gs alpha-gene in nonfunctioning pituitary tumors.

    Science.gov (United States)

    Tordjman, K; Stern, N; Ouaknine, G; Yossiphov, Y; Razon, N; Nordenskjöld, M; Friedman, E

    1993-09-01

    The majority of pituitary tumors are of monoclonal origin; however, the molecular basis for their formation is poorly understood. Somatic mutations in the alpha-subunit of the GTP-binding protein, Gs alpha (gsp oncogene) have been found in about one third of GH-secreting tumors. Mutations in another alpha-subunit of a GTP-binding protein, Gi2 alpha (gip mutations) have been described in other endocrine tumors. In this study, we examined 21 nonfunctioning pituitary tumors and 4 macroprolactinomas for gsp mutations and 27 nonfunctioning tumors and 4 macroprolactinomas for gip mutations. Using the polymerase chain reaction and denaturing gradient gel electrophoresis, 2 nonfunctioning pituitary tumors displayed migration abnormalities when the Gs alpha-gene was analyzed. Sequence analysis of these abnormally migrating polymerase chain reaction products revealed two previously known gsp mutations: arginine at codon 201 altered to cysteine, and glutamine at codon 227 changed to leucine. No gip mutations could be demonstrated. These findings emphasize the monoclonal origin of nonfunctioning pituitary tumors and suggest that cAMP may play a role in tumorigenesis of nonfunctioning pituitary tumors.

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

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    Takashi Egashira

    2015-03-01

    Full Text Available Background The effects of stellate ganglion block (SGB on radicular pain associated with cervical spondylosis remain to be clarified. So we measured salivary alpha-amylase which reflects sympathetic nerve activity under psychological stress after SGB block or trigger points injection (TPI. Study Design A randomized, prospective, controlled trial Setting After institutional approval and informed consent, 40 patients who was suffered from neck-shoulder pain associated with cervical radiculopathy were randomly divided into two groups according to nerve block treatment. Group A (n=20, male 10 patients, female 10 patients, 50±8yr, mean±SD received SGB and group B (n=20, male 10 patients, female 10 patients, 52±6yr received TPI. SGB or TPI was produced by 6 ml of 1% mepivacaine a total of 5 times (twice per week. Visual analogue scale (VAS and the concentration of salivary alpha-amylase were measured before (T0 each nerve block and 3 days (T1, 6 days (T2, 9 days (T3, 12 days (T4 and 15days (T5 after each nerve block. The consumption of non-steroidal anti-inflammatory drug (NSAID was measured at T0 and T5 in each group. Results In group A, VAS was median 74 (range 60, 78 at T0 and showed a significant decrease at T3 [53 (48, 65, p<0.05], T4 [50 (42, 66, p<0.05] and T5 [48 (26,57, p<0.05]. The concentration of salivary alpha-amylase was median 116 (range 96, 144 KU/ml at T0 and showed a significant decrease at T3 [86 (79, 105, p<0.05], T4 [79 (68, 88] and T5 [70 (55, 84, p<0.05]. In group B, VAS and the concentration of salivary alpha-amylase showed no change throughout the time course. VAS in group A was significant lower than that in group B at T3, T4 and T5. The concentration of salivary alpha-amylase was significant lower than that in group B at T4 and T5. The consumption of NSAID in group A was significantly lower than that in group B at T5. Limitations Subjects are out patients. Patients include radicular pain due to different pathogenesis, e

  18. Studies on the 1. cap alpha. ,25-dihydroxycholecalciferol-like activity in a calcinagenic plant, Cestrum diurnum, in the chick

    Energy Technology Data Exchange (ETDEWEB)

    Wasserman, R.H. (Cornell Univ., Ithaca, NY); Corradino, R.A.; Krook, L.; Hughes, M.R.; Haussler, M.R.

    1976-04-01

    Cestrum diurnum (day-blooming jessamine) has been proposed to cause calcinosis in horses and cattle in Florida. The present studies investigated some physiological properties of the plant, using the chick as the experimental animal. The inclusion of dried leaf powder in a rachitogenic diet restored intestinal calcium-binding protein synthesis (CaBP) and increased calcium absorption in the cholecalciferol-deficient chick. The estimated level of cholecalciferol-equivalents in the dried leaf was about 30,000 to 35,000 IU/kg. Most of the activity was extractable with methanol : chloroform (2:1), indicating that the major cholecalciferol-like component in C. diurnum was different from the water soluble factor(s) in Solanum malacoxylon. The time course of effect of C. diurnum extract in rachitic chicks was similar to that of 1,25-dihydroxycholecalciferol but the former had a longer lag time. The strontium fed chick, in which the kidney 25-hydroxycholecaliciferol-1..cap alpha..-hydroxylase is inhibited, responded to C. diurnum extract, confirming the 1..cap alpha..,25-dihydroxycholecalciferol-like character of the Cestrum factor. The extract also appeared to interact with the intestinal 1..cap alpha..,25-dihydroxycholecalciferol cytosol receptor although this observation is preliminary. These findings indicate that the 1..cap alpha..,25-dihydroxycholecalciferol-like principle in C. diurnum may cause excessive calcium and phosphate absorption leading to calcinosis.

  19. Studies on the 1alpha, 25-dihydroxycholecalciferol-like activity in a calcinogenic plant. Cestrum diurnum, in the chick.

    Science.gov (United States)

    Wasserman, R H; Corradino, R A; Krook, L; Hughes, M R; Haussler, M R

    1976-04-01

    Cestrum diurnum (day-blooming jessamine) has been proposed to cause calcinosis in horses and cattle in Florida. The present studies investigated some physiological properties of the plant, using the chick as the experimental animal. The inclusion of dried leaf powder in a rachitogenic diet restored intestinal calcium-binding protein synthesis (CaBP) and increased calcium absorption in the cholecalciferol-deficient chick. The estimated level of cholecalciferol-equivalents in the dried leaf was about 30,000 to 35,000 IU/kg. Most of the activity was extractable with methanol:chloroform (2:1), indicating that the major cholecalciferol-like component in C. diurnum was different from the water soluble factor(s) in Solanum malacoxylon. The time course of effect of C. diurnum extract in rachitic chicks was similar to that ot 1,25-dihydroxycholecalciferol but the former had a longer lag time. The strontium fed chick, in which the kidney 25-hydroxycholecalciferol-1alpha-hydroxylase is inhibited, responded to C. diurnum extract, confirming the 1alpha,25-dihydroxycholecalciferol-like character of the Cestrum factor. The extract also appeared to interact with the intestinal 1 alpha,25-dihydroxycholecalciferol cytosol receptor although this observation is preliminary. These findings indicate that the l alpha,25-dihydroxycholecalciferol-like principle in C. diurnum many cause excessive calcium and phosphate absorption leading to calcinosis.

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    C S James Ho

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

  2. Effect of moxonidine on contractile activity of isolated large intestine in mice: role of alpha2-adrenoceptors and Ii-imidazoline receptors.

    Science.gov (United States)

    Kozaeva, L P; Korobov, N V; Medvedev, O S

    2004-03-01

    We studied the ability of moxonidine to interact with alpha2-adrenoceptors and Ii-imidazoline receptors in isolated mouse large intestine. Moxonidine caused contractions of longitudinal muscles in the large intestine, which depended on the dose of this preparation. Pretreatment with yohimbine (alpha2-adrenoceptor antagonist with low affinity for Ii-imidazoline receptors) and efaroxan (Ii-imidazoline receptor antagonist with low affinity for alpha2-adrenoceptors) abolished the effect of moxonidine. Antagonistic activity and relative selectivity of yohimbine and efaroxan suggest that the effects of moxonidine on mouse large intestine are realized via alpha2-adrenoceptors.

  3. 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.

  4. Measures of Gross National Happiness

    Directory of Open Access Journals (Sweden)

    Ruut Veenhoven

    2010-02-01

    Full Text Available Happiness is rising on the political agenda and this calls for measures of how well nations perform in creating great happiness for a great number, analogous to measures of success in creating wealth, such as GDP. Happiness is defined as subjective enjoyment of one’s life as-a-whole and this can be measured using self-reports. Question on happiness are currently used in large scale surveys of the general population in nations. As a result we have now comparable data on happiness in 144 contemporary nations and time-series of 25 years and longer on 11 developed nations. These data can be aggregated in different ways: If the aim is simply greater happiness for a greater number of citizens, Average happiness (AH is an appropriate measure. If the focus is on enduring happiness, it is better to combine average happiness with longevity in an index of Happy Life Years (HLY. If the aim is to reduce disparity among citizens a relevant indicator is the Inequality of Happiness (IH in the nations as measured with the standard deviation. Average and dispersion can also be combined in an index of Inequality-Adjusted Happiness (IAH. Comparison across nations shows sizable differences on all these measures of gross national happiness and these differences correspond with societal characteristics that can be influenced by policy makers, such as freedom and justice. Comparison over time shows major improvement during the last decade.

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

    DEFF Research Database (Denmark)

    Søderman, Andreas; Thomsen, Morten Skøtt; Hansen, Henrik H;

    2008-01-01

    Recent studies have demonstrated that amyloid-beta1-42 (Abeta1-42) binds to the nicotinergic alpha7 acetylcholine receptor (alpha7 nAChR) and that the application of Abeta1-42 to cells inhibits the function of the alpha7 nAChR. The in vivo consequences of the pharmacological activation of the alpha...... through the use of co-immunoprecipitation that human Abeta-immunoreactive peptides bind to mice alpha7 nAChR in vivo. Agonists of the alpha7 nAChR improve memory and attentional properties and increase immediate early gene expression in the prefrontal cortex and the nucleus accumbens. We show that acute...

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

    CERN Document Server

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

    2015-01-01

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

  7. Defective activation of c-Src in cystic fibrosis airway epithelial cells results in loss of tumor necrosis factor-alpha-induced gap junction regulation

    NARCIS (Netherlands)

    Huang, Song; Dudez, Tecla; Scerri, Isabelle; Thomas, Marc A; Giepmans, Ben N G; Suter, Susanne; Chanson, Marc

    2003-01-01

    Tumor necrosis factor-alpha (TNF-alpha) signaling is central to the transmission of the innate immune response and subsequent activation of the adaptive immune system. The functioning of both systems is required for optimal clearance of pathogens from the airways. In cystic fibrosis (CF),

  8. Defective activation of c-Src in cystic fibrosis airway epithelial cells results in loss of tumor necrosis factor-alpha-induced gap junction regulation

    NARCIS (Netherlands)

    Huang, Song; Dudez, Tecla; Scerri, Isabelle; Thomas, Marc A; Giepmans, Ben N G; Suter, Susanne; Chanson, Marc

    2003-01-01

    Tumor necrosis factor-alpha (TNF-alpha) signaling is central to the transmission of the innate immune response and subsequent activation of the adaptive immune system. The functioning of both systems is required for optimal clearance of pathogens from the airways. In cystic fibrosis (CF), dysfunctio

  9. 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.

  10. 5alpha-Reductase activity in Lycopersicon esculentum: cloning and functional characterization of LeDET2 and evidence of the presence of two isoenzymes.

    Science.gov (United States)

    Rosati, Fabiana; Bardazzi, Irene; De Blasi, Paola; Simi, Lisa; Scarpi, Dina; Guarna, Antonio; Serio, Mario; Racchi, Milvia L; Danza, Giovanna

    2005-08-01

    The full-length cDNA (LeDET2) encoding a 257 amino acid protein homolog of Arabidopsis DET2 (AtDET2) was isolated in tomato (Lycopersicon esculentum). LeDET2 has 76% similarity with AtDET2 and structural characteristics conserved among plant and mammalian steroid 5alpha-reductases (5alphaRs). LeDET2 is ubiquitously expressed in tomato tissues with higher levels in leaf than in stem, root, seed and callus. When expressed in mammalian cells (COS-7), recombinant LeDET2 was active on substrates typical of mammalian 5alphaRs (progesterone, testosterone, androstenedione), but reduced at very low levels campestenone, the substrate described for AtDET2. Similar results were obtained with the expression in COS-7 of recombinant AtDET2 that showed 5alphaR activity for progesterone and not for campestenone. Recombinant LeDET2 was inhibited by several inhibitors of the human 5alphaRs and the application of an active inhibitor to tomato seedlings induced dwarfism and morphological changes similar to BR-deficient mutants. In tomato tissues, campestenone was 5alpha-reduced in leaf, stem and root homogenates, like progesterone and testosterone, while androstenedione was converted to testosterone, evidencing for the first time a 17beta-hydroxysteroid dehydrogenase activity in plants. Moreover, two separate 5alphaR activities with different kinetic characteristic and response to inhibitors were characterized in tomato tissues. The presence of two 5alphaR isoenzymes was demonstrated also in Arabidopsis using the det2-1 mutant, in which a residual 5alphaR activity for campestenone and progesterone was evidenced and characterized. Therefore, the existence of two isoenzymes of 5alphaR is probably characteristic of the whole plant kingdom highlighting the similarities between the animal and plant steroid biosynthetic pathways.

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

    Directory of Open Access Journals (Sweden)

    Robert Becker

    2015-09-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-09-05

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

  13. Alpha Thalassemia

    Science.gov (United States)

    Alpha Thalassemia Physicians often mistake alpha thalassemia trait for iron deficiency anemia and incorrectly prescribe iron supplements that have no effect 1 on the anemia. αα αα Normal alpha ...

  14. Facilitation and inhibition in attention: Functional dissociation of pre-stimulus alpha activity, P1, and N1 components.

    Science.gov (United States)

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

    2016-01-15

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

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

    Directory of Open Access Journals (Sweden)

    Dineshkumar B

    2010-01-01

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

  16. The Mechanics of Gross Moist Stability

    Directory of Open Access Journals (Sweden)

    Zeljka Fuchs

    2009-08-01

    Full Text Available The gross moist stability relates the net lateral outflow of moist entropy or moist static energy from an atmospheric convective region to some measure of the strength of the convection in that region. If the gross moist stability can be predicted as a function of the local environmental conditions, then it becomes the key element in understanding how convection is controlled by the large-scale flow. This paper provides a guide to the various ways in which the gross moist stability is defined and the subtleties of its calculation from observations and models. Various theories for the determination of the gross moist stability are presented and its roles in current conceptual models for the tropical atmospheric circulation are analyzed. The possible effect of negative gross moist stability on the development and dynamics of tropical disturbances is currently of great interest.

  17. 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.

  18. 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.

  19. 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.

  20. 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

    1992-01-01

    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 expre

  1. 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

  2. Syntheses and structure-activity relationships for some triazolyl p38 alpha MAPK inhibitors

    NARCIS (Netherlands)

    Seerden, Jean-Paul G.; Leusink-Ionescu, Gabriela; Leguijt, Robin; Saccavini, Catherine; Gelens, Edith; Dros, Bas; Woudenberg-Vrenken, Titia; Molema, Grietje; Kamps, Jan A. A. M.; Kellogg, Richard M.

    2014-01-01

    The design, synthesis and biological evaluation of novel triazolyl p38 alpha MAPK inhibitors with improved water solubility for formulation in cationic liposomes (SAINT-O-Somes) targeted at diseased endothelial cells is described. Water-solubilizing groups were introduced via a 'click' reaction of f

  3. ALPHA-AMYLASE ACTIVITY IN VARIOUS CONCENTRATIONS OF THE IONIC LIQUID, 1-BUTYL-3-METHYLIMIDAZOLIUM CHLORIDE

    Science.gov (United States)

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

  4. 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.

  5. 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...

  6. Indications for active case searches and intravenous alpha-1 antitrypsin treatment for patients with alpha-1 antitrypsin deficiency chronic pulmonary obstructive disease: an update.

    Science.gov (United States)

    Casas, Francisco; Blanco, Ignacio; Martínez, María Teresa; Bustamante, Ana; Miravitlles, Marc; Cadenas, Sergio; Hernández, José M; Lázaro, Lourdes; Rodríguez, Esther; Rodríguez-Frías, Francisco; Torres, María; Lara, Beatriz

    2015-04-01

    The effect of hereditary alpha-1 antitrypsin (AAT) deficiency can manifest clinically in the form of chronic obstructive pulmonary disease (COPD). AAT deficiency (AATD) is defined as a serum concentration lower than 35% of the expected mean value or 50 mg/dl (determined by nephelometry). It is associated in over 95% of cases with Pi*ZZ genotypes, and much less frequently with other genotypes resulting from combinations of Z, S, rare and null alleles. A systematic qualitative review was made of 107 articles, focusing mainly on an active search for AATD in COPD patients and intravenous (iv) treatment with AAT. On the basis of this review, the consultant committee of the Spanish Registry of Patients with AATD recommends that all COPD patients be screened for AATD with the determination of AAT serum concentrations, and when these are low, the evaluation must be completed with phenotyping and, on occasions, genotyping. Patients with severe AATD COPD should receive the pharmacological and non-pharmacological treatment recommended in the COPD guidelines. There is enough evidence from large observational studies and randomized placebo-controlled clinical trials to show that the administration of iv AAT reduces mortality and slows the progression of emphysema, hence its indication in selected cases that meet the inclusion criteria stipulated in international guidelines. The administration of periodic infusions of AAT is the only specific treatment for delaying the progression of emphysema associated with AATD.

  7. Alpha-emitting isotopes and chromium in a coastal California aquifer

    Science.gov (United States)

    Densmore, Jill N.; Izbicki, John A.; Murtaugh, Joseph M.; Swarzenski, Peter W.; Bullen, Thomas D.

    2014-01-01

    The unadjusted 72-h gross alpha activities in water from two wells completed in marine and alluvial deposits in a coastal southern California aquifer 40 km north of San Diego were 15 and 25 picoCuries per liter (pCi/L). Although activities were below the Maximum Contaminant Level (MCL) of 15 pCi/L, when adjusted for uranium activity; there is concern that new wells in the area may exceed MCLs, or that future regulations may limit water use from the wells. Coupled well-bore flow and depth-dependent water-quality data collected from the wells in 2011 (with analyses for isotopes within the uranium, actinium, and thorium decay-chains) show gross alpha activity in marine deposits is associated with decay of naturally-occurring 238U and its daughter 234U. Radon activities in marine deposits were as high as 2230 pCi/L. In contrast, gross alpha activities in overlying alluvium within the Piedra de Lumbre watershed, eroded from the nearby San Onofre Hills, were associated with decay of 232Th, including its daughter 224Ra. Radon activities in alluvium from Piedra de Lumbre of 450 pCi/L were lower than in marine deposits. Chromium VI concentrations in marine deposits were less than the California MCL of 10 μg/L (effective July 1, 2014) but δ53Cr compositions were near zero and within reported ranges for anthropogenic chromium. Alluvial deposits from the nearby Las Flores watershed, which drains a larger area having diverse geology, has low alpha activities and chromium as a result of geologic and geochemical conditions and may be more promising for future water-supply development.

  8. 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

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

  9. Inhibition by N'-nitrosonornicotine of the catalytic activity of glutamate dehydrogenase in alpha-ketoglutarate amination.

    Science.gov (United States)

    Mao, You-An; Zhong, Ke-Jun; Wei, Wan-Zhi; Wei, Xin-Liang; Lu, Hong-Bing

    2005-02-01

    The effect of N'-nitrosonornicotine (NNN), one of the tobacco-specific nitrosamines, on the catalytic activity of glutamate dehydrogenase (GLDH) in the alpha-ketoglutarate amination, using reduced nicotinamide adenine dinucleotide as coenzyme, was studied by a chronoamperometric method. The maximum reaction rate of the enzyme-catalyzed reaction and the Michaelis-Menten constant, or the apparent Michaelis-Menten constant, were determined in the absence and presence of NNN. NNN remarkably inhibited the bio-catalysis activity of GLDH, and was a reversible competitive inhibitior with K(i), estimated as 199 micromol l(-1) at 25 degrees C and pH 8.0.

  10. 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

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

    Science.gov (United States)

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

    2010-05-01

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

  12. 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

  13. Direct chemical synthesis of 1 alpha,25-dihydroxy(26,27-3H) vitamin D3 with high specific activity: its use in receptor studies

    Energy Technology Data Exchange (ETDEWEB)

    Napoli, J.L.; Mellon, W.S.; Fivizzani, M.A.; Schnoes, H.K.; DeLuca, H.F.

    1980-05-01

    The first direct chemical synthesis of radiolabeled 1 alpha, 25-dihydroxyvitamin D3 is reported. Unlike all previous syntheses, the new approach does not rely on enzymatic 1 alpha-hydroxylation of radiolabeled precursors. Rather, isotope is introduced in the last synthetic step by reaction of (3H) -methylmagnesium bromide with methyl 1 alpha-hydroxy-26,27-dinorvitamin D3-25-carboxylate to give 1 alpha,25-dihydroxy-(26,27-3H) vitamin D3 with a specific activity of 160 Ci/mmol. Mass spectroscopy confirmed that the radiohormone consists of a single isomer with six tritium atoms bound to carbons 26 and 27. Synthetically produced 1 alpha,25-dihydroxy (26,27-3H) vitamin D3 is indistinguishable from 1 alpha,25-dihydroxy-(26,27-3H) vitamin D3 obtained from the enzymatic 1 alpha-hydroxylation of 25-hydroxy(26,27-3H) vitamin D3 (160 Ci/mmol) by high-pressure liquid chromatography analysis and in the competitive binding assay using chick intestinal cytosol as the receptor source. Equilibrium dissociation constant measurements with the high specific activity radiohormone indicate a Kd of 8.2 x 10(-11) M for the chick intestinal cytosol 1 alpha,25-dihydroxyvitamin D3 receptor--a value considerably lower than the constants in the range of (1-5) x 10(-9) M previously reported.

  14. Granulocyte colony-stimulating factor activating HIF-1alpha acts synergistically with erythropoietin to promote tissue plasticity.

    Directory of Open Access Journals (Sweden)

    Shih-Ping Liu

    Full Text Available Stroke and peripheral limb ischemia are serious clinical problems with poor prognosis and limited treatment. The cytokines erythropoietin (EPO and granulocyte-colony stimulating factor (G-CSF have been used to induce endogenous cell repair and angiogenesis. Here, we demonstrated that the combination therapy of EPO and G-CSF exerted synergistic effects on cell survival and functional recovery from cerebral and peripheral limbs ischemia. We observed that even under normoxic conditions, G-CSF activates hypoxia-inducible factor-1alpha (HIF-1alpha, which then binds to the EPO promoter and enhances EPO expression. Serum EPO level was significantly increased by G-CSF injection, with the exception of Tg-HIF-1alpha(+f/+f mice. The neuroplastic mechanisms exerted by EPO combined with G-CSF included enhanced expression of the antiapoptotic protein of Bcl-2, augmented neurotrophic factors synthesis, and promoted neovascularization. Further, the combination therapy significantly increased homing and differentiation of bone marrow stem cells (BMSCs and intrinsic neural progenitor cells (INPCs into the ischemic area. In summary, EPO in combination with G-CSF synergistically enhanced angiogenesis and tissue plasticity in ischemic animal models, leading to greater functional recovery than either agent alone.

  15. The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling but not for alpha-secretase activity in fibroblasts.

    Science.gov (United States)

    Hartmann, Dieter; de Strooper, Bart; Serneels, Lutgarde; Craessaerts, Katleen; Herreman, An; Annaert, Wim; Umans, Lieve; Lübke, Torben; Lena Illert, Anna; von Figura, Kurt; Saftig, Paul

    2002-10-01

    The metalloprotease ADAM 10 is an important APP alpha-secretase candidate, but in vivo proof of this is lacking. Furthermore, invertebrate models point towards a key role of the ADAM 10 orthologues Kuzbanian and sup-17 in Notch signalling. In the mouse, this function is, however, currently attributed to ADAM 17/TACE, while the role of ADAM 10 remains unknown. We have created ADAM 10-deficient mice. They die at day 9.5 of embryogenesis with multiple defects of the developing central nervous system, somites, and cardiovascular system. In situ hybridization revealed a reduced expression of the Notch target gene hes-5 in the neural tube and an increased expression of the Notch ligand dll-1, supporting an important role for ADAM 10 in Notch signalling in the vertebrates as well. Since the early lethality precluded the establishment of primary neuronal cultures, APPs alpha generation was analyzed in embryonic fibroblasts and found to be preserved in 15 out of 17 independently generated ADAM 10-deficient fibroblast cell lines, albeit at a quantitatively more variable level than in controls, whereas a severe reduction was found in only two cases. The variability was not due to differences in genetic background or to variable expression of the alternative alpha-secretase candidates ADAM 9 and ADAM 17. These results indicate, therefore, either a regulation between ADAMs on the post-translational level or that other, not yet known, proteases are able to compensate for ADAM 10 deficiency. Thus, the observed variability, together with recent reports on tissue-specific expression patterns of ADAMs 9, 10 and 17, points to the existence of tissue-specific 'teams' of different proteases exerting alpha-secretase activity.

  16. Chemical engineering of a three-fingered toxin with anti-alpha7 neuronal acetylcholine receptor activity.

    Science.gov (United States)

    Mourier, G; Servent, D; Zinn-Justin, S; Ménez, A

    2000-03-01

    Though it possesses four disulfide bonds the three-fingered fold is amenable to chemical synthesis, using a Fmoc-based method. Thus, we synthesized a three-fingered curaremimetic toxin from snake with high yield and showed that the synthetic and native toxins have the same structural and biological properties. Both were characterized by the same 2D NMR spectra, identical high binding affinity (K(d) = 22 +/- 5 pM) for the muscular acetylcholine receptor (AChR) and identical low affinity (K(d) = 2.0 +/- 0.4 microM) for alpha7 neuronal AchR. Then, we engineered an additional loop cyclized by a fifth disulfide bond at the tip of the central finger. This loop is normally present in longer snake toxins that bind with high affinity (K(d) = 1-5 nM) to alpha7 neuronal AchR. Not only did the chimera toxin still bind with the same high affinity to the muscular AchR but also it displayed a 20-fold higher affinity (K(d) = 100 nM) for the neuronal alpha7 AchR, as compared with the parental short-chain toxin. This result demonstrates that the engineered loop contributes, at least in part, to the high affinity of long-chain toxins for alpha7 neuronal receptors. That three-fingered proteins with four or five disulfide bonds are amenable to chemical synthesis opens new perspectives for engineering new activities on this fold.

  17. Persistence of interleukin 7 activity and levels on tumour necrosis factor alpha blockade in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    van Roon, Joel A. G.; Hartgring, Sarita A. Y.; Wijk, Marion Wenting-van; Jacobs, Kim M. G.; Tak, Paul-Peter; Bijlsma, Johannes W. J.; Lafeber, Floris P. J. G.

    2007-01-01

    Objectives: To identify the mechanism of interleukin (IL)7-stimulated tumour necrosis factor alpha (TNF alpha) production and to determine the relationship between intra-articular IL7 and TNF alpha expression levels in patients with rheumatoid arthritis ( RA). In addition, the effect of TNF alpha bl

  18. 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.

  19. 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......-leg knee-extensor exercise at 65% maximal one-leg power output in five subjects. 2. Pre-exercise BCAA ingestion (308 mg BCAAs (kg body wt)-1) caused an increased muscle BCAA uptake, a higher intramuscular BCAA concentration and activation of BCKADH both at rest (9 +/- 1 versus 25 +/- 5% for the control...... and BCAA test, respectively) and after exercise (27 +/- 4 versus 54 +/- 7%). 3. At rest the percentage active BCKADH was not different, 6 +/- 2% versus 5 +/- 1%, in the normal and low glycogen content leg (392 +/- 21 and 147 +/- 34 mumol glycosyl units (g dry muscle)-1, respectively). The post...

  20. Human recombinant macrophage inflammatory protein-1 alpha and -beta and monocyte chemotactic and activating factor utilize common and unique receptors on human monocytes.

    Science.gov (United States)

    Wang, J M; Sherry, B; Fivash, M J; Kelvin, D J; Oppenheim, J J

    1993-04-01

    The human macrophage inflammatory proteins-1 alpha and -beta (MIP-1 alpha and -beta), which are also known as LD78 and ACT2, respectively, are distinct but highly related members of the chemoattractant cytokine (chemokine) family. rMIP-1 alpha and -beta labeled with 125I specifically bind to human peripheral blood monocytes, the monocytic cell line THP-1, peripheral blood T cells, and the YT cell line. Steady state binding experiments revealed approximately 3000 high affinity binding sites/cell for MIP-1 alpha on human monocytes and on THP-1 cells, with Kd values of 383 pM and 450 pM, respectively. Human MIP-1 alpha and -beta had nearly identical affinities for the binding sites and each competed equally well for binding. Human monocyte chemotactic and activating factor (MCAF), a member of the same chemokine family, consistently displaced about 25% of human MIP-1 alpha and -beta binding on monocytes but not on YT cells, which did not bind MCAF. On the other hand, human rMIP-1 alpha and -beta partially inhibited binding of radiolabeled MCAF to monocytes. Both MIP-1 alpha and -beta were chemotactic for human monocytes. Preincubation of monocytes with human rMIP-1 alpha or -beta markedly reduced cell migration towards the other cytokine, whereas preincubation with human rMCAF only partially desensitized the monocyte chemotaxis response to human rMIP-1 alpha or -beta. These data suggest the existence of three subtypes of receptors, i.e., one unique receptor shared by MIP-1 alpha and -beta, a second unique receptor for MCAF, and a third species that recognizes both MCAF and MIP-1 peptides.

  1. The future of gross anatomy teaching.

    Science.gov (United States)

    Malamed, S; Seiden, D

    1995-01-01

    A survey of U.S. departments of anatomy, physiology, and biochemistry shows that 39% of the respondent anatomy departments reported declines in the numbers of graduate students taking the human gross anatomy course. Similarly, 42% of the departments reported decreases in the numbers of graduate students teaching human gross anatomy. These decreases were greater in anatomy than in physiology and in biochemistry. The percentages of departments reporting increases in students taking or teaching their courses was 6% for human gross anatomy and 0% to 19% for physiology and biochemistry courses. To reverse this trend the establishment of specific programs for the training of gross anatomy teachers is advocated. These new teachers will be available as the need for them is increasingly recognized in the future.

  2. FUZZY ECCENTRICITY AND GROSS ERROR IDENTIFICATION

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The dominant and recessive effect made by exceptional interferer is analyzed in measurement system based on responsive character, and the gross error model of fuzzy clustering based on fuzzy relation and fuzzy equipollence relation is built. The concept and calculate formula of fuzzy eccentricity are defined to deduce the evaluation rule and function of gross error, on the base of them, a fuzzy clustering method of separating and discriminating the gross error is found. Utilized in the dynamic circular division measurement system, the method can identify and eliminate gross error in measured data, and reduce measured data dispersity. Experimental results indicate that the use of the method and model enables repetitive precision of the system to improve 80% higher than the foregoing system, to reach 3.5 s, and angle measurement error is less than 7 s.

  3. Validating the Rett Syndrome Gross Motor Scale

    DEFF Research Database (Denmark)

    Downs, Jenny; Stahlhut, Michelle; Wong, Kingsley;

    2016-01-01

    Rett syndrome is a pervasive neurodevelopmental disorder associated with a pathogenic mutation on the MECP2 gene. Impaired movement is a fundamental component and the Rett Syndrome Gross Motor Scale was developed to measure gross motor abilities in this population. The current study investigated...... the validity and reliability of the Rett Syndrome Gross Motor Scale. Video data showing gross motor abilities supplemented with parent report data was collected for 255 girls and women registered with the Australian Rett Syndrome Database, and the factor structure and relationships between motor scores, age...... and genotype were investigated. Clinical assessment scores for 38 girls and women with Rett syndrome who attended the Danish Center for Rett Syndrome were used to assess consistency of measurement. Principal components analysis enabled the calculation of three factor scores: Sitting, Standing and Walking...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-02-01

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

  5. Evidence for preferential repair of 3-carbethoxypsoralen plus UVA induced DNA lesions in the active MAT alpha locus in Saccharomyces cerevisiae using the UvrABC assay.

    Science.gov (United States)

    Méniel, V; Brouwer, J; Averbeck, D

    1993-09-01

    The occurrence of preferential repair in Saccharomyces cerevisiae of the active MAT alpha locus compared with the inactive HML alpha locus was confirmed after 254 nm UV irradiation. Experiments carried out using the UvrABC excinuclease assay with the monofunctional furocoumarin 3-carbethoxypsoralen (3-CPs) plus UVA radiation which induce mainly monoadducts in DNA demonstrated preferential repair of the active MAT alpha locus compared with the inactive HML alpha locus in a SIR+ strain. However, as after 254 nm UV irradiation, no difference in the rate of removal of 3-CPs plus UVA induced lesions was observed between the two loci in the sir-3 mutant in which both loci are active. Thus, it appears that 3-CPs plus UVA induced monoadducts as well as pyrimidine dimers are subject to preferential repair.

  6. The fibroblast growth factor receptor (FGFR) agonist FGF1 and the neural cell adhesion molecule-derived peptide FGL activate FGFR substrate 2alpha differently

    DEFF Research Database (Denmark)

    Chen, Yongshuo; Li, Shizhong; Berezin, Vladimir

    2010-01-01

    Activation of fibroblast growth factor (FGF) receptors (FGFRs) both by FGFs and by the neural cell adhesion molecule (NCAM) is crucial in the development and function of the nervous system. We found that FGFR substrate 2alpha (FRS2alpha), Src homologous and collagen A (ShcA), and phospholipase......-Cgamma (PLCgamma) were all required for neurite outgrowth from cerebellar granule neurons (CGNs) induced by FGF1 and FGL (an NCAM-derived peptide agonist of FGFR1). Like FGF1, FGL induced tyrosine phosphorylation of FGFR1, FRS2alpha, ShcA, and PLCgamma in a time- and dose-dependent manner. However, the activation...... of FRS2alpha by FGL was significantly lower than the activation by FGF1, indicating a differential signaling profile induced by NCAM compared with the cognate growth factor....

  7. Acute lymphoblastic leukemia presenting with gross hematuria

    OpenAIRE

    Kalbani, Naifain Al; Weitzman, Sheila; Abdelhaleem, Mohamed; Carcao, Manuel; Abla, Oussama

    2007-01-01

    A case of a six-year-old boy presenting with gross hematuria is reported. Investigations revealed the etiology of the hematuria to be thrombocytopenia in the setting of newly diagnosed acute lymphoblastic leukemia. The diagnosis of leukemia was confirmed by bone marrow examination. The patient’s hematuria completely resolved with platelet transfusions. Although thrombocytopenia is a very common presenting feature of acute lymphoblastic leukemia, gross hematuria is exceedingly rare. Thus, thro...

  8. Cytidine-5'-monophosphate-N-acetylneuraminic acid. Asialoglycoprotein sialic acid transferase activity in liver and serum of patients with juvenile hepatic cirrhosis and alpha-1-antitrypsin deficiency.

    Science.gov (United States)

    Kuhlenschmidt, M S; Peters, S P; Pinkard, O D; Glew, R H; Sharp, H

    1976-04-08

    The molecular basis for the accumulation of a substance which displays the immunological reactivity of alpha-1-antitrypsin within vesicles of liver parenchymal cells of individuals with hepatic cirrhosis and serum alpha-1-antitrypsin deficiency remains unclear. We recently reported that serum from a patient with alpha-1-antitrypsin deficiency and hepatic cirrhosis was substantially deficient in sialyltransferease (EC 2.4.99.1) an enzyme which transfers sialic acid from cytidine 5'-monophosphate-N-acetylneuraminic acid to a variety of asialoglycoprotein acceptors. In the present report we have extended these studies to include serum from five additional patients with alpha-1-antitrypsin deficiency and juvenile hepatic cirrhosis as well as a liver specimen obtained at autopsy of one of these patients. We find the sialytransferase activity in serum from six patients with alpha-1-antitrypsin deficiency and hepatic cirrhosis to be 50% of healthy pediatric control values and 30% of pediatric patients with liver disease. However, serum from family members homozygous for alpha-1-antitrypsin deficiency but without hepatic cirrhosis, and serum from patients with a variety of other kinds of liver disease, failed to exhibit the marked sialytransferase deficiency. Similar assays carried out on a homogenate of a liver sample from one patient with alpha-1-antitrypsin deficiency and hepatic cirrhosis indicated that the deficiency of sialyltransferase activity was not demonstrable in liver. Furthermore, a comparative kinetic analysis of serum and liver sialytransferase in normal and afflicted individuals failed to detect differences in substrate affinities which might account for a decrease in functional sialyltransferase capacity in individuals with alpha-1-antitrypsin deficiency and hepatic cirrhosis. These observations suggest that the serum sialyltransferase deficiency in such patients probably arises after chronic and extensive liver disease involving hepatic accumulation of

  9. Vasodilator activity of 2-(p-chloro-alpha-hydroxybenzyl)benzimidazole (HBBPC) on femoral vascular bed of the rabbit.

    Science.gov (United States)

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

    1979-01-01

    The effects of 2-(p-chloro-alpha-hydroxybenzyl) benzimidazole HCl (HBBPC) have been studied on the femoral peripheral resistance (i.v. route) and only femoral blood flow (local i.a. injection), in comparison with other vasodilators, i.e., sodium nitroprusside, dihydralazine and piribedil. The vasomotor activity of HBBPC, namely, decreased peripheral resistance and increased femoral blood flow, seems interesting because it begins after pressure has returned to normal. This substance is likely to induce a vasoconstriction in other areas (increased femoral blood flow with decreased peripheral resistance without a fall of blood pressure).

  10. Validating the Rett Syndrome Gross Motor Scale.

    Science.gov (United States)

    Downs, Jenny; Stahlhut, Michelle; Wong, Kingsley; Syhler, Birgit; Bisgaard, Anne-Marie; Jacoby, Peter; Leonard, Helen

    2016-01-01

    Rett syndrome is a pervasive neurodevelopmental disorder associated with a pathogenic mutation on the MECP2 gene. Impaired movement is a fundamental component and the Rett Syndrome Gross Motor Scale was developed to measure gross motor abilities in this population. The current study investigated the validity and reliability of the Rett Syndrome Gross Motor Scale. Video data showing gross motor abilities supplemented with parent report data was collected for 255 girls and women registered with the Australian Rett Syndrome Database, and the factor structure and relationships between motor scores, age and genotype were investigated. Clinical assessment scores for 38 girls and women with Rett syndrome who attended the Danish Center for Rett Syndrome were used to assess consistency of measurement. Principal components analysis enabled the calculation of three factor scores: Sitting, Standing and Walking, and Challenge. Motor scores were poorer with increasing age and those with the p.Arg133Cys, p.Arg294* or p.Arg306Cys mutation achieved higher scores than those with a large deletion. The repeatability of clinical assessment was excellent (intraclass correlation coefficient for total score 0.99, 95% CI 0.93-0.98). The standard error of measurement for the total score was 2 points and we would be 95% confident that a change 4 points in the 45-point scale would be greater than within-subject measurement error. The Rett Syndrome Gross Motor Scale could be an appropriate measure of gross motor skills in clinical practice and clinical trials.

  11. Transient regulation of c-fos, alpha B-crystallin, and hsp70 in muscle during recovery from contractile activity.

    Science.gov (United States)

    Neufer, P D; Ordway, G A; Williams, R S

    1998-02-01

    Endurance exercise training increases the oxidative capacity of skeletal muscles, reflecting the induction of genes encoding enzymes of intermediary metabolism. To test the hypothesis that changes in gene expression may be triggered specifically during recovery from contractile activity, we quantified c-fos, alpha B-crystallin, 70-kDa heat shock protein (hsp70), myoglobin, and citrate synthase RNA in rabbit tibialis anterior muscle during recovery from intermittent (8 h/day), low-frequency (10 Hz) motor nerve stimulation. Recovery from a single 8-h bout of stimulation was characterized by large (> 10-fold) transient increases in c-fos, alpha B-crystallin, and hsp70 mRNA. Similar changes were noted during recovery after 7 or 14 days of stimulation (8 h/day). Myoglobin and citrate synthase mRNA were also induced during recovery, but the changes were of lesser magnitude (2- to 2.5-fold) and were observed only following repeated bouts of muscle activity (7th or 14th day) that promoted sustained (> 24 h) increases in these transcripts. These findings indicate that recovery from exercise is associated with specific transient changes in the expression of immediate early and stress protein genes, suggesting that the products of these genes may have specific roles in the remodeling process evoked by repeated bouts of contractile activity.

  12. Isolation, structure determination and biological activity of 25-epi, 3{alpha}-carboxyacetylquercinic acid in daedalea dickinsii

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Kang Gyu; Min, Tae Jin [Dongguk Univ., Seoul (Korea, Republic of)

    2000-02-01

    In order to develope bioactive substances, dried fruit body of Daedalea dickinsii collected from Taeback mountain was extracted with ethanol. The compounds 1 and 2 were purified by solvent extraction, silica gel column chromatography and recrystallization from the ethanol extracts. Melting point, molecular weight and molar extinction coefficient of the compound 1 were estimated to be 167{approx}168 .deg. C, 572 and 5,040 at 208 nm. The structure of this compound 1 has been elucidated to be 24S, 25S, 3{alpha}-carboxyacetylquercinic acid using spectroscopic properties. This compound showed antibiotic activities against fungi, yeasts and bacteria and it also showed anticancer activity(IC{sub 50}=64.5 {mu}M/ml) against Korean stomach cancer cell. Melting point, molecular weight and molar extinction coefficient of the compound 2 were estimated to be 233{approx}235 .deg. C, 572 and 5,080 at 208 nm. The structure of this compound was elucidated to be 24S, 25R, 3{alpha}-carboxyacetylquercinic acid. The compound 2 showed different antibiotic activities with the compound 1.

  13. Regulation of diurnal variation of cholesterol 7alpha-hydroxylase (CYP7A1) activity in healthy subjects.

    Science.gov (United States)

    Kovár, J; Lenícek, M; Zimolová, M; Vítek, L; Jirsa, M; Pitha, J

    2010-01-01

    Cholesterol 7alpha-hydroxylase (CYP7A1), the key regulatory enzyme of bile acid synthesis, displays a pronounced diurnal variation. To better understand the regulation of CYP7A1 activity, three day-long examinations were carried out in 12 healthy men. The concentrations of 7alpha-hydroxycholest-4-en-3-one (C4), a surrogate marker of CYP7A1 activity, bile acids (BA), insulin, glucose, nonesterified fatty acids, triglycerides, and cholesterol were measured in serum in 90-min intervals from 7 AM till 10 PM. To lower and to increase BA concentration during the study, the subjects received cholestyramine and chenodeoxycholic acid (CDCA), respectively, in two examinations. No drug was used in the control examination. There was a pronounced diurnal variation of C4 concentration with a peak around 1 PM in most of the subjects. The area under the curve (AUC) of C4 concentration was five times higher and three times lower when subjects were treated with cholestyramine and CDCA, respectively. No relationship was found between AUC of C4 and AUC of BA concentration, but AUC of C4 correlated positively with that of insulin. Moreover, short-term treatment with cholestyramine resulted in about 10 % suppression of glycemia throughout the day. Our results suggest that insulin is involved in the regulation of diurnal variation of CYP7A1 activity in humans.

  14. 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.

  15. Morphological characterization of the AlphaA- and AlphaB-crystallin double knockout mouse lens

    Directory of Open Access Journals (Sweden)

    Brady James P

    2003-01-01

    Full Text Available Abstract Background One approach to resolving some of the in vivo functions of alpha-crystallin is to generate animal models where one or both of the alpha-crystallin gene products have been eliminated. In the single alpha-crystallin knockout mice, the remaining alpha-crystallin may fully or partially compensate for some of the functions of the missing protein, especially in the lens, where both alphaA and alphaB are normally expressed at high levels. The purpose of this study was to characterize gross lenticular morphology in normal mice and mice with the targeted disruption of alphaA- and alphaB-crystallin genes (alphaA/BKO. Methods Lenses from 129SvEvTac mice and alphaA/BKO mice were examined by standard scanning electron microscopy and confocal microscopy methodologies. Results Equatorial and axial (sagittal dimensions of lenses for alphaA/BKO mice were significantly smaller than age-matched wild type lenses. No posterior sutures or fiber cells extending to the posterior capsule of the lens were found in alphaA/BKO lenses. Ectopical nucleic acid staining was observed in the posterior subcapsular region of 5 wk and anterior subcapsular cortex of 54 wk alphaA/BKO lenses. Gross morphological differences were also observed in the equatorial/bow, posterior and anterior regions of lenses from alphaA/BKO mice as compared to wild mice. Conclusion These results indicated that both alphaA- and alphaB-crystallin are necessary for proper fiber cell formation, and that the absence of alpha-crystallin can lead to cataract formation.

  16. Divergent effects of estradiol and the estrogen receptor-alpha agonist PPT on eating and activation of PVN CRH neurons in ovariectomized rats and mice.

    Science.gov (United States)

    Thammacharoen, Sumpun; Geary, Nori; Lutz, Thomas A; Ogawa, Sonoko; Asarian, Lori

    2009-05-01

    Eating is modulated by estradiol in females of many species and in women. To further investigate the estrogen receptor mechanism mediating this effect, ovariectomized rats and mice were treated with estradiol benzoate or the estrogen receptor-alpha (ER-alpha)-selective agonist PPT. PPT inhibited eating in rats much more rapidly than estradiol (approximately 2-6 h versus >24 h). In contrast, the latencies to vaginal estrus after PPT and estradiol were similar (>24 h). PPT also inhibited eating within a few hours in wild-type mice, but failed to inhibit eating in transgenic mice deficient in ER-alpha (ERalphaKO mice). PPT, but not estradiol, induced the expression of c-Fos in corticotrophin-releasing hormone (CRH)-expressing cells of the paraventricular nucleus (PVN) of the hypothalamus within 90-180 min in rats. Both PPT and estradiol reduced c-Fos expression in an ER-alpha-containing area of the nucleus of the solitary tract. The anomalously rapid eating-inhibitory effect of PPT suggests that PPT's neuropharmacological effect differs from estradiol's, perhaps because PPT differentially activates membrane versus nuclear ER-alpha or because PPT activates non-ER-alpha membrane estrogen receptors in addition to ER-alpha. The failure of PPT to inhibit eating in ERalphaKO mice, however, indicates that ER-alpha is necessary for PPT's eating-inhibitory action and that any PPT-induced activation of non-ER-alpha estrogen receptors is not sufficient to inhibit eating. Finally, the rapid induction of c-Fos in CRH-expressing cells in the PVN by PPT suggests that PPT elicits a neural response that is similar to that elicited by stress or aversive emotional stimuli.

  17. Characterization of the lys2 gene of Acremonium chrysogenum encoding a functional alpha-aminoadipate activating and reducing enzyme.

    Science.gov (United States)

    Hijarrubia, M J; Aparicio, J F; Casqueiro, J; Martín, J F

    2001-02-01

    A 5.2-kb NotI DNA fragment isolated from a genomic library of Acremonium chrysogenum by hybridization with a probe internal to the Penicillium chrysogenum lys2 gene, was able to complement an alpha-aminoadipate reductase-deficient mutant of P. chrysogenum (lysine auxotroph L-G-). Enzyme assays showed that the alpha-aminoadipate reductase activity was restored in all the transformants tested. The lys2-encoded enzyme catalyzed both the activation and reduction of alpha-aminoadipic acid to its semialdehyde, as shown by reaction of the product with p-dimethylaminobenzaldehyde. The reaction required NADPH, and was not observed in the presence of NADH. Sequence analysis revealed that the gene encodes a protein with relatively high similarity to members of the superfamily of acyladenylate-forming enzymes. The Lys2 protein contained all nine motifs that are conserved in the adenylating domain of this enzyme family, a peptidyl carrier domain, and a reduction domain. In addition, a new NADP-binding motif located at the N-terminus of the reduction domain that may form a Rossmann-like betaalphabeta-fold has been identified and found to be shared by all known Lys2 proteins. The lys2 gene was mapped to chromosome I (2.2 Mb, the smallest chromosome) of A. chrysogenum C10 (the chromosome that contains the "late" cephalosporin cluster) and is transcribed as a monocistronic 4.5-kb mRNA although at relatively low levels compared with the beta-actin gene.

  18. TNF-alpha increases ubiquitin-conjugating activity in skeletal muscle by up-regulating UbcH2/E220k

    Science.gov (United States)

    Li, Yi-Ping; Lecker, Stewart H.; Chen, Yuling; Waddell, Ian D.; Goldberg, Alfred L.; Reid, Michael B.

    2003-01-01

    In some inflammatory diseases, TNF-alpha is thought to stimulate muscle catabolism via an NF-kappaB-dependent process that increases ubiquitin conjugation to muscle proteins. The transcriptional mechanism of this response has not been determined. Here we studied the potential role of UbcH2, a ubiquitin carrier protein and homologue of murine E220k. We find that UbcH2 is constitutively expressed by human skeletal and cardiac muscles, murine limb muscle, and cultured myotubes. TNF-alpha stimulates UbcH2 expression in mouse limb muscles in vivo and in cultured myotubes. The UbcH2 promoter region contains a functional NF-kappaB binding site; NF-kappaB binding to this sequence is increased by TNF-alpha stimulation. A dominant negative inhibitor of NF-kappaB activation blocks both UbcH2 up-regulation and the increase in ubiquitin-conjugating activity stimulated by TNF-alpha. In extracts from TNF-alpha-treated myotubes, ubiquitin-conjugating activity is limited by UbcH2 availability; activity is inhibited by an antiserum to UbcH2 or a dominant negative mutant of UbcH2 and is enhanced by wild-type UbcH2. Thus, UbcH2 up-regulation is a novel response to TNF-alpha/NF-kappaB signaling in skeletal muscle that appears to be essential for the increased ubiquitin conjugation induced by this cytokine.

  19. Can Clinical Assessment of Locomotive Body Function Explain Gross Motor Environmental Performance in Cerebral Palsy?

    Science.gov (United States)

    Sanz Mengibar, Jose Manuel; Santonja-Medina, Fernando; Sanchez-de-Muniain, Paloma; Canteras-Jordana, Manuel

    2016-03-01

    Gross Motor Function Classification System has discriminative purposes but does not assess short-term therapy goals. Locomotion Stages (LS) classify postural body functions and independent activity components. Assessing the relation between Gross Motor Function Classification System level and Locomotion Stages will make us understand if clinical assessment can explain and predict motor environmental performance in cerebral palsy. A total of 462 children were assessed with both scales. High reliability and strong negative correlation (-0.908) for Gross Motor Function Classification System and Locomotion Stages at any age was found. Sensitivity was 83%, and specificity and positive predictive value were 100% within the same age range. Regression analysis showed detailed probabilities for the realization of the Gross Motor Function Classification System depending on the Locomotion Stages and the age group. Postural body function measure with Locomotion Stages is reliable, sensitive, and specific for gross motor function and able to predict environmental performance.

  20. Acyl-CoA esters antagonize the effects of ligands on peroxisome proliferator-activated receptor alpha conformation, DNA binding, and interaction with Co-factors

    DEFF Research Database (Denmark)

    Elholm, M; Dam, I; Jorgensen, C;

    2001-01-01

    The peroxisome proliferator-activated receptor alpha (PPARalpha) is a ligand-activated transcription factor and a key regulator of lipid homeostasis. Numerous fatty acids and eicosanoids serve as ligands and activators for PPARalpha. Here we demonstrate that S-hexadecyl-CoA, a nonhydrolyzable...

  1. Peroxisome proliferators-activated alpha agonist treatment ameliorates hepatic damage in rats with obstructive jaundice: an experimental study

    Directory of Open Access Journals (Sweden)

    Alper Murat

    2007-11-01

    Full Text Available Abstract Background Peroxisome proliferators-activated receptor alpha (PPARα activation modulates cholesterol metabolism and suppresses bile acid synthesis. This study aims to evaluate the effect of short-term administration of fenofibrate, a PPARα agonist, on proinflammatory cytokines, apoptosis, and hepatocellular damage in cholestasis. Methods Forty male Wistar rats were randomly divided into four groups: I = sham operated, II = bile duct ligation (BDL, III = BDL + vehicle (gum Arabic, IV = BDL + fenofibrate (100 mg/kg/day. All rats were sacrificed on 7th day after obtaining blood samples and liver tissue. Total bilirubin, aminotransferase (AST, alanine aminotransferase (ALT and alkaline phosphatase (ALP, gamma-glutamyl transferase, (GGT, tumor necrosis factor alpha (TNF-α, interleukin 1 beta (IL-1 β, and total bile acid (TBA in serum, and liver damage scores; portal inflammation, necrosis, bile duct number, in liver tissue were evaluated. Apoptosis in liver was also assessed by immunohistochemical staining. Results Fenofibrate administration significantly reduced serum total bilirubin, AST, ALT, ALP, and GGT, TNF-α, IL-1 β levels, and TBA (P P P P Conclusion Short-term administration of fenofibrate to the BDL rats exerts beneficial effects on hepatocellular damage and apoptosis.

  2. Dehydroepiandrosterone formation is independent of cytochrome P450 17alpha-hydroxylase/17, 20 lyase activity in the mouse brain.

    Science.gov (United States)

    Liu, Ying; Pocivavsek, Ana; Papadopoulos, Vassilios

    2009-07-01

    Cytochrome P450 17alpha-hydroxylase/17, 20 lyase (CYP17) is a microsomal enzyme reported to have two distinct catalytic activities, 17alpha-hydroxylase and 17, 20 lyase, that are essential for the biosynthesis of peripheral androgens such as dehydroepiandrosterone (DHEA). Paradoxically, DHEA is present and plays a role in learning and memory in the adult rodent brain, while CYP17 activity and protein are undetectable. To determine if CYP17 is required for DHEA formation and function in the adult rodent brain, we generated CYP17 chimeric mice that had reduced circulating testosterone levels. There were no detectable differences in cognitive spatial learning between CYP17 chimeric and wild-type mice. In addition, while CYP17 mRNA levels were reduced in CYP17 chimeric compared to wild-type mouse brain, the levels of brain DHEA levels were comparable. To determine if adult brain DHEA is formed by an alternative Fe(2+)-dependent pathway, brain microsomes were isolated from wild-type and CYP17 chimeric mice and treated with FeSO(4). Fe(2+) caused comparable levels of DHEA production by both wild-type and CYP17 chimeric mouse brain microsomes; DHEA production was not reduced by a CYP17 inhibitor. Taken together these in vivo studies suggest that in the adult mouse brain DHEA is formed via a Fe(2+)-sensitive CYP17-independent pathway.

  3. Fasting-induced increases in aquaporin 7 and adipose triglyceride lipase mRNA expression in adipose tissue are attenuated by peroxisome proliferator-activated receptor alpha deficiency.

    Science.gov (United States)

    Walker, C G; Holness, M J; Gibbons, G F; Sugden, M C

    2007-07-01

    To investigate the impact of peroxisome proliferator-activated receptor alpha deficiency on gene expression of adipose triglyceride lipase and the glycerol transporter aquaglyceroporin 7 in white adipose tissue in the fed and fasted states in relation to glycerol release by isolated adipocytes. Studies using wild-type and peroxisome proliferator-activated receptor alpha null mice. Hormone and metabolite concentrations, real-time polymerase chain reaction (PCR), basal and stimulated adipocyte lipolysis, estimated by glycerol release. Peroxisome proliferator-activated receptor alpha deficiency blocked the increase in aquaglyceroporin 7 transcript level and attenuated the increase in adipose triglyceride lipase transcript level in white adipose tissue elicited by fasting. Fasting glycerol levels were lower in peroxisome proliferator-activated receptor alpha null than wild-type mice, despite increased mobilization of adipocyte fat reserves in vivo as indicated by reduced adipose tissue masses (three distinct depots) and a significantly lower epididymal adipocyte diameter. Basal net glycerol release was unchanged but beta-adrenergic-stimulated net glycerol release was higher with isolated adipocytes from fasted peroxisome proliferator-activated receptor alpha null mice compared with those of fasted wild-type mice. Peroxisome proliferator-activated receptor alpha deficiency prevents effects of fasting to increase adipocyte aquaglyceroporin 7 gene expression, and influences the regulation of inter-tissue glycerol flux after fasting via lowered adipocyte aquaglyceroporin 7 expression. Lowered gene expression of adipose triglyceride lipase and aquaglyceroporin 7 in peroxisome proliferator-activated receptor alpha null mice is not limiting for adipose triglyceride breakdown in vivo during fasting.

  4. Nuclear factor YY1 activates the mammalian F0F1 ATP synthase alpha-subunit gene.

    Science.gov (United States)

    Breen, G A; Vander Zee, C A; Jordan, E M

    1996-01-01

    Analysis of the promoters of the bovine and human nuclear-encoded mitochondrial F0F1 ATP synthase alpha-subunit genes (ATPA) has identified several positive cis-acting regulatory regions that are important for basal promoter activity in human HeLa cells. We have previously determined that the binding of a protein factor, termed ATPF1, to an E-box sequence (CANNTG) located within one of these cis-acting regions is critical for transcriptional activation of the ATPA gene. In this article, we describe a second positive cis-acting regulatory element of the ATPA gene that is important for expression of the ATPA gene. We show that this cis-acting element also contains a binding site for a protein present in HeLa cells. On the basis of electrophoretic mobility shift patterns, oligonucleotide competition assays, and immunological cross-reactivity, we conclude that this protein factor is Yin-Yang 1 (YY1). Experiments carried out to examine the functional role of YY1 within the context of the ATPA promoter demonstrated that YY1 acts as a positive regulator of the ATPA gene. For example, when the YY1 binding site of the ATPA promoter was placed upstream of a reporter gene it was found to activate transcription in transient transfection assays. In addition, disruption of the YY1 binding site in the ATPA gene resulted in a loss of transcriptional activity. Furthermore, in cotransfection experiments overexpression of YY1 in trans was found to activate transcription of ATPA promoter-CAT constructs. Thus, at least two positive trans-acting regulatory factors, ATPF1 and YY1, are important for expression of the bovine and human F0F1 ATP synthase alpha-subunit genes.

  5. Insulin-like growth factor-binding protein-5 (IGFBP-5) inhibits TNF-{alpha}-induced NF-{kappa}B activity by binding to TNFR1

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Jae Ryoung; Huh, Jae Ho; Lee, Yoonna; Lee, Sang Il [Molecular Therapy Research Center, Sungkyunkwan University, Seoul 135-710 (Korea, Republic of); Rho, Seung Bae [Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do 411-769 (Korea, Republic of); Lee, Je-Ho, E-mail: jeholee@gmail.com [Molecular Therapy Research Center, Sungkyunkwan University, Seoul 135-710 (Korea, Republic of); Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2011-02-25

    Research highlights: {yields} Binding assays demonstrated that secreted- and cellular-IGFBP-5 interacted with TNFR1. {yields} The interaction between IGFBP-5 and TNFR1 was inhibited by TNF-{alpha} and was blocked TNF-{alpha}-activated NF-{kappa}B activity. {yields} IGFBP-5 interacted with TNFR1 through its N- and L-domains but the binding of L-domain to TNFR1 was blocked by TNF-{alpha}. {yields} Competition between the L-domain of IGFBP-5 and TNF-{alpha} blocked TNF-{alpha}-induced NF-{kappa}B activity. {yields} This study suggests that the L-domain of IGFBP-5 is a novel TNFR1 ligand that functions as a competitive TNF-{alpha} inhibitor. -- Abstract: IGFBP-5 is known to be involved in various cell phenomena such as proliferation, differentiation, and apoptosis. However, the exact mechanisms by which IGFBP-5 exerts its functions are unclear. In this study, we demonstrate for the first time that IGFBP-5 is a TNFR1-interacting protein. We found that ectopic expression of IGFBP-5 induced TNFR1 gene expression, and that IGFBP-5 interacted with TNFR1 in both an in vivo and an in vitro system. Secreted IGFBP-5 interacted with GST-TNFR1 and this interaction was blocked by TNF-{alpha}, demonstrating that IGFBP-5 might be a TNFR1 ligand. Furthermore, conditioned media containing secreted IGFBP-5 inhibited PMA-induced NF-{kappa}B activity and IL-6 expression in U-937 cells. Coimmunoprecipitation assays of TNFR1 and IGFBP-5 wild-type and truncation mutants revealed that IGFBP-5 interacts with TNFR1 through its N- and L-domains. However, only the interaction between the L-domain of IGFBP-5 and TNFR1 was blocked by TNF-{alpha} in a dose-dependent manner, suggesting that the L-domain of IGFBP-5 can function as a TNFR1 ligand. Competition between the L-domain of IGFBP-5 and TNF-{alpha} resulted in inhibition of TNF-{alpha}-induced NF-{kappa}{Beta} activity. Taken together, our results suggest that the L-domain of IGFBP-5 is a novel TNFR1 ligand that functions as a competitive TNF-{alpha

  6. Selective disruption of ER{alpha} DNA-binding activity alters uterine responsiveness to estradiol.

    Science.gov (United States)

    Hewitt, Sylvia C; O'Brien, Jeanne E; Jameson, J Larry; Kissling, Grace E; Korach, Kenneth S

    2009-12-01

    In vitro models have been used to demonstrate that estrogen receptors (ERs) can regulate estrogen-responsive genes either by directly interacting with estrogen-responsive element (ERE) DNA motifs or by interacting with other transcription factors such as AP1. In this study, we evaluated estrogen (E(2))-dependent uterine gene profiles by microarray in the KIKO mouse, an in vivo knock-in mouse model that lacks the DNA-binding function of ERalpha and is consequently restricted to non-ERE-mediated responses. The 2- or 24-h E(2)-mediated uterine gene responses were distinct in wild-type (WT), KIKO, and alphaERKO genotypes, indicating that unique sets of genes are regulated by ERE and non-ERE pathways. After 2 h E(2) treatment, 38% of the WT transcripts were also regulated in the KIKO, demonstrating that the tethered mechanism does operate in this in vivo model. Surprisingly, 1438 E(2)-regulated transcripts were unique in the KIKO mouse and were not seen in either WT or alphaERKO. Pathway analyses revealed that some canonical pathways, such as the Jak/Stat pathway, were affected in a similar manner by E(2) in WT and KIKO. In other cases, however, the WT and KIKO differed. One example is the Wnt/beta-catenin pathway; this pathway was impacted, but different members of the pathway were regulated by E(2) or were regulated in a different manner, consistent with differences in biological responses. In summary, this study provides a comprehensive analysis of uterine genes regulated by E(2) via ERE and non-ERE pathways.

  7. Integrin alpha1beta1 controls reactive oxygen species synthesis by negatively regulating epidermal growth factor receptor-mediated Rac activation.

    Science.gov (United States)

    Chen, Xiwu; Abair, Tristin D; Ibanez, Maria R; Su, Yan; Frey, Mark R; Dise, Rebecca S; Polk, D Brent; Singh, Amar B; Harris, Raymond C; Zent, Roy; Pozzi, Ambra

    2007-05-01

    Integrins control many cell functions, including generation of reactive oxygen species (ROS) and regulation of collagen synthesis. Mesangial cells, found in the glomerulus of the kidney, are able to produce large amounts of ROS via the NADPH oxidase. We previously demonstrated that integrin alpha1-null mice develop worse fibrosis than wild-type mice following glomerular injury and this is due, in part, to excessive ROS production by alpha1-null mesangial cells. In the present studies, we describe the mechanism whereby integrin alpha1-null mesangial cells produce excessive ROS. Integrin alpha1-null mesangial cells have constitutively increased basal levels of activated Rac1, which result in its increased translocation to the cell membrane, excessive ROS production, and consequent collagen IV deposition. Basal Rac1 activation is a direct consequence of ligand-independent increased epidermal growth factor receptor (EGFR) phosphorylation in alpha1-null mesangial cells. Thus, our study demonstrates that integrin alpha1beta1-EGFR cross talk is a key step in negatively regulating Rac1 activation, ROS production, and excessive collagen synthesis, which is a hallmark of diseases characterized by irreversible fibrosis.

  8. 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.

  9. 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...

  10. EASY-II: a system for modelling of n, d, p, {\\gamma} and {\\alpha} activation and transmutation processes

    CERN Document Server

    Sublet, Jean-Christophe; Morgan, Guy; Koning, Arjan; Rochman, Dimitri

    2013-01-01

    EASY-II is designed as a functional replacement for the previous European Activation System, EASY-2010. It has extended nuclear data and new software, FISPACT-II, written in object-style Fortran to provide new capabilities for predictions of activation, transmutation, depletion and burnup. The new FISPACT-II code has allowed us to implement many more features in terms of energy range, up to GeV; incident particles: alpha, gamma, proton, deuteron and neutron; and neutron physics: self-shielding effects, temperature dependence, pathways analysis, sensitivity and error estimation using covariance data. These capabilities cover most application needs: nuclear fission and fusion, accelerator physics, isotope production, waste management and many more. In parallel, the maturity of modern general-purpose libraries such as TENDL-2012 encompassing thousands of target nuclides, the evolution of the ENDF format and the capabilities of the latest generation of processing codes PREPRO-2012, NJOY2012 and CALENDF-2010 have ...

  11. 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.

  12. Concurrent Validity of Preschooler Gross Motor Quality Scale with Test of Gross Motor Development-2

    Science.gov (United States)

    Sun, Shih-Heng; Sun, Hsiao-Ling; Zhu, Yi-Ching; Huang, Li-chi; Hsieh, Yueh-Ling

    2011-01-01

    Preschooler Gross Motor Quality Scale (PGMQ) was recently developed to evaluate motor skill quality of preschoolers. The purpose of this study was to establish the concurrent validity of PGMQ using Test of Gross Motor Development-2 (TGMD-2) as the gold standard. One hundred and thirty five preschool children aged from three to six years were…

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

    Science.gov (United States)

    Pahan, K; Khan, M; Singh, I

    1996-05-01

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

  14. Activation of retinoic acid receptor alpha is sufficient for full induction of retinoid responses in SK-BR-3 and T47D human breast cancer cells.

    Science.gov (United States)

    Schneider, S M; Offterdinger, M; Huber, H; Grunt, T W

    2000-10-01

    Retinoid signaling via retinoic acid (RA) and retinoid X receptors (RARs and RXRs) regulates mammary epithelial cell growth and differentiation. Loss of RAR-beta might represent an early event during breast carcinogenesis. Higher differentiated, estrogen-dependent, estrogen receptor (ER)-positive (ER+) mammary carcinoma cells have been found to contain relatively high levels of RAR-alpha and to be responsive to retinoids, whereas most undifferentiated, estrogen-independent, ER-negative (ER-) cells are characterized by low RAR-alpha expression and by retinoid resistance. In contrast, RAR-gamma is detectable at equal levels in both ER+ and ER- cells. In the present investigation, we directly examined the relative contribution of the distinct retinoid receptors to the retinoid response of breast cancer cells by comparing the effects of low concentrations of specific retinoids, which selectively activate individual receptor subtypes, on growth, cell cycle distribution, apoptosis, and on the autoregulation of RAR-alpha and RAR-gamma in ER- SK-BR-3 and ER+ T47D breast cancer cells. In vitro growth activity was determined by using a colorimetric cell viability assay and analysis of cell cycle distribution, and apoptosis was performed by flow cytometry of propidium iodide-stained or fluorescent Annexin V-labeled cells, respectively, whereas expression of RAR-alpha and RAR-gamma was determined by Northern blotting. Both cell lines are retinoid sensitive and express high amounts of RAR-alpha, RAR-gamma, and RXR-alpha. RAR-alpha-selective compounds (AM80 and AM580) inhibit cell growth, induce G1 arrest, stimulate apoptosis, and up-regulate RAR-alpha and RAR-gamma mRNA as efficiently as RAR/RXR-pan-reactive (9-cis RA) and RAR-pan-reactive retinoids (all-trans RA, TTNPB). Remarkably, an RAR-alpha antagonist (Ro 41-5253) not only blocks the RAR-alpha-selective agonists but also the pan-reactive compounds. In contrast, RAR-13-selective (CD417), RAR-gamma-selective (CD437/AHPN

  15. The response of cortical alpha activity to pain and neuromuscular changes caused by exercise-induced muscle damage.

    Science.gov (United States)

    Plattner, K; Lambert, M I; Tam, N; Baumeister, J

    2014-02-01

    Exercise-induced muscle damage (EIMD) is characterized by pain, swelling, and shortening of the muscle; increased serum creatine kinase; decreased force output; and altered neuromuscular function. The aim of this study was to investigate the effects of EIMD to determine the relationship between the peripheral symptoms, neuromuscular changes, and delayed pain sensation during a submaximal movement of the biceps brachii on cortical alpha (α) activity. In contrast to the control (n = 12) group, the experimental (n = 16) group participated in an EIMD protocol, and both groups were monitored for 132 h post-EIMD protocol. At 12 h, neuromuscular functioning was already disturbed while the sensation of pain was perceived, but not fully developed. Muscle pain scores in the experimental group peaked after 36 h with the lowest torque reported at 12 h. α-1 activity increased significantly in the motor and somatosensory area 12 h post-EIMD while α-2 activity increased in the contralateral fronto-central area. At 36 h, pain had further increased and neuromuscular function improved while α-1 and α-2 activities had decreased. We hypothesize that α-1 activity over the motor and somatosensory cortex of the experimental group displays a compensatory increase in response to the changes in neuromuscular function during movement, while an increase in α-2 activity is related to the suppression of pain experienced within the first 12 h.

  16. Ca2+/calmodulin-dependent kinase kinase alpha is expressed by monocytic cells and regulates the activation profile.

    Directory of Open Access Journals (Sweden)

    Christopher B Guest

    Full Text Available Macrophages are capable of assuming numerous phenotypes in order to adapt to endogenous and exogenous challenges but many of the factors that regulate this process are still unknown. We report that Ca(2+/calmodulin-dependent kinase kinase alpha (CaMKKalpha is expressed in human monocytic cells and demonstrate that its inhibition blocks type-II monocytic cell activation and promotes classical activation. Affinity chromatography with paramagnetic beads isolated an approximately 50 kDa protein from nuclear lysates of U937 human monocytic cells activated with phorbol-12-myristate-13-acetate (PMA. This protein was identified as CaMKKalpha by mass spectrometry and Western analysis. The function of CaMKKalpha in monocyte activation was examined using the CaMKKalpha inhibitors (STO-609 and forskolin and siRNA knockdown. Inhibition of CaMKKalpha, enhanced PMA-dependent CD86 expression and reduced CD11b expression. In addition, inhibition was associated with decreased translocation of CaMKKalpha to the nucleus. Finally, to further examine monocyte activation profiles, TNFalpha and IL-10 secretion were studied. CaMKKalpha inhibition attenuated PMA-dependent IL-10 production and enhanced TNFalpha production indicating a shift from type-II to classical monocyte activation. Taken together, these findings indicate an important new role for CaMKKalpha in the differentiation of monocytic cells.

  17. Phospholipase C Produced by Clostridium botulinum Types C and D:Comparison of Gene, Enzymatic, and Biological Activities with Those of Clostridium perfringens Alpha-toxin

    Directory of Open Access Journals (Sweden)

    Sakurai,Jun

    2013-02-01

    Full Text Available Clostridium botulinum type C and D strains recently have been found to produce PLC on egg yolk agar plates. To characterize the gene, enzymatic and biological activities of C. botulinum PLCs (Cb-PLCs, the cb-plc genes from 8 strains were sequenced, and 1 representative gene was cloned and expressed as a recombinant protein. The enzymatic and hemolytic activities of the recombinant Cb-PLC were measured and compared with those of the Clostridium perfringens alpha-toxin. Each of the eight cb-plc genes encoded a 399 amino acid residue protein preceded by a 27 residue signal peptide. The protein consists of 2 domains, the N- and C-domains, and the overall amino acid sequence identity between Cb-PLC and alpha-toxin was greater than 50%, suggesting that Cb-PLC is homologous to the alpha-toxin. The key residues in the N-domain were conserved, whereas those in the C-domain which are important in membrane interaction were different than in the alpha-toxin. As expected, Cb-PLC could hydrolyze egg yolk phospholipid, p-nitrophenylphosphorylcholine, and sphingomyelin, and also exhibited hemolytic activity;however, its activities were about 4- to over 200-fold lower than those of alpha-toxin. Although Cb-PLC showed weak enzymatic and biological activities, it is speculated that Cb-PLC might play a role in the pathogenicity of botulism or for bacterial survival.

  18. Phospholipase C produced by Clostridium botulinum types C and D: comparison of gene, enzymatic, and biological activities with those of Clostridium perfringens alpha-toxin.

    Science.gov (United States)

    Fatmawati, Ni Nengah Dwi; Sakaguchi, Yoshihiko; Suzuki, Tomonori; Oda, Masataka; Shimizu, Kenta; Yamamoto, Yumiko; Sakurai, Jun; Matsushita, Osamu; Oguma, Keiji

    2013-01-01

    Clostridium botulinum type C and D strains recently have been found to produce PLC on egg yolk agar plates. To characterize the gene, enzymatic and biological activities of C. botulinum PLCs (Cb-PLCs), the cb-plc genes from 8 strains were sequenced, and 1 representative gene was cloned and expressed as a recombinant protein. The enzymatic and hemolytic activities of the recombinant Cb-PLC were measured and compared with those of the Clostridium perfringens alpha-toxin. Each of the eight cb-plc genes encoded a 399 amino acid residue protein preceded by a 27 residue signal peptide. The protein consists of 2 domains, the N- and C-domains, and the overall amino acid sequence identity between Cb-PLC and alpha-toxin was greater than 50%, suggesting that Cb-PLC is homologous to the alpha-toxin. The key residues in the N-domain were conserved, whereas those in the C-domain which are important in membrane interaction were different than in the alpha-toxin. As expected, Cb-PLC could hydrolyze egg yolk phospholipid, p-nitrophenylphosphorylcholine, and sphingomyelin, and also exhibited hemolytic activity;however, its activities were about 4- to over 200-fold lower than those of alpha-toxin. Although Cb-PLC showed weak enzymatic and biological activities, it is speculated that Cb-PLC might play a role in the pathogenicity of botulism or for bacterial survival.

  19. [Topographic characteristics of cortex activity in delta-, alpha2-, and gamma2- frequency bands related to social creativity].

    Science.gov (United States)

    Razumnikova, O M; Finikov, S B

    2011-01-01

    Social creativity-related topographic changes of the delta, alpha2, and gamma2 power were studied using 19-channel EEG. Originality and fluency indices of social thinking were evaluated on basis of specially developed 'divergent' task solution that stimulated different interpretations of social scenes; complex visual stimuli (architectural building) were used as control task. 'Divergent' task performing was characterized by both the greater power of the delta and alpha2 rhythms mostly in the right hemisphere and widespread increase in the gamma2 power as compared with the control task. Positive correlations between delta and gamma2 rhythms in baseline condition were revealed in the fronto-parietal cortex, and this relationship between low- and high-frequency oscillations while 'divergent' task performing was found in the right posterior cortex. Special topographic patterns of delta and gamma2 activity as predictors of social creativity were obtained using multiple regression analysis. These patterns can be interpreted as EEG correlates of a summation of endogenous and exogenous components of social thinking.

  20. 7 CFR 1424.7 - Gross payable units.

    Science.gov (United States)

    2010-01-01

    ...) Biodiesel producers will be eligible for payments on gross payable units for all biodiesel production from... rates. Unless otherwise determined by CCC, gross payable units for biodiesel production from eligible... biodiesel production gross payable units. (3) Adding the APP and BPP to determine biodiesel gross...

  1. DMPD: Distinct functions of IRF-3 and IRF-7 in IFN-alpha gene regulation and controlof anti-tumor activity in primary macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16846591 Distinct functions of IRF-3 and IRF-7 in IFN-alpha gene regulation and controlof anti...Distinct functions of IRF-3 and IRF-7 in IFN-alpha gene regulation and controlof anti... IFN-alpha gene regulation and controlof anti-tumor activity in primary macrophages. Authors Solis M, Goubau

  2. Multiregional estimation of gross internal migration flows.

    Science.gov (United States)

    Foot, D K; Milne, W J

    1989-01-01

    "A multiregional model of gross internal migration flows is presented in this article. The interdependence of economic factors across all regions is recognized by imposing a non-stochastic adding-up constraint that requires total inmigration to equal total outmigration in each time period. An iterated system estimation technique is used to obtain asymptotically consistent and efficient parameter estimates. The model is estimated for gross migration flows among the Canadian provinces over the period 1962-86 and then is used to examine the likelihood of a wash-out effect in net migration models. The results indicate that previous approaches that use net migration equations may not always be empirically justified."

  3. The Gross conjecture over rational function fields

    Institute of Scientific and Technical Information of China (English)

    OUYANG; Yi

    2005-01-01

    We study the Gross conjecture for the cyclotomic function field extension k(∧f)/k where k = Fq(t) is the rational function field and f is a monic polynomial in Fq[t].We prove the conjecture in the Fermat curve case(i.e., when f = t(t - 1)) by a direct calculation. We also prove the case when f is irreducible, which is analogous to the Weil reciprocity law. In the general case, we manage to show the weak version of the Gross conjecture here.

  4. Activation of the FAK-src molecular scaffolds and p130Cas-JNK signaling cascades by alpha1-integrins during colon cancer cell invasion.

    Science.gov (United States)

    Van Slambrouck, Severine; Grijelmo, Clara; De Wever, Olivier; Bruyneel, Erik; Emami, Shahin; Gespach, Christian; Steelant, Wim F A

    2007-12-01

    Increased src tyrosine kinase expression and activity has been associated with colon cancer cell invasion and survival. Several signaling pathways are involved in the oncogenic activation of src during the adenoma to carcinoma progression and cellular invasion. In the present study, the synthetic ether lipid analog ET-18-OMe was shown to promote invasion of HCT-8/S11 colon cancer cells into collagen type I through the concomitant activation of src by phosphorylation at Tyr416 (5-30 min) in alpha1-integrin immunoprecipitates containing the integrin binding proteins talin and paxillin, as well as the phoshorylated and activated forms of focal adhesion kinase (FAK) at Tyr397 (a FAK kinase activation signal), Tyr576 and Tyr861. This was associated with the lateral redistribution of alpha1-integrins in focal aggregates and persistent activation of the p130Cas/JNK pathways at 5-30 min, with the subsequent induction and activation of the matrix metalloproteinases MMP-2 and MMP-9 (2-12 h). These activated molecular scaffolds and signaling cascades were not observed in immunoprecipitates of alpha2- and beta1-integrins, and tetraspanin CD9, an invasion and metastasis suppressor linked to integrins and FAK signaling. Our data demonstrate that the lateral redistribution and clustering of alpha1-integrins results in the recruitment of the FAK/src motility-promoting signaling complex involved in cancer cell invasion. Disruption of this proinvasive pathway was accomplished by the dominant negative mutant of src (K295R, kinase dead), src pharmacological inhibitor (PP1) and alpha1-integrin function blocking antibodies. These findings support the notion that the alpha1-integrin- and src-dependent signalosome is a relevant therapeutic target against tumor progression in colon cancer patients.

  5. 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-ter...... of neurons in the rat prefrontal cortex and this activation likely is important for the attentional effects of this new class of drugs.......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...

  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...

  7. Activity of alpha-fucosidase and beta-glucuronidase in serum and urine of patients administered parenteral nutrition.

    Science.gov (United States)

    Raczkowska, Katarzyna; Szajda, Slawomir Dariusz; Raczkowski, Krzysztof; Zasadowska, Wioletta; Chojnowska, Sylwia; Kepka, Alina; Zalewska-Szajda, Beata; Waszkiewicz, Napoleon; Knaś, Malgorzata; Snarska, Jadwiga; Zwierz, Krzysztof; Ladny, Jerzy Robert

    2013-01-01

    In hospital patients suffering from adverse clinical and biochemical symptoms of malnutrition, it is often necessary to employ parenteral nutrition to avoid the body's tissue becoming broken down by being metabolised. Thus, the patient's welfare and survival can be supported throughout any periods of medical crisis. Two of the enzymes responsible for metabolising glycoconjugates are alpha-fucosidase (FUC) and beta-glucuronidase (GLU), present in lysosomes. They release fucose or glucuronic acid from the non-reducing end of oligosaccharide chains. To determine the effect of parenteral nutrition administered to ill patients, on glycoconjugate metabolism, by measuring serum and urinary activities of FUC and GLU. Material and methods. Blood samples and the daily urine collection were taken from 23 patients' who had been undergoing parenteral nutrition for either 5 or 10 days, as well as from a baseline sample. Enzyme activities in serum and urine were determined by the method of Zwierz et al. Serum FUC activities were significantly lower after 10 days compared to 5, (p< 0.0172), whereas GLU activities were significantly lower after both 5 and 10 days, (p< 0.0007 and p< 0.0208 respectively), compared to levels before starting parenteral nutrition. GLU activities were however higher after 10 days than those after 5 days, (p< 0.0023). In urine, FUC activities were significantly decreased after 10 days compared to 5 days after starting parenteral nutrition, (p< 0.0245). Urine GLU activities were unaffected by parenteral nutrition nor was any effect seen on FUC or GLU activities when calculated per 1mg creatinine. Serum FUC and GLU activities can be used for assessing the effect of parenteral nutrition on glycoconjugate metabolism. The significant decreases of serum GLU activity observed after 5 and 10 days, may serve to indicate that the components of parental nutrition are appropriate and that the body has become suitably adapted to this form of nutrition.

  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. Neurophysiological Correlates of the Rubber Hand Illusion in Late Evoked and Alpha/Beta Band Activity

    Directory of Open Access Journals (Sweden)

    Isa S. Rao

    2017-07-01

    Full Text Available The rubber hand illusion (RHI allows insights into how the brain resolves conflicting multisensory information regarding body position and ownership. Previous neuroimaging studies have reported a variety of neurophysiological correlates of illusory hand ownership, with conflicting results likely originating from differences in experimental parameters and control conditions. Here, we overcome these limitations by using a fully automated and precisely-timed visuo-tactile stimulation setup to record evoked responses and oscillatory responses in participants who felt the RHI. Importantly, we relied on a combination of experimental conditions to rule out confounds of attention, body-stimulus position and stimulus duration and on the combination of two control conditions to identify neurophysiological correlates of illusory hand ownership. In two separate experiments we observed a consistent illusion-related attenuation of ERPs around 330 ms over frontocentral electrodes, as well as decreases of frontal alpha and beta power during the illusion that could not be attributed to changes in attention, body-stimulus position or stimulus duration. Our results reveal neural correlates of illusory hand ownership in late and likely higher-order rather than early sensory processes, and support a role of premotor and possibly intraparietal areas in mediating illusory body ownership.

  10. 1alpha(OH)D3 One-alpha-hydroxy-cholecalciferol--an active vitamin D analog. Clinical studies on prophylaxis and treatment of secondary hyperparathyroidism in uremic patients on chronic dialysis.

    Science.gov (United States)

    Brandi, Lisbet

    2008-11-01

    Chronic uremia is characterized by decreased levels of plasma 1,25(OH)2D3 due to decreased renal 1-hydroxylase activity and by decreased renal phosphate excretion. The consequence is an increased synthesis and secretion of parathyroid hormone--secondary hyperparathyroidism--due to the low levels of plasma calcium, low levels of plasma 1,25(OH)2D3 and high levels of phosphate. The association between renal bone disease and chronic renal failure is well described. Epidemiological studies have indicated that an association also exists between secondary hyperparathyroidism and increased mortality and cardiovascular calcifications in chronic uremic patients. Treatment of secondary hyperparathyroidism in chronic uremia focuses on avoiding hyperphosphatemia by the use of oral phosphate binders, which bind phosphate in the intestine and a concomitant substitution by a 1 alpha-hydroxylated vitamin D analog in order to compensate for the reduced renal hydroxylation. Additional treatment with aluminum containing phosphate binders to overcome phosphate absorption and retention was initiated already in the 1960s and used extensively until aluminum toxicity was disclosed in the mid-1980s. Instead calcium carbonate and calcium acetate were used as phosphate binders. Until recently, the most commonly used active vitamin D drug was either the natural 1,25(OH)2D3, or the 1 alpha-hydroxylated analog, 1alpha(OH)D3 which after 25-hydroxylation in the liver is converted to 1,25(OH)2D3. 1alpha(OH)D3 was produced by LEO Pharma in 1973. The two vitamin D analogs were used in different geographical areas: In Europe 1alpha(OH)D3 was mainly used, while 1,25(OH)2D3 was mainly used in the USA. 1,25(OH)2D3 increases the intestinal absorption of calcium and improves skeletal abnormalities. The combined treatment with calcium containing phosphate binders and active vitamin D induces an increase in plasma Ca 2+ and hypercalcemia became a clinical problem. Subsequently therefore, dialysis fluid with

  11. Measurement of alpha-amylase activity in white wheat flour, milled malt, and microbial enzyme preparations, using the Ceralpha assay: collaborative study.

    Science.gov (United States)

    McCleary, Barry V; McNally, Marian; Monaghan, Dympna; Mugford, David C

    2002-01-01

    This study was conducted to evaluate the method performance of a rapid procedure for the measurement of alpha-amylase activity in flours and microbial enzyme preparations. Samples were milled (if necessary) to pass a 0.5 mm sieve and then extracted with a buffer/salt solution, and the extracts were clarified and diluted. Aliquots of diluted extract (containing alpha-amylase) were incubated with substrate mixture under defined conditions of pH, temperature, and time. The substrate used was nonreducing end-blocked p-nitrophenyl maltoheptaoside (BPNPG7) in the presence of excess quantities of thermostable alpha-glucosidase. The blocking group in BPNPG7 prevents hydrolysis of this substrate by exo-acting enzymes such as amyloglucosidase, alpha-glucosidase, and beta-amylase. When the substrate is cleaved by endo-acting alpha-amylase, the nitrophenyl oligosaccharide is immediately and completely hydrolyzed to p-nitrophenol and free glucose by the excess quantities of alpha-glucosidase present in the substrate mixture. The reaction is terminated, and the phenolate color developed by the addition of an alkaline solution is measured at 400 nm. Amylase activity is expressed in terms of Ceralpha units; 1 unit is defined as the amount of enzyme required to release 1 micromol p-nitrophenyl (in the presence of excess quantities of alpha-glucosidase) in 1 min at 40 degrees C. In the present study, 15 laboratories analyzed 16 samples as blind duplicates. The analyzed samples were white wheat flour, white wheat flour to which fungal alpha-amylase had been added, milled malt, and fungal and bacterial enzyme preparations. Repeatability relative standard deviations ranged from 1.4 to 14.4%, and reproducibility relative standard deviations ranged from 5.0 to 16.7%.

  12. The integrin antagonist cilengitide activates alphaVbeta3, disrupts VE-cadherin localization at cell junctions and enhances permeability in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Gian Carlo Alghisi

    Full Text Available Cilengitide is a high-affinity cyclic pentapeptdic alphaV integrin antagonist previously reported to suppress angiogenesis by inducing anoikis of endothelial cells adhering through alphaVbeta3/alphaVbeta5 integrins. Angiogenic endothelial cells express multiple integrins, in particular those of the beta1 family, and little is known on the effect of cilengitide on endothelial cells expressing alphaVbeta3 but adhering through beta1 integrins. Through morphological, biochemical, pharmacological and functional approaches we investigated the effect of cilengitide on alphaVbeta3-expressing human umbilical vein endothelial cells (HUVEC cultured on the beta1 ligands fibronectin and collagen I. We show that cilengitide activated cell surface alphaVbeta3, stimulated phosphorylation of FAK (Y(397 and Y(576/577, Src (S(418 and VE-cadherin (Y(658 and Y(731, redistributed alphaVbeta3 at the cell periphery, caused disappearance of VE-cadherin from cellular junctions, increased the permeability of HUVEC monolayers and detached HUVEC adhering on low-density beta1 integrin ligands. Pharmacological inhibition of Src kinase activity fully prevented cilengitide-induced phosphorylation of Src, FAK and VE-cadherin, and redistribution of alphaVbeta3 and VE-cadherin and partially prevented increased permeability, but did not prevent HUVEC detachment from low-density matrices. Taken together, these observations reveal a previously unreported effect of cilengitide on endothelial cells namely its ability to elicit signaling events disrupting VE-cadherin localization at cellular contacts and to increase endothelial monolayer permeability. These effects are potentially relevant to the clinical use of cilengitide as anticancer agent.

  13. Interaction with extracellular matrix proteins influences Lsh/Ity/Bcg (candidate Nramp) gene regulation of macrophage priming/activation for tumour necrosis factor-alpha and nitrite release.

    Science.gov (United States)

    Formica, S; Roach, T I; Blackwell, J M

    1994-05-01

    The murine resistance gene Lsh/Ity/Bcg regulates activation of macrophages for tumour necrosis factor-alpha (TNF-alpha)-dependent production of nitric oxide mediating antimicrobial activity against Leishmania, Salmonella and Mycobacterium. As Lsh is differentially expressed in macrophages from different tissue sites, experiments were performed to determine whether interaction with extracellular matrix (ECM) proteins would influence the macrophage TNF-alpha response. Plating of bone marrow-derived macrophages onto purified fibrinogen or fibronectin-rich L929 cell-derived matrices, but not onto mannan, was itself sufficient to stimulate TNF-alpha release, with significantly higher levels released from congenic B10.L-Lshr compared to C57BL/10ScSn (Lshs) macrophages. Only macrophages plated onto fibrinogen also released measurable levels of nitrites, again higher in Lshr compared to Lshs macrophages. Addition of interferon-gamma (IFN-gamma), but not bacterial lipopolysaccharide or mycobacterial lipoarabinomannan, as a second signal enhanced the TNF-alpha and nitrite responses of macrophages plated onto fibrinogen, particularly in the Lshr macrophages. Interaction with fibrinogen and fibronectin also primed macrophages for an enhanced TNF-alpha response to leishmanial parasites, but this was only translated into enhanced nitrite responses in the presence of IFN-gamma. In these experiments, Lshr macrophages remained superior in their TNF-alpha responses throughout, but to a degree which reflected the magnitude of the difference observed on ECM alone. Hence, the specificity for the enhanced TNF-alpha responses of Lshr macrophages lay in their interaction with fibrinogen and fibronectin ECM, while a differential nitrite response was only observed with fibrinogen and/or IFN-gamma. The results are discussed in relation to the possible function of the recently cloned candidate gene Nramp, which has structural identity to eukaryote transporters and an N-terminal cytoplasmic

  14. Synthesis and biochemical studies of 7 alpha-substituted androsta-1,4-diene-3,17-diones as enzyme-activated irreversible inhibitors of aromatase.

    Science.gov (United States)

    Ebrahimian, S; Chen, H H; Brueggemeier, R W

    1993-09-01

    Several 7 alpha-thiosubstituted derivatives of androstenedione have demonstrated effective inhibition of aromatase, the cytochrome P450 enzyme complex responsible for the biosynthesis of estrogens. Introduction of an additional double bond in the A ring resulted in 7 alpha-(4'-amino)phenylthioandrosta-1,4-diene-3,17-dione (7 alpha-APTADD), a potent inhibitor that inactivated aromatase by an enzyme-catalyzed process. Additional 7 alpha-thiosubstituted androsta-1,4-diene-3,17-dione derivatives were designed to further examine enzyme-catalyzed inactivation. Two halogenated and one unsubstituted 7 alpha-phenylthioandrosta-1,4-diene-3,17-diones were synthesized via an acid-catalyzed conjugate Michael addition of substituted thiophenols with androsta-1,4,6-triene-3,17-dione. Two 7 alpha-naphthylthioandrosta-1,4-diene-3,17-diones were synthesized via either acid-catalyzed or based-catalyzed conjugate Michael addition of substituted thionaphthols with androsta-1,4,6-triene-3,17-dione. These agents were evaluated for aromatase inhibitory activity in the human placental microsomal preparation. Under initial velocity assay conditions of low product formation, the inhibitors demonstrated potent inhibition of aromatase, with apparent Ki's ranging from 12 to 27 nM. Furthermore, these compounds produced time-dependent, first-order inactivation of aromatase in the presence of NADPH, whereas no aromatase inactivation was observed in the absence of NADPH. This enzyme-activated irreversible inhibition, also referred to as mechanism-based inhibition, can be prevented by the substrate androstenedione. Thus, the apparent Ki values for these inhibitors are consistent with earlier studies on 7 alpha-substituted competitive inhibitors that indicate bulky substituents can be accommodated at the 7 alpha-position.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. The alpha(2)-adrenoceptors do not modify the activity of tyrosine hydroxylase, corticoliberine, and neuropeptide Y producing hypothalamic magnocellular neurons ion the Long Evans and Brattleboro rats

    DEFF Research Database (Denmark)

    Bundzikova, J; Pirnik, Z; Zelena, D

    2010-01-01

    The hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei are activated by body salt-fluid variations. Stimulation of alpha(2)-adrenoceptors by an agonist-xylazine (XYL) activates oxytocinergic but not vasopressinergic magnocellular neurons. In this study, tyrosine hydroxylase (TH), cort...

  16. Effects of budesonide on P38 MAPK activation, apoptosis and IL-8 secretion, induced by TNF-alpha and Haemophilus influenzae in human bronchial epithelial cells.

    Science.gov (United States)

    Gallelli, L; Pelaia, G; Fratto, D; Muto, V; Falcone, D; Vatrella, A; Curto, L S; Renda, T; Busceti, M T; Liberto, M C; Savino, R; Cazzola, M; Marsico, S A; Maselli, R

    2010-01-01

    Non-typeable Haemophilus influenzae (NTHi) is one of the most frequently involved pathogens in bacterial exacerbations of chronic obstructive pulmonary disease (COPD). In the airways, the main tissue target of NTHi is bronchial epithelium, where this pathogen can further amplify the inflammatory and structural changes induced by proinflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha). Therefore, the aim of this study is to investigate, in primary cultures of human bronchial epithelial cells, the effects of NTHi on signal transduction pathways, apoptotic events and chemokine production activated by TNF-alpha. Moreover, we also evaluated the effects exerted on such cellular and molecular phenomena by a corticosteroid drug. p38 mitogen-activated protein kinase (MAPK) phosphorylation was analyzed by Western blotting, using an anti-phospho-p38 MAPK monoclonal antibody. Apoptosis was assayed by active caspase-3 expression. Interleukin-8 (IL-8/CXCL8) was detected in cell-free culture supernatants by ELISA. TNF-alpha induced a significant increase in p38 MAPK phosphorylation. NTHi was able to potentiate the stimulatory actions of TNF-alpha on caspase-3 expression and, to a lesser extent, on IL-8 secretion. These effects were significantly (P less than 0.01) inhibited by a pharmacological pre-treatment with budesonide. These results suggest that TNF-alpha is able to stimulate, via activation of p38 MAPK signalling pathway, IL-8 release and airway epithelial cell apoptosis; the latter effect can be markedly potentiated by NTHi. Furthermore, budesonide can be very effective in preventing, through inhibition of p38 MAPK phosphorylation, both structural and proinflammatory changes elicited in bronchial epithelium by TNF-alpha and NTHi.

  17. Collagen I-induced dendritic cells activation is regulated by TNF-alpha production through down-regulation of IRF4.

    Science.gov (United States)

    Poudel, Barun; Ki, Hyeon-Hui; Lee, Young-Mi; Kim, Dae-Ki

    2015-03-01

    Previously we have shown that collagen I enhances the maturation and function of dendritic cells (DCs). Inflammatory mediators such as tumour necrosis factor (TNF)- alpha, interleukin (IL)-1 beta and lipopolysaccharide (LPS) are also known to activate DCs. Here we investigated the involvement of TNF-alpha on the collagen I-induced DCs activation. TNF-a neutralization inhibited collagen I-induced IL-12 secretions by DCs. Additionally, we observed suppression of collagen I-induced costimulatory molecules expression along with down-regulation of genes involved in DCs activation pathway. Furthermore, TNF- alpha inhibition upon collagen Istimulation up-regulated the expression of interferon regulatory transcription factor IRF4, when compared to collagen I only treated cells. Collectively, our data demonstrate that collagen I induce TNF- alpha production, which is crucial for the activation and function of DCs, through down-regulation of IRF4, and implicates the importance in development of anti- TNF-alpha therapeutics for several inflammatory diseases.

  18. Gross Revenue risk in Swiss dairy farming

    NARCIS (Netherlands)

    Benni, El N.; Finger, R.

    2013-01-01

    This study investigated how agricultural policy reforms, including market liberalization and market deregulation, have influenced gross revenue risk of Swiss dairy producers using farm-level panel data between 1990 and 2009. Based on detrended data, variance decomposition was applied to assess how o

  19. Gross Revenue risk in Swiss dairy farming

    NARCIS (Netherlands)

    Benni, El N.; Finger, R.

    2013-01-01

    This study investigated how agricultural policy reforms, including market liberalization and market deregulation, have influenced gross revenue risk of Swiss dairy producers using farm-level panel data between 1990 and 2009. Based on detrended data, variance decomposition was applied to assess how

  20. 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

    We tested the hypothesis that 5'AMP-activated protein kinase (AMPK) plays an important role in regulating the acute, exercise-induced activation of metabolic genes in skeletal muscle, which were dissected from whole-body a2- and a1-AMPK knockout (KO) and wild-type (WT) mice at rest, after treadmi...

  1. 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.

  2. The peroxisome proliferator-activated receptor alpha regulates amino acid metabolism

    NARCIS (Netherlands)

    Kersten, S.; Mandard, S.; Escher, P.; Gonzalez, F.J.; Tafuri, S.; Desvergne, B.; Wahli, W.

    2001-01-01

    The peroxisome proliferator-activated receptor is a ligand-activated transcription factor that plays an important role in the regulation of lipid homeostasis. PPAR mediates the effects of fibrates, which are potent hypolipidemic drugs, on gene expression. To better understand the biological effects

  3. Cytotoxic activity of interferon alpha induced dendritic cells as a biomarker of glioblastoma

    Science.gov (United States)

    Mishinov, S. V.; Stupak, V. V.; Tyrinova, T. V.; Leplina, O. Yu.; Ostanin, A. A.; Chernykh, E. R.

    2016-08-01

    Dendritic cells (DCs) are the most potent antigen presenting cells that can play direct role in anti-tumor immune response as killer cells. DC tumoricidal activity can be stimulated greatly by type I IFN (IFNα and IFNβ). In the present study, we examined cytostatic and cytotoxic activity of monocyte-derived IFNα-induced DCs generated from patients with brain glioma and evaluated the potential use of these parameters in diagnostics of high-grade gliomas. Herein, we demonstrated that patient DCs do not possess the ability to inhibit the growth of tumor HEp-2 cell line but low-grade and high-grade glioma patients do not differ significantly in DC cytostatic activity. However, glioma patient DCs are characterized by reduced cytotoxic activity against HEp-2 cells. The impairment of DC cytotoxic function is observed mainly in glioblastoma patients. The cytotoxic activity of DCs against HEp-2 cells below 9% is an informative marker for glioblastomas.

  4. Growth hormone regulation of p85alpha expression and phosphoinositide 3-kinase activity in adipose tissue: mechanism for growth hormone-mediated insulin resistance.

    Science.gov (United States)

    del Rincon, Juan-Pablo; Iida, Keiji; Gaylinn, Bruce D; McCurdy, Carrie E; Leitner, J Wayne; Barbour, Linda A; Kopchick, John J; Friedman, Jacob E; Draznin, Boris; Thorner, Michael O

    2007-06-01

    Phosphoinositide (PI) 3-kinase is involved in insulin-mediated effects on glucose uptake, lipid deposition, and adiponectin secretion from adipocytes. Genetic disruption of the p85alpha regulatory subunit of PI 3-kinase increases insulin sensitivity, whereas elevated p85alpha levels are associated with insulin resistance through PI 3-kinase-dependent and -independent mechanisms. Adipose tissue plays a critical role in the antagonistic effects of growth hormone (GH) on insulin actions on carbohydrate and lipid metabolism through changes in gene transcription. The objective of this study was to assess the role of the p85alpha subunit of PI 3-kinase and PI 3-kinase signaling in GH-mediated insulin resistance in adipose tissue. To do this, p85alpha mRNA and protein expression and insulin receptor substrate (IRS)-1-associated PI 3-kinase activity were measured in white adipose tissue (WAT) of mice with GH excess, deficiency, and sufficiency. Additional studies using 3T3-F442A cells were conducted to confirm direct effects of GH on free p85alpha protein abundance. We found that p85alpha expression 1) is decreased in WAT from mice with isolated GH deficiency, 2) is increased in WAT from mice with chronic GH excess, 3) is acutely upregulated in WAT from GH-deficient and -sufficient mice after GH administration, and 4) is directly upregulated by GH in 3T3-F442A adipocytes. The insulin-induced increase in PI 3-kinase activity was robust in mice with GH deficiency, but not in mice with GH excess. In conclusion, GH regulates p85alpha expression and PI 3-kinase activity in WAT and provides a potential explanation for 1) the insulin hypersensitivity and associated obesity and hyperadiponectinemia of GH-deficient mice and 2) the insulin resistance and associated reduced fat mass and hypoadiponectinemia of mice with GH excess.

  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. Evolution and Activity in the Solar Corona: A Comparison of Coronal and Chromospheric Structures Seen in Soft X-Rays, White Light and H-Alpha Emission

    Science.gov (United States)

    Bagenal, Fran

    2001-01-01

    The work completed under this project, 'Evolution and Activity in the Solar Corona: A Comparison of Coronal and Chromospheric Structures Seen in Soft X-Rays, White Light and H-Alpha Emission', includes the following presentations: (1) Analysis of H-alpha Observations of High-altitude Coronal Condensations; (2) Multi-spectral Imaging of Coronal Activity; (3) Measurement and Modeling of Soft X-ray Loop Arcades; (4) A Study of the Origin and Dynamics of CMEs; and various poster presentations and thesis dissertations.

  7. Alpha-Pinene as the Main Component of Ducrosia anethifolia (Boiss Essential Oil is Responsible for its Effect on Locomotor Activity in Rats

    Directory of Open Access Journals (Sweden)

    Zamyad

    2016-05-01

    Full Text Available Background Ducrosia anethifolia (DA is a medicinal plant traditionally used to treat a wide spectrum of illnesses. DA contains a series of antioxidant compounds, including alpha-pinene, which give it a sedative and relaxing effect. In spite of these effects of DA, the effects of DA essential oil on anxiety and locomotor activity in open field tests have not yet been studied. In the present study, the effects of DA essential oil and its main component of alpha-pinene on locomotor activity and anxiety were studied using open field tests. Objectives The purpose of this study was to investigate the effects of DA essential oil and its main component, alpha-pinene, on locomotor activity and anxiety behaviors using open field and antioxidant capacity tests in Wistar rats. Methods Sixty-three adult male Wistar rats (weighing 200 - 250 g were divided into 9 groups: control, positive control (diazepam, essential oil treated groups (25, 50, 100, 200, and 500 mg/kg administered intraperitoneally, (i.p. and alpha-pinene groups (0.2 and 0.4 mg/kg, i.p.. For precisely 30 minutes after each injection in all groups, open field tests were used to assess behaviors such as rearing, line crossing, walling, grooming, and stretched attend posturing. In addition, oxidant and antioxidant parameters (malondialdehyde [MDA] and catalase [CAT] were assessed in the rats’ temporal lobes. Results DA (200 and 500 mg/kg doses and alpha-pinene (0.2 and 0.4 mg/kg doses significantly reduced locomotor activity, whereas doses of 25, 50, and 100 mg/kg of DA failed to show such an effect. Treatment with DA and alpha-pinene resulted in a significant decrease in MDA levels and a significant increase in CAT activity in comparison to controls. Conclusions The results of this study suggest that the main component of DA (alpha-pinene is responsible for DA’s ability to reduce locomotor activity and anxiety, which is indicative of CNS depressant activity. Moreover, it is possible that

  8. Feasibility studies for assaying alpha-fetoprotein using antibody-activated magnetic nanoparticles

    Directory of Open Access Journals (Sweden)

    Huang KW

    2012-04-01

    Full Text Available Kai-Wen Huang1, Shieh-Yueh Yang2,3, Yu-Wei Hong3, Jen-Jie Chieh3, Che-Chuan Yang3, Herng-Er Horng3, Chau-Chung Wu4, Chin-Yih Hong5, Hong-Chang Yang61Department of Surgery and Hepatitis Research Center, National Taiwan University Hospital, National Taiwan University, Taipei, 2MagQu Co, Ltd, Sindian Dist, New Taipei City, 3Institute of Electro-optical Science and Technology, National Taiwan Normal University, Taipei, 4Departments of Internal Medicine and Primary Care Medicine, College of Medicine, National Taiwan University, Taipei, 5Graduate Institute of Bio-medical Engineering, National Chung Hsing University, Taichung, 6Department of Physics, National Taiwan University, Taipei, TaiwanAbstract: Some previous reports have already shown the characterizations of immunomagnetic reduction (IMR. The assay technology involves the utilities of biofunctionalized magnetic nanoparticles to label target biomolecules. However, the detection threshold and interference tests for IMR have not been investigated in detail. In this study, alpha-fetoprotein (AFP was used as a target biomolecule. The signals for AFP solutions of various concentrations, or with interfering materials, were detected via IMR. These samples were also used for characterizing the detection threshold and interference with enzyme-linked immunosorbent assay (ELISA. The results of assaying AFP level with IMR and ELISA were compared. The detection threshold for assaying AFP with IMR was found to be 3 ng/mL, which is 15 times lower than that of ELISA, and definitely suppresses false negative. For the interfering materials noted commonly in serum such as hemoglobin, bilirubin, triglyceride, and vascular endothelial growth factor, there was no detectable interfering effect when assaying AFP with IMR. Several serum samples from normal people and liver-tumor-bearing patients were used for the detections of AFP concentration via IMR. These results reveal the feasibilities of assaying AFP in blood

  9. Salivary Alpha Amylase Activity in Human Beings of Different Age Groups Subjected to Psychological Stress

    National Research Council Canada - National Science Library

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

    2014-01-01

    ... 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...

  10. 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

    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......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......-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....

  11. Receptor Density Is Key to the Alpha2/Beta Interferon Differential Activities

    OpenAIRE

    Moraga, I.; Harari, D.; Schreiber, G.; Uze, G.; Pellegrini, S.

    2009-01-01

    Multiple type I interferons (IFN-α/β) elicit Jak/Stat activation, rapid gene induction, and pleiotropic effects, such as differentiation, antiviral protection, and blocks in proliferation, which are dependent on the IFN subtype and the cellular context. To date, ligand- and receptor-specific molecular determinants underlying IFN-α/β differential activities or potencies have been well characterized. To analyze cellular determinants that impact subtype-specific potency, human fibrosarcoma U5A-d...

  12. Relationship of changing delta 4-steroid 5 alpha-reductase activity to (125I)iododeoxyuridine uptake during regeneration of involuted rat prostates

    Energy Technology Data Exchange (ETDEWEB)

    Kitahara, S.; Higashi, Y.; Takeuchi, S.; Oshima, H. (Tokyo Medical and Dental Univ. (Japan))

    1989-04-01

    To elucidate the phenotypic expression of proliferating prostatic cells, rats were castrated, and the regenerating process of involuted ventral prostates during testosterone propionate (TP) administration was investigated by examining morphology, (5-{sup 125}I)iododeoxyuridine ({sup 125}I-UdR) uptake, DNA content, weight, acid phosphatase, and delta 4-steroid 5 alpha-reductase (5 alpha-reductase) activities. Morphologically, TP treatment initially increased the number of epithelial cells lining glandular lobules and subsequently restored the shape of epithelial cells. {sup 125}I-UdR uptake peaked on Day 3 of TP treatment and stayed at higher levels than for uncastrated controls until Day 14 of treatment. Prostatic weight, protein content, acid phosphatase, and DNA content returned to uncastrated control levels by Day 14 of TP treatment. TP administration markedly stimulated prostatic 5 alpha-reductase activity, which peaked on the Day 5 of treatment and decreased to uncastrated control levels by Day 14 of treatment. It is concluded that TP administration to castrated rats initially induced active mitotic division of the remaining stem cells, followed by formation of differentiated functional epithelial cells. Prostatic 5 alpha-reductase was highly active at the initial phase of active mitotic cell division. The major portion of the increased enzyme activity can be regarded as a phenotypic expression of stem or transient cells of prostatic epithelium.

  13. Glucose decouples intracellular Ca2+ activity from glucagon secretion in mouse pancreatic islet alpha-cells.

    Directory of Open Access Journals (Sweden)

    Sylvain J Le Marchand

    Full Text Available The mechanisms of glucagon secretion and its suppression by glucose are presently unknown. This study investigates the relationship between intracellular calcium levels ([Ca(2+](i and hormone secretion under low and high glucose conditions. We examined the effects of modulating ion channel activities on [Ca(2+](i and hormone secretion from ex vivo mouse pancreatic islets. Glucagon-secreting α-cells were unambiguously identified by cell specific expression of fluorescent proteins. We found that activation of L-type voltage-gated calcium channels is critical for α-cell calcium oscillations and glucagon secretion at low glucose levels. Calcium channel activation depends on K(ATP channel activity but not on tetrodotoxin-sensitive Na(+ channels. The use of glucagon secretagogues reveals a positive correlation between α-cell [Ca(2+](i and secretion at low glucose levels. Glucose elevation suppresses glucagon secretion even after treatment with secretagogues. Importantly, this inhibition is not mediated by K(ATP channel activity or reduction in α-cell [Ca(2+](i. Our results demonstrate that glucose uncouples the positive relationship between [Ca(2+](i and secretory activity. We conclude that glucose suppression of glucagon secretion is not mediated by inactivation of calcium channels, but instead, it requires a calcium-independent inhibitory pathway.

  14. Interferon-alpha administration enhances CD8+ T cell activation in HIV infection.

    Directory of Open Access Journals (Sweden)

    Maura Manion

    Full Text Available BACKGROUND: Type I interferons play important roles in innate immune defense. In HIV infection, type I interferons may delay disease progression by inhibiting viral replication while at the same time accelerating disease progression by contributing to chronic immune activation. METHODS: To investigate the effects of type I interferons in HIV-infection, we obtained cryopreserved peripheral blood mononuclear cell samples from 10 subjects who participated in AIDS Clinical Trials Group Study 5192, a trial investigating the activity of systemic administration of IFNα for twelve weeks to patients with untreated HIV infection. Using flow cytometry, we examined changes in cell cycle status and expression of activation antigens by circulating T cells and their maturation subsets before, during and after IFNα treatment. RESULTS: The proportion of CD38+HLA-DR+CD8+ T cells increased from a mean of 11.7% at baseline to 24.1% after twelve weeks of interferon treatment (p = 0.006. These frequencies dropped to an average of 20.1% six weeks after the end of treatment. In contrast to CD8+ T cells, the frequencies of activated CD4+ T cells did not change with administration of type I interferon (mean percentage of CD38+DR+ cells = 2.62% at baseline and 2.17% after 12 weeks of interferon therapy. As plasma HIV levels fell with interferon therapy, this was correlated with a "paradoxical" increase in CD8+ T cell activation (p<0.001. CONCLUSION: Administration of type I interferon increased expression of the activation markers CD38 and HLA DR on CD8+ T cells but not on CD4+ T cells of HIV+ persons. These observations suggest that type I interferons may contribute to the high levels of CD8+ T cell activation that occur during HIV infection.

  15. Evidence for the presence of both peroxisome proliferator-activated receptors alpha and beta in the rat spinal cord.

    Science.gov (United States)

    Benani, A; Krémarik-Bouillaud, P; Bianchi, A; Netter, P; Minn, A; Dauça, M

    2003-01-01

    Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily. Different subtypes of PPARs (alpha, beta, and gamma) have been described. Their distinct physiological functions depend on their differential ligand activation profiles but also on their specific tissue expression. Previous studies have described their presence in the central nervous system. However, their expression in the adult rat spinal cord in normal physiological conditions has never been investigated. We demonstrated by using reverse-transcription-polymerase chain reaction, and Western blotting, the mRNA and protein expression of PPARalpha and PPARbeta, but not PPARgamma in cervical, thoracic, and lumbar segments of the spinal cord. Using immunohistochemistry, we also showed for the first time the specific cellular distribution of these transcription factors in the different segments of the spinal cord. In the gray matter, the distribution of PPARalpha was homogenous whereas PPARbeta was specifically localized in motoneurons and in medial part of laminae IV, V, VI, VII, VIII, and X. These latter areas are known as nociceptive afferent pathways to supra-spinal structures such as the medulla reticular nucleus and the thalamus. In the white matter, PPARalpha was localized exclusively in astrocytes while PPARbeta was present in oligodendrocytes. The possible functions of PPARalpha and PPARbeta expressed in both white and gray matters of the spinal cord will be discussed but need further studies.

  16. TNF-alpha: an activator of CD4+FoxP3+TNFR2+ regulatory T cells.

    Science.gov (United States)

    Chen, Xin; Oppenheim, Joost J

    2010-01-01

    TNF-alpha (TNF) is a pleiotropic cytokine which can have proinflammatory or immunosuppressive effects, depending on the context, duration of exposure and disease state. The basis for the opposing actions of TNF remains elusive. The growing appreciation of CD4+FoxP3+ regulatory T cells (Tregs), which comprise approximately 10% of peripheral CD4 cells, as pivotal regulators of immune responses has provided a new framework to define the cellular and molecular basis underlying the contrasting action of TNF. TNF by itself can overcome the profound anergic state of T cell receptor-stimulated Tregs. Furthermore, in concert with IL-2, TNF selectively activates Tregs, resulting in proliferation, upregulation of FoxP3 expression and increases in their suppressive activity. Both human and mouse Tregs predominantly express TNFR2, making it possible for TNF to enhance Treg activity, which helps limit the collateral damage caused by excessive immune responses and eventually terminates immune response. TNFR2-expressing CD4+FoxP3+ Tregs comprise approximately 40% of peripheral Tregs in normal mice and present the maximally suppressive subset of Tregs. In this review, studies describing the action of TNF on Treg function will be discussed. The role of Tregs in the autoimmune disorders and cancer as well as the effect of anti-TNF therapy on Tregs, especially in rheumatoid arthritis, will also be considered. Copyright (c) 2010 S. Karger AG, Basel.

  17. 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 planchett