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Sample records for alpha selectively activates

  1. 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. 

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-01-01

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

  3. 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

    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...... regions critically involved in working memory and attention. Furthermore, this effect is more pronounced in juvenile than adult rats, indicating that the juvenile forebrain is more responsive to alpha7 nAChR stimulation. This observation may be relevant in the treatment of juvenile-onset schizophrenia....

  4. Bi209 alpha activity

    International Nuclear Information System (INIS)

    Araujo Penna, M.M. de.

    1970-01-01

    The study for measuring Bi 209 alpha activity is presented. Ilford L4 nuclear emulsion pellicles loaded with bismuth citrate to obtain a load of 100 mg/cm 3 of dry emulsion, were prepared. Other pellicles were prepared with the same. Ilford L4 gel to estimate the background radiation. To observe 'fading' effect, pellicles loaded with bismuth were submitted to neutrons of high energy, aiming to record recoil proton tracks. The pellicles were confined in nitrogen atmosphere at temperature lower than -10 0 C. The Bi 209 experimental half-life was obtained and compared with the estimated theoretical data. (M.C.K.) [pt

  5. Acute lymphoid and gastrointestinal toxicity induced by selective p38alpha map kinase and map kinase-activated protein kinase-2 (MK2) inhibitors in the dog.

    Science.gov (United States)

    Morris, Dale L; O'Neil, Shawn P; Devraj, Rajesh V; Portanova, Joseph P; Gilles, Richard W; Gross, Cindy J; Curtiss, Sandra W; Komocsar, Wendy J; Garner, Debra S; Happa, Fernando A; Kraus, Lori J; Nikula, Kristen J; Monahan, Joseph B; Selness, Shaun R; Galluppi, Gerald R; Shevlin, Kimberly M; Kramer, Jeffrey A; Walker, John K; Messing, Dean M; Anderson, David R; Mourey, Robert J; Whiteley, Laurence O; Daniels, John S; Yang, Jerry Z; Rowlands, Philip C; Alden, Carl L; Davis, John W; Sagartz, John E

    2010-06-01

    Exposure to moderately selective p38alpha mitogen-activated protein kinase (MAPK) inhibitors in the Beagle dog results in an acute toxicity consisting of mild clinical signs (decreased activity, diarrhea, and fever), lymphoid necrosis and depletion in the gut-associated lymphoid tissue (GALT), mesenteric lymph nodes and spleen, and linear colonic and cecal mucosal hemorrhages. Lymphocyte apoptosis and necrosis in the GALT is the earliest and most prominent histopathologic change observed, followed temporally by neutrophilic infiltration and acute inflammation of the lymph nodes and spleen and multifocal mucosal epithelial necrosis and linear hemorrhages in the colon and cecum. These effects are not observed in the mouse, rat, or cynomolgus monkey. To further characterize the acute toxicity in the dog, a series of in vivo, in vitro, and immunohistochemical studies were conducted to determine the relationship between the lymphoid and gastrointestinal (GI) toxicity and p38 MAPK inhibition. Results of these studies demonstrate a direct correlation between p38alpha MAPK inhibition and the acute lymphoid and gastrointestinal toxicity in the dog. Similar effects were observed following exposure to inhibitors of MAPK-activated protein kinase-2 (MK2), further implicating the role of p38alpha MAPK signaling pathway inhibition in these effects. Based on these findings, the authors conclude that p38alpha MAPK inhibition results in acute lymphoid and GI toxicity in the dog and is unique among the species evaluated in these studies.

  6. Selective inhibition of sheep kidney 11 beta-hydroxysteroid dehydrogenase isoform 2 activity by 5 alpha-reduced (but not 5 beta) derivatives of adrenocorticosteroids.

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    Latif, S A; Sheff, M F; Ribeiro, C E; Morris, D J

    1997-02-01

    We have previously reported that 5 alpha and 5 beta pathways of steroid metabolism are controlled in vivo by dietary Na+ and glycyrrhetinic acid, see Gorsline et al. 1988; Latif et al. 1990. The present investigations provide evidence supporting the suggestion that endogenous substances may regulate the glucocorticoid inactivating isoenzymes, 11 beta-HSD (hydroxysteroid dehydrogenase) 1 (liver) and 11 beta-HSD2 (kidney). The activity of 11 beta-HSD is impaired in essential hypertension, following licorice ingestion, and in patients with apparent mineralocorticoid excess where 11 beta-HSD2 is particularly affected. In all three conditions, excretion of the less common 5 alpha metabolites is elevated in urine. We now report on the differential abilities of a series of Ring A reduced (5 alpha and 5 beta) adrenocorticosteroid and progesterone metabolites to inhibit these isoenzymes. Using liver microsomes with NADP+ as co-factor (11 beta-HSD1), and sheep kidney microsomes with NAD+ as co-factor (11 beta-HSD2), we have systematically investigated the abilities of a number of adrenocorticosteroids and their derivatives to inhibit the individual isoforms of 11 beta-HSD. A striking feature is the differential sensitivity of the two isoenzymes to inhibition by 5 alpha and 5 beta derivatives. 11 beta-HSD1 is inhibited by both 5 alpha and certain 5 beta derivatives. 11 beta-HSD-2 was selectively inhibited only by 5 alpha derivatives: 5 beta derivatives were without inhibitory activity toward this isoform of 11 beta-HSD. These results indicate the importance of the structural conformation of the A and B Rings in conferring specific inhibitory properties on these compounds. In addition, we discuss the effects of additions or substitutions of other functional groups on the inhibitory potency of these steroid molecules against 11 beta-HSD1 and 11 beta-HSD2.

  7. Resting alpha activity predicts learning ability in alpha neurofeedback

    Directory of Open Access Journals (Sweden)

    Wenya eNan

    2014-07-01

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

  8. S100A7, a novel Alzheimer's disease biomarker with non-amyloidogenic alpha-secretase activity acts via selective promotion of ADAM-10.

    Directory of Open Access Journals (Sweden)

    Weiping Qin

    Full Text Available Alzheimer's disease (AD is the most common cause of dementia among older people. At present, there is no cure for the disease and as of now there are no early diagnostic tests for AD. There is an urgency to develop a novel promising biomarker for early diagnosis of AD. Using surface-enhanced laser desorption ionization-mass spectrometry SELDI-(MS proteomic technology, we identified and purified a novel 11.7-kDa metal- binding protein biomarker whose content is increased in the cerebrospinal fluid (CSF and in the brain of AD dementia subjects as a function of clinical dementia. Following purification and protein-sequence analysis, we identified and classified this biomarker as S100A7, a protein known to be involved in immune responses. Using an adenoviral-S100A7 expression system, we continued to examine the potential role of S100A7 in AD amyloid neuropathology in in vitro model of AD. We found that the expression of exogenous S100A7 in primary cortico-hippocampal neuron cultures derived from Tg2576 transgenic embryos inhibits the generation of beta-amyloid (Abeta(1-42 and Abeta(1-40 peptides, coincidental with a selective promotion of "non- amyloidogenic" alpha-secretase activity via promotion of ADAM (a disintegrin and metalloproteinase-10. Finally, a selective expression of human S100A7 in the brain of transgenic mice results in significant promotion of alpha-secretase activity. Our study for the first time suggests that S100A7 may be a novel biomarker of AD dementia and supports the hypothesis that promotion of S100A7 expression in the brain may selectively promote alpha-secretase activity in the brain of AD precluding the generation of amyloidogenic peptides. If in the future we find that S1000A7 protein content in CSF is sensitive to drug intervention experimentally and eventually in the clinical setting, S100A7 might be developed as novel surrogate index (biomarker of therapeutic efficacy in the characterization of novel drug agents for

  9. 3-[2,4-Dimethoxybenzylidene]anabaseine (DMXB) selectively activates rat alpha7 receptors and improves memory-related behaviors in a mecamylamine-sensitive manner.

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    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.

  10. Anticonvulsant activity of a mGlu(4alpha) receptor selective agonist, (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid.

    Science.gov (United States)

    Chapman, A G; Talebi, A; Yip, P K; Meldrum, B S

    2001-07-20

    The metabotropic Group III agonist, (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid (ACPT-1), selective for the mGlu(4alpha) receptor, suppresses sound-induced seizures in DBA/2 mice following its intracerebroventricular (i.c.v.) administration (ED(50) 5.6 [2.9-10.7], nmol i.c.v., 15 min, clonic phase) and in genetically epilepsy-prone (GEP) rats following focal administration into the inferior colliculus (ED(50) 0.08 [0.01-0.50], nmol, 60 min, clonic phase). ACPT-1 also protects against clonic seizures induced in DBA/2 mice by the Group I agonist, (RS)-3,5-dihydroxyphenylglycine (3,5-DHPG) (ED(50) 0.60 [0.29-1.2], nmol i.c.v.) and by the Group III antagonist, (RS)-alpha-methylserine-O-phosphate (MSOP) (ED(50) 49.3 [37.9-64.1], nmol i.c.v.). Another Group III agonist, (RS)-4-phosphonophenyl-glycine (PPG), preferentially activating the mGlu(8) receptor, previously shown to protect against sound-induced seizures in DBA/2 mice and GEP rats, also protects against seizures induced in DBA/2 by 3,5-DHPG (ED(50) 3.7 [2.4-5.7], nmol i.c.v.) and by the Group III antagonist, MSOP (ED(50) 40.2 [21.0-77.0], nmol i.c.v.). At very high doses (500 nmol i.c.v. and above), Group III antagonists have pro-convulsant and convulsant activity. The anticonvulsant protection against sound-induced seizures in DBA/2 mice provided by a fully protective dose (20 nmol, i.c.v.) of the mGlu(4) receptor agonist ACPT-1, is partially reversed by the co-administration of the Group III antagonists, MSOP, (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG) or (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP4), in the 20-50 nmol dose range. At doses of 50-200 nmol, MPPG and MAP4 cause further reversal of the ACPT-1 anticonvulsant protection, while the MSOP effect on ACPT-1 protection is abolished at higher doses. In contrast, the anticonvulsant protection against sound-induced seizures in DBA/2 mice provided by a fully protective dose (20 nmol, i.c.v.) of the mGlu(8) receptor agonist PPG, is not

  11. The importance of ignoring: Alpha oscillations protect selectivity.

    Science.gov (United States)

    Payne, Lisa; Sekuler, Robert

    2014-06-01

    Selective attention is often thought to entail an enhancement of some task-relevant stimulus or attribute. We discuss the perspective that ignoring irrelevant, distracting information plays a complementary role in information processing. Cortical oscillations within the alpha (8-14 Hz) frequency band have emerged as a marker of sensory suppression. This suppression is linked to selective attention for visual, auditory, somatic, and verbal stimuli. Inhibiting processing of irrelevant input makes responses more accurate and timely. It also helps protect material held in short-term memory against disruption. Furthermore, this selective process keeps irrelevant information from distorting the fidelity of memories. Memory is only as good as the perceptual representations on which it is based, and on whose maintenance it depends. Modulation of alpha oscillations can be exploited as an active, purposeful mechanism to help people pay attention and remember the things that matter.

  12. Naturally-occurring alpha activity

    Energy Technology Data Exchange (ETDEWEB)

    Mayneord, W V

    1960-12-01

    In view of the difficulties of assessing the significance of man-made radioactivity it is important to study for comparison the background of natural radioactivity against which the human race has evolved and lives. It is also important to define the present levels of activity so that it will be possible to detect and study as quickly as possible any changes which may occur owing to the release into the environment of new radioactive materials. Moreover, by the study of the behaviour of natural radioactivity light may be shed upon that of the artificially produced isotopes and a number of analogies traced between the two groups. These concepts have led to studies of naturally-occurring radioactive materials alongside a programme of research into fission products in food, water and air, as well as studies of the metabolism of both sets of materials in the human body. Since the last report there has been a useful increase in our knowledge of natural radioactivity in the biosphere, and its levels relative to the new man-made activities. These studies have necessitated technical developments, particularly in the methods of measuring and identifying alpha-ray emitters, to which group many of the more important natural radioactive materials belong.

  13. Cortical Alpha Activity in Schizoaffective Patients.

    Science.gov (United States)

    Moeini, Mahdi; Khaleghi, Ali; Mohammadi, Mohammad Reza; Zarafshan, Hadi; Fazio, Rachel L; Majidi, Hamid

    2017-01-01

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

  14. Coefficient alpha and interculture test selection.

    Science.gov (United States)

    Thurber, Steven; Kishi, Yasuhiro

    2014-04-01

    The internal consistency reliability of a measure can be a focal point in an evaluation of the potential adequacy of an instrument for adaptation to another cultural setting. Cronbach's alpha (α) coefficient is often used as the statistical index for such a determination. However, alpha presumes a tau-equivalent test and may constitute an inaccurate population estimate for multidimensional tests. These notions are expanded and examined with a Japanese version of a questionnaire on nursing attitudes toward suicidal patients, originally constructed in Sweden using the English language. The English measure was reported to have acceptable internal consistency (α) albeit the dimensionality of the questionnaire was not addressed. The Japanese scale was found to lack tau-equivalence. An alternative to alpha, "composite reliability," was computed and found to be below acceptable standards in magnitude and precision. Implications for research application of the Japanese instrument are discussed. © The Author(s) 2012.

  15. The selective alpha7 nicotinic acetylcholine receptor agonist PNU-282987 [N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride] enhances GABAergic synaptic activity in brain slices and restores auditory gating deficits in anesthetized rats.

    Science.gov (United States)

    Hajós, M; Hurst, R S; Hoffmann, W E; Krause, M; Wall, T M; Higdon, N R; Groppi, V E

    2005-03-01

    Schizophrenic patients are thought to have an impaired ability to process sensory information. This deficit leads to disrupted auditory gating measured electrophysiologically as a reduced suppression of the second of paired auditoryevoked responses (P50) and is proposed to be associated with decreased function and/or expression of the homomeric alpha7 nicotinic acetylcholine receptor (nAChR). Here, we provide evidence that N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride (PNU-282987), a novel selective agonist of the alpha7 nAChR, evoked whole-cell currents from cultured rat hippocampal neurons that were sensitive to the selective alpha7 nAChR antagonist methyllycaconitine (MLA) and enhanced GABAergic synaptic activity when applied to hippocampal slices. Amphetamine-induced sensory gating deficit, determined by auditory-evoked potentials in hippocampal CA3 region, was restored by systemic administration of PNU-282987 in chloral hydrate-anesthetized rats. Auditory gating of rat reticular thalamic neurons was also disrupted by amphetamine; however, PNU-282987 normalized gating deficit only in a subset of tested neurons (6 of 11). Furthermore, PNU-282987 improved the inherent hippocampal gating deficit occurring in a subpopulation of anesthetized rats, and enhanced amphetamine-induced hippocampal oscillation. We propose that the alpha7 nAChR agonist PNU-282987, via modulating/enhancing hippocampal GABAergic neurotransmission, improves auditory gating and enhances hippocampal oscillatory activity. These results provide further support for the concept that drugs that selectively activate alpha7 nAChRs may offer a novel, potential pharmacotherapy in treatment of schizophrenia.

  16. Discovery of an Oxybenzylglycine Based Peroxisome Proliferator Activated Receptor [alpha] Selective Agonist 2-((3-((2-(4-Chlorophenyl)-5-methyloxazol-4-yl)methoxy)benzyl)(methoxycarbonyl)amino)acetic Acid (BMS-687453)

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jun; Kennedy, Lawrence J.; Shi, Yan; Tao, Shiwei; Ye, Xiang-Yang; Chen, Stephanie Y.; Wang, Ying; Hernndez, Andrs S.; Wang, Wei; Devasthale, Pratik V.; Chen, Sean; Lai, Zhi; Zhang, Hao; Wu, Shung; Smirk, Rebecca A.; Bolton, Scott A.; Ryono, Denis E.; Zhang, Huiping; Lim, Ngiap-Kie; Chen, Bang-Chi; Locke, Kenneth T.; O’Malley, Kevin M.; Zhang, Litao; Srivastava, Rai Ajit; Miao, Bowman; Meyers, Daniel S.; Monshizadegan, Hossain; Search, Debra; Grimm, Denise; Zhang, Rongan; Harrity, Thomas; Kunselman, Lori K.; Cap, Michael; Kadiyala, Pathanjali; Hosagrahara, Vinayak; Zhang, Lisa; Xu, Carrie; Li, Yi-Xin; Muckelbauer, Jodi K.; Chang, Chiehying; An, Yongmi; Krystek, Stanley R.; Blanar, Michael A.; Zahler, Robert; Mukherjee, Ranjan; Cheng, Peter T.W.; Tino, Joseph A. (BMS)

    2010-04-12

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

  17. Selective alpha autoradiography for monitoring thorium distribution in UO2-ThO2 fuel pellets

    International Nuclear Information System (INIS)

    Shriwastwa, B.B.; Raghunath, B.; Ghosh, J.K.

    1992-01-01

    Although natural uranium and thorium decay with similar alpha energies (4.20 and 3.98 MeV), their daughter products have different alpha characteristics. This has been exploited for selective alpha autoradiography for thoria in urania-thoria mixed nuclear fuel pellets. Difficulties in getting sufficient track density in alpha sensitive films due to the very low specific activity of natural uranium and thorium material were overcome by using a special film with annealing and pre-etching treatment. (orig./HP) [de

  18. Independent causal contributions of alpha- and beta-band oscillations during movement selection

    NARCIS (Netherlands)

    Brinkman, L.; Stolk, A.; Marshall, T.R.; Esterer, S.; Sharp, P.; Dijkerman, H.C.; Lange, F.P. de; Toni, I.

    2016-01-01

    To select a movement, specific neuronal populations controlling particular features of that movement need to be activated, whereas other populations are downregulated. The selective (dis)inhibition of cortical sensorimotor populations is governed by rhythmic neural activity in the alpha (8-12 Hz)

  19. Activity monitoring of alpha-bearing wastes

    International Nuclear Information System (INIS)

    Birkhoff, G.; Bondar, L.

    1980-01-01

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

  20. The importance of ignoring: Alpha oscillations protect selectivity

    OpenAIRE

    Payne, Lisa; Sekuler, Robert

    2014-01-01

    Selective attention is often thought to entail an enhancement of some task-relevant stimulus or attribute. We discuss the perspective that ignoring irrelevant, distracting information plays a complementary role in information processing. Cortical oscillations within the alpha (8–14 Hz) frequency band have emerged as a marker of sensory suppression. This suppression is linked to selective attention for visual, auditory, somatic, and verbal stimuli. Inhibiting processing of irrelevant input mak...

  1. Miniature Neutron-Alpha Activation Spectrometer

    Science.gov (United States)

    Rhodes, E.; Goldsten, J.

    2001-01-01

    We are developing a miniature neutron-alpha activation spectrometer for in situ analysis of samples including rocks, fines, ices, and drill cores, suitable for a lander or Rover platform, that would meet the severe mass, power, and environmental constraints of missions to the outer planets. In the neutron-activation mode, a gamma-ray spectrometer will first perform a penetrating scan of soil, ice, and loose material underfoot (depths to 10 cm or more) to identify appropriate samples. Chosen samples will be analyzed in bulk in neutron-activation mode, and then the sample surfaces will be analyzed in alpha-activation mode using Rutherford backscatter and x-ray spectrometers. The instrument will provide sample composition over a wide range of elements, including rock-forming elements (such as Na, Mg, Si, Fe, and Ca), rare earths (Sm and Eu for example), radioactive elements (K, Th, and U), and light elements present in water, ices, and biological materials (mainly H, C, O, and N). The instrument is expected to have a mass of about l kg and to require less than 1 W power. Additional information is contained in the original extended abstract.

  2. Miniature neutron-alpha activation spectrometer

    International Nuclear Information System (INIS)

    Rhodes, Edgar; Goldsten, John; Holloway, James Paul; He, Zhong

    2002-01-01

    We are developing a miniature neutron-alpha activation spectrometer for in-situ analysis of chem-bio samples, including rocks, fines, ices, and drill cores, suitable for a lander or Rover platform for Mars or outer-planet missions. In the neutron-activation mode, penetrating analysis will be performed of the whole sample using a γ spectrometer and in the α-activation mode, the sample surface will be analyzed using Rutherford-backscatter and x-ray spectrometers. Novel in our approach is the development of a switchable radioactive neutron source and a small high-resolution γ detector. The detectors and electronics will benefit from remote unattended operation capabilities resulting from our NEAR XGRS heritage and recent development of a Ge γ detector for MESSENGER. Much of the technology used in this instrument can be adapted to portable or unattended terrestrial applications for detection of explosives, chemical toxins, nuclear weapons, and contraband

  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. Selection of filter media in alpha air monitors for emergency environmental monitoring

    International Nuclear Information System (INIS)

    Kinouchi, N.; Oishi, T.; Noguchi, H.; Kato, S.

    2000-01-01

    We have developed an alpha air monitor which is possible to measure rapidly and sensitively the concentrations of airborne alpha-emitting particles, such as plutonium, for the environmental monitoring at an accident of nuclear reprocessing plant. The monitor is designed to collect airborne alpha-emitting particles by drawing the ambient air through a filter and to detect the activity by alpha spectroscopy. In order to achieve high-sensitive measurements, selection of a suitable filter used in the monitor is considerably important. The most important requirement for the filter is that it has a high surface collection efficiency to obtain the sharpness of the alpha energy spectrum. This makes it easy to distinguish the alpha-ray peak of plutonium from the alpha spectrum of naturally occurring radon decay products in the environment. And the filter is also desired to have low resistance of the air flow so that particles can be collected at a high flowrate. We have made a comparison of the surface collection efficiency and pressure drop for the various filters. Types of the test filters, most of which are commercially available in Japan, were glass fiber, cellulose-glass fiber, membrane and so on. The surface collection efficiency has been evaluated by the following two indices. One was the sharpness of alpha-ray energy peaks of thoron decay products generated in a laboratory and collected in the fibers. The other was the background counts of radon decay products in a plutonium region by measuring alpha-ray energy spectrum of radon decay products collected in the filters by sampling of dust in the atmosphere. It was found that the PTFE (polytetrafluoroethylene) membrane filter with backing had a high surface collection efficiency and low pressure drop. The results of the test are described in detail in this paper. (author)

  5. Selective alpha autoradiography for monitoring thorium distribution in UO[sub 2]-ThO[sub 2] fuel pellets

    Energy Technology Data Exchange (ETDEWEB)

    Shriwastwa, B.B.; Raghunath, B.; Ghosh, J.K. (Bhabha Atomic Research Centre, Bombay (India))

    1992-10-01

    Although natural uranium and thorium decay with similar alpha energies (4.20 and 3.98 MeV), their daughter products have different alpha characteristics. This has been exploited for selective alpha autoradiography for thoria in urania-thoria mixed nuclear fuel pellets. Difficulties in getting sufficient track density in alpha sensitive films due to the very low specific activity of natural uranium and thorium material were overcome by using a special film with annealing and pre-etching treatment. (orig./HP).

  6. 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.

  7. The alpha7 nicotinic acetylcholine receptor-selective antagonist, methyllycaconitine, partially protects against beta-amyloid1-42 toxicity in primary neuron-enriched cultures.

    Science.gov (United States)

    Martin, Shelley E; de Fiebre, Nancy Ellen C; de Fiebre, Christopher M

    2004-10-01

    Studies have suggested that the neuroprotective actions of alpha7 nicotinic agonists arise from activation of receptors and not from the extensive desensitization which rapidly follows activation. Here, we report that the alpha7-selective nicotinic antagonist, methyllycaconitine (MLA), protects against beta-amyloid-induced neurotoxicity; whereas the alpha4beta2-selective antagonist, dihydro-beta-erythroidine, does not. These findings suggest that neuroprotective actions of alpha7-acting agents arise from receptor inhibition/desensitization and that alpha7 antagonists may be useful neuroprotective agents.

  8. EEG alpha rhythm, ocular activity and basal skin resistance

    NARCIS (Netherlands)

    Verbaten, M.N.; Beaujon, J.N.R.; Sjouw, W.

    Most hypotheses about the origin of the occipital alpha rhythm stress the specific influence of ocular activity. In this study, the influence of eye-movement frequency and extreme upward deviation of the eyeballs (enlarging the corneo-retinal potential) on occipital alpha activity and basal skin

  9. 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....

  10. Actions of alpha2 adrenoceptor ligands at alpha2A and 5-HT1A receptors: the antagonist, atipamezole, and the agonist, dexmedetomidine, are highly selective for alpha2A adrenoceptors.

    Science.gov (United States)

    Newman-Tancredi, A; Nicolas, J P; Audinot, V; Gavaudan, S; Verrièle, L; Touzard, M; Chaput, C; Richard, N; Millan, M J

    1998-08-01

    This study examined the activity of chemically diverse alpha2 adrenoceptor ligands at recombinant human (h) and native rat (r) alpha2A adrenoceptors compared with 5-HT1A receptors. First, in competition binding experiments at h alpha2A and h5-HT1A receptors expressed in CHO cells, several compounds, including the antagonists 1-(2-pyrimidinyl)piperazine (1-PP), (+/-)-idazoxan, benalfocin (SKF 86466), yohimbine and RX 821,002, displayed preference for h alpha2A versus h5-HT1A receptors of only 1.4-, 3.6-, 4-, 10- and 11-fold, respectively (based on differences in pKi values). Clonidine, brimonidine (UK 14304), the benzopyrrolidine fluparoxan and the guanidines guanfacine and guanabenz exhibited intermediate selectivity (22- to 31-fold) for h alpha2A receptors. Only the antagonist atipamezole and the agonist dexmedetomidine (DMT) displayed high preference for alpha2 adrenoceptors (1290- and 91-fold, respectively). Second, the compounds were tested for their ability to induce h5-HT1A receptor-mediated G-protein activation, as indicated by the stimulation of [35S]GTPgammaS binding. All except atipamezole and RX 821,002 exhibited agonist activity, with potencies which correlated with their affinity for h5-HT1A receptors. Relative efficacies (Emax values) were 25-35% for guanabenz, guanfacine, WB 4101 and benalfocin, 50-65% for 1-PP, (+/-)-idazoxan and clonidine, and over 70% for fluparoxan, oxymetazoline and yohimbine (relative to 5-HT = 100%). Yohimbine-induced [35S]GTPgammaS binding was inhibited by the selective 5-HT1A receptor antagonist WAY 100,635. In contrast, RX 821,002 was the only ligand which exhibited antagonist activity at h5-HT1A receptors, inhibiting 5-HT-stimulated [35S]GTPgammaS binding. Atipamezole, which exhibited negligeable affinity for 5-HT1A receptors, was inactive. Third, the affinities for r alpha2A differed considerably from the affinities for h alpha2A receptors whereas the affinities for r5-HT1A differed much less from the affinities for h5-HT

  11. In vitro pharmacological characterization of a novel selective alpha7 neuronal nicotinic acetylcholine receptor agonist ABT-107.

    Science.gov (United States)

    Malysz, John; Anderson, David J; Grønlien, Jens H; Ji, Jianguo; Bunnelle, William H; Håkerud, Monika; Thorin-Hagene, Kirten; Ween, Hilde; Helfrich, Rosalind; Hu, Min; Gubbins, Earl; Gopalakrishnan, Sujatha; Puttfarcken, Pamela S; Briggs, Clark A; Li, Jinhe; Meyer, Michael D; Dyhring, Tino; Ahring, Philip K; Nielsen, Elsebet Ø; Peters, Dan; Timmermann, Daniel B; Gopalakrishnan, Murali

    2010-09-01

    Enhancement of alpha7 nicotinic acetylcholine receptor (nAChR) activity is considered a therapeutic approach for ameliorating cognitive deficits present in Alzheimer's disease and schizophrenia. In this study, we describe the in vitro profile of a novel selective alpha7 nAChR agonist, 5-(6-[(3R)-1-azabicyclo[2,2,2]oct-3-yloxy]pyridazin-3-yl)-1H-indole (ABT-107). ABT-107 displayed high affinity binding to alpha7 nAChRs [rat or human cortex, [(3)H](1S,4S)-2,2-dimethyl-5-(6-phenylpyridazin-3-yl)-5-aza-2-azoniabicyclo[2.2.1]heptane (A-585539), K(i) = 0.2-0.6 nM or [(3)H]methyllycaconitine (MLA), 7 nM] that was at least 100-fold selective versus non-alpha7 nAChRs and other receptors. Functionally, ABT-107 did not evoke detectible currents in Xenopus oocytes expressing human or nonhuman alpha3beta4, chimeric (alpha6/alpha3)beta4, or 5-HT(3A) receptors, and weak or negligible Ca(2+) responses in human neuroblastoma IMR-32 cells (alpha3* function) and human alpha4beta2 and alpha4beta4 nAChRs expressed in human embryonic kidney 293 cells. ABT-107 potently evoked human and rat alpha7 nAChR current responses in oocytes (EC(50), 50-90 nM total charge, approximately 80% normalized to acetylcholine) that were enhanced by the positive allosteric modulator (PAM) 4-[5-(4-chloro-phenyl)-2-methyl-3-propionyl-pyrrol-1-yl]-benzenesulfonamide (A-867744). In rat hippocampus, ABT-107 alone evoked alpha7-like currents, which were inhibited by the alpha7 antagonist MLA. In dentate gyrus granule cells, ABT-107 enhanced spontaneous inhibitory postsynaptic current activity when coapplied with A-867744. In the presence of an alpha7 PAM [A-867744 or N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride (PNU-120596)], the addition of ABT-107 elicited MLA-sensitive alpha7 nAChR-mediated Ca(2+) signals in IMR-32 cells and rat cortical cultures and enhanced extracellular signal-regulated kinase phosphorylation in differentiated PC-12 cells. ABT-107 was also effective in protecting rat

  12. Glutamine 57 at the complementary binding site face is a key determinant of morantel selectivity for {alpha}7 nicotinic receptors.

    Science.gov (United States)

    Bartos, Mariana; Price, Kerry L; Lummis, Sarah C R; Bouzat, Cecilia

    2009-08-07

    Nicotinic receptors (AChRs) play key roles in synaptic transmission. We explored activation of neuronal alpha7 and mammalian muscle AChRs by morantel and oxantel. Our results revealed a novel action of morantel as a high efficacy and more potent agonist than ACh of alpha7 receptors. The EC(50) for activation by morantel of both alpha7 and alpha7-5HT(3A) receptors is 7-fold lower than that determined for ACh. The minimum morantel concentration required to activate alpha7-5HT(3A) channels is 6-fold lower than that of ACh, and activation episodes are more prolonged than in the presence of ACh. By contrast, oxantel is a weak agonist of alpha7 and alpha7-5HT(3A), and both drugs are very low efficacy agonists of muscle AChRs. The replacement of Gln(57) in alpha7 by glycine, which is found in the equivalent position of the muscle AChR, decreases the efficacy for activation and turns morantel into a partial agonist. The reverse mutation in the muscle AChR (epsilonG57Q) increases 7-fold the efficacy of morantel. The mutations do not affect activation by ACh or oxantel, indicating that this position is selective for morantel. In silico studies show that the tetrahydropyrimidinyl group, common to both drugs, is close to Trp(149) of the principal face of the binding site, whereas the other cyclic group is proximal to Gln(57) of the complementary face in morantel but not in oxantel. Thus, position 57 at the complementary face is a key determinant of the high selectivity of morantel for alpha7. These results provide new information for further progress in drug design.

  13. Human fat cell alpha-2 adrenoceptors. I. Functional exploration and pharmacological definition with selected alpha-2 agonists and antagonists

    International Nuclear Information System (INIS)

    Galitzky, J.; Mauriege, P.; Berlan, M.; Lafontan, M.

    1989-01-01

    This study was undertaken to investigate more fully the pharmacological characteristics of the human fat cell alpha-2 adrenoceptor. Biological assays were performed on intact isolated fat cells while radioligand binding studies were carried out with [ 3 H]yohimbine in membranes. These pharmacological studies brought: (1) a critical definition of the limits of the experimental conditions required for the exploration of alpha-2 adrenergic responsiveness on human fat cells and membranes; (2) an improvement in the pharmacological definition of the human fat cell postsynaptic alpha-2 adrenoceptor. Among alpha-2 agonists, UK-14,304 was the most potent and the relative order of potency was: UK-14,304 greater than p-aminoclonidine greater than clonidine = B-HT 920 greater than rilmenidine. For alpha-2 antagonists, the potency order was: yohimbine greater than idazoxan greater than SK ampersand F-86,466 much greater than benextramine; (3) a description of the impact of benextramine (irreversible alpha-1/alpha-2 antagonist) on human fat cell alpha-2 adrenergic receptors and on human fat cell function; the drug inactivates the alpha-2 adrenergic receptors with a minor impact on beta adrenergic receptors and without noticeable alterations of fat cell function as assessed by preservation of beta adrenergic and Al-adenosine receptor-mediated lipolytic responses; and (4) a definition of the relationship existing between alpha-2 adrenergic receptor occupancy, inhibition of adenylate cyclase activity and antilipolysis with full and partial agonists. The existence of a receptor reserve must be taken into account when evaluating alpha-2 adrenergic receptor distribution and regulation of human fat cells

  14. The selective estrogen receptor alpha agonist Org 37663 induces estrogenic effects but lacks antirheumatic activity: a phase IIa trial investigating efficacy and safety of Org 37663 in postmenopausal female rheumatoid arthritis patients receiving stable background methotrexate or sulfasalazine.

    Science.gov (United States)

    van Vollenhoven, Ronald F; Houbiers, Jos G A; Buttgereit, Frank; In 't Hout, Joanna; Boers, Maarten; Leij, Susanne; Kvien, Tore K; Dijkmans, Ben A C; Szczepański, Leszek; Szombati, Istvan; Sierakowski, Stanislaw; Miltenburg, André M M

    2010-02-01

    Multiple lines of evidence suggest that sex hormones may play a role in the pathogenesis or clinical expression of rheumatoid arthritis (RA). Studies on the effects of exogenous estrogens in RA patients have yielded contradictory results. We undertook this study to determine the effects of the selective estrogen receptor alpha (ERalpha) agonist Org 37663 in patients with RA, in terms of both its estrogenic effects and its ability to ameliorate disease activity. A 10-week, multicenter, randomized, double-blind, placebo-controlled, parallel group, dose-finding, proof-of-concept trial was initiated to obtain data on the efficacy and safety of Org 37663 in postmenopausal female patients with RA who were receiving background treatment with either methotrexate or sulfasalazine. Patients were randomized to receive placebo or Org 37663 at doses of 4 mg/day, 15 mg/day, or 50 mg/week. The primary efficacy variable was the Disease Activity Score in 28 joints (DAS28). Org 37663 induced a clear biologic, estrogenic response in several organ systems, including a dose-related increase in levels of sex hormone binding globulin. However, the DAS28 decreased similarly for all treatment groups including placebo, indicating lack of clinical efficacy of Org 37663 in this trial. The observed lack of clinical benefit in RA patients treated with an ERalpha agonist, in association with a clear biologic response to the study drug, provides evidence that a biologically relevant ERalpha-mediated estrogenic effect is not associated with a clinically relevant effect on RA symptoms and signs.

  15. 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.

  16. The alpha activity of soils in relation to landscape development

    Energy Technology Data Exchange (ETDEWEB)

    Pepper, R G; Quirk, J P [Western Australia Univ., Nedlands. Dept. of Soil Science and Plant Nutrition

    1976-02-01

    The alpha activity of soils and the degree of the equilibrium of the thorium series has been related to the age of soils developed on a truncated laterite landscape in southwestern Australia. The uplift of the old lateritic plateau has formed a sequence of erosional and depositional surfaces which form the parent materials of the present-day soils. These surfaces because of their different relative ages have been subjected to different degrees of weathering and leaching. The alpha activity of the soils formed on these different landscape surfaces is influenced firstly by the amount of weathering that the surface has undergone, and secondly by the degree of leaching that the soil has undergone as evidenced by profile development. It has been found that the younger soils have higher alpha activities with the thorium series tending more towards equilibrium when compared with older soils, where the alpha activity is lower due to the leaching of the daughter nuclides from the profile.

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

    International Nuclear Information System (INIS)

    Tobias, C.C.B.

    1982-01-01

    The absolute activity of U-235 contained in a UO 2 sample, using a sum-coincidence circuit which selected only the alpha particles which were simultaneous with the well known 184 Kev gamma radiation from Th-231. The alpha particles were detected by ZnS(Ag) scintillator specially designed to show its maximun efficiency for U-235 alpha particles, whereas the gamma radiation was detected by NaI(Tl) scintillation detector. The values obtained for the half-life of U-235 was compared with data from various observers using different experimental techniques. (Author) [pt

  18. Combinations of ERK and p38 MAPK inhibitors ablate tumor necrosis factor-alpha (TNF-alpha ) mRNA induction. Evidence for selective destabilization of TNF-alpha transcripts.

    Science.gov (United States)

    Rutault, K; Hazzalin, C A; Mahadevan, L C

    2001-03-02

    Tumor necrosis factor-alpha (TNF-alpha) is a potent proinflammatory cytokine whose synthesis and secretion are implicated in diverse pathologies. Hence, inhibition of TNF-alpha transcription or translation and neutralization of its protein product represent major pharmaceutical strategies to control inflammation. We have studied the role of ERK and p38 mitogen-activated protein (MAP) kinase in controlling TNF-alpha mRNA levels in differentiated THP-1 cells and in freshly purified human monocytes. We show here that it is possible to produce virtually complete inhibition of lipopolysaccharide-stimulated TNF-alpha mRNA accumulation by using a combination of ERK and p38 MAP kinase inhibitors. Furthermore, substantial inhibition is achievable using combinations of 1 microm of each inhibitor, whereas inhibitors used individually are incapable of producing complete inhibition even at high concentrations. Finally, addressing mechanisms involved, we show that inhibition of p38 MAP kinase selectively destabilizes TNF-alpha transcripts but does not affect degradation of c-jun transcripts. These results impinge on the controversy in the literature surrounding the mode of action of MAP kinase inhibitors on TNF-alpha mRNA and suggest the use of combinations of MAP kinase inhibitors as an effective anti-inflammatory strategy.

  19. [(35)S]-GTPgammaS autoradiography reveals alpha(2) adrenoceptor-mediated G-protein activation in amygdala and lateral septum.

    Science.gov (United States)

    Newman-Tancredi, A; Chaput, C; Touzard, M; Millan, M J

    2000-04-03

    alpha(2)-adrenoceptor-mediated G-protein activation was examined by [(35)S]-GTPgammaS autoradiography. In alpha(2)-adrenoceptor-rich regions (amygdala, lateral septum), noradrenaline stimulated [(35)S]-GTPgammaS binding. These actions were abolished by the selective alpha(2) antagonist, atipamezole. Conversely, in caudate nucleus, which expresses few alpha(2) receptors, noradrenaline-induced stimulation was not inhibited by atipamezole, suggesting that it is not mediated by alpha(2)-adrenoceptors.

  20. Selective effects of alpha interferon on human T-lymphocyte subsets during mixed lymphocyte cultures

    DEFF Research Database (Denmark)

    Hokland, M; Hokland, P; Heron, I

    1983-01-01

    Mixed lymphocyte reaction (MLR) cultures of human lymphocyte subsets with or without the addition of physiological doses of human alpha interferon (IFN-alpha) were compared with respect to surface marker phenotypes and proliferative capacities of the responder cells. A selective depression on the T...... T4 cells and decreased numbers of T4 cells harvested from IFN MLRs (days 5-6 of culture). In contrast, it was shown that the T8 (cytotoxic/suppressor) subset in MLRs was either not affected or slightly stimulated by the addition of IFN. The depression of the T4 cells by IFN was accompanied...... by a decrease in the number of activated T cells expressing Ia antigens. On the other hand, IFN MLRs contained greater numbers of cells expressing the T10 differentiation antigen. In experiments with purified T-cell subsets the IFN effect was exerted directly on the T4 cells and not mediated by either T8...

  1. An Oral Selective Alpha-1A Adrenergic Receptor Agonist Prevents Doxorubicin Cardiotoxicity

    Directory of Open Access Journals (Sweden)

    Ju Youn Beak, PhD

    2017-02-01

    Full Text Available Summary: Alpha-1 adrenergic receptors (α1-ARs play adaptive and protective roles in the heart. Dabuzalgron is an oral selective α1A-AR agonist that was well tolerated in multiple clinical trials of treatment for urinary incontinence, but has never been used to treat heart disease in humans or animal models. In this study, the authors administered dabuzalgron to mice treated with doxorubicin (DOX, a widely used chemotherapeutic agent with dose-limiting cardiotoxicity that can lead to heart failure (HF. Dabuzalgron protected against DOX-induced cardiotoxicity, likely by preserving mitochondrial function. These results suggest that activating cardiac α1A-ARs with dabuzalgron, a well-tolerated oral agent, might represent a novel approach to treating HF. Key Words: alpha adrenergic receptors, anthracyclines, cardioprotection, catecholamines, heart failure

  2. Alpha particle losses during sawtooth activity in Tokamaks

    International Nuclear Information System (INIS)

    Anderson, D.; Lisak, M.

    1988-01-01

    The time evolution of the direct losses of fusion produced alpha particles in Tokamak plasmas characterized by sawtooth activity is investigated. The alpha particle loss rate during a sawtooth period is predicted to change invertedly with the change in bulk plasma parameters but also to contain a characteristic burst at the sawtooth crash. The spectrum of the lost alpha particles is also discussed. The predictions for the time evolution and the spectrum of the losses are in qualitative agreement with recently obtained losses of 15 MeV fusion produced protons in JET. (authors)

  3. [Acetylcholine activation of alpha-ketoglutarate oxidation in liver mitochondria].

    Science.gov (United States)

    Shostakovskaia, I V; Doliba, N M; Gordiĭ, S K; Babskiĭ, A M; Kondrashova, M N

    1986-01-01

    Activation of alpha-ketoglutarate oxidation in the rat liver mitochondria takes place 15 and 30 min after intraperitoneal injection of acetyl choline. This mediator in doses of 25, 50 and 100 micrograms per 100 g of body weight causes a pronounced stimulation of phosphorylation respiration rate and calcium capacity of mitochondria with alpha-ketoglutarate oxidation. Acetyl choline is found to have a moderate inhibitory action on oxidation of lower (physiological) concentrations of succinate. Its stimulating action on alpha-ketoglutarate oxidation is associated with activation of M-cholinoreceptors; atropine, a choline-blocker, removes completely this effect. It is supposed that alpha-ketoglutarate and succinate are included into the composition of two reciprocal hormonal-substrate nucleotide systems.

  4. Selection within working memory based on a color retro-cue modulates alpha oscillations.

    Science.gov (United States)

    Poch, Claudia; Capilla, Almudena; Hinojosa, José Antonio; Campo, Pablo

    2017-11-01

    Working Memory (WM) maintains flexible representations. Retrospective cueing studies indicate that selective attention can be directed to memory representations in WM improving performance. While most of the work has explored the neural substrates of orienting attention based on a spatial retro-cue, behavioral studies show that a feature other than location can also improve WM performance. In the present work we explored the oscillatory underpinnings of orienting attention to a relevant representation held in WM guided by a feature value. We recorded EEG data in a group of 36 healthy human subjects (20 females) performing a WM task in which they had to memorize the orientation of four rectangles of different colors. After a maintenance period, a cue was presented indicating the color of the relevant item. We showed that directing attention to a memory item based on its color resulted in a modulation of posterior alpha activity, which appears as more desynchronization in the contralateral than in the ipsilateral hemisphere. Alpha lateralization is considered a neurophysiological marker of external and internal spatial attention. We propose that current findings support the idea that selection of a memory item based on a non-location feature could be accomplished by a spatial attentional mechanism. Moreover, using a centrally presented color retro-cue allowed us to surpass the confounds inherent to the use of spatial retro-cues, supporting that the observed lateralized alpha results from an endogenous attentional mechanism. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2010-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Daria Osipova

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

  8. 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.

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

    International Nuclear Information System (INIS)

    Zakrzewska, I.; Wolska, K.; Koput, A.

    1993-01-01

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

  10. 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.

  11. 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.

  12. Characterization of a series of anabaseine-derived compounds reveals that the 3-(4)-dimethylaminocinnamylidine derivative is a selective agonist at neuronal nicotinic alpha 7/125I-alpha-bungarotoxin receptor subtypes.

    Science.gov (United States)

    de Fiebre, C M; Meyer, E M; Henry, J C; Muraskin, S I; Kem, W R; Papke, R L

    1995-01-01

    Investigation of the naturally occurring, nicotinic agonist anabaseine and novel derivatives has shown that these compounds have cytoprotective and memory-enhancing effects. The hypothesis that these arise at least in part through actions on brain nicotinic receptors was evaluated by examining the ability of these compounds to displace the binding of nicotinic ligands and to affect the function of the alpha 4 beta 2 and alpha 7 receptor subtypes expressed in Xenopus oocytes. The derivative 3-(4)-dimethylaminocinnamylidine anabaseine (DMAC) was found to be a selective alpha 7 receptor agonist; it was more potent than nicotine, acetylcholine, anabaseine, and other derivatives at activating the alpha 7 receptor subtype, while displaying little agonist activity at alpha 4 beta 2 and other receptor subtypes. Compared with anabaseine and the other derivatives, DMAC was the most potent at displacing 125I-alpha-bungarotoxin binding (putative alpha 7) and the least potent at displacing [3H]cytisine binding (putative alpha 4 beta 2) to brain membranes. Independently of agonist activities, all of the novel compounds displayed secondary inhibitory activity at both receptor subtypes. At the alpha 4 beta 2 receptor subtype, inhibition by the 3-(2,4)-dimethoxybenzylidene derivative was enhanced by coapplication of acetylcholine, suggesting a noncompetitive form of inhibition. Anabaseine and nicotine prolonged the time course of activation of alpha 4 beta 2 receptors, compared with acetylcholine, suggesting sequential channel-blocking activity. As selective agonists, anabaseine derivatives such as DMAC may be useful for elucidating the function of alpha 7 nicotinic receptors, including their potential role(s) in the cytoprotective and memory-enhancing effects of nicotinic agents.

  13. Synthesis and biological evaluation of 2-heteroarylthioalkanoic acid analogues of clofibric acid as peroxisome proliferator-activated receptor alpha agonists.

    Science.gov (United States)

    Giampietro, Letizia; Ammazzalorso, Alessandra; Giancristofaro, Antonella; Lannutti, Fabio; Bettoni, Giancarlo; De Filippis, Barbara; Fantacuzzi, Marialuigia; Maccallini, Cristina; Petruzzelli, Michele; Morgano, Annalisa; Moschetta, Antonio; Amoroso, Rosa

    2009-10-22

    A series of 2-heteroarylthioalkanoic acids were synthesized through systematic structural modifications of clofibric acid and evaluated for human peroxisome proliferator-activated receptor alpha (PPARalpha) transactivation activity, with the aim of obtaining new hypolipidemic compounds. Some thiophene and benzothiazole derivatives showing a good activation of the receptor alpha were screened for activity against the PPARgamma isoform. The gene induction of selected compounds was also investigated in the human hepatoma cell line.

  14. Gross alpha and beta activities in Tunisian mineral water

    International Nuclear Information System (INIS)

    Hamrouni Benbelgacem, Samar

    2011-01-01

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

  15. alpha7 Nicotinic acetylcholine receptor knockout selectively enhances ethanol-, but not beta-amyloid-induced neurotoxicity.

    Science.gov (United States)

    de Fiebre, Nancyellen C; de Fiebre, Christopher M

    2005-01-03

    The alpha7 subtype of nicotinic acetylcholine receptor (nAChR) has been implicated as a potential site of action for two neurotoxins, ethanol and the Alzheimer's disease related peptide, beta-amyloid. Here, we utilized primary neuronal cultures of cerebral cortex from alpha7 nAChR null mutant mice to examine the role of this receptor in modulating the neurotoxic properties of subchronic, "binge" ethanol and beta-amyloid. Knockout of the alpha7 nAChR gene selectively enhanced ethanol-induced neurotoxicity in a gene dosage-related fashion. Susceptibility of cultures to beta-amyloid induced toxicity, however, was unaffected by alpha7 nAChR gene null mutation. Further, beta-amyloid did not inhibit the binding of the highly alpha7-selective radioligand, [(125)I]alpha-bungarotoxin. On the other hand, in studies in Xenopus oocytes ethanol efficaciously inhibited alpha7 nAChR function. These data suggest that alpha7 nAChRs modulate the neurotoxic effects of binge ethanol, but not the neurotoxicity produced by beta-amyloid. It is hypothesized that inhibition of alpha7 nAChRs by ethanol provides partial protection against the neurotoxic properties of subchronic ethanol.

  16. 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

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

    Directory of Open Access Journals (Sweden)

    Ingrid Funke

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

  18. alpha-Tocopheryl succinate promotes selective cell death induced by vitamin K3 in combination with ascorbate.

    Science.gov (United States)

    Tomasetti, M; Strafella, E; Staffolani, S; Santarelli, L; Neuzil, J; Guerrieri, R

    2010-04-13

    A strategy to reduce the secondary effects of anti-cancer agents is to potentiate the therapeutic effect by their combination. A combination of vitamin K3 (VK3) and ascorbic acid (AA) exhibited an anti-cancer synergistic effect, associated with extracellular production of H(2)O(2) that promoted cell death. The redox-silent vitamin E analogue alpha-tocopheryl succinate (alpha-TOS) was used in combination with VK3 and AA to evaluate their effect on prostate cancer cells. Prostate cancer cells were sensitive to alpha-TOS and VK3 treatment, but resistant to AA upto 3.2 mM. When combined, a synergistic effect was found for VK3-AA, whereas alpha-TOS-VK3 and alpha-TOS-AA combination showed an antagonist and additive effect, respectively. However, sub-lethal doses of AA-VK3 combination combined with a sub-toxic dose of alpha-TOS showed to induce efficient cell death that resembles autoschizis. Associated with this cell demise, lipid peroxidation, DNA damage, cytoskeleton alteration, lysosomal-mitochondrial perturbation, and release of cytochrome c without caspase activation were observed. Inhibition of lysosomal proteases did not attenuate cell death induced by the combined agents. Furthermore, cell deaths by apoptosis and autoschizis were detected. These finding support the emerging idea that synergistic combinations of some agents can overcome toxicity and other side-effects associated with high doses of single drugs creating the opportunity for therapeutically relevant selectivity.

  19. NEBULAR ATTENUATION IN H{alpha}-SELECTED STAR-FORMING GALAXIES AT z = 0.8 FROM THE NewH{alpha} SURVEY

    Energy Technology Data Exchange (ETDEWEB)

    Momcheva, Ivelina G. [Astronomy Department, Yale University, New Haven, CT 06511 (United States); Lee, Janice C.; Ouchi, Masami [Carnegie Observatories, Pasadena, CA 91101 (United States); Ly, Chun [Space Telescope Science Institute, Baltimore, MD 21218 (United States); Salim, Samir [Astronomy Department, Indiana University, Bloomington, IN 47405 (United States); Dale, Daniel A. [Department of Physics and Astronomy, University of Wyoming, Laramie, WY 82071 (United States); Finn, Rose [Physics Department, Siena College, Loudonville, NY 12211 (United States); Ono, Yoshiaki, E-mail: ivelina.momcheva@yale.edu [Department of Astronomy, Graduate School of Science, University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan)

    2013-02-01

    We present measurements of the dust attenuation of H{alpha}-selected emission-line galaxies at z = 0.8 from the NewH{alpha} narrowband survey. The analysis is based on deep follow-up spectroscopy with Magellan/IMACS, which captures the strong rest-frame optical emission lines from [O II] {lambda}3727 to [O III] {lambda}5007. The spectroscopic sample used in this analysis consists of 341 confirmed H{alpha} emitters. We place constraints on the active galactic nucleus (AGN) fraction using diagnostics that can be applied at intermediate redshift. We find that at least 5% of the objects in our spectroscopic sample can be classified as AGNs and 2% are composite, i.e., powered by a combination of star formation and AGN activity. We measure the dust attenuation for individual objects from the ratios of the higher order Balmer lines. The H{beta} and H{gamma} pair of lines is detected with S/N > 5 in 55 individual objects and the H{beta} and H{delta} pair is detected in 50 individual objects. We also create stacked spectra to probe the attenuation in objects without individual detections. The median attenuation at H{alpha} based on the objects with individually detected lines is A(H{alpha}) = 0.9 {+-} 1.0 mag, in good agreement with the attenuation found in local samples of star-forming galaxies. We find that the z = 0.8 galaxies occupy a similar locus of attenuation as a function of magnitude, mass, and star formation rate (SFR) as a comparison sample drawn from the SDSS DR4. Both the results from the individual z = 0.8 galaxies and from the stacked spectra show consistency with the mass-attenuation and SFR-attenuation relations found in the local universe, indicating that these relations are also applicable at intermediate redshift.

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

    OpenAIRE

    Reka Palanivel; Thahira Banu Azeez; Seethalakshmi Muthaya

    2017-01-01

    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...

  1. 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...

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

    Directory of Open Access Journals (Sweden)

    Freya M Mowat

    2010-06-01

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

  3. Incineration of alpha-active solid waste by microwaves

    Energy Technology Data Exchange (ETDEWEB)

    Mallik, G K; Bhargava, V K; Kamath, H S; Purushotham, D S.C. [Bhabha Atomic Research Centre, Tarapur (India). Advanced Fuel Fabrication Facility

    1996-12-31

    The conventional techniques for treatment of alpha-active compressible solid waste involve incineration using electrically heated incinerators and subsequent recovery of special nuclear materials (SNM) from the ash by acid leaching. A microwave incineration followed by microwave digestion and SNM recovery from ash has specific advantages from maintenance and productivity consideration. The paper describes a preliminary work carried out with simulated uranium containing compressible solid waste using microwave heating technique. (author). 3 refs., 1 tab.

  4. Fusion alpha loss diagnostic for ITER using activation technique

    Czech Academy of Sciences Publication Activity Database

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

    2011-01-01

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

  5. Gas lantern mantle: a low activity alpha particle source

    International Nuclear Information System (INIS)

    Mukherjee, B.; Manzoor, S.

    1991-01-01

    Commercially available gas lantern mantles contain a substantial amount of radioactive ThO 2 . Gas lantern mantles purchased from a Sydney camping shop were incinerated, deposited as a thin layer on a aluminium planchette, and the emitted alpha spectrum was measured with a silicon surfacer barrier detector. The specific activity of the samples was estimated by high resolution gamma spectroscopy using a high purity germanium detector as well as CR-39 solid state nuclear track detectors. The micro-morphology of the incinerated powder was analysed by scanning electron microscopy. The depth dose and LET distribution of alpha particles in soft tissue were calculated from the energy spectrum. 12 refs., 2 tabs., 5 figs

  6. 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,

  7. The T alpha 2 nuclear protein binding site from the human T cell receptor alpha enhancer functions as both a T cell-specific transcriptional activator and repressor

    OpenAIRE

    1990-01-01

    T cell-specific expression of the human T cell receptor alpha (TCR- alpha) gene is regulated by the interaction of variable region promoter elements with a transcriptional enhancer that is located 4.5 kb 3' of the TCR-alpha constant region (C alpha) gene segment. The minimal TCR- alpha enhancer is composed of two nuclear protein binding sites, T alpha 1 and T alpha 2, that are both required for the T cell-specific activity of the enhancer. The T alpha 1 binding site contains a consensus cAMP ...

  8. Variant Selection during Alpha Precipitation in Titanium Alloys: A Simulation Study

    Science.gov (United States)

    Shi, Rongpei

    Variant selection of alpha phase during its precipitation from beta matrix plays a key role in determining transformation texture and final mechanical properties of alpha/beta and beta titanium alloys. In this study we develop a three-dimensional quantitative phase field model (PFM) to predict variant selection and microstructure evolution during beta to alpha transformation in polycrystalline Ti-6Al-4V under the influence of different processing variables. The model links its inputs directly to thermodynamic and mobility databases, and incorporates crystallography of BCC to HCP transformation, elastic anisotropy, defects within semi-coherent alpha/beta interfaces and elastic inhomogeneities among different beta grains. In particular, microstructure and transformation texture evolution are treated simultaneously via orientation distribution function (ODF) modeling of alpha/beta two-phase microstructure in beta polycrystalline obtained by PFM. It is found that, for a given undercooling, the development of transformation texture of the alpha phase due to variant selection during precipitation depends on both externally applied stress or strain, initial texture state of parent beta sample and internal stress generated by the precipitation reaction itself. Moreover, the growth of pre-existing widmanstatten alpha precipitates is accompanied by selective nucleation and growth of secondary alpha plates of preferred variants. We further develop a crystallographic model based on the ideal Burgers orientation relationship (BOR) between GBalpha and one of the two adjacent beta grains to investigate how a prior beta grain boundary contributes to variant selection of grain boundary allotriomorph (GBalpha). The model is able to predict all possible special beta grain boundaries where GBalpha is able to maintain BOR with two neighboring grain. In particular, the model has been used to evaluate the validity of all current empirical variant selection rules to obtain more insight of

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

    International Nuclear Information System (INIS)

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

    2001-01-01

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

  10. A SUCCESSFUL BROADBAND SURVEY FOR GIANT Ly{alpha} NEBULAE. I. SURVEY DESIGN AND CANDIDATE SELECTION

    Energy Technology Data Exchange (ETDEWEB)

    Prescott, Moire K. M. [Department of Physics, Broida Hall, Mail Code 9530, University of California, Santa Barbara, CA 93106 (United States); Dey, Arjun; Jannuzi, Buell T., E-mail: mkpresco@physics.ucsb.edu [National Optical Astronomy Observatory, 950 North Cherry Avenue, Tucson, AZ 85719 (United States)

    2012-04-01

    Giant Ly{alpha} nebulae (or Ly{alpha} 'blobs') are likely sites of ongoing massive galaxy formation, but the rarity of these powerful sources has made it difficult to form a coherent picture of their properties, ionization mechanisms, and space density. Systematic narrowband Ly{alpha} nebula surveys are ongoing, but the small redshift range covered and the observational expense limit the comoving volume that can be probed by even the largest of these surveys and pose a significant problem when searching for such rare sources. We have developed a systematic search technique designed to find large Ly{alpha} nebulae at 2 {approx}< z {approx}< 3 within deep broadband imaging and have carried out a survey of the 9.4 deg{sup 2} NOAO Deep Wide-Field Survey Booetes field. With a total survey comoving volume of Almost-Equal-To 10{sup 8} h{sup -3}{sub 70} Mpc{sup 3}, this is the largest volume survey for Ly{alpha} nebulae ever undertaken. In this first paper in the series, we present the details of the survey design and a systematically selected sample of 79 candidates, which includes one previously discovered Ly{alpha} nebula.

  11. Estrogen alters the diurnal rhythm of alpha 1-adrenergic receptor densities in selected brain regions

    Energy Technology Data Exchange (ETDEWEB)

    Weiland, N.G.; Wise, P.M.

    1987-11-01

    Norepinephrine regulates the proestrous and estradiol-induced LH surge by binding to alpha 1-adrenergic receptors. The density of alpha 1-receptors may be regulated by estradiol, photoperiod, and noradrenergic neuronal activity. We wished to determine whether alpha 1-receptors exhibit a diurnal rhythm in ovariectomized and/or estradiol-treated female rats, whether estradiol regulates alpha 1-receptors in those areas of brain involved with LH secretion and/or sexual behavior, and whether the concentrations of alpha-receptors vary inversely relative to previously reported norepinephrine turnover patterns. Young female rats, maintained on a 14:10 light-dark cycle were ovariectomized. One week later, half of them were outfitted sc with Silastic capsules containing estradiol. Groups of animals were decapitated 2 days later at 0300, 1000, 1300, 1500, 1800, and 2300 h. Brains were removed, frozen, and sectioned at 20 micron. Sections were incubated with (/sup 3/H)prazosin in Tris-HCl buffer, washed, dried, and exposed to LKB Ultrofilm. The densities of alpha 1-receptors were quantitated using a computerized image analysis system. In ovariectomized rats, the density of alpha 1-receptors exhibited a diurnal rhythm in the suprachiasmatic nucleus (SCN), medial preoptic nucleus (MPN), and pineal gland. In SCN and MPN, receptor concentrations were lowest during the middle of the day and rose to peak levels at 1800 h. In the pineal gland, the density of alpha 1-receptors was lowest at middark phase, rose to peak levels before lights on, and remained elevated during the day. Estradiol suppressed the density of alpha 1 binding sites in the SCN, MPN, median eminence, ventromedial nucleus, and the pineal gland but had no effect on the lateral septum. Estrogen treatment altered the rhythm of receptor densities in MPN, median eminence, and the pineal gland.

  12. Estrogen alters the diurnal rhythm of alpha 1-adrenergic receptor densities in selected brain regions

    International Nuclear Information System (INIS)

    Weiland, N.G.; Wise, P.M.

    1987-01-01

    Norepinephrine regulates the proestrous and estradiol-induced LH surge by binding to alpha 1-adrenergic receptors. The density of alpha 1-receptors may be regulated by estradiol, photoperiod, and noradrenergic neuronal activity. We wished to determine whether alpha 1-receptors exhibit a diurnal rhythm in ovariectomized and/or estradiol-treated female rats, whether estradiol regulates alpha 1-receptors in those areas of brain involved with LH secretion and/or sexual behavior, and whether the concentrations of alpha-receptors vary inversely relative to previously reported norepinephrine turnover patterns. Young female rats, maintained on a 14:10 light-dark cycle were ovariectomized. One week later, half of them were outfitted sc with Silastic capsules containing estradiol. Groups of animals were decapitated 2 days later at 0300, 1000, 1300, 1500, 1800, and 2300 h. Brains were removed, frozen, and sectioned at 20 micron. Sections were incubated with [ 3 H]prazosin in Tris-HCl buffer, washed, dried, and exposed to LKB Ultrofilm. The densities of alpha 1-receptors were quantitated using a computerized image analysis system. In ovariectomized rats, the density of alpha 1-receptors exhibited a diurnal rhythm in the suprachiasmatic nucleus (SCN), medial preoptic nucleus (MPN), and pineal gland. In SCN and MPN, receptor concentrations were lowest during the middle of the day and rose to peak levels at 1800 h. In the pineal gland, the density of alpha 1-receptors was lowest at middark phase, rose to peak levels before lights on, and remained elevated during the day. Estradiol suppressed the density of alpha 1 binding sites in the SCN, MPN, median eminence, ventromedial nucleus, and the pineal gland but had no effect on the lateral septum. Estrogen treatment altered the rhythm of receptor densities in MPN, median eminence, and the pineal gland

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

    International Nuclear Information System (INIS)

    Blanchis, P.

    1983-01-01

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

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

    International Nuclear Information System (INIS)

    Labarre, S.; Bardy, N.

    1985-10-01

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

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

    DEFF Research Database (Denmark)

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

    2003-01-01

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

  16. 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.

  17. Category-specific visual responses: an intracranial study comparing gamma, beta, alpha and ERP response selectivity

    Directory of Open Access Journals (Sweden)

    Juan R Vidal

    2010-11-01

    Full Text Available The specificity of neural responses to visual objects is a major topic in visual neuroscience. In humans, functional magnetic resonance imaging (fMRI studies have identified several regions of the occipital and temporal lobe that appear specific to faces, letter-strings, scenes, or tools. Direct electrophysiological recordings in the visual cortical areas of epileptic patients have largely confirmed this modular organization, using either single-neuron peri-stimulus time-histogram or intracerebral event-related potentials (iERP. In parallel, a new research stream has emerged using high-frequency gamma-band activity (50-150 Hz (GBR and low-frequency alpha/beta activity (8-24 Hz (ABR to map functional networks in humans. An obvious question is now whether the functional organization of the visual cortex revealed by fMRI, ERP, GBR, and ABR coincide. We used direct intracerebral recordings in 18 epileptic patients to directly compare GBR, ABR, and ERP elicited by the presentation of seven major visual object categories (faces, scenes, houses, consonants, pseudowords, tools, and animals, in relation to previous fMRI studies. Remarkably both GBR and iERP showed strong category-specificity that was in many cases sufficient to infer stimulus object category from the neural response at single-trial level. However, we also found a strong discrepancy between the selectivity of GBR, ABR, and ERP with less than 10% of spatial overlap between sites eliciting the same category-specificity. Overall, we found that selective neural responses to visual objects were broadly distributed in the brain with a prominent spatial cluster located in the posterior temporal cortex. Moreover, the different neural markers (GBR, ABR, and iERP that elicit selectivity towards specific visual object categories present little spatial overlap suggesting that the information content of each marker can uniquely characterize high-level visual information in the brain.

  18. 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.

  19. A quick method for estimation of long-lived alpha activity in work atmospheres

    International Nuclear Information System (INIS)

    Srivastava, G.K.; Ramakrishna Rao, A.; Balbudhe, A.Y.; Sarma, P.S.

    2003-01-01

    In an operating plant quick reporting of the status of long-lived alpha activity concentrations in the work atmosphere is required. This will help in taking any corrective control measures if required. Radon and thoron progeny concentrations prevalent in the general atmosphere predominantly interfere in measurement of long-lived alpha activity in air. The alpha counts due to radon and thoron progeny vary widely in many atmospheric conditions. Therefore, conventionally, 5 days delay is allowed for all interfering activity to decay completely and true alpha air activity is then estimated. An approach for quick assessment of long-lived alpha activity by eliminating interference due to radon and thoron progeny in air, is made here. Based on the study of the pattern of alpha count rate due to radon and thoron progeny in air, a method for estimation of long-lived alpha activity within 8 hours delay time is suggested in this paper. (author)

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  1. Inhibitory activity and conformational transition of alpha 1-proteinase inhibitor variants

    NARCIS (Netherlands)

    Schulze, A.J.; Huber, R.; Degryse, E.; Speck, D.; Bischoff, Rainer

    1991-01-01

    Several variants of alpha 1-proteinase inhibitor (alpha 1-PI) were investigated by spectroscopic methods and characterized according to their inhibitory activity. Replacement of Thr345 (P14) with Arg in alpha 1-PI containing an Arg residue in position 358 (yielding [Thr345----Arg,

  2. Individual Alpha Peak Frequency Predicts 10 Hz Flicker Effects on Selective Attention.

    Science.gov (United States)

    Gulbinaite, Rasa; van Viegen, Tara; Wieling, Martijn; Cohen, Michael X; VanRullen, Rufin

    2017-10-18

    Rhythmic visual stimulation ("flicker") is primarily used to "tag" processing of low-level visual and high-level cognitive phenomena. However, preliminary evidence suggests that flicker may also entrain endogenous brain oscillations, thereby modulating cognitive processes supported by those brain rhythms. Here we tested the interaction between 10 Hz flicker and endogenous alpha-band (∼10 Hz) oscillations during a selective visuospatial attention task. We recorded EEG from human participants (both genders) while they performed a modified Eriksen flanker task in which distractors and targets flickered within (10 Hz) or outside (7.5 or 15 Hz) the alpha band. By using a combination of EEG source separation, time-frequency, and single-trial linear mixed-effects modeling, we demonstrate that 10 Hz flicker interfered with stimulus processing more on incongruent than congruent trials (high vs low selective attention demands). Crucially, the effect of 10 Hz flicker on task performance was predicted by the distance between 10 Hz and individual alpha peak frequency (estimated during the task). Finally, the flicker effect on task performance was more strongly predicted by EEG flicker responses during stimulus processing than during preparation for the upcoming stimulus, suggesting that 10 Hz flicker interfered more with reactive than proactive selective attention. These findings are consistent with our hypothesis that visual flicker entrained endogenous alpha-band networks, which in turn impaired task performance. Our findings also provide novel evidence for frequency-dependent exogenous modulation of cognition that is determined by the correspondence between the exogenous flicker frequency and the endogenous brain rhythms. SIGNIFICANCE STATEMENT Here we provide novel evidence that the interaction between exogenous rhythmic visual stimulation and endogenous brain rhythms can have frequency-specific behavioral effects. We show that alpha-band (10 Hz) flicker impairs stimulus

  3. 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.

  4. Molecular design and structure--activity relationships leading to the potent, selective, and orally active thrombin active site inhibitor BMS-189664.

    Science.gov (United States)

    Das, Jagabandhu; Kimball, S David; Hall, Steven E; Han, Wen Ching; Iwanowicz, Edwin; Lin, James; Moquin, Robert V; Reid, Joyce A; Sack, John S; Malley, Mary F; Chang, Chiehying Y; Chong, Saeho; Wang-Iverson, David B; Roberts, Daniel G M; Seiler, Steven M; Schumacher, William A; Ogletree, Martin L

    2002-01-07

    A series of structurally novel small molecule inhibitors of human alpha-thrombin was prepared to elucidate their structure-activity relationships (SARs), selectivity and activity in vivo. BMS-189664 (3) is identified as a potent, selective, and orally active reversible inhibitor of human alpha-thrombin which is efficacious in vivo in a mouse lethality model, and at inhibiting both arterial and venous thrombosis in cynomolgus monkey models.

  5. Rapid determination of gross alpha and beta activity in seafood utilizing microwave digestion and liquid scintillation counting

    International Nuclear Information System (INIS)

    Daniel Sas; Jiri Janda; Alena Tokarova

    2015-01-01

    This paper describes a method for rapid determination of gross alpha and beta activity in seafood using liquid scintillation counting and microwave digestion for fast sample decomposition. The general group of seafood was divided into two groups based on its structure, whether it has shell or not. The selected group of radionuclides was chosen with respect to military significance, radiotoxicity, and possibility of potential misuse. 90 Sr and 239 Pu were selected as model radionuclides. (author)

  6. Selective alpha-particle mediated depletion of tumor vasculature with vascular normalization.

    Directory of Open Access Journals (Sweden)

    Jaspreet Singh Jaggi

    2007-03-01

    Full Text Available Abnormal regulation of angiogenesis in tumors results in the formation of vessels that are necessary for tumor growth, but compromised in structure and function. Abnormal tumor vasculature impairs oxygen and drug delivery and results in radiotherapy and chemotherapy resistance, respectively. Alpha particles are extraordinarily potent, short-ranged radiations with geometry uniquely suitable for selectively killing neovasculature.Actinium-225 ((225Ac-E4G10, an alpha-emitting antibody construct reactive with the unengaged form of vascular endothelial cadherin, is capable of potent, selective killing of tumor neovascular endothelium and late endothelial progenitors in bone-marrow and blood. No specific normal-tissue uptake of E4G10 was seen by imaging or post-mortem biodistribution studies in mice. In a mouse-model of prostatic carcinoma, (225Ac-E4G10 treatment resulted in inhibition of tumor growth, lower serum prostate specific antigen level and markedly prolonged survival, which was further enhanced by subsequent administration of paclitaxel. Immunohistochemistry revealed lower vessel density and enhanced tumor cell apoptosis in (225Ac-E4G10 treated tumors. Additionally, the residual tumor vasculature appeared normalized as evident by enhanced pericyte coverage following (225Ac-E4G10 therapy. However, no toxicity was observed in vascularized normal organs following (225Ac-E4G10 therapy.The data suggest that alpha-particle immunotherapy to neovasculature, alone or in combination with sequential chemotherapy, is an effective approach to cancer therapy.

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

    Directory of Open Access Journals (Sweden)

    Reini F Luco

    2008-05-01

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

  8. 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.

  9. On alpha activity relationships in 226Ra and U/sub nat/

    International Nuclear Information System (INIS)

    Krejbichova, Z.

    1982-01-01

    A gross alpha activity of 0.1 Bq/l is permitted for drinking and surface waters. If gross activity is higher, it is suitable to determine the 226 Ra content which must not exceed 0.1 Bq/l. The permissible content of natural uranium is 0.05 mg/l. In most samples of ground and surface waters gross alpha activity was below the permissible limit. In some samples with a high content of salts a higher Ra+U activity was found which exceeded gross activity. This was caused by the interference of nonradioactive admixtures. In other samples a higher gross alpha activity was found than was the sum Ra+U which may have been caused by alpha sources from radon decay. It was found that the gross alpha activity of waters is rather caused by uranium than by radium. (E.S.)

  10. Variability of the Lyman alpha flux with solar activity

    International Nuclear Information System (INIS)

    Lean, J.L.; Skumanich, A.

    1983-01-01

    A three-component model of the solar chromosphere, developed from ground based observations of the Ca II K chromospheric emission, is used to calculate the variability of the Lyman alpha flux between 1969 and 1980. The Lyman alpha flux at solar minimum is required in the model and is taken as 2.32 x 10 11 photons/cm 2 /s. This value occurred during 1975 as well as in 1976 near the commencement of solar cycle 21. The model predicts that the Lyman alpha flux increases to as much as 5 x 10 11 photons/cm 2 /s at the maximum of the solar cycle. The ratio of the average fluxes for December 1979 (cycle maximum) and July 1976 (cycle minimum) is 1.9. During solar maximum the 27-day solar rotation is shown to cause the Lyman alpha flux to vary by as much as 40% or as little as 5%. The model also shows that the Lyman alpha flux varies over intermediate time periods of 2 to 3 years, as well as over the 11-year sunspot cycle. We conclude that, unlike the sunspot number and the 10.7-cm radio flux, the Lyman alpha flux had a variability that was approximately the same during each of the past three cycles. Lyman alpha fluxes calculated by the model are consistent with measurements of the Lyman alpha flux made by 11 of a total of 14 rocket experiments conducted during the period 1969--1980. The model explains satisfactorily the absolute magnitude, long-term trends, and the cycle variability seen in the Lyman alpha irradiances by the OSO 5 satellite experiment. The 27-day variability observed by the AE-E satellite experiment is well reproduced. However, the magntidue of the AE-E 1 Lyman alpha irradiances are higher than the model calculations by between 40% and 80%. We suggest that the assumed calibration of the AE-E irradiances is in error

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  13. A method of alpha-radiating nuclide activity measuring in aerosol filters

    International Nuclear Information System (INIS)

    Ignatov, V.P.; Galkina, V.N.

    1992-01-01

    Scintillation method of determination of alpha-radiating nuclide activity in aerosol filters was suggested. The method involves dissolution of the filter in organic solvent, introduction of luminophore into solution prepared, drying of the preparation and measurement of radionuclide activity. Dependences of alpha-radiation detection efficiency on the content of luminophore, filter material, colourless and coloured substances in preparations analyzed were considered

  14. 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.

  15. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Dipak [School of Studies in Environmental Radiation and Archaeological Sciences, Jadavpur University, Kolkata 700 032 (India); Nuclear and Particle Physics Research Centre, Department of Physics, Jadavpur University, Kolkata 700 032 (India)], E-mail: dipakghosh_in@yahoo.com; Deb, Argha; Bera, Sukumar; Sengupta, Rosalima; Patra, Kanchan Kumar [School of Studies in Environmental Radiation and Archaeological Sciences, Jadavpur University, Kolkata 700 032 (India); Nuclear and Particle Physics Research Centre, Department of Physics, Jadavpur University, Kolkata 700 032 (India)

    2008-02-15

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

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

    International Nuclear Information System (INIS)

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

    2008-01-01

    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 ± 16.8 Bq kg -1 . The alpha activity of ceramic tiles was highest and provides additional data to estimate the effect of environmental radiation exposure on human health

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

    Science.gov (United States)

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

    2006-03-01

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

  19. Causality analysis of alpha activities by multidimensional directed coherence; Tajigen yuko coherence ni yoru {alpha}ritsudo no ingasei kaiseki

    Energy Technology Data Exchange (ETDEWEB)

    Sakata, O.; Shimada, N.; Shiina, T. [University of Tsukuba, Tsukuba (Japan); Saito, Y.; Imanishi, N.

    1998-07-01

    Alpha activities as a basic component of EEG (electroencephalogram) are mainly observed with eye-closed and reported state, and indicates rhythmic and diffused pattern on the scalp. Therefore analysis of the relation among many sequences of alpha activities measured at different positions on the scalp is expected to be useful not only for diagnosing psychiatric but also for investigating mechanism of brain information processing by means of causality analysis that is, macroscopic estimation of flow pattern within brain. Although coherence analysis has been proposed as a method for estimating the direction and magnitude of information flow between two sequences, superposition of results for each pair of sequences can not represent true relation among the whole sequences. In this paper, we proposed the multidimensional directed coherence analysis by modifying two-channel formula in order to apply it to the analysis of multi-channel sequence of alpha activities. Results of simulation revealed that multidimensional directed coherence can indicate more quantitatively the relation among the multi-channel sequences compared with conventional two-channel formula. Moreover, the proposed method was applied to the analysis of EEG data of normal volunteer and patient. Results show the method can provide a useful diagnostic information by assessment of the signal flow pattern within brain. 16 refs., 10 figs.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  1. Activation of the skeletal alpha-actin promoter during muscle regeneration.

    Science.gov (United States)

    Marsh, D R; Carson, J A; Stewart, L N; Booth, F W

    1998-11-01

    Little is known concerning promoter regulation of genes in regenerating skeletal muscles. In young rats, recovery of muscle mass and protein content is complete within 21 days. During the initial 5-10 days of regeneration, mRNA abundance for IGF-I, myogenin and MyoD have been shown to be dramatically increased. The skeletal alpha-actin promoter contains E box and serum response element (SRE) regulatory regions which are directly or indirectly activated by myogenin (or MyoD) and IGF-I proteins, respectively. We hypothesized that the skeletal alpha-actin promoter activity would increase during muscle regeneration, and that this induction would occur before muscle protein content returned to normal. Total protein content and the percentage content of skeletal alpha-actin protein was diminished at 4 and 8 days and re-accumulation had largely occurred by 16 days post-bupivacaine injection. Skeletal alpha-actin mRNA per whole muscle was decreased at day 8, and thereafter returned to control values. During regeneration at day 8, luciferase activity (a reporter of promoter activity) directed by -424 skeletal alpha-actin and -99 skeletal alpha-actin promoter constructs was increased by 700% and 250% respectively; however, at day 16, skeletal alpha-actin promoter activities were similar to control values. Thus, initial activation of the skeletal alpha-actin promoter is associated with regeneration of skeletal muscle, despite not being sustained during the later stages of regrowth. The proximal SRE of the skeletal alpha-actin promoter was not sufficient to confer a regeneration-induced promoter activation, despite increased serum response factor protein binding to this regulatory element in electrophoretic mobility shift assays. Skeletal alpha-actin promoter induction during regeneration is due to a combination of regulatory elements, at least including the SRE and E box.

  2. A right-ear bias of auditory selective attention is evident in alpha oscillations.

    Science.gov (United States)

    Payne, Lisa; Rogers, Chad S; Wingfield, Arthur; Sekuler, Robert

    2017-04-01

    Auditory selective attention makes it possible to pick out one speech stream that is embedded in a multispeaker environment. We adapted a cued dichotic listening task to examine suppression of a speech stream lateralized to the nonattended ear, and to evaluate the effects of attention on the right ear's well-known advantage in the perception of linguistic stimuli. After being cued to attend to input from either their left or right ear, participants heard two different four-word streams presented simultaneously to the separate ears. Following each dichotic presentation, participants judged whether a spoken probe word had been in the attended ear's stream. We used EEG signals to track participants' spatial lateralization of auditory attention, which is marked by interhemispheric differences in EEG alpha (8-14 Hz) power. A right-ear advantage (REA) was evident in faster response times and greater sensitivity in distinguishing attended from unattended words. Consistent with the REA, we found strongest parietal and right frontotemporal alpha modulation during the attend-right condition. These findings provide evidence for a link between selective attention and the REA during directed dichotic listening. © 2016 Society for Psychophysiological Research.

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

    International Nuclear Information System (INIS)

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

    1996-02-01

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

  4. 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.

  5. 6-Mercaptopurine, an activator of Nur77, enhances transcriptional activity of HIF-1alpha resulting in new vessel formation.

    Science.gov (United States)

    Yoo, Y-G; Na, T-Y; Yang, W-K; Kim, H-J; Lee, I-K; Kong, G; Chung, J-H; Lee, M-O

    2007-05-31

    Hypoxia-inducible factor-1alpha (HIF-1alpha) plays a central role in oxygen homeostasis. Previously, we reported that the orphan nuclear receptor Nur77 functions in stabilizing HIF-1alpha. Here, we demonstrate that 6-mercaptopurine (6-MP), an activator of the NR4A family members, enhances transcriptional activity of HIF-1. 6-MP enhanced the protein-level of HIF-1alpha as well as vascular endothelial growth factor (VEGF) in a dose- and time-dependent manner. The induction of HIF-1alpha was abolished by the transfection of either a dominant-negative Nur77 mutant or si-Nur77, indicating a critical role of Nur77 in the 6-MP action. The HIF-1alpha protein level remained up to 60 min in the presence of 6-MP when de novo protein synthesis was blocked by cycloheximide, suggesting that 6-MP induces stabilization of the HIF-1alpha protein. The fact that 6-MP decreased the association of HIF-1alpha with von Hippel-Lindau protein and the acetylation of HIF-1alpha, may explain how 6-MP induced stability of HIF-1alpha. Further, 6-MP induced the transactivation function of HIF-1alpha by recruiting co-activator cyclic-AMP-response-element-binding protein. Finally, 6-MP enhanced the expression of HIF-1alpha and VEGF, and the formation of capillary tubes in human umbilical vascular endothelial cells. Together, our results provide a new insight for 6-MP action in the stabilization of HIF-1alpha and imply a potential application of 6-MP in hypoxia-associated human vascular diseases.

  6. Determination of alpha activity and fissile mass content in solid waste by systems using neutron interrogation

    International Nuclear Information System (INIS)

    Romeyer Dherbey, J.; Lacruche, G.; Berne, R.; Auge, J.; Martin Deidier, L.; Butez, M.

    1990-01-01

    The Quantitative control (determination of heavy nuclides and alpha activity) of alpha radioactive wastes is necessary, particularly to determine if the waste is in accordance with the surface storage limits. In order to reduce the uncertainty on the alpha activity resulting from unknown isotopic composition, inhomogeneity of heavy nuclides in the matrix, combination of several methods is necessary. In the paper we present the Cadarache development work in the NDA of solid waste using the Californium shuffler, 14 Mev neutron generator, and also passive techniques such as neutron emission measurement and gamma spectrometry. Experimental systems combining active and passive methods are presented (COSAC, BANCO, DANAIDE, PROMETHEE)

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

    DEFF Research Database (Denmark)

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

    1998-01-01

    The ADAMs (a disintegrin and metalloprotease) are a family of multidomain proteins with structural homology to snake venom metalloproteases. We recently described the cloning and sequencing of human ADAM 12 (meltrin alpha). In this report we provide evidence that the metalloprotease domain of ADAM...

  8. Measurement of very low alpha activity in water

    International Nuclear Information System (INIS)

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

    1987-01-01

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

  9. Different responses of spontaneous and stimulus-related alpha activity to ambient luminance changes.

    Science.gov (United States)

    Benedetto, Alessandro; Lozano-Soldevilla, Diego; VanRullen, Rufin

    2017-12-04

    Alpha oscillations are particularly important in determining our percepts and have been implicated in fundamental brain functions. Oscillatory activity can be spontaneous or stimulus-related. Furthermore, stimulus-related responses can be phase- or non-phase-locked to the stimulus. Non-phase-locked (induced) activity can be identified as the average amplitude changes in response to a stimulation, while phase-locked activity can be measured via reverse-correlation techniques (echo function). However, the mechanisms and the functional roles of these oscillations are far from clear. Here, we investigated the effect of ambient luminance changes, known to dramatically modulate neural oscillations, on spontaneous and stimulus-related alpha. We investigated the effect of ambient luminance on EEG alpha during spontaneous human brain activity at rest (experiment 1) and during visual stimulation (experiment 2). Results show that spontaneous alpha amplitude increased by decreasing ambient luminance, while alpha frequency remained unaffected. In the second experiment, we found that under low-luminance viewing, the stimulus-related alpha amplitude was lower, and its frequency was slightly faster. These effects were evident in the phase-locked part of the alpha response (echo function), but weaker or absent in the induced (non-phase-locked) alpha responses. Finally, we explored the possible behavioural correlates of these modulations in a monocular critical flicker frequency task (experiment 3), finding that dark adaptation in the left eye decreased the temporal threshold of the right eye. Overall, we found that ambient luminance changes impact differently on spontaneous and stimulus-related alpha expression. We suggest that stimulus-related alpha activity is crucial in determining human temporal segmentation abilities. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

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

    International Nuclear Information System (INIS)

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

    1996-01-01

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

  11. Measurement of gross alpha - activity in some thermal water sources in Yugoslavia by SSNTDs

    International Nuclear Information System (INIS)

    Benderac, R.; Ristic, D.; Antanasijevic, R.; Vukovic, J.

    1991-01-01

    The possible application of the CN-BDH (type 1) nitrocellulose detector synthesized in laboratory conditions, and also the CR-39 detector, to the measurement of the gross alpha-activity of geothermal and mineral water has been investigated. (author)

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

    International Nuclear Information System (INIS)

    Tobias, C.C.B.

    1987-01-01

    The absolute activity of U-235 contained in a U 3 O 8 sample was measured utilizing a sum-coincidence circuit which selects only the alpha particles which are simultaneous with the 143 KeV and 186 KeV gamma radiations from the Th-231 (product nucleus). The alpha particles were detected by means of a new type of a gas scintillating chamber, in which the light emitted by excitation of the gas atoms, due to the passage of a charged incoming particle, has its intensity increased by the action of an applied electric field. The gamma radiations were detected by means of a NaI(Tl) 1'' x 1 1/2'' scintillation detector. The value obtained for the half-life of U-235 was compared with the data available from various observers which used different experimental techniques. It is shown tht the results, are in excellent agreement with the best international data available on the subject and that, therefore, the sum-coincidence technique constitutes an important method for such measurements. (Author) [pt

  13. Orgasm is preserved regardless of ejaculatory dysfunction with selective alpha1A-blocker administration.

    Science.gov (United States)

    Kobayashi, K; Masumori, N; Kato, R; Hisasue, S; Furuya, R; Tsukamoto, T

    2009-01-01

    We evaluated whether ejaculatory dysfunction induced with a selective alpha1A-blocker influenced orgasm. Fifteen healthy male volunteers took silodosin or a placebo in a randomized, double-blind crossover design. We investigated the ejaculatory volume before and after administration of the agents. After each ejaculation, participants self-reported the answers to an original questionnaire, which was about discomfort on ejaculation, orgasm and satisfaction with the discomforting ejaculation. All participants on silodosin had a complete lack of seminal emission and expulsion. All participants felt orgasm in spite of a complete lack of seminal emission. Of the 15, 12 (80%) who had a somewhat uncomfortable feeling during orgasm were dissatisfied with this feeling, although 9 of the 12 reported that its degree was mild. Orgasm is preserved regardless of the loss of seminal emission with silodosin administration. Although most participants reported mild discomfort during orgasm, they were greatly dissatisfied with the loss of seminal emission.

  14. Faint H-alpha emission objects near the equatorial selected areas

    International Nuclear Information System (INIS)

    Robertson, T.H.; Jordan, T.M.

    1989-01-01

    An objective-prism survey of fields centered on the 24 Kapteyn Selected Areas along the celestial equator has resulted in the detection of 120 faint H-alpha emission-line objects. Diffuse objects and stars having molecular bands in their spectra are not included. Only 18 of these stars were identified in previous lists of emission-line objects. Identifications were found for an additional three stars. Images of these objects appear to be stellar on direct plates. The magnitude range for these stars is V = 10.1-19.00. Positions and V magnitudes of these objects are provided, as are identifications of objects which have been reported in other lists. Frequency distributions of the apparent magnitudes and Galactic latitudes of these emission-line objects are discussed, and finding charts are provided. 14 refs

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

    Directory of Open Access Journals (Sweden)

    Yuichi Kitaura

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

  16. Evidence for a prolonged role of alpha 4 integrin throughout active experimental allergic encephalomyelitis.

    Science.gov (United States)

    Keszthelyi, E; Karlik, S; Hyduk, S; Rice, G P; Gordon, G; Yednock, T; Horner, H

    1996-10-01

    The leukocyte integrin receptor, alpha 4 beta 1, and its endothelial cell ligand, vascular cell adhesion molecule 1, appear to be of critical importance in the leukocyte trafficking that accompanies CNS damage in experimental allergic encephalomyelitis (EAE). In this study, the persistence of the role for alpha 4 beta 1/VCAM-1 in EAE was established by observing antibody-mediated disease reversal up to 1 month following disease onset. Limited treatment with a monoclonal antibody against alpha 4 integrin, GG5/3, resulted in a significant decrease in both clinical and histopathologic signs. This was not observed in isotype control experiments. In the latter phase of progressive disease, widespread demyelination occurred in the animals that did not respond to 6 days of anti-alpha 4 treatment. These results demonstrate an essential role for alpha 4 beta 1 interactions throughout active EAE and illustrate the difference between reversible clinical deficits caused by edema and irreversible deficits associated with demyelination.

  17. 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...... gene contains several consensus C/EBP binding sites, only one of these sites appears to be functional. DNase I cleavage inhibition patterns (footprinting) of the ob gene promoter revealed that recombinant C/EBP alpha, as well as a nuclear factor present in fully differentiated 3T3-L1 adipocytes...... to a consensus C/EBP binding site at nucleotides -55 to -47 generated a specific protein-oligonucleotide complex that was supershifted by antibody against C/EBP alpha. Probes corresponding to two upstream consensus C/EBP binding sites failed to generate protein-oligonucleotide complexes. Cotransfection of a C...

  18. Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres.

    Science.gov (United States)

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

    2002-08-15

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

  19. Activity in X-ray-selected late-type stars

    International Nuclear Information System (INIS)

    Takalo, L.O.; Nousek, J.A.

    1988-01-01

    A spectroscopic study has been conducted of nine X-ray bright late-type stars selected from two Einstein X-ray surveys: the Columbia Astrophysical Laboratory Survey (five stars) and the CFA Medium Sensitivity Survey (MSS; four stars). Spectral classes were determined and radial and V sin(i) velocities were measured for the stars. Four of the Columbia Survey stars were found to be new RS CVn-type binaries. The fifth Columbia survey star was found to be an active G dwarf star without evidence for binarity. None of the four MSS stars were found to be either binaries or optically active stars. Activity in these stars was assessed by measuring the excess emission in H-alpha and the Ca II IRT (8498, 8542) lines in comparison with inactive stars of similar spectral types. A correlation was found between X-ray luminosity and V sin(i) and H-alpha line excess. The measured excess line emission in H-alpha was also correlated with V sin(i) but not with the IRT line excess. 36 references

  20. 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.

  1. Point mutations in the post-M2 region of human alpha-ENaC regulate cation selectivity.

    Science.gov (United States)

    Ji, H L; Parker, S; Langloh, A L; Fuller, C M; Benos, D J

    2001-07-01

    We tested the hypothesis that an arginine-rich region immediately following the second transmembrane domain may constitute part of the inner mouth of the epithelial Na+ channel (ENaC) pore and, hence, influence conduction and/or selectivity properties of the channel by expressing double point mutants in Xenopus oocytes. Double point mutations of arginines in this post-M2 region of the human alpha-ENaC (alpha-hENaC) led to a decrease and increase in the macroscopic conductance of alphaR586E,R587Ebetagamma- and alphaR589E,R591Ebetagamma-hENaC, respectively, but had no effect on the single-channel conductance of either double point mutant. However, the apparent equilibrium dissociation constant for Na+ was decreased for both alphaR586E,R587Ebetagamma- and alphaR589E,R591Ebetagamma-hENaC, and the maximum amiloride-sensitive Na+ current was decreased for alphaR586E,R587Ebetagamma-hENaC and increased for alphaR589E,R591Ebetagamma-hENaC. The relative permeabilities of Li+ and K+ vs. Na+ were increased 11.25- to 27.57-fold for alphaR586E,R587Ebetagamma-hENaC compared with wild type. The relative ion permeability of these double mutants and wild-type ENaC was inversely related to the crystal diameter of the permeant ions. Thus the region of positive charge is important for the ion permeation properties of the channel and may form part of the pore itself.

  2. Determination of total alpha and beta activities on vegetable samples by LSC

    International Nuclear Information System (INIS)

    Nogueira, Regina Apolinaria; Santos, Eliane Eugenia dos; Bakker, Alexandre Pereira; Vavassori, Giullia

    2011-01-01

    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

  3. Nitric oxide production and monoamine oxidase activity in cancer patients during interferon-alpha therapy.

    Science.gov (United States)

    Fekkes, Durk; Van Gool, Arthur R; Bannink, Marjolein; Sleijfer, Stefan; Kruit, Wim H J; van der Holt, Bronno; Eggermont, Alexander M M; Hengeveld, Michiel W; Stoter, Gerrit

    2009-10-01

    Both increased and decreased nitric oxide (NO) synthesis have been reported in patients treated with interferon-alpha (IFN-alpha). Animal studies showed that IFN-alpha administration results in increased levels of biogenic amines, subsequent activation of monoamine oxidases (MAOs), and finally in a change in NO production due to the H(2)O(2) generated by MAOs. We examined the potential relationship between NO production in plasma and MAO-B activity in platelets of 43 cancer patients during 8 weeks of treatment with IFN-alpha. NO synthesis was quantitated by measuring both the ratio of citrulline and arginine (CIT/ARG-ratio) and total nitrite/nitrate (NOx) levels. Compared to baseline, MAO activity and NOx increased, while the CIT/ARG-ratio decreased. No associations were found between NOx, MAO and CIT/ARG-ratio. Only few associations were observed between changes in the biochemical parameters and changes in psychopathology induced by IFN-alpha, of which the association between changes in CIT and lassitude was the most consistent. The results suggest that peripheral NO production and MAO activity are unrelated to each other, and that peripheral changes in these biochemical parameters induced by IFN-alpha are unlikely to contribute to definite psychiatric disturbance.

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

    International Nuclear Information System (INIS)

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

    2001-01-01

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

  5. [G-protein potentiates the activation of TNF-alpha on calcium-activated potassium channel in ECV304].

    Science.gov (United States)

    Lin, L; Zheng, Y; Qu, J; Bao, G

    2000-06-01

    Observe the effect of tumor necrosis factor-alpha (TNF-alpha) on calcium-activated potassium channel in ECV304 and the possible involvement of G-protein mediation in the action of TNF-alpha. Using the cell-attached configuration of patch clamp technique. (1) the activity of high-conductance calcium-activated potassium channel (BKca) was recorded. Its conductance is (202.54 +/- 16.62) pS; (2) the activity of BKca was potentiated by 200 U/ml TNF-alpha; (3) G-protein would intensify this TNF-alpha activation. TNF-alpha acted on vascular endothelial cell ECV304 could rapidly activate the activity of BKca. Opening of BKca resulted in membrane hyper-polarization which could increase electro-chemical gradient for the resting Ca2+ influx and open leakage calcium channel, thus resting cytoplasmic free Ca2+ concentration could be elevated. G-protein may exert an important regulation in this process.

  6. 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)

  7. Interleukin 2 and 15 activate Stat3alpha in human T lymphocytes

    DEFF Research Database (Denmark)

    Nielsen, M; Nordahl, M; Svejgaard, A

    1998-01-01

    Signal transducer and activator of transcription 3 (Stat3) has recently been shown to exist in two alternatively spliced isoforms, a short form, Stat3beta, and a longer form, Stat3alpha, displaying differences in transcriptional activity. It is unknown which Stat3 isoform(s) is activated in respo...

  8. Reactivation of the chloroplast CF1-ATPase beta subunit by trace amounts of the CF1 alpha subunit suggests a chaperonin-like activity for CF1 alpha.

    Science.gov (United States)

    Avni, A; Avital, S; Gromet-Elhanan, Z

    1991-04-25

    Incubation of tobacco and lettuce thylakoids with 2 M LiCl in the presence of MgATP removes the beta subunit from their CF1-ATPase (CF1 beta) together with varying amounts of the CF1 alpha subunit (CF1 alpha). These 2 M LiCl extracts, as with the one obtained from spinach thylakoids (Avital, S., and Gromet-Elhanan, Z. (1991) J. Biol. Chem. 266, 7067-7072), could form active hybrid ATPases when reconstituted into inactive beta-less Rhodospirillum rubrum chromatophores. Pure CF1 beta fractions that have been isolated from these extracts could not form such active hybrids by themselves, but could do so when supplemented with trace amounts (less than 5%) of CF1 alpha. A mitochondrial F1-ATPase alpha subunit was recently reported to be a heat-shock protein, having two amino acid sequences that show a highly conserved identity with sequences found in molecular chaperones (Luis, A. M., Alconada, A., and Cuezva, J. M. (1990) J. Biol. Chem. 265, 7713-7716). These sequences are also conserved in CF1 alpha isolated from various plants, but not in F1 beta subunits. The above described reactivation of CF1 beta by trace amounts of CF1 alpha could thus be due to a chaperonin-like function of CF1 alpha, which involves the correct, active folding of isolated pure CF1 beta.

  9. Estimation of low level gross alpha activities in the radioactive effluent using liquid scintillation counting technique

    International Nuclear Information System (INIS)

    Bhade, Sonali P.D.; Johnson, Bella E.; Singh, Sanjay; Babu, D.A.R.

    2012-01-01

    A technique has been developed for simultaneous measurement of gross alpha and gross beta activity concentration in low level liquid effluent samples in presence of higher activity concentrations of tritium. For this purpose, alpha beta discriminating Pulse Shape Analysis Liquid Scintillation Counting (LSC) technique was used. Main advantages of this technique are easy sample preparation, rapid measurement and higher sensitivity. The calibration methodology for Quantulus1220 LSC based on PSA technique using 241 Am and 90 Sr/ 90 Y as alpha and beta standards respectively was described in detail. LSC technique was validated by measuring alpha and beta activity concentrations in test samples with known amount of 241 Am and 90 Sr/ 90 Y activities spiked in distilled water. The results obtained by LSC technique were compared with conventional planchet counting methods such as ZnS(Ag) and end window GM detectors. The gross alpha and gross beta activity concentrations in spiked samples, obtained by LSC technique were found to be within ±5% of the reference values. (author)

  10. Selective oxidation of methyl {alpha}-D-glucopyranoside with oxygen over supported platinum: Kinetic modeling in the presence of deactivation by overoxidation of the catalyst

    Energy Technology Data Exchange (ETDEWEB)

    Vleeming, J.H.; Kuster, B.F.M.; Marin, G.B. [Eindhoven Univ. of Technology (Netherlands)

    1997-09-01

    The selective oxidation of alcohols and carbohydrates with molecular oxygen in aqueous media is an industrial and environmental attractive process. A kinetic model is presented, which describes the platinum-catalyzed selective oxidation of methyl {alpha}-D-glucopyranoside to sodium methyl {alpha}-D-glucuronate with molecular oxygen in the presence of deactivation by overoxidation. Overoxidation is completely reversible and most adequately described by a reversible transformation of oxygen adatoms into inactive subsurface oxygen. A clear distinction is made between the rapid establishment of the steady-state degree of coverage by the reaction intermediates at the platinum surface and the much slower reversible process of overoxidation. This clear distinction is reflected in the rate equation, which can be written as the product of an initial rate and a deactivation function. The deactivation function is given as a function of the degree of coverage by inactive subsurface oxygen. The rate-determining step in the selective oxidation consists of the reaction between dissociatively chemisorbed oxygen and physisorbed methyl {alpha}-D-glucopyranoside. The corresponding standard activation entropy and enthalpy amount to respectively {minus}111 {+-} 12 J/mol K and 51 {+-} 4 kJ/mol. The standard reaction entropy for the transformation of oxygen atoms into subsurface oxygen amounts to {minus}35 {+-} 16 J/mol K and the standard reaction enthalpy to {minus}36 {+-} 15 kJ/mol.

  11. A sequential extraction procedure to determine Ra and U isotopes by alpha-particle spectrometry in selective leachates

    International Nuclear Information System (INIS)

    Aguado, J.L.; Bolivar, J.P.; San-Miguel, E.G.; Garcia-Tenorio, R.

    2003-01-01

    A radiochemical sequential extraction procedure has been developed in our laboratory to determine 226 Ra and 234,238 U by alpha spectrometry in environmental samples. This method has been validated for both radionuclides by comparing in selected samples the values obtained through its application with the results obtained by applying alternative procedures. Recoveries obtained, counting periods applied and background levels found in the alpha spectra give suitable detection limits to allow the Ra and U determination in operational forms defined in riverbed contaminated sediments. Results obtained in these speciation studies show that 226 Ra and 234,238 U contamination tend to be associated to precipitated forms of the sediments. (author)

  12. Development of methodology for detection of long lived alpha emitters in air based on simultaneous alpha and beta activity measurement

    International Nuclear Information System (INIS)

    Kaushik, Vivek; Rath, D.P.; Vinayagami, Bhakti; Ashokkumar, P.; Umashankar, C.; Gopalakrishnan, R.K.; Kulkarni, M.S.

    2018-01-01

    Interference of the radon and thoron progeny co-deposited on the filtration media is the long-standing problem related to prompt analyses in continuous air sampling or monitoring of any potential suspect radionuclides. The solutions to this problem have been quite diverse, and included, for example, simple gross-alpha counting, the use of beta-to-alpha ratios, and the use of alpha spectrum analyses. The techniques based on beta to alpha disintegration ratios make use of the naturally occurring alpha to beta disintegration ratios and departures therefrom. This ratio is found empirically to be relatively constant. With the help of the solution of differential equation, which govern the deposition of radionuclide on filter paper, one can easily estimate theoretically the behavior of the radon progeny alpha to beta disintegration (or count) rate ratio

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

    International Nuclear Information System (INIS)

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

    1996-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Hironori eNakatani

    2013-05-01

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

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

    International Nuclear Information System (INIS)

    Bains, M.E.D.

    1963-07-01

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

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2014-08-01

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

  18. Correlation between protein kinase C alpha activity and membrane phase behavior.

    Science.gov (United States)

    Micol, V; Sánchez-Piñera, P; Villalaín, J; de Godos, A; Gómez-Fernández, J C

    1999-02-01

    Lipid activation of protein kinase C alpha (PKC alpha) was studied by using a model mixture containing 1, 2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1, 2-dimyristoyl-sn-glycero-3-phosphoserine (DMPS), and 1, 2-dimyristoyl-sn-glycerol (1,2-DMG). This lipid mixture was physically characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and 31P-nuclear magnetic resonance (31P-NMR). Based on these techniques, a phase diagram was constructed by keeping a constant DMPC/DMPS molar ratio of 4:1 and changing the concentration of 1,2-DMG. This phase diagram displayed three regions and two compounds: compound 1 (C1), with 45 mol% 1,2-DMG, and compound 2 (C2), with 60 mol% 1,2-DMG. When the phase diagram was elaborated in the presence of Ca2+ and Mg2+, at concentrations similar to those used in the PKC alpha activity assay, the boundaries between the regions changed slightly and C1 had 35 mol% 1,2-DMG. The activity of PKC alpha was studied at several temperatures and at different concentrations of 1,2-DMG, with a maximum of activity reached at 30 mol% 1,2-DMG and lower values at higher concentrations. In the presence of Ca2+ and Mg2+, maximum PKC alpha activity occurred at concentrations of 1,2-DMG that were close to the boundary in the phase diagram between region 1, where compound C1 and the pure phospholipid coexisted in the gel phase, and region 2, where compounds C1 and C2 coexisted. These results suggest that the membrane structure corresponding to a mixture of 1,2-DMG/phospholipid complex and free phospholipid is better able to support the activity of PKC alpha than the 1,2-DMG/phospholipid complex alone.

  19. 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.

  20. 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.

  1. Frontal alpha EEG asymmetry before and after behavioral activation treatment for depression.

    Science.gov (United States)

    Gollan, Jackie K; Hoxha, Denada; Chihade, Dietta; Pflieger, Mark E; Rosebrock, Laina; Cacioppo, John

    2014-05-01

    Mid-frontal and mid-lateral (F3/F4 and F7/F8) EEG asymmetry has been associated with motivation and affect. We examined alpha EEG asymmetry in depressed and healthy participants before and after Behavioral Activation treatment for depression; examined the association between alpha EEG asymmetry and motivational systems and affect; and evaluated the utility of alpha EEG asymmetry in predicting remission. Depressed (n=37) and healthy participants (n=35) were assessed before and after treatment using a clinical interview, a task to measure baseline EEG, and questionnaires of behavioral activation and inhibition, avoidance, and affect. Alpha EEG asymmetry was significantly higher in depressed than healthy participants at pre-treatment, positively correlated with negative affect and behavioral inhibition, and inversely correlated with lower behavioral activation sensitivity. Heightened alpha EEG asymmetry in depressed participants was significantly associated with increased behavioral inhibition and negative emotion and was independent of clinical remission. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. 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....

  3. Alpha activity of 190 Pt isotope measured with CR-39 track detector

    International Nuclear Information System (INIS)

    Tavares, O.A.P.; Terranova, M.L.

    1996-11-01

    A new method to measure alpha activity of long-lived radioisotopes is reported. The method consists basically in using CR-39 track detectors in close contact with thick samples of the radioelement to be investigated. Accordingly, a long-term exposure experiment has been performed using metallic sheets of natural platinum to measure alpha activity of platinum 190 isotope. The half-life of platinum 190 has been obtained in good agreement with two recent theoretical half-life predictions. (author). 21 refs., 3 figs., 2 tabs

  4. 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

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

    International Nuclear Information System (INIS)

    Galicia C, F. J.

    2015-01-01

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

  6. Alpha-helical hydrophobic polypeptides form proton-selective channels in lipid bilayers

    Science.gov (United States)

    Oliver, A. E.; Deamer, D. W.

    1994-01-01

    Proton translocation is important in membrane-mediated processes such as ATP-dependent proton pumps, ATP synthesis, bacteriorhodopsin, and cytochrome oxidase function. The fundamental mechanism, however, is poorly understood. To test the theoretical possibility that bundles of hydrophobic alpha-helices could provide a low energy pathway for ion translocation through the lipid bilayer, polyamino acids were incorporated into extruded liposomes and planar lipid membranes, and proton translocation was measured. Liposomes with incorporated long-chain poly-L-alanine or poly-L-leucine were found to have proton permeability coefficients 5 to 7 times greater than control liposomes, whereas short-chain polyamino acids had relatively little effect. Potassium permeability was not increased markedly by any of the polyamino acids tested. Analytical thin layer chromatography measurements of lipid content and a fluorescamine assay for amino acids showed that there were approximately 135 polyleucine or 65 polyalanine molecules associated with each liposome. Fourier transform infrared spectroscopy indicated that a major fraction of the long-chain hydrophobic peptides existed in an alpha-helical conformation. Single-channel recording in both 0.1 N HCl and 0.1 M KCl was also used to determine whether proton-conducting channels formed in planar lipid membranes (phosphatidylcholine/phosphatidylethanolamine, 1:1). Poly-L-leucine and poly-L-alanine in HCl caused a 10- to 30-fold increase in frequency of conductive events compared to that seen in KCl or by the other polyamino acids in either solution. This finding correlates well with the liposome observations in which these two polyamino acids caused the largest increase in membrane proton permeability but had little effect on potassium permeability. Poly-L-leucine was considerably more conductive than poly-L-alanine due primarily to larger event amplitudes and, to a lesser extent, a higher event frequency. Poly-L-leucine caused two

  7. Optimization methods for activities selection problems

    Science.gov (United States)

    Mahad, Nor Faradilah; Alias, Suriana; Yaakop, Siti Zulaika; Arshad, Norul Amanina Mohd; Mazni, Elis Sofia

    2017-08-01

    Co-curriculum activities must be joined by every student in Malaysia and these activities bring a lot of benefits to the students. By joining these activities, the students can learn about the time management and they can developing many useful skills. This project focuses on the selection of co-curriculum activities in secondary school using the optimization methods which are the Analytic Hierarchy Process (AHP) and Zero-One Goal Programming (ZOGP). A secondary school in Negeri Sembilan, Malaysia was chosen as a case study. A set of questionnaires were distributed randomly to calculate the weighted for each activity based on the 3 chosen criteria which are soft skills, interesting activities and performances. The weighted was calculated by using AHP and the results showed that the most important criteria is soft skills. Then, the ZOGP model will be analyzed by using LINGO Software version 15.0. There are two priorities to be considered. The first priority which is to minimize the budget for the activities is achieved since the total budget can be reduced by RM233.00. Therefore, the total budget to implement the selected activities is RM11,195.00. The second priority which is to select the co-curriculum activities is also achieved. The results showed that 9 out of 15 activities were selected. Thus, it can concluded that AHP and ZOGP approach can be used as the optimization methods for activities selection problem.

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  9. Measurement of gross alpha and gross beta activity concentrations in human tooth

    International Nuclear Information System (INIS)

    Soeguet, Omer; Aydin, Mehmet Fatih; Kuecuekoender, Erdal; Zorer, Ozlem Selcuk; Dogru, Mahmut

    2010-01-01

    The gross alpha and gross beta activity concentrations were measured in human tooth taken from 3 to 6 age-groups to 40 and over ones. Accumulated teeth samples are investigated in two groups as under and above 18 years. The gross alpha and beta radioactivity of human tooth samples was measured by using a gas-flow proportional counter (PIC-MPC 9604-α/β counter). In tooth samples, for female age-groups, the obtained results show that the mean gross alpha and gross beta activity concentrations varied between 0.534-0.203 and 0.010-0.453 Bq g -1 and the same concentrations for male age-groups varied between 0.009-1.168 and 0.071-0.204 Bq g -1 , respectively.

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

    Science.gov (United States)

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

    2018-02-20

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

  11. Tumor necrosis factor alpha selectively sensitizes human immunodeficiency virus-infected cells to heat and radiation

    International Nuclear Information System (INIS)

    Wong, G.H.; McHugh, T.; Weber, R.; Goeddel, D.V.

    1991-01-01

    We report here that infection of the human T-cell line HUT-78 with human immunodeficiency virus (HIV) increases its sensitivity to heat and radiation toxicity. A possible explanation for this result may be the reduced expression of manganous superoxide dismutase (MnSOD) in HIV-infected cells compared to uninfected cells. Tumor necrosis factor alpha (TNF-alpha) further sensitizes HIV-infected cells but not uninfected cells to heat and radiation. This is consistent with the ability of TNF-alpha to induce the expression of MnSOD in uninfected but not in HIV-infected cells. HIV-infected HUT-78 cell lines engineered to overexpress MnSOD are more resistant to heat and radiation than HIV-infected cells that do not overexpress MnSOD. However, treatment with TNF-alpha still sensitizes these cells to heat and radiation

  12. Varenicline: a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist approved for smoking cessation.

    Science.gov (United States)

    Lam, Sum; Patel, Priti N

    2007-01-01

    Tobacco smoking remains a significant health problem in the United States. It has been associated with staggering morbidity and mortality, specifically due to malignancies and cardiovascular disease. Smoking cessation can be difficult and frequently requires pharmacologic interventions in addition to nonpharmacologic measures. Previously available agents are nicotine replacement products and bupropion, which increased quit rates by about 2-fold compared with placebo. Varenicline is the first drug in a new class known as the selective alpha4beta2 nicotinic receptor partial agonists. In several randomized, double-blind, 52-week clinical trials involving healthy chronic smokers, varenicline demonstrated superiority to placebo and bupropion in terms of efficacy measures. Additionally, it improved tobacco withdrawal symptoms and reinforcing effects of smoking in relapsed patients. Patients should start therapy in combination with tobacco cessation counseling 1 week before quit date and continue the regimen for 12 weeks. The dose of varenicline should be titrated to minimize nausea. The recommended dosage is 0.5 mg once daily (QD) on days 1-3; titrate to 0.5 mg twice daily (BID) on days 4-7; and 1 mg BID starting on day 8. An additional 12-week maintenance therapy may be considered for those who achieve abstinence. The most common side effects are nausea (30%), insomnia (18%), headache (15%), abnormal dreams (13%), constipation (8%), and abdominal pain (7%). Overall, varenicline is a breakthrough in the management of tobacco addiction and has demonstrated good efficacy in motivated quitters. It also provides an option for smokers who cannot tolerate other pharmacologic interventions.

  13. 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

  14. 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....... 1232-1244) demonstrated that phosphorylation of PGC-1α by the p70 ribosomal protein S6 kinase 1 (S6K1) specifically interfered with the interaction between PGC-1α and HNF4α in liver and blocked the coactivation of the gluconeogenic target genes. This demonstrates how independent fine-tuning of gene...

  15. FcepsilonRI-alpha siRNA inhibits the antigen-induced activation of mast cells.

    Science.gov (United States)

    Safaralizadeh, Reza; Soheili, Zahra-Soheila; Deezagi, Abdolkhaleg; Pourpak, Zahra; Samiei, Shahram; Moin, Mostafa

    2009-12-01

    FcepsilonRI, The high affinity receptor for IgE plays a critical role in triggering the allergic reactions. It is responsible for inducing mast cell degranulation and deliberation of allergy mediators when it is aggregated by allergen and IgE complexes. FcepsilonRI on the mast cells consists of three subunits; alpha chain directly binds IgE, beta chain and dimmer of gamma chains together mediate intracellular signaling. Cross-linking of IgE-bound FcepsilonRI on the surface of mast cells and basophils by the multivalent antigen induces release of chemical mediators. The present in vitro study was designed to investigate the effect of synthetic FcepsilonRI-alpha siRNA on the antigen-induced activation of MC/9 cells. MC/9 cells which are murine mast cells were transfected by FcepsilonRI-alpha siRNA and negative control siRNA. After 6 h, anti-DNP (Dinitrophenyl) IgE was used for the cells sensitization. Then the cells were challenged with Dinitrophenyl-Human Serum Albumin (DNP-HSA) for mast cell degranulation induction before collection of supernatants. The amount of mRNA and protein expression was measured by Real Time PCR and western blot analysis, respectively. Determination of the expression rate of FcepsilonRI-alpha on cell surface was achieved by flow cytometry. ELISA and spectrophotometry methods were used subsequently for measuring the effects of FcepsilonRI-alpha siRNA on antigen-induced histamine and beta-hexosaminidase release. FcepsilonRI-alpha siRNA treated cells showed significant decrease in FcepsilonRI-alpha mRNA and protein expression in comparison to control cells. FcepsilonRI-mediated mast cell release of beta-hexosaminidase and histamine were also inhibited. In this study it was shown that FcepsilonRI-alpha siRNA could suppress FcepsilonRI-alpha expression and inhibited degranulation and histamine release in antigen-stimulated MC/9 cells. In conclusion, knock-down of FcepsilonRI-alpha by siRNA could be a promising method for inhibition of the mast

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

    African Journals Online (AJOL)

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

  17. Epigenetic Basis for the Regulation of Estrogen Receptor Alpha Activity in Breast Cancer Cells

    Science.gov (United States)

    2009-04-01

    Contreras, J.I., Prescott , M.S., Dagenais, S.L., Wu, R., Yee, J., Orringer, M.B., Misek, D.E., Hanash, S.M., et al. (2002). The hepatocyte nuclear... Microbiology . All Rights Reserved. Coactivator Function Defines the Active Estrogen Receptor Alpha Cistrome† Mathieu Lupien,1‡ Jérôme Eeckhoute,1

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

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

    OpenAIRE

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2017-04-01

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

  1. Determination of Alpha Activity from Radium-226 and its Decay Products in Human Blood

    International Nuclear Information System (INIS)

    Kenawy, M.A.; Morsy, A.A.; Abdel Hameid, M.M.

    1999-01-01

    During the last few years new and elaborate technique for the quantitative determination of alpha emitting particles in biological samples have been developed using the highly sensitive solid state nuclear track detector CR-39 which allows activities as low as 10 -15 Ci.g -1 to be detected. Blood samples (10 ml) were taken from volunteers. Three pieces of CR-39 were inserted in each blood container and stored at 20 degree for 15 weeks. The pre-etching condition were 6N NaOH+40% C 2 H 5 OH at 60 degree for 3 hours to reduce the background alpha tracks from the environmental radon

  2. Low level alpha activity measurements with pulse shape discrimination

    International Nuclear Information System (INIS)

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

    1984-01-01

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

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

  4. Selective targeted delivery of the TNF-alpha receptor p75 and uteroglobin to the vasculature of inflamed tissues: a preliminary report

    Directory of Open Access Journals (Sweden)

    Ventura Elisa

    2011-11-01

    Full Text Available Abstract Background Ligand-targeted approaches have proven successful in improving the therapeutic index of a number of drugs. We hypothesized that the specific targeting of TNF-alpha antagonists to inflamed tissues could increase drug efficacy and reduce side effects. Results Using uteroglobin (UG, a potent anti-inflammatory protein, as a scaffold, we prepared a bispecific tetravalent molecule consisting of the extracellular ligand-binding portion of the human TNF-alpha receptor P75 (TNFRII and the scFv L19. L19 binds to the ED-B containing fibronectin isoform (B-FN, which is expressed only during angiogenesis processes and during tissue remodeling. B-FN has also been demonstrated in the pannus in rheumatoid arthritis. L19-UG-TNFRII is a stable, soluble homodimeric protein that maintains the activities of both moieties: the immuno-reactivity of L19 and the capability of TNFRII to inhibit TNF-alpha. In vivo bio-distribution studies demonstrated that the molecule selectively accumulated on B-FN containing tissues, showing a very fast clearance from the blood but a very long residence time on B-FN containing tissues. Despite the very fast clearance from the blood, this fusion protein was able to significantly improve the severe symptomatology of arthritis in collagen antibody-induced arthritis (CAIA mouse model. Conclusions The recombinant protein described here, able to selectively deliver the TNF-alpha antagonist TNFRII to inflamed tissues, could yield important contributions for the therapy of degenerative inflammatory diseases.

  5. Zolpidem, a selective GABA(A) receptor alpha1 subunit agonist, induces comparable Fos expression in oxytocinergic neurons of the hypothalamic paraventricular and accessory but not supraoptic nuclei in the rat

    DEFF Research Database (Denmark)

    Kiss, Alexander; Søderman, Andreas; Bundzikova, Jana

    2006-01-01

    Functional activation of oxytocinergic (OXY) cells in the hypothalamic paraventricular (PVN), supraoptic (SON), and accessory (ACC) nuclei was investigated in response to acute treatment with Zolpidem (a GABA(A) receptor agonist with selectivity for alpha(1) subunits) utilizing dual Fos/OXY immun...

  6. Co-receptor choice by V alpha14i NKT cells is driven by Th-POK expression rather than avoidance of CD8-mediated negative selection.

    Science.gov (United States)

    Engel, Isaac; Hammond, Kirsten; Sullivan, Barbara A; He, Xi; Taniuchi, Ichiro; Kappes, Dietmar; Kronenberg, Mitchell

    2010-05-10

    Mouse natural killer T (NKT) cells with an invariant V alpha14-J alpha18 rearrangement (V alpha14 invariant [V alpha14i] NKT cells) are either CD4(+)CD8(-) or CD4(-)CD8(-). Because transgenic mice with forced CD8 expression in all T cells exhibited a profound NKT cell deficit, the absence of CD8 has been attributed to negative selection. We now present evidence that CD8 does not serve as a coreceptor for CD1d recognition and that the defect in development in CD8 transgene homozygous mice is the result of a reduction in secondary T cell receptor alpha rearrangements. Thymocytes from mice hemizygous for the CD8 transgene have a less severe rearrangement defect and have functional CD8(+) V alpha14i NKT cells. Furthermore, we demonstrate that the transcription factor Th, Poxviruses and Zinc finger, and Krüppel family (Th-POK) is expressed by V alpha14i NKT cells throughout their differentiation and is necessary both to silence CD8 expression and for the functional maturity of V alpha14i NKT cells. We therefore suggest that Th-POK expression is required for the normal development of V alpha14i NKT cells and that the absence of CD8 expression by these cells is a by-product of such expression, as opposed to the result of negative selection of CD8-expressing V alpha14i NKT cells.

  7. Temporal and Spatial Patterns of Neural Activity Associated with Information Selection in Open-ended Creativity.

    Science.gov (United States)

    Zhou, Siyuan; Chen, Shi; Wang, Shuang; Zhao, Qingbai; Zhou, Zhijin; Lu, Chunming

    2018-02-10

    Novel information selection is a crucial process in creativity and was found to be associated with frontal-temporal functional connectivity in the right brain in closed-ended creativity. Since it has distinct cognitive processing from closed-ended creativity, the information selection in open-ended creativity might be underlain by different neural activity. To address this issue, a creative generation task of Chinese two-part allegorical sayings was adopted, and the trials were classified into novel and normal solutions according to participants' self-ratings. The results showed that (1) novel solutions induced a higher lower alpha power in the temporal area, which might be associated with the automatic, unconscious mental process of retrieving extensive semantic information, and (2) upper alpha power in both frontal and temporal areas and frontal-temporal alpha coherence were higher in novel solutions than in normal solutions, which might reflect the selective inhibition of semantic information. Furthermore, lower alpha power in the temporal area showed a reduction with time, while the frontal-temporal and temporal-temporal coherence in the upper alpha band appeared to increase from the early to the middle phase. These dynamic changes in neural activity might reflect the transformation from divergent thinking to convergent thinking in the creative progress. The advantage of the right brain in frontal-temporal connectivity was not found in the present work, which might result from the diversity of solutions in open-ended creativity. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Water quality - Measurement of gross alpha activity in non-saline water - Thick source method. 2. ed.

    International Nuclear Information System (INIS)

    2007-01-01

    This International Standard specifies a method for the determination of gross alpha activity in non-saline waters for alpha-emitting radionuclides which are not volatile at 350 degree Centigrade. It is possible to determine supported volatile radionuclides measured to an extent determined by half-life, matrix retention (of the volatile species) and the duration of measurement (counting time). The method is applicable to raw and potable waters. The range of application depends on the amount of suspended matter in the water and on the performance characteristics (background count rate and counting efficiency) of the counter. Gross alpha radioactivity is determined by using proportional counting or solid scintillation counting on water residue deposited on a planchet. Due to the strong absorption of the residue deposit, it is considered that the alpha emission from the surface is proportional to the alpha activity of the deposit. Gross alpha determination is not an absolute determination of the sample alpha radioactive content, but a relative determination referring to a specific alpha emitter which constitutes the standard calibration source. This type of determination is also known as alpha index. The sample is acidified to stabilize it, evaporated almost to dryness, converted to the sulfate form and then ignited at 350 degree Centigrade. A portion of the residue is transferred to a planchet and the alpha activity measured by counting in an alpha-particle detector or counting system previously calibrated against an alpha-emitting standard and the alpha activity concentration calculated. The paper provides information about scope, normative references, symbols, definitions and units, principle, reagents and equipment, procedure, contamination check, expression of results and test report

  9. Antagonist effect of triptolide on AKT activation by truncated retinoid X receptor-alpha.

    Directory of Open Access Journals (Sweden)

    Na Lu

    Full Text Available BACKGROUND: Retinoid X receptor-alpha (RXRα is a key member of the nuclear receptor superfamily. We recently demonstrated that proteolytic cleavage of RXRα resulted in production of a truncated product, tRXRα, which promotes cancer cell survival by activating phosphatidylinositol-3-OH kinase (PI3K/AKT pathway. However, how the tRXRα-mediated signaling pathway in cancer cells is regulated remains elusive. METHODOLOGY/PRINCIPAL FINDINGS: We screened a natural product library for tRXRα targeting leads and identified that triptolide, an active component isolated from traditional Chinese herb Trypterygium wilfordii Hook F, could modulate tRXRα-mediated cancer cell survival pathway in vitro and in animals. Our results reveal that triptolide strongly induces cancer cell apoptosis dependent on intracellular tRXRα expression levels, demonstrating that tRXRα serves as an important intracellular target of triptolide. We show that triptolide selectively induces tRXRα degradation and inhibits tRXRα-dependent AKT activity without affecting the full-length RXRα. Interestingly, such effects of triptolide are due to its activation of p38. Although triptolide also activates Erk1/2 and MAPK pathways, the effects of triptolide on tRXRα degradation and AKT activity are only reversed by p38 siRNA and p38 inhibitor. In addition, the p38 inhibitor potently inhibits tRXRα interaction with p85α leading to AKT inactivation. Our results demonstrate an interesting novel signaling interplay between p38 and AKT through tRXRα mediation. We finally show that targeting tRXRα by triptolide strongly activates TNFα death signaling and enhances the anticancer activity of other chemotherapies. CONCLUSIONS/SIGNIFICANCE: Our results identify triptolide as a new xenobiotic regulator of the tRXRα-dependent survival pathway and provide new insight into the mechanism by which triptolide acts to induce apoptosis of cancer cells. Triptolide represents one of the most

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

    International Nuclear Information System (INIS)

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

    1994-01-01

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

  11. An isozyme of acid alpha-glucosidase with reduced catalytic activity for glycogen.

    OpenAIRE

    Beratis, N G; LaBadie, G U; Hirschhorn, K

    1980-01-01

    Both the common and a variant isozyme of acid alpha-glucosidase have been purified from a heterozygous placenta with CM-Sephadex, ammonium sulfate precipitation, dialysis, Amicon filtration, affinity chromatography by Sephadex G-100, and DEAE-cellulose chromatography. Three and two activity peaks, from the common and variant isozymes, respectively, were obtained by DEAE-cellulose chromatography using a linear NaCl gradient. The three peaks of activity of the common isozyme were eluted with 0....

  12. Rational design, synthesis, biologic evaluation, and structure-activity relationship studies of novel 1-indanone alpha(1)-adrenoceptor antagonists.

    Science.gov (United States)

    Li, Minyong; Xia, Lin

    2007-11-01

    In the present report, a novel series of 1-indanone alpha(1)-adrenoceptor antagonists were designed and synthesized based on 3D-pharmacophore model. Their in vitro alpha(1)-adrenoceptor antagonistic assay showed that three compounds (2a, 2m, and 2o) had similar or improved alpha(1)-adrenoceptor antagonistic activities relative to the positive control prazosin. Based on these results, a three-dimensional quantitative structure-activity relationship study was performed using a Self-Organizing Molecular Field Analysis method to provide insight for the future development of alpha(1)-adrenoceptor antagonists.

  13. Cell motility in chronic lymphocytic leukemia: defective Rap1 and alphaLbeta2 activation by chemokine.

    Science.gov (United States)

    Till, Kathleen J; Harris, Robert J; Linford, Andrea; Spiller, David G; Zuzel, Mirko; Cawley, John C

    2008-10-15

    Chemokine-induced activation of alpha4beta1 and alphaLbeta2 integrins (by conformational change and clustering) is required for lymphocyte transendothelial migration (TEM) and entry into lymph nodes. We have previously reported that chemokine-induced TEM is defective in chronic lymphocytic leukemia (CLL) and that this defect is a result of failure of the chemokine to induce polar clustering of alphaLbeta2; engagement of alpha4beta1 and autocrine vascular endothelial growth factor (VEGF) restore clustering and TEM. The aim of the present study was to characterize the nature of this defect in alphaLbeta2 activation and determine how it is corrected. We show here that the alphaLbeta2 of CLL cells is already in variably activated conformations, which are not further altered by chemokine treatment. Importantly, such treatment usually does not cause an increase in the GTP-loading of Rap1, a GTPase central to chemokine-induced activation of integrins. Furthermore, we show that this defect in Rap1 GTP-loading is at the level of the GTPase and is corrected in CLL cells cultured in the absence of exogenous stimuli, suggesting that the defect is the result of in vivo stimulation. Finally, we show that, because Rap1-induced activation of both alpha4beta1 and alphaLbeta2 is defective, autocrine VEGF and chemokine are necessary to activate alpha4beta1 for ligand binding. Subsequently, this binding and both VEGF and chemokine stimulation are all needed for alphaLbeta2 activation for motility and TEM. The present study not only clarifies the nature of the alphaLbeta2 defect of CLL cells but is the first to implicate activation of Rap1 in the pathophysiology of CLL.

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

    Science.gov (United States)

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

    2004-03-01

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

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

    Science.gov (United States)

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

    2005-07-01

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

  16. Design aspects of the Alpha Repository: VI. Selection and cost analysis of large hole drilling equipment

    International Nuclear Information System (INIS)

    Ellis, D.B.; Grams, W.H.

    1975-01-01

    An evaluation of common drilling practices and technology and applicability of currently available drilling machinery in the excavation of the canister emplacement holes for the Alpha Repository is presented. Sections are included on drilling system applications, descriptions of drilling operations, and drill system performance

  17. Alpha-Band Brain Oscillations Shape the Processing of Perceptible as well as Imperceptible Somatosensory Stimuli during Selective Attention.

    Science.gov (United States)

    Forschack, Norman; Nierhaus, Till; Müller, Matthias M; Villringer, Arno

    2017-07-19

    Attention filters and weights sensory information according to behavioral demands. Stimulus-related neural responses are increased for the attended stimulus. Does alpha-band activity mediate this effect and is it restricted to conscious sensory events (suprathreshold), or does it also extend to unconscious stimuli (subthreshold)? To address these questions, we recorded EEG in healthy male and female volunteers undergoing subthreshold and suprathreshold somatosensory electrical stimulation to the left or right index finger. The task was to detect stimulation at the randomly alternated cued index finger. Under attention, amplitudes of somatosensory evoked potentials increased 50-60 ms after stimulation (P1) for both suprathreshold and subthreshold events. Prestimulus amplitude of peri-Rolandic alpha, that is mu, showed an inverse relationship to P1 amplitude during attention compared to when the finger was unattended. Interestingly, intermediate and high amplitudes of mu rhythm were associated with the highest P1 amplitudes during attention and smallest P1 during lack of attention, that is, these levels of alpha rhythm seemed to optimally support the behavioral goal ("detect" stimuli at the cued finger while ignoring the other finger). Our results show that attention enhances neural processing for both suprathreshold and subthreshold stimuli and they highlight a rather complex interaction between attention, Rolandic alpha activity, and their effects on stimulus processing. SIGNIFICANCE STATEMENT Attention is crucial in prioritizing processing of relevant perceptible (suprathreshold) stimuli: it filters and weights sensory input. The present study investigates the controversially discussed question whether this attention effect extends to imperceptible (subthreshold) stimuli as well. We found noninvasive EEG signatures for attentional modulation of neural events following perceptible and imperceptible somatosensory stimulation in human participants. Specifically

  18. Changes in alpha-L-arabinofuranosidase activity in peel and pulp of banana (Musa sp.) fruits during ripening and softening.

    Science.gov (United States)

    Zhuang, Jun-Ping; Su, Jing; Li, Xue-Ping; Chen, Wei-Xin

    2007-04-01

    Arabinose is one of the most dynamic cell wall glycosyl residues released during fruit ripening, alpha-L-arabinofuranosidase (alpha-Arab) are major glycosidases that may remove arabinose units from fruit cell wall polysaccharides. To find out whether alpha-Arab plays important roles in banana fruit softening, the enzyme activities in peel and pulp, fruit firmness, respiration rate and ethylene release rate were assayed during banana softening. The results showed that alpha-Arab activities in banana pulp and peel increased slightly at the beginning of storage and reached their maxima when the fruit firmness decreased drastically, alpha-Arab activity increased by more than ten folds in both pulp and peel during ripening and alpha-Arab activities were higher in pulp than in peel. Treatment of banana fruits with ethylene absorbent postponed the time of reaching of its maxima of respiration and ethylene, enhanced the firmness of pup and decreased alpha-Arab activity in the peel and pulp. These results suggest that alpha-Arab induced the decrease of fruit firmness and played an important role in banana fruit softening, and its activity was regulated by ethylene.

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

    Science.gov (United States)

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

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

    International Nuclear Information System (INIS)

    Warburton, W.K.

    2005-01-01

    processor we easily distinguish between these two risetimes and thereby count only alpha particles emitted by the sample. Alpha particles emitted from the sample tray are absorbed in the rear of the sample, so the tray's emissivity does not contribute to the background either. Extensions of the method to the counter's sidewalls similarly allow us to reject alpha particles emitted from the sidewalls. We can thus able obtain background rates over a factor of 1000 lower than in conventional instruments without active background rejection. Extending this principle to count at the 0.00001 alpha/cm 2 /hour, level encounters difficulties because there will typically be only 2.4 alpha particles per square meter per day. Since about 6 counts are required to measure activity at the 95% confidence level, large sample areas are required to make measurements in reasonable times. Unfortunately, increasing the counter's anode area to a square meter raises its capacitance so much that the preamplifier noise levels swamp the alpha particle signals and make counting impossible. In this SBIR we worked to solve this dilemma by segmenting the single large area electrode into several smaller, lower capacitance electrodes that could still detect the alpha particles reliably. Each electrode would have its own electronic and we would capture signals from all of them in coincidence (since an alpha track might well deposit charge on more than one electrode), a technique in which XIA is experienced. Therefore, in Phase I we worked to show proof of principle by subdividing our original 1,800 cm 2 electrode into 4 square segments, each 625 cm 2 and demonstrating that signal noise on individual channels reduced as expected. Because the Phase II counter with a 1 m 2 segmented anode would require 16 segments plus a segmented guard as well, we also designed low cost signal processing electronics to instrument it in Phase II. Our Phase I effort met our major proof of principle goals. In particular, reducing

  1. Branching enzyme assay: selective quantitation of the alpha 1,6-linked glucosyl residues involved in the branching points.

    Science.gov (United States)

    Krisman, C R; Tolmasky, D S; Raffo, S

    1985-06-01

    Methods previously described for glycogen or amylopectin branching enzymatic activity are insufficiently sensitive and not quantitative. A new, more sensitive, specific, and quantitative one was developed. It is based upon the quantitation of the glucose residues joined by alpha 1,6 bonds introduced by varying amounts of branching enzyme. The procedure involved the synthesis of a polysaccharide from Glc-1-P and phosphorylase in the presence of the sample to be tested. The branched polysaccharide was then purified and the glucoses involved in the branching points were quantitated after degradation with phosphorylase and debranching enzymes. This method appeared to be useful, not only in enzymatic activity determinations but also in the study of the structure of alpha-D-glucans when combined with those of total polysaccharide quantitation, such as iodine and phenol-sulfuric acid.

  2. Site selection factors for repositories of solid high-level and alpha-bearing wastes in geological formations

    International Nuclear Information System (INIS)

    1977-01-01

    The purpose of this report is to provide guidelines for the selection and evaluation of suitable areas and sites for the disposal of solid high-level and alpha-bearing wastes into geological formations. This report is also intended to provide summary information on many types of geological formations underlying the land masses that might be considered as well as guidance on the geological and hydrological factors that should be investigated to demonstrate the suitability of the formations. In addition, other factors that should be considered in selecting a site for a radioactive waste repository are discussed briefly. The information, as presented, was developed to the extent of current technology for application to the evaluation of deep (greater than about 300 metres below ground level) geological formations in the selection of suitable areas for the disposal of solid or solidified high-level and alpha-bearing wastes. The extreme complexity of many geological environments and of the rock features that govern the presence and circulation of groundwater does not make it feasible to derive strict criteria for the selection of a site for a radioactive waste repository in a geological formation. Each potential repository location must be evaluated according to its own unique geological and hydrological setting. Therefore, only general guidance is offered, and this is done through discussion of the many factors that need to be considered in order to obtain the necessary assurances that the radionuclides will be confined in the geological repository over the required period of time

  3. Site selection factors for repositories of solid high-level and alpha-bearing wastes in geological formations

    Energy Technology Data Exchange (ETDEWEB)

    1977-01-01

    The purpose of this report is to provide guidelines for the selection and evaluation of suitable areas and sites for the disposal of solid high-level and alpha-bearing wastes into geological formations. This report is also intended to provide summary information on many types of geological formations underlying the land masses that might be considered as well as guidance on the geological and hydrological factors that should be investigated to demonstrate the suitability of the formations. In addition, other factors that should be considered in selecting a site for a radioactive waste repository are discussed briefly. The information, as presented, was developed to the extent of current technology for application to the evaluation of deep (greater than about 300 meters below ground level) geological formations in the selection of suitable areas for the disposal of solid or solidified high-level and alpha-bearing wastes. The extreme complexity of many geological environments and of the rock features that govern the presence and circulation of groundwater does not make it feasible to derive strict criteria for the selection of a site for a radioactive waste repository in a geological formation. Each potential repository location must be evaluated according to its own unique geological and hydrological setting. Therefore, only general guidance is offered, and this is done through discussion of the many factors that need to be considered in order to obtain the necessary assurances that the radionuclides will be confined in the geological repository over the required period of time.

  4. Selective adsorption of volatile organic compounds in micropore aluminum methylphosphonate-alpha: a combined molecular simulation-experimental approach.

    Science.gov (United States)

    Herdes, Carmelo; Valente, Anabela; Lin, Zhi; Rocha, João; Coutinho, João A P; Medina, Francisco; Vega, Lourdes F

    2007-06-19

    Results concerning the adsorption capacity of aluminum methylphosphonate polymorph alpha (AlMePO-alpha) for pure ethyl chloride and vinyl chloride by measured individual adsorption isotherms of these pure compounds are presented and discussed here. The experimental data supports the idea of using these materials as selective adsorbents for separating these compounds in mixtures. To explore this possibility further, we have performed grand canonical Monte Carlo simulations using a recently proposed molecular simulation framework for gas adsorption on AlMePO, and the results are presented here. The molecular model of the material was used in a purely transferable manner from a previous work (Herdes, C.; Lin, Z.; Valente, A.; Coutinho, J. A. P.; Vega, L. F. Langmuir 2006, 22, 3097). Regarding the molecular model of the fluids, an existing model for ethyl chloride was improved to capture the experimental dipole value better; an equivalent force field for the vinyl chloride molecule was also developed for simulation purposes. Simulations of the pure compounds were found to be in excellent agreement with the measured experimental data at the three studied temperatures. Simulations were also carried out in a purely predictive manner as a tool to find the optimal conditions for the selective adsorption of these compounds prior experimental measurements are carried out. The influence of the temperature and the bulk composition on the adsorption selectivity was also investigated. Results support the use of AlMePO-alpha as an appropriate adsorbent for the purification process of vinyl chloride, upholding the selective adsorption of ethyl chloride.

  5. Concentration levels of alpha emitting radionuclides in natural waters. Implications in the use of various radionuclides of reference for the determination of total alpha activity index

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Baeza, A.; Corbacho, J.A. [LARUEX, Caceres (Spain). Environmental Radioactivity Lab.

    2013-07-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-07-01

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

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

    Science.gov (United States)

    Alias, A G

    2004-12-01

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

  9. PCNA mono-ubiquitination and activation of translesion DNA polymerases by DNA polymerase {alpha}.

    Science.gov (United States)

    Suzuki, Motoshi; Niimi, Atsuko; Limsirichaikul, Siripan; Tomida, Shuta; Miao Huang, Qin; Izuta, Shunji; Usukura, Jiro; Itoh, Yasutomo; Hishida, Takashi; Akashi, Tomohiro; Nakagawa, Yoshiyuki; Kikuchi, Akihiko; Pavlov, Youri; Murate, Takashi; Takahashi, Takashi

    2009-07-01

    Translesion DNA synthesis (TLS) involves PCNA mono-ubiquitination and TLS DNA polymerases (pols). Recent evidence has shown that the mono-ubiquitination is induced not only by DNA damage but also by other factors that induce stalling of the DNA replication fork. We studied the effect of spontaneous DNA replication errors on PCNA mono-ubiquitination and TLS induction. In the pol1L868F strain, which expressed an error-prone pol alpha, PCNA was spontaneously mono-ubiquitinated. Pol alpha L868F had a rate-limiting step at the extension from mismatched primer termini. Electron microscopic observation showed the accumulation of a single-stranded region at the DNA replication fork in yeast cells. For pol alpha errors, pol zeta participated in a generation of +1 frameshifts. Furthermore, in the pol1L868F strain, UV-induced mutations were lower than in the wild-type and a pol delta mutant strain (pol3-5DV), and deletion of the RAD30 gene (pol eta) suppressed this defect. These data suggest that nucleotide misincorporation by pol alpha induces exposure of single-stranded DNA, PCNA mono-ubiquitination and activates TLS pols.

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

    International Nuclear Information System (INIS)

    Terini, R.A.

    1991-01-01

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

  11. Selective effects of alpha-MSH and MIF-1 on the blood-brain barrier

    International Nuclear Information System (INIS)

    Sankar, R.; Domer, F.R.; Kastin, A.J.

    1981-01-01

    The effects of intravenously-injected alpha-MSH and MIF-1 (Pro-Leu-Gly-NH2) on the permeability of the blood-brain barrier (BBB) to a large protein and a small anion were studied using radioiodinated serum albumin (RISA) and 99mTc-labeled sodium pertechnetate. The permeability of the BBB to RISA was unaltered by either peptide. Permeability to the inorganic pertechnetate anion, however, was significantly increased by alpha-MSH but not by MIF-1 at doses known to evoke EEG and behavioral responses. The peptides did not cause a change in the systemic blood pressure. It is possible, therefore, that at least some CNS effects of peripherally administered peptides are exerted by alteration of the permeability of the BBB to other substances

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    Phosphoinositide-3-kinases are important targets for drug development because many proteins in the PI3 kinase signaling pathway are mutated, hyperactivated, or overexpressed in human cancers. Here, the authors coexpressed the human class Ia PI3 kinase p110alpha catalytic domain with an N-terminal....... In parallel, a second assay format using the AlphaScreen technology was optimized to measure PI3 kinase activity. Both assay formats used should be suitable for high-throughput screening for the identification of PI3 kinase inhibitors. (Journal of Biomolecular Screening XXXX:xx-xx)....

  13. Recombinant alpha-L-rhamnosidase from Aspergillus terreus in selective trimming of rutin

    Czech Academy of Sciences Publication Activity Database

    Gerstorferová, Daniela; Fliedrová, Barbora; Halada, Petr; Marhol, Petr; Křen, Vladimír; Weignerová, Lenka

    2012-01-01

    Roč. 47, č. 5 (2012), s. 828-835 ISSN 1359-5113 R&D Projects: GA ČR(CZ) GAP301/11/0662; GA ČR GD305/09/H008; GA ČR(CZ) GAP301/11/0767; GA MŠk(CZ) 7E11010 Keywords : alpha-L-Rhamnosidase * Aspergillus terreus * Isoquercitrin Subject RIV: CE - Biochemistry Impact factor: 2.414, year: 2012

  14. 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.

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

    OpenAIRE

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

    2017-01-01

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

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

    International Nuclear Information System (INIS)

    Hayakawa, Hironobu; Oonishi, Masaki; Matsuura, Hiroyuki

    1990-01-01

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

  17. 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.…

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

    International Nuclear Information System (INIS)

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

    1982-01-01

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

  19. Activation of c-Raf-1 kinase signal transduction pathway in alpha(7) integrin-deficient mice.

    Science.gov (United States)

    Saher, G; Hildt, E

    1999-09-24

    Integrin alpha(7)-deficient mice develop a novel form of muscular dystrophy. Here we report that deficiency of alpha(7) integrin causes an activation of the c-Raf-1/mitogen-activated protein (MAP) 2 kinase signal transduction pathway in muscle cells. The observed activation of c-Raf-1/MAP2 kinases is a specific effect, because the alpha(7) integrin deficiency does not cause unspecific stress as determined by measurement of the Hsp72/73 level and activity of the JNK2 kinase. Because an increased level of activated FAK was found in muscle of alpha(7) integrin-deficient mice, the activation of c-Raf-1 kinase is triggered most likely by an integrin-dependent pathway. In accordance with this, in the integrin alpha(7)-deficient mice, part of the integrin beta(1D) variant in muscle is replaced by the beta(1A) variant, which permits the FAK activation. A recent report describes that integrin activity can be down-modulated by the c-Raf-1/MAP2 kinase pathway. Specific activation of the c-Raf-1/MAP2 kinases by cell-permeable peptides in skeletal muscle of rabbits causes degeneration of muscle fibers. Therefore, we conclude that in alpha(7) integrin-deficient mice, the continuous activation of c-Raf-1 kinase causes a permanent reduction of integrin activity diminishing integrin-dependent cell-matrix interactions and thereby contributing to the development of the dystrophic phenotype.

  20. Characterization of high specific activity [16 alpha-123I]Iodo-17 beta-estradiol as an estrogen receptor-specific radioligand capable of imaging estrogen receptor-positive tumors

    International Nuclear Information System (INIS)

    Pavlik, E.J.; Nelson, K.; Gallion, H.H.; van Nagell, J.R. Jr.; Donaldson, E.S.; Shih, W.J.; Spicer, J.A.; Preston, D.F.; Baranczuk, R.J.; Kenady, D.E.

    1990-01-01

    16 alpha-[123I]Iodo-17 beta-estradiol (16 alpha-[123I]E2) has been characterized for use as a selective radioligand for estrogen receptor (ERc) that is capable of generating in situ images of ERc-positive tumors. High specific activity 16 alpha-[123I]E2 (7,500-10,000 Ci/mmol) was used in all determinations. Radiochemical purity was determined by thin layer chromatography, and the selectivity of radioligand for ERc was evaluated using size exclusion high performance liquid chromatography on ERc prepared from rodent uteri. Efficiencies of radioidination approaching 100% were achieved, and excellent receptor selectivity was obtained even when the efficiency of radioiodination was as low as 10%. Low radiochemical purity was always associated with poor selectivity for ERc. No new radioligand species was generated during the course of radiodecay; however, reduced binding over time, even when increased activity was used to compensate for radiodecay, indicated that the formation of a radioinert competitor does occur. 16 alpha-[123I]E2 demonstrated stable, high affinity binding to ERc and was concentrated by ERc-positive tissues. After injecting 16 alpha-[123I]E2 in vivo, images of ERc-containing tissues were obtained, including rabbit reproductive tract and dimethylbenzanthracene-induced tumors. The demonstrations of ERc selectivity and image formation both indicate that 16 alpha-[123I]E2 should have promise as a useful new radiopharmaceutical for imaging ERc-positive cancers

  1. Antibacterial activity of selected Myanmar medicinal plants

    International Nuclear Information System (INIS)

    Nwe Yee Win; Nyunt Wynn; Mar Mar Nyein; Win Myint; Saw Hla Myint; Myint Khine

    2001-01-01

    Thirteen plants which are traditionally used for the treatment of dysentery and diarrhoea in Myanmar were selected and tested for antibacterial activity by using agar disc diffusion technique. Polar and nonpolar solvents were employed for extraction of plants. The minimum inhibitory concentration (MIC) of the extracts with the most significant predominant activity were evaluated by plate dilution method. The plants Eugenia jambolana, Quisqualis indica, Leucaena glauca and Euphorbia splendens var. 1 were found to show significant antibacterial activity. It was also observed that extracts using nonpolar solvents did not show any antibacterial activity and extracts using polar solvents showed antibacterial activity on tested bacteria, indicating that the active chemical compound responsible for the antibacterial action must be a polar soluble compound. (author)

  2. PPAR alpha-activation results in enhanced carnitine biosynthesis and OCTN2-mediated hepatic carnitine accumulation

    NARCIS (Netherlands)

    van Vlies, Naomi; Ferdinandusse, Sacha; Turkenburg, Marjolein; Wanders, Ronald J. A.; Vaz, Frédéric M.

    2007-01-01

    In fasted rodents hepatic carnitine concentration increases considerably which is not observed in PPAR alpha-/- mice, indicating that PPAR alpha is involved in carnitine homeostasis. To investigate the mechanisms underlying the PPAR alpha-dependent hepatic carnitine accumulation we measured

  3. Negative feedback regulation of human platelets via autocrine activation of the platelet-derived growth factor alpha-receptor.

    Science.gov (United States)

    Vassbotn, F S; Havnen, O K; Heldin, C H; Holmsen, H

    1994-05-13

    Human platelets contain platelet-derived growth factor (PDGF) in their alpha-granules which is released during platelet exocytosis. We show by immunoprecipitation and 125I-PDGF binding experiments that human platelets have functionally active PDGF alpha-receptors, but not beta-receptors. The PDGF alpha-receptor (PDGFR-alpha) was identified as a 170-kDa glycosylated protein-tyrosine kinase as found in other cell types. Stimulation of platelets with 0.1 unit/ml thrombin resulted in a significant increase (2-5-fold) of the tyrosine phosphorylation of the PDGFR-alpha, as determined by immunoprecipitation with phosphotyrosine antiserum as well as with PDGFR-alpha antiserum. The observed thrombin-induced autophosphorylation of the PDGFR-alpha was inhibited by the addition of a neutralizing monoclonal PDGF antibody. Thus, our results suggest that the platelet PDGFR-alpha is stimulated in an autocrine manner by PDGF secreted during platelet activation. Preincubation of platelets with PDGF inhibited thrombin-induced platelet aggregation and secretion of ATP + ADP and beta-hexosaminidase. Thrombin-induced platelet aggregation was also reversed when PDGF was added 30 s after thrombin stimulation. Inhibition of the autocrine PDGF pathway during platelet activation by the PDGF antibody led to a potentiation of thrombin-induced beta-hexosaminidase secretion. Thus, the PDGFR-alpha takes part in a negative feedback regulation during platelet activation. Our demonstration of PDGF alpha-receptors on human platelets and its inhibitory function during platelet activation identifies a new possible role of PDGF in the regulation of thrombosis.

  4. Table of specific activities of selected isotopes

    International Nuclear Information System (INIS)

    Shipley, G.

    The bulk of this publication consists of a table of the half-lives, decay modes, and specific activities of isotopes selected for their particular interest to the Environmental Health and Safety Department, LBL. The specific activities were calculated with a PDP 9/15 computer. Also included in the report is a table of stable isotopes, the Th and U decay chains, a chart of the nuclides for elements 101 through 106, the heavy element region of the periodic table, and a specific activity monograph. 5 figures, 2 tables

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-11-20

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

  6. 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

  7. 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.

  8. [Cost-effectiveness of drotrecogin alpha [activated] in the treatment of severe sepsis in Spain].

    Science.gov (United States)

    Sacristán, José A; Prieto, Luis; Huete, Teresa; Artigas, Antonio; Badia, Xavier; Chinn, Christopher; Hudson, Peter

    2004-01-01

    The PROWESS clinical trial has shown that treatment with drotrecogin alpha (activated) in patients with severe sepsis is associated with a reduction in the absolute risk of death compared with standard treatment. The aim of the present study was to assess the cost-effectiveness of drotrecogin alpha (activated) versus that of standard care in the treatment of severe sepsis in Spain. A decision analysis model was drawn up to compare costs to hospital discharge and the long-term efficacy of drotrecogin alpha (activated) versus those of standard care in the treatment of severe sepsis in Spain from the perspective of the health care payer. Most of the information for creating the model was obtained from the PROWESS clinical trial. A two-fold baseline analysis was performed: a) for all patients included in the PROWESS clinical trial and b) for the patients with two or more organ failures. The major variables for clinical assessment were the reduction in mortality and years of life gained (YLG). Cost-effectiveness was expressed as cost per YLG. A sensitivity analysis was applied using 3% and 5% discount rates for YLG and by modifying the patterns of health care, intensive care unit costs, and life expectancy by initial co-morbidity and therapeutic efficacy of drotrecogin alpha (activated). Treatment with drotrecogin alfa (activated) was associated with a 6.0% drop in the absolute risk of death (p = 0.005) when all of the patients from the PROWESS trial were included and with a 7.3% reduction (p = 0.005) when the analysis was restricted to patients with two or more organ failures. The cost-effectiveness of drotrecogin alfa (activated) was 13,550 euros per YLG with respect to standard care after analysing all of the patients and 9,800 euros per YLG in the group of patients with two or more organ failures. In the sensitivity analysis, the results ranged from 7,322 to 16,493 euros per YLG. The factors with the greatest impact on the results were the change in the efficacy of

  9. Efficient sensor selection for active information fusion.

    Science.gov (United States)

    Zhang, Yongmian; Ji, Qiang

    2010-06-01

    In our previous paper, we formalized an active information fusion framework based on dynamic Bayesian networks to provide active information fusion. This paper focuses on a central issue of active information fusion, i.e., the efficient identification of a subset of sensors that are most decision relevant and cost effective. Determining the most informative and cost-effective sensors requires an evaluation of all the possible subsets of sensors, which is computationally intractable, particularly when information-theoretic criterion such as mutual information is used. To overcome this challenge, we propose a new quantitative measure for sensor synergy based on which a sensor synergy graph is constructed. Using the sensor synergy graph, we first introduce an alternative measure to multisensor mutual information for characterizing the sensor information gain. We then propose an approximated nonmyopic sensor selection method that can efficiently and near-optimally select a subset of sensors for active fusion. The simulation study demonstrates both the performance and the efficiency of the proposed sensor selection method.

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

    International Nuclear Information System (INIS)

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

    2002-01-01

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

  11. 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......% IA/g at 4 h) in the outer tumor layer and a sharp drop beyond a depth of 50 µm. Small-scale dosimetry was performed on a multi-cellular micrometastasis model, using time-integrated activities derived from the experimental data. With injected activity of 400 kBq, tumors exhibiting uniform activity...... distribution received 100 µm might not be effectively treated by the examined regimen....

  12. Rapid One-Step Selection Method for Generating Nucleic Acid Aptamers: Development of a DNA Aptamer against alpha-Bungarotoxin

    DEFF Research Database (Denmark)

    Lauridsen, Lasse Holm; Shamaileh, Hadi A.; Edwards, Stacey L.

    2012-01-01

    Background: Nucleic acids based therapeutic approaches have gained significant interest in recent years towards the development of therapeutics against many diseases. Recently, research on aptamers led to the marketing of Macugen (R), an inhibitor of vascular endothelial growth factor (VEGF......) for the treatment of age related macular degeneration (AMD). Aptamer technology may prove useful as a therapeutic alternative against an array of human maladies. Considering the increased interest in aptamer technology globally that rival antibody mediated therapeutic approaches, a simplified selection, possibly...... in one-step, technique is required for developing aptamers in limited time period. Principal Findings: Herein, we present a simple one-step selection of DNA aptamers against alpha-bungarotoxin. A toxin immobilized glass coverslip was subjected to nucleic acid pool binding and extensive washing followed...

  13. 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.

  14. Measurement of gross alpha - activity in some thermal water sources in Yugoslavia by SSNTDs. [Solid state nuclear track detectors

    Energy Technology Data Exchange (ETDEWEB)

    Benderac, R.; Ristic, D. (Inst. of Security, Belgrade (Yugoslavia)); Antanasijevic, R.; Vukovic, J. (Belgrade Univ. (Yugoslavia))

    1991-01-01

    The possible application of the CN-BDH (type 1) nitrocellulose detector synthesized in laboratory conditions, and also the CR-39 detector, to the measurement of the gross alpha-activity of geothermal and mineral water has been investigated. (author).

  15. Removal Of Labeled ALPHA-Fetoprotein (AFP) Using Rice Husk-Based Activated Carbon

    International Nuclear Information System (INIS)

    ABDEL-MOUHTY, N.R.

    2009-01-01

    Biomass agricultural waste materials, rice husk (RH) or saw dust (SD), were used for the preparation of activated carbons. RH was activated by chemical activation using phosphoric acid or potassium hydroxide. The prepared activated carbons were characterized and used for the adsorption of labeled alpha-fetoprotein ( 125 I-AFP) from the lab waste of iodine labeled alpha-fetoprotein tracer. The effects of various factors, e.g. carbon type, carbon dosage, temperature, particle size of carbon, effect of different waste volumes on the adsorption capacity, were quantitatively determined. Desorption of activated carbon was also investigated. From the experimental results, it was found that SDK had the lowest ability for adsorption of 125I-AFP and the highest uptake was 83% by carbon RHH. The amount of adsorption accomplished per unit weight of a solid adsorbent was greater, the more finely divided and the more porous the solid. 0.5 g for RHH carbon was found to be optimum dose of adsorbent for the removal of 125I-AFP. The optimum volume of waste with 0.5 g dose of RHH was 15 ml. The increased adsorption with temperature may be due to the increase of the intra-particle diffusion rate of sorbate ions into the pores at higher temperature as diffusion is an endothermic process.

  16. Stochastic cycle selection in active flow networks

    Science.gov (United States)

    Woodhouse, Francis; Forrow, Aden; Fawcett, Joanna; Dunkel, Jorn

    2016-11-01

    Active biological flow networks pervade nature and span a wide range of scales, from arterial blood vessels and bronchial mucus transport in humans to bacterial flow through porous media or plasmodial shuttle streaming in slime molds. Despite their ubiquity, little is known about the self-organization principles that govern flow statistics in such non-equilibrium networks. By connecting concepts from lattice field theory, graph theory and transition rate theory, we show how topology controls dynamics in a generic model for actively driven flow on a network. Through theoretical and numerical analysis we identify symmetry-based rules to classify and predict the selection statistics of complex flow cycles from the network topology. Our conceptual framework is applicable to a broad class of biological and non-biological far-from-equilibrium networks, including actively controlled information flows, and establishes a new correspondence between active flow networks and generalized ice-type models.

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

    Science.gov (United States)

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

    2007-12-01

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

  18. INFLUENCE OF SELECTED PHARMACEUTICALS ON ACTIVATED SLUDGE DEHYDROGENASE ACTIVITY

    Directory of Open Access Journals (Sweden)

    Agnieszka Tomska

    2016-06-01

    The aim of this work was to evaluate the effect of selected antibiotics - sulfanilamide and erythromycin on activated sludge dehydrogenase activity with use of trifenyltetrazolinum chloride (TTC test. Dehydrogenases activity is an indicator of biochemical activity of microorganisms present in activated sludge or the ability to degrade organic compounds in waste water. TTC test is particularly useful for the regularity of the course of treatment, in which the presence of inhibitors of biochemical reactions and toxic compounds are present. It was observed that the dehydrogenase activity decreases with the increase of a antibiotics concentration. The lowest value of the dehydrogenase activity equal to 32.4 μmol TF / gMLSS obtained at sulfanilamide concentration 150mg / l. For this sample, an inhibition of dehydrogenase activity was 31%.

  19. An isozyme of acid alpha-glucosidase with reduced catalytic activity for glycogen.

    Science.gov (United States)

    Beratis, N G; LaBadie, G U; Hirschhorn, K

    1980-03-01

    Both the common and a variant isozyme of acid alpha-glucosidase have been purified from a heterozygous placenta with CM-Sephadex, ammonium sulfate precipitation, dialysis, Amicon filtration, affinity chromatography by Sephadex G-100, and DEAE-cellulose chromatography. Three and two activity peaks, from the common and variant isozymes, respectively, were obtained by DEAE-cellulose chromatography using a linear NaCl gradient. The three peaks of activity of the common isozyme were eluted with 0.08, 0.12, and 0.17 M NaCl, whereas the two peaks of the variant, with 0.01 and 0.06 M NaCl. The pH optimum and thermal denaturation at 57 degrees C were the same in all enzyme peaks of both isozymes. Rabbit antiacid alpha-glucosidase antibodies produced against the common isozyme were found to cross-react with both peaks of the variant isozyme. The two isozymes shared antigenic identity and had similar Km's with maltose as substrate. Normal substrate saturation kinetics were observed with the common isozyme when glycogen was the substrate, but the variant produced an S-shaped saturation curve indicating a phase of negative and positive cooperativity at low and high glycogen concentrations, respectively. The activity of the variant was only 8.6% and 19.2% of the common isozyme when assayed with nonsaturating and saturating concentrations of glycogen, respectively. A similar rate of hydrolysis of isomaltose by both isozymes was found indicating that the reduced catalytic activity of the variant isozyme toward glycogen is not the result of a reduced ability of this enzyme to cleave the alpha-1,6 linkages of glycogen.

  20. Characteristics of chemical binding to alpha 2u-globulin in vitro--evaluating structure-activity relationships

    International Nuclear Information System (INIS)

    Borghoff, S.J.; Miller, A.B.; Bowen, J.P.; Swenberg, J.A.

    1991-01-01

    alpha 2u-Globulin (alpha 2u) has been shown to accumulate in the kidneys of male rats treated with 2,2,4-trimethylpentane (TMP). 2,4,4-Trimethyl-2-pentanol (TMP-2-OH), a metabolite of TMP, is found reversibly bound to alpha 2u isolated from the kidneys of these treated rats. The objectives of the following study were to characterize the ability of [3H]TMP-2-OH to bind to alpha 2u in vitro and to determine whether other compounds that cause this protein to accumulate have the same binding characteristics. Although compounds that have been shown to cause the accumulation of alpha 2u in male rat kidneys compete in vitro with [3H]TMP-2-OH for binding to alpha 2u, they do so to varying degrees. The binding affinity (Kd) of the [3H]TMP-2-OH-alpha 2u complex was calculated to be on the order of 10(-7) M. The inhibition constant values (Ki) determined for d-limonene, 1,4-dichlorobenzene, and 2,5-dichlorophenol were all in the range 10(-4) M, whereas the Ki values for isophorone, 2,4,4- or 2,2,4-trimethyl-1-pentanol, and d-limonene oxide were determined to be in the range 10(-6) and 10(-7) M, respectively. TMP and 2,4,4- and 2,2,4-trimethylpentanoic acid did not compete for binding. This suggests that other factors, besides binding, are involved in the accumulation of alpha 2u. In this study the ability of a chemical to bind to alpha 2u was used as a measure of biological activity to assess structure-activity relationships among the chemicals tested and known to cause the accumulation of alpha 2u. The results so far suggest that binding is dependent on both hydrophobic interactions and hydrogen bonding

  1. 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. 

  2. Antioxidant, cytotoxic and alpha-glucosidase inhibition activities from the Mexican berry "Anacahuita" (Cordia boissieri).

    Science.gov (United States)

    Viveros-Valdez, Ezequiel; Jaramillo-Mora, Carlos; Oranday-Cardenas, Azucena; Mordn-Martinez, Javier; Carranza-Rosales, Pilar

    2016-09-01

    This study describes the total phenolic and flavonoid content as well as cytotoxic, alpha-glucosidase inhibition and antiradical/antioxidant potential of extracts obtained from the edible fruits of Cordia boissieri, which is widely distributed throughout northeastern Mexico. Phenolic and flavonoid content were evaluated by means of the Folin-Ciocalteu method and aluminum chloride colorimetric assay respectively. The antiradical/antioxidant activity was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging and Trolox Equivalent Antioxidant Capacity (TEAC) assays. Cytotoxic activity was assessed by means of human cancer cell lines (MCF-7 and HeLa), alpha-glucosidase inhibition was determined by colorimetric assay using p-Nitrophenyl a-D-glucopyranoside (PNPG) as a substrate. Results indicate that extract of C. boissieri fruit has a good antioxidant potential to show a EC₅₀: 137.76 ± 35 ptg/mL and 65 ±2 ltM/g in the DPPH and TEAC assays respectively, inhibitor of the enzyme alpha-glu- cosidase involved in sugar uptake (ICSO: 215.20 ± 35 μg/ mL), cytotoxic activities against MCF-7 (IC50: 310 ± 42 μg/mL) and HeLa (IC₅₀0: 450.4 ±21μgg/mL) cancer cell lines as well as an important phenolic content with 230 t 23 mg/1OOg and 54±11 mg100g g of phenols and flavonoids totals respectively. These results point towards an interesting potential for the fruits of C. boissieri as chemopreventive properties and expand the possibilities.

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

    OpenAIRE

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

    2006-01-01

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

  4. 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.

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

    Science.gov (United States)

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

    2008-12-01

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

  6. Assessment of radiological risk parameters associated with some selected rivers around oil mineral producing sites in Abia State, Nigeria due to gross alpha and beta radiations

    International Nuclear Information System (INIS)

    Enyinna, Paschal Ikenna; Uzochukwu, Francis C.

    2016-01-01

    The study of gross alpha and beta radiation in environmental components and water bodies in particular is very crucial to the environmental, radiation and medical Physicist as this helps to promote good water quality and environmental hygiene. This research work understudied the radiological risk parameters due to gross alpha and beta radiations associated with three selected rivers around crude oil production sites in Abia State, Nigeria. Gross alpha and beta activities were computed for the three rivers based on analytical measurements carried out using a well-calibrated IN-20 model gas-flow proportional counter. Radiological risk parameters were computed from the activity concentrations which included; annual effective dose equivalent of radiation from ingested water (AEDE), annual gonadal dose equivalent (AGDE), and excess lifetime cancer risk (ELCR). The mean of the total AEDE due to the sum of alpha and beta radiations for the three rivers are 0.868 ± 0.221 mSv/y, 1.008 ± 0.156 mSv/y, and 0.917 ± 0.214 mSv/y; and are above the World Health Organization (WHO) permissible limit of 0.1 mSv/y. The mean of the total AGDE are 4.048 ± 1.063 mSv/y, 4.756 ± 0.739 mSv/y, and 4.295 ± 1.026 mSv/y; and are above the world average limit of 0.3 mSv/y. The mean of the total ELCR are (3.038 ± 0.774) X 10"-"3, (3.529 ± 0.547) X 10"-"3, and (3.210 ± 0.748) X 10"-"3; and are above the world average limit of 0.29 X 10"-"3. Most values of ELCR computed in this work are >6.0 X 10"-"4 estimated to be the risk of fatal and weighted nonfatal health conditions over a lifetime (70 years) derived from the radiation dose of 0.1 mSv/y (WHO permissible limit for drinking water). Drinking water from these surveyed sources could impact negatively on the end users. (author)

  7. 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

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

    International Nuclear Information System (INIS)

    Romero, L.; Travesi, A.

    1983-01-01

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

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

    International Nuclear Information System (INIS)

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

    2002-01-01

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

  10. On active current selection for Lagrangian profilers

    DEFF Research Database (Denmark)

    Jouffroy, Jerome; Zhou, Qiuyang; Zielinski, Oliver

    2013-01-01

    simple and computationally-efficient control strategies to actively select and use ocean currents so that a profiler can autonomously reach a desired destination. After briefly presenting a typical profiler and possible mechanical modifications for a coastal environment, we introduce simple mathematical...... models for the profiler and the currents it will use. We then present simple feedback controllers that, using the direction of the currents and taking into account the configuration of the environment (coastal or deep-sea), is able to steer the profiler to any desired horizontal location. To illustrate...

  11. Activity and action screening of selected disinfectants

    Directory of Open Access Journals (Sweden)

    Kateřina Balharová

    2006-01-01

    Full Text Available This research work is aimed to monitoring of selected disinfectants´activity in operational conditions. Hereby there have been monitored two acidic disinfectants Despon K and Mikasan D, which have had-by their producer-stated different recommended concentration. These solutions were monitored in viewpoint of their activity at different temperature, time of circulation, pH and water hardness. In this work there were measured pH of solutions in unloaded medium to be compared with pH of solutions in loaded medium and this measuring was carried out regularly each week within a one month period. During this period there was also monitored total plate count (TPC, which was stated in the dairy, where samples were taken two-times monthly. It has been found, that the disinfectants Mikasan D and Mikal 94D are effective even by high water hardness.

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

    International Nuclear Information System (INIS)

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

    2002-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-07-08

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-09-15

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

  15. The anti-apoptotic activity associated with phosphatidylinositol transfer protein alpha activates the MAPK and Akt/PKB pathway.

    Science.gov (United States)

    Schenning, Martijn; Goedhart, Joachim; Gadella, Theodorus W J; Avram, Diana; Wirtz, Karel W A; Snoek, Gerry T

    2008-10-01

    The conditioned medium (CM) from mouse NIH3T3 fibroblast cells overexpressing phosphatidylinositol transfer protein alpha (PI-TPalpha; SPIalpha cells) demonstrates an increased anti-apoptotic activity compared with CM from wild type NIH3T3 (wtNIH3T3) cells. As previously shown, the anti-apoptotic activity acts by activating a G protein-coupled receptor, most probably a cannabinoid 1 (CB1)-like receptor as the activity was blocked by both pertussis toxin and rimonabant [M. Schenning, C.M. van Tiel, D. Van Manen, J.C. Stam, B.M. Gadella, K.W. Wirtz and G.T. Snoek, Phosphatidylinositol transfer protein alpha regulates growth and apoptosis of NIH3T3 cells: involvement of a cannabinoid 1-like receptor, J. Lipid Res. 45 (2004) 1555-1564]. The CB1 receptor appears to be expressed in mouse fibroblast cells, at levels in the order SPIalpha>wtNIH3T3>SPIbeta cells (i.e. wild type cells overexpressing PI-TPbeta). Upon incubation of SPIbeta cells with the PI-TPalpha-dependent anti-apoptotic factors, both the ERK/MAP kinase and the Akt/PKB pathway are activated in a CB1 receptor dependent manner as shown by Western blotting. In addition, activation of ERK2 was also shown by EYFP-ERK2 translocation to the nucleus, as visualized by confocal laser scanning microscopy. The subsequent activation of the anti-apoptotic transcription factor NF-kappaB is in line with the increased resistance towards UV-induced apoptosis. On the other hand, receptor activation by CM from SPIalpha cells was not linked to phospholipase C activation as the YFP-labelled C2-domain of protein kinase C was not translocated to the plasma membrane of SPIbeta cells as visualized by confocal laser scanning microscopy.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  17. Increase in posterior alpha activity during rehearsal predicts successful long-term memory formation of word sequences.

    Science.gov (United States)

    Meeuwissen, Esther B; Takashima, Atsuko; Fernández, Guillén; Jensen, Ole

    2011-12-01

    It is becoming increasingly clear that demanding cognitive tasks rely on an extended network engaging task-relevant areas and, importantly, disengaging task-irrelevant areas. Given that alpha activity (8-12 Hz) has been shown to reflect the disengagement of task-irrelevant regions in attention and working memory tasks, we here ask if alpha activity plays a related role for long-term memory formation. Subjects were instructed to encode and maintain the order of word sequences while the ongoing brain activity was recorded using magnetoencephalography (MEG). In each trial, three words were presented followed by a 3.4 s rehearsal interval. Considering the good temporal resolution of MEG this allowed us to investigate the word presentation and rehearsal interval separately. The sequences were grouped in trials where word order either could be tested immediately (working memory trials; WM) or later (LTM trials) according to instructions. Subjects were tested on their ability to retrieve the order of the three words. The data revealed that alpha power in parieto-occipital regions was lower during word presentation compared to rehearsal. Our key finding was that parieto-occipital alpha power during the rehearsal period was markedly stronger for successfully than unsuccessfully encoded LTM sequences. This subsequent memory effect demonstrates that high posterior alpha activity creates an optimal brain state for successful LTM formation possibly by actively reducing parieto-occipital activity that might interfere with sequence encoding. Copyright © 2010 Wiley Periodicals, Inc.

  18. Potent, selective, orally bioavailable inhibitors of tumor necrosis factor-alpha converting enzyme (TACE): discovery of indole, benzofuran, imidazopyridine and pyrazolopyridine P1' substituents.

    Science.gov (United States)

    Lu, Zhonghui; Ott, Gregory R; Anand, Rajan; Liu, Rui-Qin; Covington, Maryanne B; Vaddi, Krishna; Qian, Mingxin; Newton, Robert C; Christ, David D; Trzaskos, James; Duan, James J-W

    2008-03-15

    Potent and selective inhibitors of tumor necrosis factor-alpha converting enzyme (TACE) were discovered with several new heterocyclic P1' groups in conjunction with cyclic beta-amino hydroxamic acid scaffolds. Among them, the pyrazolopyridine provided the best overall profile when combined with tetrahydropyran beta-amino hydroxamic acid scaffold. Specifically, inhibitor 49 showed IC(50) value of 1 nM against porcine TACE and 170 nM in the suppression of LPS-induced TNF-alpha of human whole blood. Compound 49 also displayed excellent selectivity over a wide panel of MMPs as well as excellent oral bioavailability (F%>90%) in rat n-in-1 PK studies.

  19. 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)

  20. Glycogen synthase kinase 3 alpha phosphorylates and regulates the osteogenic activity of Osterix.

    Science.gov (United States)

    Li, Hongyan; Jeong, Hyung Min; Choi, You Hee; Lee, Sung Ho; Jeong, Hye Gwang; Jeong, Tae Cheon; Lee, Kwang Youl

    2013-05-10

    Osteoblast-specific transcription factor Osterix is a zinc-finger transcription factor that required for osteoblast differentiation and new bone formation. The function of Osterix can be modulated by post-translational modification. Glycogen synthase kinase 3 alpha (GSK3α) is a multifunctional serine/threonine protein kinase that plays a role in the Wnt signaling pathways and is implicated in the control of several regulatory proteins and transcription factors. In the present study, we investigated how GSK3α regulates Osterix during osteoblast differentiation. Wide type GSK3α up-regulated the protein level, protein stability and transcriptional activity of Osterix. These results suggest that GSK3α regulates osteogenic activity of Osterix. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Salivary type alpha-amylase activity in serum and in urine of patients with lung adenocarcinoma; Aktywnosc alfa-amylazy sliniankowej w surowicy i moczu chorych na gruczolakoraka pluca

    Energy Technology Data Exchange (ETDEWEB)

    Zakrzewska, I.; Wolska, K.; Koput, A. [Zaklad Laboratoryjnej Diagnostyki Klinicznej, Akademia Medyczna, Bialystok (Poland)

    1993-12-31

    Total alpha-amylase activity in sera and urine of 30 patients with lung adenocarcinoma has been tested. The results were compared with control group of 30 healthy voluntaries. The activity of pancreatic type was differentiated from salivary alpha amylase. Salivary type was inhibited selectively by Triticum aestivum. Higher levels of total and salivary type amylase were noted in patients with lung adenocarcinoma in comparison to healthy control. The increase was significant (p<0.005). Correlation was observed between the activity of salivary type amylase and the stage of adenocarcinoma. (author). 12 refs, 3 figs, 1 tab.

  2. 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

  3. [Activity of alpha-amylase and concentration of protein in saliva of pregnant women].

    Science.gov (United States)

    Ciejak, Magdalena; Olszewska, Maria; Jakubowska, Katarzyna; Zebiełowicz, Dariusz; Safranow, Krzysztof; Chlubek, Dariusz

    2007-01-01

    One of the hypothetical reasons of the increased incidence of caries in women during the pregnancy may be the increased activity of alpha-amylase, which can be found in their saliva. The enzyme takes part in the process of decomposition of simple sugars, which make basic substrate for caries-causing bacteria. The aim of the paper was the evaluation of the influence of pregnancy and gestational age on the activity of alpha-amylase and the concentration of protein in women's saliva. The examined group consisted of 64 pregnant women at age 17-39, between 21st and 40th week of pregnancy. The control group consisted of 44 healthy women at age 20-35, who were not pregnant. In saliva, which was taken before morning meal, without stimulation, protein concentration was determined by Bradford method and the activity of amylase was determined by kinetic method. The activity of amylase correlated strongly and positively with protein concentration in saliva of both the pregnant (RS = +0.65; p women. There were no significant differences between examined parameters in the examined and the control group. It has been observed in the examined group, that there is the significant negative correlation between protein concentration in saliva and the week of pregnancy (RS = -0.35; p increased caries incidence of pregnant women. However, the observed changes of total protein concentration in saliva during pregnancy, suggest that the exact cognition of proteins in pregnant women's saliva may reveal new mechanisms, which lead to an increase of caries risk.

  4. Selection of active spaces for multiconfigurational wavefunctions

    Energy Technology Data Exchange (ETDEWEB)

    Keller, Sebastian; Boguslawski, Katharina; Reiher, Markus, E-mail: markus.reiher@phys.chem.ethz.ch [Laboratorium für Physikalische Chemie, ETH Zürich, Vladimir-Prelog-Weg 2, CH-8093 Zürich (Switzerland); Janowski, Tomasz; Pulay, Peter, E-mail: pulay@uark.edu [Department of Chemistry and Biochemistry, Fulbright College of Arts and Sciences, University of Arkansas, Fayetteville, Arkansas 72701 (United States)

    2015-06-28

    The efficient and accurate description of the electronic structure of strongly correlated systems is still a largely unsolved problem. The usual procedures start with a multiconfigurational (usually a Complete Active Space, CAS) wavefunction which accounts for static correlation and add dynamical correlation by perturbation theory, configuration interaction, or coupled cluster expansion. This procedure requires the correct selection of the active space. Intuitive methods are unreliable for complex systems. The inexpensive black-box unrestricted natural orbital (UNO) criterion postulates that the Unrestricted Hartree-Fock (UHF) charge natural orbitals with fractional occupancy (e.g., between 0.02 and 1.98) constitute the active space. UNOs generally approximate the CAS orbitals so well that the orbital optimization in CAS Self-Consistent Field (CASSCF) may be omitted, resulting in the inexpensive UNO-CAS method. A rigorous testing of the UNO criterion requires comparison with approximate full configuration interaction wavefunctions. This became feasible with the advent of Density Matrix Renormalization Group (DMRG) methods which can approximate highly correlated wavefunctions at affordable cost. We have compared active orbital occupancies in UNO-CAS and CASSCF calculations with DMRG in a number of strongly correlated molecules: compounds of electronegative atoms (F{sub 2}, ozone, and NO{sub 2}), polyenes, aromatic molecules (naphthalene, azulene, anthracene, and nitrobenzene), radicals (phenoxy and benzyl), diradicals (o-, m-, and p-benzyne), and transition metal compounds (nickel-acetylene and Cr{sub 2}). The UNO criterion works well in these cases. Other symmetry breaking solutions, with the possible exception of spatial symmetry, do not appear to be essential to generate the correct active space. In the case of multiple UHF solutions, the natural orbitals of the average UHF density should be used. The problems of the UNO criterion and their potential solutions

  5. Selection of active spaces for multiconfigurational wavefunctions

    International Nuclear Information System (INIS)

    Keller, Sebastian; Boguslawski, Katharina; Reiher, Markus; Janowski, Tomasz; Pulay, Peter

    2015-01-01

    The efficient and accurate description of the electronic structure of strongly correlated systems is still a largely unsolved problem. The usual procedures start with a multiconfigurational (usually a Complete Active Space, CAS) wavefunction which accounts for static correlation and add dynamical correlation by perturbation theory, configuration interaction, or coupled cluster expansion. This procedure requires the correct selection of the active space. Intuitive methods are unreliable for complex systems. The inexpensive black-box unrestricted natural orbital (UNO) criterion postulates that the Unrestricted Hartree-Fock (UHF) charge natural orbitals with fractional occupancy (e.g., between 0.02 and 1.98) constitute the active space. UNOs generally approximate the CAS orbitals so well that the orbital optimization in CAS Self-Consistent Field (CASSCF) may be omitted, resulting in the inexpensive UNO-CAS method. A rigorous testing of the UNO criterion requires comparison with approximate full configuration interaction wavefunctions. This became feasible with the advent of Density Matrix Renormalization Group (DMRG) methods which can approximate highly correlated wavefunctions at affordable cost. We have compared active orbital occupancies in UNO-CAS and CASSCF calculations with DMRG in a number of strongly correlated molecules: compounds of electronegative atoms (F 2 , ozone, and NO 2 ), polyenes, aromatic molecules (naphthalene, azulene, anthracene, and nitrobenzene), radicals (phenoxy and benzyl), diradicals (o-, m-, and p-benzyne), and transition metal compounds (nickel-acetylene and Cr 2 ). The UNO criterion works well in these cases. Other symmetry breaking solutions, with the possible exception of spatial symmetry, do not appear to be essential to generate the correct active space. In the case of multiple UHF solutions, the natural orbitals of the average UHF density should be used. The problems of the UNO criterion and their potential solutions are discussed

  6. Selection of active spaces for multiconfigurational wavefunctions

    Science.gov (United States)

    Keller, Sebastian; Boguslawski, Katharina; Janowski, Tomasz; Reiher, Markus; Pulay, Peter

    2015-06-01

    The efficient and accurate description of the electronic structure of strongly correlated systems is still a largely unsolved problem. The usual procedures start with a multiconfigurational (usually a Complete Active Space, CAS) wavefunction which accounts for static correlation and add dynamical correlation by perturbation theory, configuration interaction, or coupled cluster expansion. This procedure requires the correct selection of the active space. Intuitive methods are unreliable for complex systems. The inexpensive black-box unrestricted natural orbital (UNO) criterion postulates that the Unrestricted Hartree-Fock (UHF) charge natural orbitals with fractional occupancy (e.g., between 0.02 and 1.98) constitute the active space. UNOs generally approximate the CAS orbitals so well that the orbital optimization in CAS Self-Consistent Field (CASSCF) may be omitted, resulting in the inexpensive UNO-CAS method. A rigorous testing of the UNO criterion requires comparison with approximate full configuration interaction wavefunctions. This became feasible with the advent of Density Matrix Renormalization Group (DMRG) methods which can approximate highly correlated wavefunctions at affordable cost. We have compared active orbital occupancies in UNO-CAS and CASSCF calculations with DMRG in a number of strongly correlated molecules: compounds of electronegative atoms (F2, ozone, and NO2), polyenes, aromatic molecules (naphthalene, azulene, anthracene, and nitrobenzene), radicals (phenoxy and benzyl), diradicals (o-, m-, and p-benzyne), and transition metal compounds (nickel-acetylene and Cr2). The UNO criterion works well in these cases. Other symmetry breaking solutions, with the possible exception of spatial symmetry, do not appear to be essential to generate the correct active space. In the case of multiple UHF solutions, the natural orbitals of the average UHF density should be used. The problems of the UNO criterion and their potential solutions are discussed

  7. Portable instrument for selectively detecting alpha-particles derived from radon

    International Nuclear Information System (INIS)

    Chapuis, A.M.; DaJlevic, D.

    1975-01-01

    A portable instrument of the pocket type designed primarily for monitoring atmospheric contamination in uranium mines by selectively detecting the α-particles emitted simultaneously by the daughter products of radon, namely radium A and radium C' is described. The instrument comprises in combination a tube containing a suction fan for drawing external air through a filter which retains the α-emitting aerosols, a detector in which the α-particles corresponding to the respective energies of the α-emissions of radium A and of radium C' are detected separately, and two collimators placed between the filter and the detector

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

    DEFF Research Database (Denmark)

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

    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 alp...

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

    Science.gov (United States)

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

    2017-07-01

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

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

    Science.gov (United States)

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

    2003-09-01

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

  11. 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)

  12. An immunocapture/scintillation proximity analysis of G alpha q/11 activation by native serotonin (5-HT)2A receptors in rat cortex: blockade by clozapine and mirtazapine.

    Science.gov (United States)

    Mannoury La Cour, C; Chaput, C; Touzard, M; Millan, M J

    2009-02-01

    Though transduction mechanisms recruited by heterologously expressed 5-HT(2A) receptors have been extensively studied, their interaction with specific subtypes of G-protein remains to be directly evaluated in cerebral tissue. Herein, as shown by an immunocapture/scintillation proximity analysis, 5-HT, the prototypical 5-HT(2A) agonist, DOI, and Ro60,0175 all enhanced [(35)S]GTPgammaS binding to G alpha q/11 in rat cortex with pEC(50) values of 6.22, 7.24 and 6.35, respectively. No activation of G o or G s/olf was seen at equivalent concentrations of DOI. Stimulation of G alpha q/11 by 5-HT (30 microM) and DOI (30 microM) was abolished by the selective 5-HT(2A) vs. 5-HT(2C)/5-HT(2B) antagonists, ketanserin (pK(B) values of 9.11 and 8.88, respectively) and MDL100,907 (9.82 and 9.68). By contrast, 5-HT-induced [(35)S]GTPgammaS binding to G alpha q/11 was only weakly inhibited by the preferential 5-HT(2C) receptor antagonists, RS102,221 (6.94) and SB242,084 (7.39), and the preferential 5-HT(2B) receptor antagonist, LY266,097 (6.66). The antipsychotic, clozapine, which had marked affinity for 5-HT(2A) receptors, blocked the recruitment of G alpha q/11 by 5-HT and DOI with pK(B) values of 8.54 and 8.14, respectively. Its actions were mimicked by the "atypical" antidepressant and 5-HT(2A) receptor antagonist, mirtazapine, which likewise blocked 5-HT and DOI-induced G alpha q/11 protein activation with pK(B) values of 7.90 and 7.76, respectively. In conclusion, by use of an immunocapture/scintillation proximity strategy, this study shows that native 5-HT(2A) receptors in rat frontal cortex specifically recruit G alpha q/11 and that this action is blocked by clozapine and mirtazapine. Quantification of 5-HT(2A) receptor-mediated G alpha q/11 activation in frontal cortex should prove instructive in characterizing the actions of diverse classes of psychotropic agent. 2008 Wiley-Liss, Inc.

  13. Nanostructured electrocatalysts with tunable activity and selectivity

    Science.gov (United States)

    Mistry, Hemma; Varela, Ana Sofia; Kühl, Stefanie; Strasser, Peter; Cuenya, Beatriz Roldan

    2016-04-01

    The field of electrocatalysis has undergone tremendous advancement in the past few decades, in part owing to improvements in catalyst design at the nanoscale. These developments have been crucial for the realization of and improvement in alternative energy technologies based on electrochemical reactions such as fuel cells. Through the development of novel synthesis methods, characterization techniques and theoretical methods, rationally designed nanoscale electrocatalysts with tunable activity and selectivity have been achieved. This Review explores how nanostructures can be used to control electrochemical reactivity, focusing on three model reactions: O2 electroreduction, CO2 electroreduction and ethanol electrooxidation. The mechanisms behind nanoscale control of reactivity are discussed, such as the presence of low-coordinated sites or facets, strain, ligand effects and bifunctional effects in multimetallic materials. In particular, studies of how particle size, shape and composition in nanostructures can be used to tune reactivity are highlighted.

  14. 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.

  15. Effect of gelatinization and hydrolysis conditions on the selectivity of starch hydrolysis with alpha-amylase from Bacillus licheniformis.

    Science.gov (United States)

    Baks, Tim; Bruins, Marieke E; Matser, Ariette M; Janssen, Anja E M; Boom, Remko M

    2008-01-23

    Enzymatic hydrolysis of starch can be used to obtain various valuable hydrolyzates with different compositions. The effects of starch pretreatment, enzyme addition point, and hydrolysis conditions on the hydrolyzate composition and reaction rate during wheat starch hydrolysis with alpha-amylase from Bacillus licheniformis were compared. Suspensions of native starch or starch gelatinized at different conditions either with or without enzyme were hydrolyzed. During hydrolysis, the oligosaccharide concentration, the dextrose equivalent, and the enzyme activity were determined. We found that the hydrolyzate composition was affected by the type of starch pretreatment and the enzyme addition point but that it was just minimally affected by the pressure applied during hydrolysis, as long as gelatinization was complete. The differences between hydrolysis of thermally gelatinized, high-pressure gelatinized, and native starch were explained by considering the granule structure and the specific surface area of the granules. These results show that the hydrolyzate composition can be influenced by choosing different process sequences and conditions.

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    Robert C McDermid

    2006-01-01

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

  18. 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

  19. Uranium trace and alpha activity characterization of coal and fly ash using particle track etch technique

    International Nuclear Information System (INIS)

    Chakravarti, S.K.

    1991-01-01

    Uranium is extensively found in carbonaceous components of sedimentary rocks and is considered to be accumulated in coals during the coalification process through the geological times. Burning of coal is mainly responsible for a manifold increase in the concentration of radioactive nuclides in atmosphere precipitates. Fly ash being an incombustible residue and formed from 90% of the inorganic material in coal, escapes into the atmosphere and constitutes a potential hazard. Also its use as one of the pozzolanic materials in the products of concrete, bricks etc and filling of ground cavities is even more hazardous because of the wall radioactivity, besides emission and diffusion of radon. This paper reports a simple method called Particle Track Etch (PTE) technique, for trace determination of uranium content in coal and fly ash samples by making use of low cost and versatile plastic detectors known as Solid State Nuclear Track Detectors (SSNTDs). Total alpha activity has also been estimated using these SSNTDs. The values of uranium concentration in coal samples are found to range from 1.1 to 3.6 ppm (uniform component) and 33 to 46 ppm (non-uniform part) whereas in fly ash, it varies from 8 to 11 ppm (uniform) and 55 to 71 ppm in non-uniform range. It is also observed that the alpha activity is a function of uranium concentration for most of the natural samples of coal studied except for mixtures of fly ash samples where relationship is found to be on higher side. (author). 13 refs., 2 tabs., 1 fig

  20. Active tuberculosis patients have high levels of IgA anti-alpha-crystallin and isocitrate lyase proteins.

    Science.gov (United States)

    Talavera-Paulín, M; García-Morales, L; Ruíz-Sánchez, B P; Caamal-Ley, Á D; Hernández-Solis, A; Ramírez-Casanova, E; Cicero-Sabido, R; Espitia, C; Helguera-Repetto, C; González-Y-Merchand, J A; Flores-Mejía, R; Estrada-Parra, S; Estrada-García, I; Chacón-Salinas, R; Wong-Baeza, I; Serafín-López, J

    2016-12-01

    Mexico City, Mexico. To identify proteins synthetised by Mycobacterium tuberculosis in hypoxic culture, which resemble more closely a granuloma environment than aerobic culture, and to determine if they are recognised by antibodies from patients with active pulmonary tuberculosis (PTB). Soluble extracts from M. tuberculosis H37Rv cultured under aerobic or hypoxic conditions were analysed using two-dimensional polyacrylamide gel electrophoresis, and proteins over-expressed under hypoxia were identified by mass spectrometry. The presence of immunoglobulin (Ig) G, IgA and IgM antibodies against these proteins was determined in the serum of 42 patients with active PTB and 42 healthy controls. We selected three M. tuberculosis H37Rv proteins (alpha-crystallin protein [Acr, Rv2031c], universal stress protein Rv2623 and isocitrate lyase [ICL, RV0467]) that were over-expressed under hypoxia. Titres of anti-Acr and anti-ICL IgA antibodies were higher in patients than in healthy controls, with an area under the receiver operating characteristic curve of 0.71 for anti-ICL IgA antibodies. ICL could be used in combination with other M. tuberculosis antigens to improve the sensitivity and specificity of current serological TB diagnostic methods.

  1. 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.

  2. Classification of alpha-active workplace aerosols based on coefficient of transportability as measured by the dialysis method

    International Nuclear Information System (INIS)

    Khokhryakov, V.F.; Suslova, K.G.; Tseveloyova, I.A.; Aladova, E.E.; Filipy, R.E.

    1998-01-01

    This report describes a method by which potentially inhaled workplace aerosols containing plutonium compounds are classified on the basis of measured transportability in Ringer's solution. It is suggested that the criterion 'transportability' be used in the ICRP respiratory tract model. Transportability is measured as the fraction of plutonium alpha activity, deposited on a collecting filter, that passes through a semi-permeable membrane in Ringer's physiological solution during two days of dialysis. First order kinetic equations are used for explanation of dialysis results. The dissolution characteristics of alpha-active aerosols are important in interpretation of their passage from the lungs after inhalation. (author)

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  5. 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.

  6. Oridonin stabilizes retinoic acid receptor alpha through ROS-activated NF-κB signaling.

    Science.gov (United States)

    Cao, Yang; Wei, Wei; Zhang, Nan; Yu, Qing; Xu, Wen-Bin; Yu, Wen-Jun; Chen, Guo-Qiang; Wu, Ying-Li; Yan, Hua

    2015-04-10

    Retinoic acid receptor alpha (RARα) plays an essential role in the regulation of many biological processes, such as hematopoietic cell differentiation, while abnormal RARα function contributes to the pathogenesis of certain diseases including cancers, especially acute promyelocytic leukemia (APL). Recently, oridonin, a natural diterpenoid isolated from Rabdosia rubescens, was demonstrated to regulate RARα by increasing its protein level. However, the underlying molecular mechanism for this action has not been fully elucidated. In the APL cell line, NB4, the effect of oridonin on RARα protein was analyzed by western blot and real-time quantitative RT-PCR analyses. Flow cytometry was performed to detect intracellular levels of reactive oxygen species (ROS). The association between nuclear factor-kappa B (NF-κB) signaling and the effect of oridonin was assessed using specific inhibitors, shRNA gene knockdown, and immunofluorescence assays. In addition, primary leukemia cells were treated with oridonin and analyzed by western blot in this study. RARα possesses transcriptional activity in the presence of its ligand, all-trans retinoic acid (ATRA). Oridonin remarkably stabilized the RARα protein, which retained transcriptional activity. Oridonin also moderately increased intracellular ROS levels, while pretreatment with the ROS scavenger, N-acetyl-l-cysteine (NAC), dramatically abrogated RARα stabilization by oridonin. More intriguingly, direct exposure to low concentrations of H2O2 also increased RARα protein but not mRNA levels, suggesting a role for ROS in oridonin stabilization of RARα protein. Further investigations showed that NAC antagonized oridonin-induced activation of NF-κB signaling, while the NF-κB signaling inhibitor, Bay 11-7082, effectively blocked the oridonin increase in RARα protein levels. In line with this, over-expression of IκΒα (A32/36), a super-repressor form of IκΒα, or NF-κB-p65 knockdown inhibited oridonin or H2O2-induced

  7. 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 (palpha 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.

  8. Spinal activation of alpha7-nicotinic acetylcholine receptor attenuates posttraumatic stress disorder-related chronic pain via suppression of glial activation.

    Science.gov (United States)

    Sun, Rao; Zhang, Wei; Bo, Jinhua; Zhang, Zuoxia; Lei, Yishan; Huo, Wenwen; Liu, Yue; Ma, Zhengliang; Gu, Xiaoping

    2017-03-06

    The high prevalence of chronic pain in posttraumatic stress disorder (PTSD) individuals has been widely reported by clinical studies, which emphasized an urgent need to uncover the underlying mechanisms and identify potential therapeutic targets. Recent studies suggested that targeting activated glia and their pro-inflammatory products may provide a novel and effective therapy for the stress-related pain. In this study, we investigated whether activation of alpha-7 nicotinic acetylcholine receptor (α7 nAChR), a novel anti-inflammatory target, could attenuate PTSD-related chronic pain. The experiments were conducted in a rat model of single prolonged stress (SPS), an established model of PTSD-pain comorbidity. We found that SPS exposure produced persistent mechanical allodynia. Immunohistochemical and enzyme-linked immuno sorbent assay analysis showed that SPS also induced elevated activation of glia cells (including microglia and astrocytes) and accumulation of pro-inflammatory cytokines in spinal cord. In another experiment, we found that intrathecal injection of PHA-543613, a selective α7 nAchR agonist, attenuated the SPS-evoked allodynia in a dose dependent manner. However, this anti-hyperalgesic effect was blocked by pretreatment with methyllycaconitine (MLA), a selective α7 nAchR antagonist. Further analyses showed that PHA-543613 suppressed SPS-induced spinal glial activation and SPS-elevated spinal pro-inflammatory cytokines, and these were abolished by MLA. Taken together, the present study showed that spinal activation of α7 nAChR by PHA-543613 attenuated mechanical allodynia induced by PTSD-like stress, and the suppression of spinal glial activation may underlie this anti-hyperalgesic effect. Our study demonstrated the therapeutic potential of targeting α7 nAChR in the treatment of PTSD-related chronic pain. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. 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)

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

    Science.gov (United States)

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

    2014-01-01

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

  11. Clofibric acid, a peroxisome proliferator-activated receptor alpha ligand, inhibits growth of human ovarian cancer.

    Science.gov (United States)

    Yokoyama, Yoshihito; Xin, Bing; Shigeto, Tatsuhiko; Umemoto, Mika; Kasai-Sakamoto, Akiko; Futagami, Masayuki; Tsuchida, Shigeki; Al-Mulla, Fahd; Mizunuma, Hideki

    2007-04-01

    Recent reports have shown that peroxisome proliferator-activated receptor (PPAR)alpha ligands reduce growth of some types of malignant tumors and prevent carcinogenesis. In this study, we investigated the inhibitory effect of clofibric acid (CA), a ligand for PPARalpha on growth of ovarian malignancy, in in vivo and in vitro experiments using OVCAR-3 and DISS cells derived from human ovarian cancer and aimed to elucidate the molecular mechanism of its antitumor effect. CA treatment significantly suppressed the growth of OVCAR-3 tumors xenotransplanted s.c. and significantly prolonged the survival of mice with malignant ascites derived from DISS cells as compared with control. CA also dose-dependently inhibited cell proliferation of cultured cell lines. CA treatment increased the expression of carbonyl reductase (CR), which promotes the conversion of prostaglandin E(2) (PGE(2)) to PGF(2alpha), in implanted OVCAR-3 tumors as well as cultured cells. CA treatment decreased PGE(2) level as well as vascular endothelial growth factor (VEGF) amount in both of OVCAR-3-tumor and DISS-derived ascites. Reduced microvessel density and induced apoptosis were found in solid OVCAR-3 tumors treated by CA. Transfection of CR expression vector into mouse ovarian cancer cells showed significant reduction of PGE(2) level as well as VEGF expression. These results indicate that CA produces potent antitumor effects against ovarian cancer in conjunction with a reduction of angiogenesis and induction of apoptosis. We conclude that CA could be an effective agent in ovarian cancer and should be tested alone and in combination with other anticancer drugs.

  12. 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.

  13. 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.

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Guolin Li

    2018-01-01

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

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

    Science.gov (United States)

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

    2017-10-23

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

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

    Science.gov (United States)

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

    2014-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Boonyadist Vongsak

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

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

    DEFF Research Database (Denmark)

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

    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...

  20. 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.

    2015-01-01

    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

  1. Increase in posterior alpha activity during rehearsal predicts successful long-term memory formation of word sequences.

    NARCIS (Netherlands)

    Meeuwissen, E.B.; Takashima, A.; Fernandez, G.S.E.; Jensen, O.

    2011-01-01

    It is becoming increasingly clear that demanding cognitive tasks rely on an extended network engaging task-relevant areas and, importantly, disengaging task-irrelevant areas. Given that alpha activity (8-12 Hz) has been shown to reflect the disengagement of task-irrelevant regions in attention and

  2. Increase in posterior alpha activity during rehearsal predicts successful long-term memory formation of word sequences

    NARCIS (Netherlands)

    Meeuwissen, E.B.; Takashima, A.; Fernandez, G.S.E.; Jensen, O.

    2011-01-01

    It is becoming increasingly clear that demanding cognitive tasks rely on an extended network engaging task-relevant areas and, importantly, disengaging task-irrelevant areas. Given that alpha activity (8–12 Hz) has been shown to reflect the disengagement of task-irrelevant regions in attention and

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

    Science.gov (United States)

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

    2007-01-01

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

  4. 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

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    Ma L

    2018-02-01

    Full Text Available Ling Ma,1 Yong Jiang,2 Yanan Dong,2 Jun Gao,2 Bin Du,2 Dianwei Liu2 1Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Neurosurgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China Background: Subarachnoid hemorrhage (SAH can induce apoptosis in many regions of the brain including the cortex and hippocampus. However, few studies have focused on apoptosis in the hypothalamus after SAH. Although some antiapoptotic strategies have been developed for SAH, such as anti-tumor necrosis factor-alpha (TNF-α antibody, the molecular mechanisms underlying this condition have yet to be elucidated. Therefore, the purpose of this study was to evaluate whether SAH could induce apoptosis in the hypothalamus and identify the potential molecular mechanisms underlying the actions of anti-TNF-α antibody, as a therapeutic regimen, upon apoptosis. Materials and methods: SAH was induced in a rat model. Thirty minutes prior to SAH, anti-TNF-α antibody or U0126, an extracellular signal-regulated kinase (Erk inhibitor, was microinjected into the left lateral cerebral ventricle. In addition, phorbol-12-myristate-13-acetate was injected intraperitoneally immediately after the anti-TNF-α antibody microinjection. Then, real-time polymerase chain reaction, Western blotting and immunohistochemistry were used to detect the expression of caspase-3, bax, bcl-2, phosphorylated Erk (p-Erk and Erk. Finally, anxiety-like behavior was identified by using open field. Results: Levels of caspase-3, bax and bcl-2, all showed a temporary rise after SAH in the hypothalamus, indicating the induction of apoptosis in this brain region. Interestingly, we found that the microinjection of anti-TNF-α antibody could selectively block the elevated levels of bax, suggesting the potential role of anti-TNF-α antibody in the inhibition of SAH

  7. 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, L; Rasmussen, S; Fenger, Mogens

    2005-01-01

    The peroxisome proliferator-activated receptor gamma co-activator 1alpha (PGC-1alpha) is a novel transcriptional co-activator that holds an important role in lipid and glucose metabolism. PGC-1alpha is a candidate gene for the metabolic syndrome (MS) as well as type 2 diabetes. Recent studies...... related to this syndrome. The variant was examined, using PCR-RFLP, in the DanMONICA cohort comprising a population-based sample of 2349 subjects. MS was defined using the National Cholesterol Education Program -- Adult Treatment Panel III (NCEP-ATPIII) criteria. The allelic frequency of the Ser482 allele...... and insulin secretion, 24-ambulatory blood pressure or left ventricular mass index. In conclusion, the Gly482Ser polymorphism of the PGC-1alpha gene is not associated with the metabolic syndrome, related quantitative traits or cardiac hypertrophy among Danish Caucasian subjects...

  8. Characterization of the human pH- and PKA-activated ClC-2G(2 alpha) Cl- channel.

    Science.gov (United States)

    Sherry, A M; Stroffekova, K; Knapp, L M; Kupert, E Y; Cuppoletti, J; Malinowska, D H

    1997-08-01

    A ClC-2G(2 alpha) Cl- channel was identified to be present in human lung and stomach, and a partial cDNA for this Cl- channel was cloned from a human fetal lung library. A full-length expressible human ClC-2G(2 alpha) cDNA was constructed by ligation of mutagenized expressible rabbit ClC-2G(2 alpha) cDNA with the human lung ClC-2G(2 alpha) cDNA, expressed in oocytes, and characterized at the single-channel level. Adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA) treatment increased the probability of opening of the channel (Po). After PKA activation, the channel exhibited a linear (r = 0.99) current-voltage curve with a slope conductance of 22.1 +/- 0.8 pS in symmetric 800 mM tetraethylammonium chloride (TEACl; pH 7.4). Under fivefold gradient conditions of TEACl, a reversal potential of +21.5 +/- 2.8 mV was measured demonstrating anion-to-cation discrimination. As previously demonstrated for the rabbit ClC-2G(2 alpha) Cl- channel, the human analog, hClC-2G(2 alpha), was active at pH 7.4 as well as when the pH of the extracellular face of the channel (trans side of the bilayer; pHtrans) was asymmetrically reduced to pH 3.0. The extent of PKA activation was dependent on pHtrans. With PKA treatment, Po increased fourfold with a pHtrans of 7.4 and eightfold with a pHtrans of 3.0. Effects of sequential PKA addition followed by pHtrans reduction on the same channel suggested that the PKA- and pH-dependent increases in channel Po were separable and cumulative. Northern analysis showed ClC-2G(2 alpha) mRNA to be present in human adult and fetal lung and adult stomach, and quantitative reverse transcriptase-polymerase chain reaction showed this channel to be present in the adult human lung and stomach at about one-half the level found in fetal lung. The findings of the present study suggest that the ClC-2G(2 alpha) Cl- channel may play an important role in Cl- transport in the fetal and adult human lung.

  9. Pupil Dilation and EEG Alpha Frequency Band Power Reveal Load on Executive Functions for Link-Selection Processes during Text Reading.

    Directory of Open Access Journals (Sweden)

    Christian Scharinger

    Full Text Available Executive working memory functions play a central role in reading comprehension. In the present research we were interested in additional load imposed on executive functions by link-selection processes during computer-based reading. For obtaining process measures, we used a methodology of concurrent electroencephalographic (EEG and eye-tracking data recording that allowed us to compare epochs of pure text reading with epochs of hyperlink-like selection processes in an online reading situation. Furthermore, this methodology allowed us to directly compare the two physiological load-measures EEG alpha frequency band power and pupil dilation. We observed increased load on executive functions during hyperlink-like selection processes on both measures in terms of decreased alpha frequency band power and increased pupil dilation. Surprisingly however, the two measures did not correlate. Two additional experiments were conducted that excluded potential perceptual, motor, or structural confounds. In sum, EEG alpha frequency band power and pupil dilation both turned out to be sensitive measures for increased load during hyperlink-like selection processes in online text reading.

  10. In Vitro Selection of Single-Stranded DNA Molecular Recognition Elements against S. aureus Alpha Toxin and Sensitive Detection in Human Serum

    Directory of Open Access Journals (Sweden)

    Ka L. Hong

    2015-01-01

    Full Text Available Alpha toxin is one of the major virulence factors secreted by Staphylococcus aureus, a bacterium that is responsible for a wide variety of infections in both community and hospital settings. Due to the prevalence of S. aureus related infections and the emergence of methicillin-resistant S. aureus, rapid and accurate diagnosis of S. aureus infections is crucial in benefiting patient health outcomes. In this study, a rigorous Systematic Evolution of Ligands by Exponential Enrichment (SELEX variant previously developed by our laboratory was utilized to select a single-stranded DNA molecular recognition element (MRE targeting alpha toxin with high affinity and specificity. At the end of the 12-round selection, the selected MRE had an equilibrium dissociation constant (Kd of 93.7 ± 7.0 nM. Additionally, a modified sandwich enzyme-linked immunosorbent assay (ELISA was developed by using the selected ssDNA MRE as the toxin-capturing element and a sensitive detection of 200 nM alpha toxin in undiluted human serum samples was achieved.

  11. Antileishmanial Activity of Selected Turkish Medicinal Plants

    African Journals Online (AJOL)

    Centaurea calolepis, Phlomis lycia, Eryngium thorifolium, Origanum ... leishmanicidal activity of the extracts was evaluated against L. .... examined under oil immersion with a light ..... Composition and antimicrobial activity of the essential oils of ...

  12. Structural Basis for Selective Small Molecule Kinase Inhibition of Activated c-Met

    Energy Technology Data Exchange (ETDEWEB)

    Rickert, Keith W.; Patel, Sangita B.; Allison, Timothy J.; Byrne, Noel J.; Darke, Paul L.; Ford, Rachael E.; Guerin, David J.; Hall, Dawn L.; Kornienko, Maria; Lu, Jun; Munshi, Sanjeev K.; Reid, John C.; Shipman, Jennifer M.; Stanton, Elizabeth F.; Wilson, Kevin J.; Young, Jonathon R.; Soisson, Stephen M.; Lumb, Kevin J. (Merck)

    2012-03-15

    The receptor tyrosine kinase c-Met is implicated in oncogenesis and is the target for several small molecule and biologic agents in clinical trials for the treatment of cancer. Binding of the hepatocyte growth factor to the cell surface receptor of c-Met induces activation via autophosphorylation of the kinase domain. Here we describe the structural basis of c-Met activation upon autophosphorylation and the selective small molecule inhibiton of autophosphorylated c-Met. MK-2461 is a potent c-Met inhibitor that is selective for the phosphorylated state of the enzyme. Compound 1 is an MK-2461 analog with a 20-fold enthalpy-driven preference for the autophosphorylated over unphosphorylated c-Met kinase domain. The crystal structure of the unbound kinase domain phosphorylated at Tyr-1234 and Tyr-1235 shows that activation loop phosphorylation leads to the ejection and disorder of the activation loop and rearrangement of helix {alpha}C and the G loop to generate a viable active site. Helix {alpha}C adopts a orientation different from that seen in activation loop mutants. The crystal structure of the complex formed by the autophosphorylated c-Met kinase domain and compound 1 reveals a significant induced fit conformational change of the G loop and ordering of the activation loop, explaining the selectivity of compound 1 for the autophosphorylated state. The results highlight the role of structural plasticity within the kinase domain in imparting the specificity of ligand binding and provide the framework for structure-guided design of activated c-Met inhibitors.

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

    International Nuclear Information System (INIS)

    Gasco, C.; Anton, M.P.

    1996-12-01

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

  14. Evaluation of Fibroblast Activation Protein-Alpha (FAP) as a Diagnostic Marker and Therapeutic Target in Prostate Cancer

    Science.gov (United States)

    2009-12-01

    low molecular weight recombinant human gelatin: development of a substitute for animal- derived gelatin with superior features, Protein Expr. Purif...by the honey - bee , could be modified to a form that was no longer hydro- lyzed by the native activator protease DPP4 but, instead, was hydrolyzed by...TITLE: Evaluation of Fibroblast Activation Protein -Alpha (FAP) as a Diagnostic Marker and Therapeutic Target in Prostate Cancer PRINCIPAL

  15. Dopamine activates masculine sexual behavior independent of the estrogen receptor alpha.

    Science.gov (United States)

    Wersinger, S R; Rissman, E F

    2000-06-01

    Estrogen receptor alpha (ERalpha) is believed to be a critical part of the regulatory processes involved in normal reproduction and sexual behavior. However, in this study we show the ERalpha is not required for display of masculine sexual behavior. Male and female, ERalpha knock-out (ERalphaKO) and wild-type mice were gonadectomized and implanted with testosterone. Sexual behavior and social preferences were tested after injection of the dopamine agonist, apomorphine (APO), or vehicle. All wild-type mice showed normal masculine behavior, including mounts and pelvic thrusts in females, and ejaculation in males. In agreement with past reports, ERalphaKO mice, given vehicle, failed to show mating behavior. Yet, ERalphaKO males given APO showed masculine copulatory behavior and chemoinvestigatory behavior directed at females. ERalphaKO females, treated with APO, mounted and thrusted when tested with receptive females. HPLC revealed that wild-type and ERalphaKO mice had equivalent catecholamine content in brain regions associated with masculine sexual behavior. These data show that the ERalpha is not essential during development or adulthood for the expression of masculine sexual behavior in mice. Moreover, dopamine can activate sexual behavior via a mechanism that either acts on an ER other than ERalpha or via an estrogen-independent pathway.

  16. Structural basis for alpha fetoprotein-mediated inhibition of caspase-3 activity in hepatocellular carcinoma cells.

    Science.gov (United States)

    Lin, Bo; Zhu, Mingyue; Wang, Wenting; Li, Wei; Dong, Xu; Chen, Yi; Lu, Yan; Guo, Junli; Li, Mengsen

    2017-10-01

    Alpha-fetoprotein (AFP) is an early serum growth factor in the foetal liver development and hepatic carcinogenesis; However, the precise biological role of cytoplasmic AFP remains elusive. Although we recently demonstrated that cytoplasmic AFP might interact with caspase-3 and inhibit the signal transduction of apoptosis in human hepatocellular carcinoma (HCC) cells, the details of this interaction are not clear. To reveal the molecular relationship between AFP and caspase-3, we performed molecular docking, co-immunoprecipitation (Co-IP), laser confocal microscopy, site-directed mutagenesis and functional experiments to analyse the key amino acid residues in the binding site of caspase-3. The results of Co-IP, laser confocal microscopy and functional analyses were consistent with the computational model. We also used the model to explain why AFP cannot bind to caspase-8. These results provide the molecular basis for the AFP-mediated inhibition of caspase-3 activity in HCC cells. Altogether, we found that AFP interacts with caspase-3 through precise amino acids, namely loop-4 residues Glu-248, Asp-253 and His-257. The results further demonstrated that AFP plays a critical role in the inhibition of the apoptotic signal transduction that mediated by caspase-3. Thus, AFP might represent a novel biotarget for the therapy of HCC patients. © 2017 UICC.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-08-15

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

  18. Dehydro-alpha-lapachone isolated from Catalpa ovata stems: activity against plant pathogenic fungi.

    Science.gov (United States)

    Cho, Jun Young; Kim, Hae Young; Choi, Gyung Ja; Jang, Kyoung Soo; Lim, He Kyoung; Lim, Chi Hwan; Cho, Kwang Yun; Kim, Jin-Cheol

    2006-05-01

    The methanol extract of stems of Catalpa ovata G Don exhibits potent in vivo antifungal activity against Magnaporthe grisea (Hebert) Barr (rice blast) on rice plants, Botrytis cinerea Pers ex Fr (tomato grey mould) and Phytophthora infestans (Mont) de Bary (tomato late blight) on tomato plants, Puccinia recondita Rob ex Desm (wheat leaf rust) on wheat plants and Blumeria graminis (DC) Speer f. sp. hordei Marchal (barley powdery mildew) on barley plants. An antifungal substance was isolated and identified as dehydro-alpha-lapachone from mass and nuclear magnetic resonance spectral data. It completely inhibited the mycelial growth of B. cinerea, Colletotrichum acutatum Simmonds, Colletotrichum gloeosporioides Simmonds, M. grisea and Pythium ultimum Trow over a range of 0.4-33.3 mg litre(-1). It also controlled the development of rice blast, tomato late blight, wheat leaf rust, barley powdery mildew and red pepper anthracnose (Colletotrichum coccodes (Wallr) S Hughes). The chemical was particularly effective in suppressing red pepper anthracnose by 95% at a concentration of 125 mg litre(-1). Copyright 2006 Society of Chemical Industry.

  19. Dronerarone acts as a selective inhibitor of 3,5,3'-triiodothyronine binding to thyroid hormone receptor-alpha1: in vitro and in vivo evidence.

    Science.gov (United States)

    Van Beeren, H C; Jong, W M C; Kaptein, E; Visser, T J; Bakker, O; Wiersinga, W M

    2003-02-01

    Dronedarone (Dron), without iodine, was developed as an alternative to the iodine-containing antiarrhythmic drug amiodarone (AM). AM acts, via its major metabolite desethylamiodarone, in vitro and in vivo as a thyroid hormone receptor alpha(1) (TRalpha(1)) and TRbeta(1) antagonist. Here we investigate whether Dron and/or its metabolite debutyldronedarone inhibit T(3) binding to TRalpha(1) and TRbeta(1) in vitro and whether dronedarone behaves similarly to amiodarone in vivo. In vitro, Dron had a inhibitory effect of 14% on the binding of T(3) to TRalpha(1), but not on TRbeta(1). Desethylamiodarone inhibited T(3) binding to TRalpha(1) and TRbeta(1) equally. Debutyldronedarone inhibited T(3) binding to TRalpha(1) by 77%, but to TRbeta(1) by only 25%. In vivo, AM increased plasma TSH and rT(3), and decreased T(3). Dron decreased T(4) and T(3), rT(3) did not change, and TSH fell slightly. Plasma total cholesterol was increased by AM, but remained unchanged in Dron-treated animals. TRbeta(1)-dependent liver low density lipoprotein receptor protein and type 1 deiodinase activities decreased in AM-treated, but not in Dron-treated, animals. TRalpha(1)-mediated lengthening of the QTc interval was present in both AM- and Dron-treated animals. The in vitro and in vivo findings suggest that dronedarone via its metabolite debutyldronedarone acts as a TRalpha(1)-selective inhibitor.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    The mechanism of activation of the transient receptor potential vanilloid 4 (TRPV4) channel by 4alpha-phorbol esters was investigated by combining information from chemical modification of 4alpha-phorbol-didecanoate (4alpha-PDD, 2a), site-directed mutagenesis, Ca(2+) imaging, and electrophysiology....... Binding of 4alpha-phorbol esters occurs in a loop in the TM3-TM4 domain of TRPV4 that is analogous to the capsaicin binding site of TRPV1, and the ester decoration of ring C and the A,B ring junction are critical for activity. The lipophilic ester groups on ring C serve mainly as a steering element...

  1. Effect of peroxisome proliferator-activated receptor alpha activators on tumor necrosis factor expression in mice during endotoxemia.

    Science.gov (United States)

    Hill, M R; Clarke, S; Rodgers, K; Thornhill, B; Peters, J M; Gonzalez, F J; Gimble, J M

    1999-07-01

    Inflammatory mediators orchestrate the host immune and metabolic response to acute bacterial infections and mediate the events leading to septic shock. Tumor necrosis factor (TNF) has long been identified as one of the proximal mediators of endotoxin action. Recent studies have implicated peroxisome proliferator-activated receptor alpha (PPARalpha) as a potential target to modulate regulation of the immune response. Since PPARalpha activators, which are hypolipidemic drugs, are being prescribed for a significant population of older patients, it is important to determine the impact of these drugs on the host response to acute inflammation. Therefore, we examined the role of PPARalpha activators on the regulation of TNF expression in a mouse model of endotoxemia. CD-1 mice treated with dietary fenofibrate or Wy-14,643 had fivefold-higher lipopolysaccharide (LPS)-induced TNF plasma levels than LPS-treated control-fed animals. Higher LPS-induced TNF levels in drug-fed animals were reflected physiologically in significantly lower glucose levels in plasma and a significantly lower 50% lethal dose than those in LPS-treated control-fed animals. Utilizing PPARalpha wild-type (WT) and knockout (KO) mice, we showed that the effect of fenofibrate on LPS-induced TNF expression was indeed mediated by PPARalpha. PPARalpha WT mice fed fenofibrate also had a fivefold increase in LPS-induced TNF levels in plasma compared to control-fed animals. However, LPS-induced TNF levels were significantly decreased and glucose levels in plasma were significantly increased in PPARalpha KO mice fed fenofibrate compared to those in control-fed animals. Data from peritoneal macrophage studies indicate that Wy-14,643 modestly decreased TNF expression in vitro. Similarly, overexpression of PPARalpha in 293T cells decreased activity of a human TNF promoter-luciferase construct. The results from these studies suggest that any anti-inflammatory activity of PPARalpha in vivo can be masked by other

  2. QSAR of estrogen receptor modulators: exploring selectivity requirements for ER(alpha) versus ER(beta) binding of tetrahydroisoquinoline derivatives using E-state and physicochemical parameters.

    Science.gov (United States)

    Mukherjee, Subhendu; Saha, Achintya; Roy, Kunal

    2005-02-15

    Considering importance of developing selective estrogen receptor modulators (SERMs), the present paper explores selectivity requirements of tetrahydroisoquinoline derivatives for binding with ER(alpha) versus ER(beta) receptors using E-state index and physicochemical parameters. The best model [n=21, Q(2)=0.512, R(a)(2)=0.613, R=0.819, F=11.6 (df 3,17)] for ER(alpha) binding data obtained from radioligand binding assay showed importance of C(1), C(15) and lipophilicity (logP) while the best model [n=21, Q(2)=0.768, R(a)(2)=0.796, R=0.904, F=40.1 (df 2,18)] for ER(beta) binding data showed importance of C(1) and molar refractivity (MR). While modeling ER(alpha)/ER(beta) selectivity [n=21, Q(2)=0.695, R(a)(2)=0.739, R=0.882, F=19.8 (df 3,17)], C(1), C(15) and molar refractivity were found to be significant contributors. The data obtained from cellular transcription assay were also modeled. In case of ER(alpha), the best equation involving E-state values of C(1) and C(14) and logP explained 62.1% of the variance while the best equation for ER(beta) involving E-state values of C(1) and C(15) and MR explained 64.6% of the variance of the response variable. In case of ER(alpha)/ER(beta) selectivity, the best equation involving E-state values of O(8), C(14) and N(27) showed 48.3% explained variance, which increased to 63.5% on deletion of single outlier. From the analysis it appears that the nitrogen atom of the aminoethoxyphenyl substituent and 6-hydroxy substituent of the tetrahydroisoquinoline nucleus play important roles for ER(alpha)/ER(beta) selectivity in addition to R(1) and R(2) substituents.

  3. Cow's milk increases the activities of human nuclear receptors peroxisome proliferator-activated receptors alpha and delta and retinoid X receptor alpha involved in the regulation of energy homeostasis, obesity, and inflammation.

    Science.gov (United States)

    Suhara, W; Koide, H; Okuzawa, T; Hayashi, D; Hashimoto, T; Kojo, H

    2009-09-01

    The nuclear peroxisome proliferator-activated receptors (PPAR) have been shown to play crucial roles in regulating energy homeostasis including lipid and carbohydrate metabolism, inflammatory responses, and cell proliferation, differentiation, and survival. Because PPAR agonists have the potential to prevent or ameliorate diseases such as hyperlipidemia, diabetes, atherosclerosis, and obesity, we have explored new natural agonists for PPAR. For this purpose, cow's milk was tested for agonistic activity toward human PPAR subtypes using a reporter gene assay. Milk increased human PPARalpha activity in a dose-dependent manner with a 3.2-fold increase at 0.5% (vol/vol). It also enhanced human PPARdelta activity in a dose-dependent manner with an 11.5-fold increase at 0.5%. However, it only slightly affected human PPARgamma activity. Ice cream, butter, and yogurt also increased the activities of PPARalpha and PPARdelta, whereas vegetable cream affected activity of PPARdelta but not PPARalpha. Skim milk enhanced the activity of PPAR to a lesser degree than regular milk. Milk and fresh cream increased the activity of human retinoid X receptor (RXR)alpha as well as PPARalpha and PPARdelta, whereas neither affected vitamin D3 receptor, estrogen receptors alpha and beta, or thyroid receptors alpha and beta. Both milk and fresh cream were shown by quantitative real-time PCR to increase the quantity of mRNA for uncoupling protein 2 (UCP2), an energy expenditure gene, in a dose-dependent manner. The increase in UCP2 mRNA was found to be reduced by treatment with PPARdelta-short interfering (si)RNA. This study unambiguously clarified at the cellular level that cow's milk increased the activities of human PPARalpha, PPARdelta, and RXRalpha. The possible role in enhancing the activities of PPARalpha, PPARdelta, and RXRalpha, and the health benefits of cow's milk were discussed.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

  6. Selective Activation and Disengagement of Moral Control.

    Science.gov (United States)

    Bandura, Albert

    1990-01-01

    Analyzes psychological mechanisms by which moral control is selectively disengaged from inhumane conduct in ordinary and unusual circumstances. Explores the symptoms of moral exclusion as described in the literature. Presents categories that unify theory on moral exclusion and contribute practical classifications for use in empirical studies. (JS)

  7. Hypolipidaemic and antiplatelet activity of phenoxyacetic acid derivatives related to alpha-asarone.

    Science.gov (United States)

    Pérez-Pastén, Ricardo; García, Rosa Virginia; Garduño, Leticia; Reyes, Elba; Labarrios, Fernando; Tamariz, Joaquín; Chamorro, Germán

    2006-10-01

    The phenoxyacetic acid derivatives 1-6 [2-methoxy-4-(2-propenyl)phenoxyacetic acid (1); 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetic acid (2); methyl 2-methoxy-4-(2-propenyl)phenoxyacetate (3); ethyl 2-methoxy-4-(2-propenyl)phenoxyacetate (4); methyl 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetate (5); ethyl 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetate (6)] related to alpha-asarone have been reported previously as hypolipidaemic agents in diet-induced hyperlipidaemic mice. We have aimed to expand the pharmacological profile of these derivatives by investigating their hypolipidaemic activity in rats and mice under different experimental conditions. The antiplatelet activity was tested also in-vitro from blood derived from consenting healthy volunteers. In normolipidaemic rats, compounds 2, 3 and 5 at oral doses of 40 and 80 mg kg(-1) significantly decreased total cholesterol and LDL-cholesterol levels. Moreover, analogues 3 and 5 administered to hypercholesterolaemic rats at the same doses for seven days also produced a reduction in the content of these same lipoproteins. In neither case were the high-density lipoprotein cholesterol and triglyceride concentrations affected. However, practically all tested compounds were found to be hypocholesterolaemic agents, and were shown to effectively lower low-density lipoprotein cholesterol and triglyceride levels in Triton-induced hyperlipidaemic mice at oral doses of 50 and 100 mg kg(-1). In all tests, all animals appeared to be healthy throughout the experimental period in their therapeutic ranges. Triton-induced hypercholesterolaemic mice appeared to be a desirable model for this class of hypolipidaemic drugs. On the other hand, compounds 1, 2, 4 and 5 significantly inhibited ADP-induced aggregation in-vitro. These findings indicated that all of these compounds appeared to be promising for the treatment of human hyperlipidaemia and thrombotic diseases.

  8. Comparison of direct alpha spectrometry and neutron activation analysis of aerosol filters for determination of workplace thorium air concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Hoetzl, H.; Winkler, R. [Institut fuer Strahlenschutz, Oberschleibheim (Germany); Riedmann, W.; Weinmueller, K. [Strahlenschutz und Isotopentechnik, Muenchen (Germany)

    1996-05-01

    Direct alpha spectrometry with three different filter types was investigated for the determination of thorium air concentrations at workplaces in the manufacturing process of discharge lamps containing thoriated tungsten electrodes. The method was compared with neutron activation analysis over an activity range of five orders of magnitude. Within the experimental limits of error, both methods were found to be comparable with respect to sensitivity and accuracy. The advantage of direct alpha spectrometry, however, is that it is less laborious than neutron activation analysis and that it supplies information on the degree of radioactive equilibrium of the thorium series, which is important with regard to the estimation of dose. 20 refs., 2 figs., 1 tab.

  9. 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.

  10. Antibacterial and antagonistic activity of selected traditional ...

    African Journals Online (AJOL)

    S.pneumonia was found to be the most susceptible bacteria for the methanol extract of the root of Ricinus communis with inhibition zones of 20mm and MIC of 25 mg/mL. However; S.tphyrium was the most resistant to all extracts of the selected plants with no inh bition zone. The methanol extracts of all plants were most ...

  11. Selective Attention to Visual Stimuli Using Auditory Distractors Is Altered in Alpha-9 Nicotinic Receptor Subunit Knock-Out Mice.

    Science.gov (United States)

    Terreros, Gonzalo; Jorratt, Pascal; Aedo, Cristian; Elgoyhen, Ana Belén; Delano, Paul H

    2016-07-06

    During selective attention, subjects voluntarily focus their cognitive resources on a specific stimulus while ignoring others. Top-down filtering of peripheral sensory responses by higher structures of the brain has been proposed as one of the mechanisms responsible for selective attention. A prerequisite to accomplish top-down modulation of the activity of peripheral structures is the presence of corticofugal pathways. The mammalian auditory efferent system is a unique neural network that originates in the auditory cortex and projects to the cochlear receptor through the olivocochlear bundle, and it has been proposed to function as a top-down filter of peripheral auditory responses during attention to cross-modal stimuli. However, to date, there is no conclusive evidence of the involvement of olivocochlear neurons in selective attention paradigms. Here, we trained wild-type and α-9 nicotinic receptor subunit knock-out (KO) mice, which lack cholinergic transmission between medial olivocochlear neurons and outer hair cells, in a two-choice visual discrimination task and studied the behavioral consequences of adding different types of auditory distractors. In addition, we evaluated the effects of contralateral noise on auditory nerve responses as a measure of the individual strength of the olivocochlear reflex. We demonstrate that KO mice have a reduced olivocochlear reflex strength and perform poorly in a visual selective attention paradigm. These results confirm that an intact medial olivocochlear transmission aids in ignoring auditory distraction during selective attention to visual stimuli. The auditory efferent system is a neural network that originates in the auditory cortex and projects to the cochlear receptor through the olivocochlear system. It has been proposed to function as a top-down filter of peripheral auditory responses during attention to cross-modal stimuli. However, to date, there is no conclusive evidence of the involvement of olivocochlear

  12. Controlling hydrogenation activity and selectivity of bimetallic surfaces and catalysts

    Science.gov (United States)

    Murillo, Luis E.

    also discussed. Chemisorption, TPD, FTIR using a batch reactor for the self-hydrogenation of cyclohexene and CO adsorbed on the bimetallic surfaces were carried out to correlate surface science findings with experiments on supported bimetallic catalysts. To expand the studies on the effect of bimetallic structures on hydrogenation reactions, molecules with multiple functional groups such as alpha,beta-unsaturated aldehydes were also investigated. Studies of selective hydrogenation of a,ss-unsaturated aldehydes toward the desired unsaturated alcohols are of interest for the production of fine chemicals and pharmaceuticals. In these compounds, competitive hydrogenation of the C=C and C=O bonds occurs. TPD and HREELS experiments of acrolein (CH2=CH-CH=O) on Pt-based bimetallic surfaces are performed to investigate their effects on the hydrogenation activity of the C-O bond. The production of the desired unsaturated alcohol, allyl alcohol, has been observed for the first time on Pt-Ni-Pt(111) under UHV conditions. However, the propionaldehyde yield is five times higher than the allyl alcohol yield. Thus, a preferential isomerization reaction of allyl alcohol to propionaldehyde is very likely to occur on the Pt-Ni-Pt(111) surface as observed on the desorption studies of allyl alcohol on this surface. The hydrogenation of acrolein is also carried out under UHV conditions on other 3d-transition metal/Pt(111) surfaces such as Co/Pt(111), Fe/Pt(111), and Cu/Pt(111). So far, the highest activity and allyl alcohol yield are found on the Pt-Ni-Pt(111) surface with pre-adsorbed hydrogen.

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

    Directory of Open Access Journals (Sweden)

    Hua Xing

    2011-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Naoki Matsuo

    2009-09-01

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

  15. Activation of Selected Core Muscles during Pressing

    OpenAIRE

    Thomas W. Nesser; Neil Fleming; Matthew J. Gage

    2015-01-01

    Introduction: Unstable surface training is often used to activate core musculature during resistance training. Unfortunately, unstable surface training is risky and leads to detraining. Purpose: The purpose of this study was to determine core muscle activation during stable surface ground-based lifts. Methods: Fourteen recreational trained and former NCAA DI athletes (weight 84.2 ± 13.3 kg; height 176.0 ± 9.5 cm; age 20.9 ± 2.0 years) volunteered for participation. Subjects completed two grou...

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

    International Nuclear Information System (INIS)

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

    1996-02-01

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

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

    Science.gov (United States)

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

    2015-10-01

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

  18. Activation of Selected Core Muscles during Pressing

    Directory of Open Access Journals (Sweden)

    Thomas W. Nesser

    2015-10-01

    Full Text Available Introduction: Unstable surface training is often used to activate core musculature during resistance training. Unfortunately, unstable surface training is risky and leads to detraining. Purpose: The purpose of this study was to determine core muscle activation during stable surface ground-based lifts. Methods: Fourteen recreational trained and former NCAA DI athletes (weight 84.2 ± 13.3 kg; height 176.0 ± 9.5 cm; age 20.9 ± 2.0 years volunteered for participation. Subjects completed two ground-based lifts: overhead press and push-press. Surface EMG was recorded from 4 muscles on the right side of the body (Rectus Abdominus (RA, External Oblique (EO, Transverse Abdominus (TA, and Erector Spinae (ES. Results: Paired sample T-tests identified significant muscle activation differences between the overhead press and the push-press included ES and EO. Average and peak EMG for ES was significantly greater in push-press (P<0.01. Anterior displacement of COP was significantly greater in push-press compared to overhead press during the eccentric phase. Conclusion: The push-press was identified as superior in core muscle activation when compared to the overhead pressing exercise. Keywords: torso, stability, weight lifting, resistance training

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-07-01

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

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

    OpenAIRE

    Strahler, Jana

    2010-01-01

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

  1. 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.

  2. Enzyme inhibitory activity of selected Philippine plants

    International Nuclear Information System (INIS)

    Sasotona, Joseph S.; Hernandez, Christine C.

    2015-01-01

    In the Philippines, the number one cause of death are cardiovascular diseases. Diseases linked with inflammation are proliferating. This research aims to identify plant extracts that have potential activity of cholesterol-lowering, anti-hypertension, anti-gout, anti-inflammatory and fat blocker agents. Although there are commercially available drugs to treat the aforementioned illnesses, these medicine have adverse side-effects, aside from the fact that they are expensive. The results of this study will serve as added knowledge to contribute to the development of cheaper, more readily available, and effective alternative medicine. 100 plant extracts from different areas in the Philippines have been tested for potential inhibitory activity against Hydroxymethylglutaryl-coenzyme A (HMG-CoA), Lipoxygenase, and Xanthine Oxidase. The plant samples were labeled with codes and distributed to laboratories for blind testing. The effective concentration of the samples tested for Xanthine oxidase is 100 ppm. Samples number 9, 11, 14, 29, 43, 46, and 50 have shown significant inhibitory activity at 78.7%, 78.4%, 70%, 89.2%, 79%, 67.4%, and 67.5% respectively. Samples tested for Lipoxygenase inhibition were set at 33ppm. Samples number 2, 37, 901, 1202, and 1204 have shown significant inhibitory activity at 66, 84.9%, 88.55%, 93.3%, and 84.7% respectively. For HMG-CoA inhibition, the effective concentration of the samples used was 100 ppm. Samples number 1 and 10 showed significant inhibitory activity at 90.1% and 81.8% respectively. (author)

  3. 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-Cg...

  4. Tumor necrosis factor-alpha induces activation of coagulation and fibrinolysis in baboons through an exclusive effect on the p55 receptor

    NARCIS (Netherlands)

    van der Poll, T.; Jansen, P. M.; van Zee, K. J.; Welborn, M. B.; de Jong, I.; Hack, C. E.; Loetscher, H.; Lesslauer, W.; Lowry, S. F.; Moldawer, L. L.

    1996-01-01

    Tumor necrosis factor-alpha (TNF-alpha) can bind to two distinct transmembrane receptors, the p55 and p75 TNF receptors. We compared the capability of two mutant TNF proteins with exclusive affinity for the p55 or p75 TNF receptor with that of wild type TNF, to activate the hemostatic mechanism in

  5. A technical alpha-active aerosol express measurement system for volumetric activity monitoring.; Metodika ehkspressnogo opredeleniya ob`emnoj aktivnosti tekhnogennykh al`fa-aktivnykh aehrozolej.

    Energy Technology Data Exchange (ETDEWEB)

    Badovskij, V P; Dubar, L V; Tokarevskij, V V; Shevchenko, S V; Shcherbina, V G [Myizhgaluzevij Naukovo-Tekhnyichnij Tsentr ` ` Ukrittya ` ` , Natsyional` na Akademyiya Nauk Ukrayini, Chornobil` (Ukraine)

    1994-12-31

    A possibility of a volumetric aerosol activity determination at the level of MPCa for {sup 239} Pu with a measurement time less than 60 minutes is discussed. For achieving maximum reduction of the natural background the virtual impactor and alpha-spectroscopy are proposed to be employed. Results of investigation of the virtual impactor parameters at the << Shelter >> and at the laboratory are described.

  6. High-dose interferon-alpha2a exerts potent activity against human immunodeficiency virus type 1 not associated with antitumor activity in subjects with Kaposi's sarcoma

    NARCIS (Netherlands)

    Frissen, P. H.; de Wolf, F.; Reiss, P.; Bakker, P. J.; Veenhof, C. H.; Danner, S. A.; Goudsmit, J.; Lange, J. M.

    1997-01-01

    Anti-human immunodeficiency virus type 1 (HIV-1) activity was assessed in HIV-1-infected homosexual and bisexual men receiving 18-36 MIU/day of recombinant interferon (IFN)-alpha2a for Kaposi's sarcoma (KS). The median baseline HIV-1 RNA level was 4.99 log10 copies/mL. Seventeen subjects (68%)

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

    International Nuclear Information System (INIS)

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

    1991-01-01

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

  8. Spatially selective alpha oscillations reveal moment-by-moment trade-offs between working memory and attention

    NARCIS (Netherlands)

    van Moorselaar, Dirk; Foster, Joshua J.; Sutterer, David W.; Theeuwes, Jan; Olivers, Christian N.L.; Awh, Edward

    Current theories assume a functional role for covert attention in the maintenance of spatial information in working memory. Consistent with this view, both the locus of attention and positions stored in working memory can be decoded based on the topography of oscillatory alpha-band (8-12 Hz)

  9. Influence of thermodynamic parameter in Lanosterol 14alpha-demethylase inhibitory activity as antifungal agents: a QSAR approach.

    Science.gov (United States)

    Vasanthanathan, Poongavanam; Lakshmi, Manickavasagam; Arockia Babu, Marianesan; Kaskhedikar, Sathish Gopalrao

    2006-06-01

    A quantitative structure activity relationship, Hansch approach was applied on twenty compounds of chromene derivatives as Lanosterol 14alpha-demethylase inhibitory activity against eight fungal organisms. Various physicochemical descriptors and reported minimum inhibitory concentration values of different fungal organisms were used as independent variables and dependent variable respectively. The best models for eight different fungal organisms were first validated by leave-one-out cross validation procedure. It was revealed that thermodynamic parameters were found to have overall significant correlationship with anti fungal activity and these studies provide an insight to design new molecules.

  10. Coevolving residues of (beta/alpha)(8)-barrel proteins play roles in stabilizing active site architecture and coordinating protein dynamics.

    Science.gov (United States)

    Shen, Hongbo; Xu, Feng; Hu, Hairong; Wang, Feifei; Wu, Qi; Huang, Qiang; Wang, Honghai

    2008-12-01

    Indole-3-glycerol phosphate synthase (IGPS) is a representative of (beta/alpha)(8)-barrel proteins-the most common enzyme fold in nature. To better understand how the constituent amino-acids work together to define the structure and to facilitate the function, we investigated the evolutionary and dynamical coupling of IGPS residues by combining statistical coupling analysis (SCA) and molecular dynamics (MD) simulations. The coevolving residues identified by the SCA were found to form a network which encloses the active site completely. The MD simulations showed that these coevolving residues are involved in the correlated and anti-correlated motions. The correlated residues are within van der Waals contact and appear to maintain the active site architecture; the anti-correlated residues are mainly distributed on opposite sides of the catalytic cavity and coordinate the motions likely required for the substrate entry and product release. Our findings might have broad implications for proteins with the highly conserved (betaalpha)(8)-barrel in assessing the roles of amino-acids that are moderately conserved and not directly involved in the active site of the (beta/alpha)(8)-barrel. The results of this study could also provide useful information for further exploring the specific residue motions for the catalysis and protein design based on the (beta/alpha)(8)-barrel scaffold.

  11. 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.

  12. Interferon alpha as antiviral therapy in chronic active Epstein-Barr virus disease with interstitial pneumonia - case report.

    Science.gov (United States)

    Roliński, Jacek; Grywalska, Ewelina; Pyzik, Aleksandra; Dzik, Michał; Opoka-Winiarska, Violetta; Surdacka, Agata; Maj, Maciej; Burdan, Franciszek; Pirożyński, Michał; Grabarczyk, Piotr; Starosławska, Elżbieta

    2018-04-20

    Chronic active Epstein-Barr virus (EBV) disease (CAEBV) is defined as a severe, progressive lymphoproliferative disorder associated with active EBV infection persisting longer than 6 months and developing in patients without recognised immunodeficiency. Rarely, interstitial pneumonitis (IP) occurs as a serious complication in CAEBV patients. The standard therapeutic regimen for IP in CAEBV has not yet been defined. Although interferon alpha (IFN-alpha) is known to suppress viral DNA replication by affecting its basal promoter activation process, it is rarely used in CAEBV patients. A 22-year-old Caucasian woman, diagnosed with CAEBV 1.5 years earlier, was admitted to the Immunology Clinic due to a 4-week history of productive cough, fever and general weakness. Cultures of blood, urine and sputum were negative, but EBV DNA copies were found in the sputum, whole blood, isolated peripheral blood lymphocytes as well as in the blood plasma. Cytokine assessment in peripheral blood revealed the lack of IFN-alpha synthesis. Disseminated maculate infiltrative areas in both lungs were observed on a computed tomography (CT) chest scan. The patient was not qualified for the allogeneic hematopoietic stem cell transplantation (allo-HSCT) due to the risk of immunosuppression-related complications of infectious IP. Inhaled (1.5 million units 3 times a day) and subcutaneous (6 million units 3 times a week) IFN-alpha was implemented. To the best of our knowledge, this was the first documented use of inhaled IFN-alpha in a patient with CAEBV and concomitant IP. Patient's status has improved, and she was eventually qualified to allo-HSCT with reduced conditioning. Currently, the patient feels well, no EBV was detected and further regression of pulmonary changes was documented. CAEBV should be considered in patients who present with interstitial lung infiltration and involvement of other organs. Although more promising results have been obtained with allo-HSCT, inhaled IFN-alpha may

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-07-01

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

  14. Antioxidant activities and interactions of alpha- and gamma-tocopherols within canola and soybean oil emulsions

    Science.gov (United States)

    The effect of differing concentrations and ratios of alpha- and gamma-TOH on oxidative stability over time was determined by measuring the development of hydroperoxides and volatile secondary oxidation products (hexanal) within a series of oil-in-water (o/w) emulsion systems produced from both canol...

  15. Expression of active recombinant human alpha 1-antitrypsin in transgenic rabbits

    NARCIS (Netherlands)

    Massoud, M.; Bischoff, Rainer; Dalemans, W.; Pointu, H.; Attal, J.; Schultz, H.; Clesse, D.; Stinnakre, M.G.; Pavirani, A.; Houdebine, L.M.

    1991-01-01

    A DNA construct containing the human alpha 1-antitrypsin gene including 1.5 and 4 kb of 5' and 3' flanking sequences, was microinjected into the pronucleus of rabbit embryos. The recombinant human protein was (a) expressed in the blood circulation of F0 and F1 transgenic rabbits at an average

  16. Alpha low activity determination from limitter isotopes of uranium, thorium ands radium in natural waters

    International Nuclear Information System (INIS)

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

    1989-01-01

    A method to concentrate uranium, thorium and radium in natural waters has been developed. The method, based on the adsorbing propert-ies of manganes dioxide, has been applied to determine the alpha emitter isotopes of these elements in drinking water of Madrid. In this work we present the description of the method, the analytical procedu-res and the obtained results. (Author)

  17. 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

  18. 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.

  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. Gamma activity coupled to alpha phase as a mechanism for top-down controlled gating

    NARCIS (Netherlands)

    Bonnefond, M.; Jensen, O.

    2015-01-01

    Coupling between neural oscillations in different frequency bands has been proposed to coordinate neural processing. In particular, gamma power coupled to alpha phase is proposed to reflect gating of information in the visual system but the existence of such a mechanism remains untested. Here, we

  1. Relating cloud condensation nuclei activity and oxidation level of alpha-pinene secondary organic aerosols

    DEFF Research Database (Denmark)

    Foverskov, Mia Frosch Mogensbæk; Bilde, M.; DeCarlo, P. F.

    2011-01-01

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

  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

    Cold adaptation elicits a paradoxical simultaneous induction of fatty acid synthesis and beta-oxidation in brown adipose tissue. We show here that cold exposure coordinately induced liver X receptor alpha (LXRalpha), adipocyte determination and differentiation-dependent factor 1 (ADD1)/sterol...

  3. 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...

  4. 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...

  5. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Antonelli, Alessandro, E-mail: a.antonelli@med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Ferrari, Silvia Martina, E-mail: sm.ferrari@int.med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Frascerra, Silvia, E-mail: lafrasce@gmail.com [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Corrado, Alda, E-mail: dala_res@hotmail.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Pupilli, Cinzia, E-mail: c.pupilli@dfc.unifi.it [Endocrinology Unit, Azienda Ospedaliera Careggi and University of Florence, Viale Morgagni 85, I-50134, Florence (Italy); Bernini, Giampaolo, E-mail: g.bernini@int.med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Benvenga, Salvatore, E-mail: s.benvenga@me.nettuno.it [Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Messina, Piazza Pugliatti 1, I-98122, Messina (Italy); Ferrannini, Ele, E-mail: eferrannini@med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Fallahi, Poupak, E-mail: poupak@int.med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy)

    2011-07-01

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

  7. Molecular cloning of rock bream (Oplegnathus fasciatus) tumor necrosis factor-alpha and its effect on the respiratory burst activity of phagocytes.

    Science.gov (United States)

    Kim, Min Sun; Hwang, Yoon Jung; Yoon, Ki Joon; Zenke, Kosuke; Nam, Yoon Kwon; Kim, Sung Koo; Kim, Ki Hong

    2009-11-01

    Rock bream (Oplegnathus fasciatus) tumor necrosis factor-alpha (rbTNF-alpha) gene was cloned, recombinantly produced, and the effect of the recombinant rbTNF-alpha on the respiratory burst activity of rock bream phagocytes was analyzed. Structurally, genomic DNA of rbTNF-alpha was comprised with four exons and three introns, and deduced amino acid sequence of its cDNA possessed the TNF family signature, a transmembrane domain, a protease cleavage site, and two cysteine residues, which are the typical characteristics of TNF-alpha gene in mammals and fish. The chemiluminescent (CL) response of rock bream phagocytes was significantly enhanced by pre-incubation with recombinant rbTNF-alpha, when opsonized zymosan was used as a stimulant of the respiratory burst. However, CL enhancing effect of the recombinant rbTNF-alpha was very weak when the respiratory burst activity of phagocytes was triggered with phorbol-12-myristate-13-acetate (PMA) instead of zymosan. These results suggest that rock bream TNF-alpha might have an ability to prime the respiratory burst activity of phagocytes against receptor-mediated phagocytosis inducing stimulants, such as zymosan, but have little ability against stimulants not accompanying receptor-mediated phagocytosis.

  8. Influence of liquid medium on the activity of a low-alpha Fischer-Tropsch catalyst

    Energy Technology Data Exchange (ETDEWEB)

    Gormley, R.J.; Zarochak, M.F.; Deffenbaugh, P.W.; Rao, K.R.P.M.

    1995-12-31

    The purpose of this research was to measure activity, selectivity, and the maintenance of these properties in slurry autoclave experiments with a Fischer-Tropsch (FT) catalyst that was used in the {open_quotes}FT II{close_quotes} bubble-column test, conducted at the Alternative Fuels Development Unit (AFDU) at LaPorte, Texas during May 1994. The catalyst contained iron, copper, and potassium and was formulated to produce mainly hydrocarbons in the gasoline range with lesser production of diesel-range products and wax. The probability of chain growth was thus deliberately kept low. Principal goals of the autoclave work have been to find the true activity of this catalyst in a stirred tank reactor, unhindered by heat or mass transfer effects, and to obtain a steady conversion and selectivity over the approximately 15 days of each test. Slurry autoclave testing of the catalyst in heavier waxes also allows insight into operation of larger slurry bubble column reactors. The stability of reactor operation in these experiments, particularly at loadings exceeding 20 weight %, suggests the likely stability of operations on a larger scale.

  9. Evaluation of the alpha-amylase activity as an indicator of pasteurization efficiency and microbiological quality of liquid whole eggs.

    Science.gov (United States)

    Silva, Guilherme Resende da; Menezes, Liliane Denize Miranda; Lanza, Isabela Pereira; Oliveira, Daniela Duarte de; Silva, Carla Aparecida; Klein, Roger Wilker Tavares; Assis, Débora Cristina Sampaio de; Cançado, Silvana de Vasconcelos

    2017-09-01

    In order to evaluate the efficiency of the pasteurization process in liquid whole eggs, an UV/visible spectrophotometric method was developed and validated for the assessment of alpha-amylase activity. Samples were collected from 30 lots of raw eggs (n = 30) and divided into three groups: one was reserved for analysis of the raw eggs, the second group was pasteurized at 61.1°C for 3.5 minutes (n = 30), and the third group was pasteurized at 64.4°C for 2.5 minutes (n = 30). In addition to assessing alpha-amylase activity, the microbiological quality of the samples was also evaluated by counting total and thermotolerant coliforms, mesophilic aerobic microorganisms, Staphylococcus spp., and Salmonella spp. The validated spectrophotometric method demonstrated linearity, with a coefficient of determination (R2) greater than 0.99, limits of detection (LOD) and quantification (LOQ) of 0.48 mg kg-1 and 1.16 mg kg-1, respectively, and acceptable precision and accuracy with relative standard deviation (RSD) values of less than 10% and recovery rates between 98.81% and 105.40%. The results for alpha-amylase activity in the raw egg samples showed high enzyme activity due to near-complete hydrolysis of the starch, while in the eggs pasteurized at 61.1°C, partial inactivation of the enzyme was observed. In the samples of whole eggs pasteurized at 64.4°C, starch hydrolysis did not occur due to enzyme inactivation. The results of the microbiological analyses showed a decrease (P pasteurized egg samples according to the two binomials under investigation, compared to the raw egg samples, which showed high rates of contamination (P pasteurization, only one sample (3.33%) was positive for Salmonella spp., indicating failure in the pasteurization process, which was confirmed by the alpha-amylase test. It was concluded that the validated methodology for testing alpha-amylase activity is adequate for assessing the efficiency of the pasteurization process, and that the time

  10. Utilization of a Si-surface-barrier-detector for alpha-spectrometry and its application in radiation protection for the detection of law alpha-activities

    International Nuclear Information System (INIS)

    Steger, F.; Urbanich, E.; Lovranich, E.; Hefner, A.

    1974-12-01

    Due to the construction of the ''Safeguard Analytical Laboratory''(IAEA), the institute for radiation protection at the Research Center Seibersdorf is interested in a method for the alpha-spectroscopic determination of Pu-239 for personnel and environmental monitoring. Therefore an alpha-spectrometer has been built which will mainly be used for the excretion analysis. The design of the apparatus is described, results of measurements are given and other fields of its application are discussed. (C.R.)

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

    Science.gov (United States)

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

    2009-10-15

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

  12. Determination of radium activity in some natural mineral waters using radioactive chemical extraction method and alpha spectrometry

    International Nuclear Information System (INIS)

    Nguyen Thi Oanh; Duong Van Thang; Duong Duc Thang; Nguyen Van Khanh; Doan Thuy Hau; Pham Bao Ngoc

    2017-01-01

    The 226 Ra activity concentration in several of mineral water samples of Northern Vietnam was measured by using alpha spectrometry. Ra adsorption techniques on manganese oxide were applied to produce thin alpha samples. The efficiency of sample preparation process was determined by conducting similar procedures for IAEA reference materials. The 226 Ra content in mineral water ranged from (11.33 ± 1.00) mBq/l to (38.00 ± 4.50) mBq/l. The measured maximum values do not exceed the permissible limit radiation dose for all samples (100 mBq/l - USEPA ). This study may be useful for assessing impacts of radiation dose from mineral water on human health. (author)

  13. H{alpha} ACTIVITY OF OLD M DWARFS: STELLAR CYCLES AND MEAN ACTIVITY LEVELS FOR 93 LOW-MASS STARS IN THE SOLAR NEIGHBORHOOD

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, Paul; Endl, Michael; Cochran, William D.; Dodson-Robinson, Sarah E., E-mail: paul@astro.as.utexas.edu [Department of Astronomy and McDonald Observatory, University of Texas at Austin, Austin, TX 78712 (United States)

    2013-02-10

    Through the McDonald Observatory M Dwarf Planet Search, we have acquired nearly 3000 high-resolution spectra of 93 late-type (K5-M5) stars over more than a decade using the High Resolution Spectrograph on the Hobby-Eberly Telescope. This sample provides a unique opportunity to investigate the occurrence of long-term stellar activity cycles for low-mass stars. In this paper, we examine the stellar activity of our targets as reflected in the H{alpha} feature. We have identified periodic signals for six stars, with periods ranging from days to more than 10 years, and find long-term trends for seven others. Stellar cycles with P {>=} 1 year are present for at least 5% of our targets. Additionally, we present an analysis of the time-averaged activity levels of our sample, and search for correlations with other stellar properties. In particular, we find that more massive, earlier type (M0-M2) stars tend to be more active than later type dwarfs. Furthermore, high-metallicity stars tend to be more active at a given stellar mass. We also evaluate H{alpha} variability as a tracer of activity-induced radial velocity (RV) variation. For the M dwarf GJ 1170, H{alpha} variation reveals stellar activity patterns matching those seen in the RVs, mimicking the signal of a giant planet, and we find evidence that the previously identified stellar activity cycle of GJ 581 may be responsible for the recently retracted planet f in that system. In general, though, we find that H{alpha} is not frequently correlated with RV at the precision (typically 6-7 m s{sup -1}) of our measurements.

  14. 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

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

    International Nuclear Information System (INIS)

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

    1987-04-01

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

  16. 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

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

    International Nuclear Information System (INIS)

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

    1980-01-01

    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

  18. Rapid detection of hypoxia-inducible factor-1-active tumours: pretargeted imaging with a protein degrading in a mechanism similar to hypoxia-inducible factor-1{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Ueda, Masashi [Kyoto University, Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto (Japan); Kyoto University, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Kudo, Takashi; Konishi, Hiroaki; Miyano, Azusa; Ono, Masahiro; Saji, Hideo [Kyoto University, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Kuge, Yuji [Kyoto University, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan); Mukai, Takahiro [Kyushu University, Department of Biomolecular Recognition Chemistry, Graduate School of Pharmaceutical Sciences, Fukuoka (Japan); Tanaka, Shotaro; Kizaka-Kondoh, Shinae; Hiraoka, Masahiro [Kyoto University, Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto (Japan)

    2010-08-15

    Hypoxia-inducible factor-1 (HIF-1) plays an important role in malignant tumour progression. For the imaging of HIF-1-active tumours, we previously developed a protein, POS, which is effectively delivered to and selectively stabilized in HIF-1-active cells, and a radioiodinated biotin derivative, (3-{sup 123}I-iodobenzoyl)norbiotinamide ({sup 123}I-IBB), which can bind to the streptavidin moiety of POS. In this study, we aimed to investigate the feasibility of the pretargeting method using POS and {sup 123}I-IBB for rapid imaging of HIF-1-active tumours. Tumour-implanted mice were pretargeted with POS. After 24 h, {sup 125}I-IBB was administered and subsequently, the biodistribution of radioactivity was investigated at several time points. In vivo planar imaging, comparison between {sup 125}I-IBB accumulation and HIF-1 transcriptional activity, and autoradiography were performed at 6 h after the administration of {sup 125}I-IBB. The same sections that were used in autoradiographic analysis were subjected to HIF-1{alpha} immunohistochemistry. {sup 125}I-IBB accumulation was observed in tumours of mice pretargeted with POS (1.6%ID/g at 6 h). This result is comparable to the data derived from {sup 125}I-IBB-conjugated POS-treated mice (1.4%ID/g at 24 h). In vivo planar imaging provided clear tumour images. The tumoral accumulation of {sup 125}I-IBB significantly correlated with HIF-1-dependent luciferase bioluminescence (R=0.84, p<0.01). The intratumoral distribution of {sup 125}I-IBB was heterogeneous and was significantly correlated with HIF-1{alpha}-positive regions (R=0.58, p<0.0001). POS pretargeting with {sup 123}I-IBB is a useful technique in the rapid imaging and detection of HIF-1-active regions in tumours. (orig.)

  19. Homologous alpha satellite sequences on human acrocentric chromosomes with selectivity for chromosomes 13, 14, and 21: implications for recombination between nonhomologues and Robertsonian translocations

    Energy Technology Data Exchange (ETDEWEB)

    Choo, K H; Vissel, B; Brown, R; Filby, R G; Earle, E

    1988-02-25

    The authors report a new subfamily of alpha satellite DNA (pTRA-2) which is found on all the human acrocentric chromosomes. The alphoid nature of the cloned DNA was established by partial sequencing. Southern analysis of restriction enzyme-digested DNA fragments from mouse/human hybrid cells containing only human chromosome 21 showed that the predominant higher-order repeating unit for pTRA-2 is a 3.9 kb structure. Analysis of a consensus in situ hybridization profile derived from 13 normal individuals revealed the localization of 73% of all centromeric autoradiographic grains over the five acrocentric chromosomes, with the following distribution: 20.4%, 21.5%, 17.1%, 7.3% and 6.5% on chromosomes 13, 14, 21, 15 and 22 respectively. An average of 1.4% of grains was found on the centromere of each of the remaining 19 nonacrocentric chromosomes. These results indicate the presence of a common subfamily of alpha satellite DNA on the five acrocentric chromosomes and suggest an evolutionary process consistent with recombination exchange of sequences between the nonhomologues. The results further suggests that such exchanges are more selective for chromosomes 13, 14 and 21 than for chromosomes 15 and 22. The possible role of centromeric alpha satellite DNA in the aetiology of 13q14q and 14q21q Robertsonian translocation involving the common and nonrandom association of chromosomes 13 and 14, and 14 and 21 is discussed.

  20. Antioxidant activities of the selected plants from the family ...

    African Journals Online (AJOL)

    USER

    2010-02-15

    Feb 15, 2010 ... Extraction of nine plants selected from the family Euphorbiaceae, Lauraceae, Malvaceae and. Balsaminaceae ... Total phenolic contents were determined with Folin- ... levels of antioxidant activity in vitro may be of value in the.

  1. Anti-Streptococcus pyogenes Activity of Selected Medicinal Plant ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research August 2013; 12 (4): 535-540. ISSN: 1596-5996 .... Table 1: Antibacterial activity of selected Thai medicinal plants against Streptococcus pyogenes NPRC 101. Botanical ..... Naphthoquinones,.

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

    Science.gov (United States)

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

    2015-11-01

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

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

    Science.gov (United States)

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

    2001-01-01

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

  4. Design aspects of the Alpha Repository. V. Suite selection and cost analysis of excavation/hauling systems

    International Nuclear Information System (INIS)

    Zeller, T.J.; Grams, W.H.

    1975-01-01

    The various types of haulage and excavation equipment that may be suitable for use in the development and excavation of the Alpha repository are described with discussion of the advantages, disadvantages, expected costs, availability, and special features of each. The various equipment suites are delineated, and the costs of mining and transportation of the salt are presented and discussed. Individual manufacturers contacted and equipment considered are listed. Most of the equipment is ''off-the-shelf''; however, some manufactuers were contacted that do custom work because of their expertise in salt mining equipment. The costs of custom equipment are comparable to those for standard equipment

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

    Science.gov (United States)

    Vinholes, Juliana; Vizzotto, Márcia

    2017-01-01

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

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

    Science.gov (United States)

    Vinholes, Juliana; Vizzotto, Márcia

    2017-01-01

    Camellia sinensis , the most consumed and popular beverages worldwide, and Eugenia uniflora , a Brazilian native species, have been already confirmed to have beneficial effects in the treatment of diabetes mellitus. However, their potential acting together against an enzyme linked to this pathology has never been exploited. The aim of this study was to evaluate the inhibitory properties of individual and combined ethanolic extracts of the leaves of C. sinensis and E. uniflora over alpha-glucosidase, a key digestive enzyme used on the Type 2 diabetes mellitus (T2DM) control. In addition, their inhibitory activity against 2,2-diphenyl-1-picrylhydrazyl radical (DPPH • ) and peroxyl radicals was also assayed. Enzyme inhibition and antioxidant potential were assessed based on in vitro assays. Total phenolic compounds, carotenoids, and chlorophylls A and B were achieved using spectrophotometric methods. E. uniflora was almost 40 times more active on alpha-glucosidase than C. sinensis and combined extracts showed a significant synergistic effect with an obtained IC 50 value almost 5 times lower than the theoretical value. C. sinensis extract was twice more active than E. uniflora concerning DPPH • , in contrast, E. uniflora was almost 10 times more effective than C. sinensis on inhibition of peroxyl radicals with a significant synergistic effect for combined extracts. The extracts activities may be related with their phytochemicals, mainly phenolic compounds, and chlorophylls. Combined C. sinensis and E. uniflora ethanolic extracts showed synergistic effect against alpha-glucosidase and lipid peroxidation. These herbal combinations can be used to control postprandial hyperglycemia and can also provide antioxidant defenses to patients with T2DM. Alfa-glucosidase and antioxidant Interaction between Camellia sinensis L. Kuntze and Eugenia uniflora L. ethanolic extracts was investigated.Extracts showed synergistic effect over alpha-glucosidase and peroxyl radicals

  7. 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...

  8. Role of SSNTD technique in three-step method for total assay of alpha activity in air effluents

    International Nuclear Information System (INIS)

    Kolekar, R.V.; Joshi, V.B.; Bhanti, D.P.; Bhagwat, A.M.

    2000-01-01

    In the present work, low levels of alpha activity in air effluents were estimated. Currently this essay involves collection of effluent samples and assaying them for the release using ZnS(Ag) based scintillation counter (background=1 cpm). Any activity below 1 cpm (net) therefore goes unreported. Air samples showing activity -6 Bq/m 3 (3.73x10 -17 Ci/m 3 ) to 36.41x10 -6 Bq/m 3 (9.84x10 -16 Ci/m 3 ) for samples studied over twelve months period. The three step procedure helps to measure total activity without significant burden on SSNTD technique thereby improving the acceptability of the methodology. (author)

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

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  10. Antithrombotic/anticoagulant and anticancer activities of selected ...

    African Journals Online (AJOL)

    Antithrombotic/anticoagulant and anticancer activities of selected medicinal plants from South Africa. NLA Kee, N Mnonopi, H Davids, RJ Naudé, CL Frost. Abstract. Nine plants available in the Eastern Cape Province of South Africa were tested for antithrombotic and/or anticoagulant activity. Organic (methanol) and aqueous ...

  11. Physical activity in relation to selected physical health components ...

    African Journals Online (AJOL)

    The aim of this study was to determine the relation between physical activity and selected physical health components. A total of 9860 employees of a financial institution in South Africa, between the ages 18 and 64 (x̄ =35.3 ± 18.6 years), voluntary participated in the study. Health risk factors and physical activity was ...

  12. Melibiose permease and alpha-galactosidase of Escherichia coli: Identification by selective labeling using a T7 RNA polymerase/promoter expression system

    International Nuclear Information System (INIS)

    Pourcher, T.; Bassilana, M.; Sarkar, H.K.; Kaback, H.R.; Leblanc, G.

    1990-01-01

    Identification and selective labeling of the melibiose permease and alpha-galactosidase in Escherichia coli, which are encoded by the melB and melA genes, respectively, have been accomplished by selectively labeling the two gene products with a T7 RNA polymerase expression system. Following generation of a novel EcoRI restriction site in the intergenic sequence between the two genes of the mel operon by oligonucleotide-directed, site-specific mutagenesis, melA and melB were separately inserted into plasmid pT7-6 of the T7 expression system. Expression of melB was markedly enhanced by placing a strong, synthetic ribosome binding site at an optimal distance upstream from the initiation codon of melB. Expression of cloned gene products was characterized functionally and by performing autoradiographic analysis on total cell, inner membrane, and cytoplasmic proteins from cells pulse labeled with (35S)methionine in the presence of rifampicin and resolved by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The results first confirm that alpha-galactosidase is a cytoplasmic protein with an Mr of 50K; in contrast, the membrane-bound melibiose permease is identified as a protein with an apparent Mr of 39K, a value significantly higher than that of 30K previously suggested

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

    Directory of Open Access Journals (Sweden)

    Anna H. Y. Law

    2013-04-01

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

  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. Laser Induced Selective Activation For Subsequent Autocatalytic Electroless Plating

    DEFF Research Database (Denmark)

    Zhang, Yang

    . The third hypothesis is that the activation and rinsing process can be described by diffusion. This hypothesis is proved using Fick’s diffusion laws combined with the short-time-plating experiment. The influence of laser parameters on the surface structure is investigated for Nd:YAG, UV, and fiber lasers......The subject of this PhD thesis is “Laser induced selective activation for subsequent autocatalytic electroless plating.” The objective of the project is to investigate the process chains for micro structuring of polymer surfaces for selective micro metallization. Laser induced selective activation...... (LISA) is introduced and studied as a new technique for producing 3D moulded interconnect devices (3D-MIDs). This technique enables the metallization of polymer surface modified by laser and subsequently activated by a PdCl2/SnCl2 system. Various technologies exist on an industrial level...

  16. THE PHASE REACTOR INDUCTANCE SELECTION TECHNIQUE FOR POWER ACTIVE FILTER

    Directory of Open Access Journals (Sweden)

    D. V. Tugay

    2016-12-01

    Full Text Available Purpose. The goal is to develop technique of the phase inductance power reactors selection for parallel active filter based on the account both low-frequency and high-frequency components of the electromagnetic processes in a power circuit. Methodology. We have applied concepts of the electrical circuits theory, vector analysis, mathematical simulation in Matlab package. Results. We have developed a new technique of the phase reactors inductance selection for parallel power active filter. It allows us to obtain the smallest possible value of THD network current. Originality. We have increased accuracy of methods of the phase reactor inductance selection for power active filter. Practical value. The proposed technique can be used in the design and manufacture of the active power filter for real objects of energy supply.

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

    Science.gov (United States)

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

    2006-07-01

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

  18. Influence of polymer matrix and adsorption onto silica materials on the migration of alpha-tocopherol into 95% ethanol from active packaging.

    Science.gov (United States)

    Heirlings, L; Siró, I; Devlieghere, F; Van Bavel, E; Cool, P; De Meulenaer, B; Vansant, E F; Debevere, J

    2004-11-01

    In this study, the effect of polymer materials with different polarity, namely low density polyethylene (LDPE) and ethylene vinyl acetate (EVA), on the migration behaviour of alpha-tocopherol from active packaging was investigated. The antioxidant was also adsorbed onto silica materials, namely SBA-15 (Santa Barbara-15) and Syloblock, in order to protect the antioxidant during extrusion and to ensure a controlled and sufficient release during the shelf-life of the food product. Migration experiments were performed at 7.0 +/- 0.5 degrees C and 95% ethanol was used as fatty food simulant. All films contained a high concentration of alpha-tocopherol, approximately 2000 mg kg(-1), to obtain an active packaging. Polymer matrix had a small influence on the migration profile. The migration of 80% of total migrated amount of antioxidant was retarded for 2.4 days by using LDPE instead of EVA. When alpha-tocopherol was adsorbed onto both silica materials, the migration of 80% of total migrated amount of antioxidant was retarded for 3.4 days in comparison to pure alpha-tocopherol. No difference was seen between the migration profiles of alpha-tocopherol adsorbed onto both silica materials. In the case of pure alpha-tocopherol, 82% of the initial amount of alpha-tocopherol in the film migrated into the food simulant at a rather fast migration rate. In the case of adsorption on silica materials, a total migration was observed. These antioxidative films can have positive food applications.

  19. Design and synthesis of novel sulfonamide-containing bradykinin hB2 receptor antagonists. 2. Synthesis and structure-activity relationships of alpha,alpha-cycloalkylglycine sulfonamides.

    Science.gov (United States)

    Fattori, Daniela; Rossi, Cristina; Fincham, Christopher I; Caciagli, Valerio; Catrambone, Fernando; D'Andrea, Piero; Felicetti, Patrizia; Gensini, Martina; Marastoni, Elena; Nannicini, Rossano; Paris, Marielle; Terracciano, Rosa; Bressan, Alessandro; Giuliani, Sandro; Maggi, Carlo A; Meini, Stefania; Valenti, Claudio; Quartara, Laura

    2007-02-08

    Recently we reported on the design and synthesis of a novel class of selective nonpeptide bradykinin (BK) B2 receptor antagonists (J. Med. Chem. 2006, 3602-3613). This work led to the discovery of MEN 15442, an antagonist with subnanomolar affinity for the human B2 receptor (hB2R), which also displayed significant and prolonged activity in vivo (for up to 210 min) against BK-induced bronchoconstriction in the guinea-pig at a dose of 300 nmol/kg (it), while demonstrating only a slight effect on BK-induced hypotension. Here we describe the further optimization of this series of compounds aimed at maximizing the effect on bronchoconstriction and minimizing the effect on hypotension, with a view to developing topically delivered drugs for airway diseases. The work led to the discovery of MEN 16132, a compound which, after intratracheal or aerosol administration, inhibited, in a dose-dependent manner, BK-induced bronchoconstricton in the airways, while showing minimal systemic activity. This compound was selected as a preclinical candidate for the topical treatment of airway diseases involving kinin B2 receptor stimulation.

  20. Predictive Active Set Selection Methods for Gaussian Processes

    DEFF Research Database (Denmark)

    Henao, Ricardo; Winther, Ole

    2012-01-01

    We propose an active set selection framework for Gaussian process classification for cases when the dataset is large enough to render its inference prohibitive. Our scheme consists of a two step alternating procedure of active set update rules and hyperparameter optimization based upon marginal...... high impact to the classifier decision process while removing those that are less relevant. We introduce two active set rules based on different criteria, the first one prefers a model with interpretable active set parameters whereas the second puts computational complexity first, thus a model...... with active set parameters that directly control its complexity. We also provide both theoretical and empirical support for our active set selection strategy being a good approximation of a full Gaussian process classifier. Our extensive experiments show that our approach can compete with state...

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

    International Nuclear Information System (INIS)

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

    1996-02-01

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

  2. SUB-THz AND H{alpha} ACTIVITY DURING THE PREFLARE AND MAIN PHASES OF A GOES CLASS M2 EVENT

    Energy Technology Data Exchange (ETDEWEB)

    Kaufmann, Pierre; Gimenez de Castro, C. Guillermo; Raulin, Jean-Pierre; Correia, Emilia; Fernandes, Luis Olavo; De Souza, Rodney V. [CRAAM, Escola de Engenharia, Universidade Presbiteriana Mackenzie, Sao Paulo (Brazil); Marcon, Rogerio [IFGW, Universidade Estadual de Campinas (Brazil); White, Stephen M. [AFRL, Space Vehicles Directorate, Albuquerque, NM (United States); Godoy, Rodolfo; Marun, Adolfo; Pereyra, Pablo [Complejo Astronomico El Leoncito, CONICET, San Juan (Argentina)

    2011-12-01

    Radio and optical observations of the evolution of flare-associated phenomena have shown an initial and rapid burst at 0.4 THz only followed subsequently by a localized chromospheric heating producing an H{alpha} brightening with later heating of the whole active region. A major instability occurred several minutes later producing one impulsive burst at microwaves only, associated with an M2.0 GOES X-ray flare that exhibited the main H{alpha} brightening at the same site as the first flash.The possible association between long-enduring time profiles at soft X-rays, microwaves, H{alpha}, and sub-THz wavelengths is discussed. In the decay phase, the H{alpha} movie shows a disrupting magnetic arch structure ejecting dark, presumably chromospheric, material upward. The time sequence of events suggests genuine interdependent and possibly non-thermal instabilities triggering phenomena, with concurrent active region plasma heating and material ejection.

  3. Conditioning of alpha bearing wastes

    International Nuclear Information System (INIS)

    1991-01-01

    Alpha bearing wastes are generated during the reprocessing of spent fuel, mixed oxide fuel fabrication, decommissioning and other activities. The safe and effective management of these wastes is of particular importance owing to the radiotoxicity and long lived characteristics of certain transuranic (TRU) elements. The management of alpha bearing wastes involves a number of stages which include collection, characterization, segregation, treatment, conditioning, transport, storage and disposal. This report describes the currently available matrices and technologies for the conditioning of alpha wastes and relates them to their compatibility with the other stages of the waste management process. The selection of a specific immobilization process is dependent on the waste treatment state and the subsequent handling, transport, storage and disposal requirements. The overall objectives of immobilization are similar for all waste producers and processors, which are to produce: (a) Waste forms with sufficient mechanical, physical and chemical stability to satisfy all stages of handling, transport and storage (referred to as the short term requirements), and (b) Waste forms which will satisfy disposal requirements and inhibit the release of radionuclides to the biosphere (referred to as the long term requirements). Cement and bitumen processes have already been successfully applied to alpha waste conditioning on the industrial scale in many of the IAEA Member States. Cement systems based on BFS and pozzolanic cements have emerged as the principal encapsulation matrices for the full range of alpha bearing wastes. Alternative technologies, such as polymers and ceramics, are being developed for specific waste streams but are unlikely to meet widespread application owing to cost and process complexity. The merits of alpha waste conditioning are improved performance in transport, storage and disposal combined with enhanced public perception of waste management operations. These

  4. 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.

  5. Selective activation of heme oxygenase-2 by menadione.

    Science.gov (United States)

    Vukomanovic, Dragic; McLaughlin, Brian E; Rahman, Mona N; Szarek, Walter A; Brien, James F; Jia, Zongchao; Nakatsu, Kanji

    2011-11-01

    While substantial progress has been made in elucidating the roles of heme oxygenases-1 (HO-1) and -2 (HO-2) in mammals, our understanding of the functions of these enzymes in health and disease is still incomplete. A significant amount of our knowledge has been garnered through the use of nonselective inhibitors of HOs, and our laboratory has recently described more selective inhibitors for HO-1. In addition, our appreciation of HO-1 has benefitted from the availability of tools for increasing its activity through enzyme induction. By comparison, there is a paucity of information about HO-2 activation, with only a few reports appearing in the literature. This communication describes our observations of the up to 30-fold increase in the in-vitro activation of HO-2 by menadione. This activation was due to an increase in Vmax and was selective, in that menadione did not increase HO-1 activity.

  6. Hantaan Virus Nucleocapsid Protein Binds to Importin alpha Proteins and Inhibits Tumor Necrosis Factor Alpha-Induced Activation of Nuclear Factor Kappa B

    Science.gov (United States)

    2008-11-19

    Microbiology . All Rights Reserved. Hantaan Virus Nucleocapsid Protein Binds to Importin Proteins and Inhibits Tumor Necrosis Factor Alpha-Induced...Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21702,1 and Department of Microbiology , Mount Sinai...34–36. 32. Prescott , J., C. Ye, G. Sen, and B. Hjelle. 2005. Induction of innate immune response genes by Sin Nombre hantavirus does not require

  7. Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans.

    Science.gov (United States)

    Valle, Marta; Maqueda, Ana Elda; Rabella, Mireia; Rodríguez-Pujadas, Aina; Antonijoan, Rosa Maria; Romero, Sergio; Alonso, Joan Francesc; Mañanas, Miquel Àngel; Barker, Steven; Friedlander, Pablo; Feilding, Amanda; Riba, Jordi

    2016-07-01

    Ayahuasca is an Amazonian psychotropic plant tea typically obtained from two plants, Banisteriopsis caapi and Psychotria viridis. It contains the psychedelic 5-HT2A and sigma-1 agonist N,N-dimethyltryptamine (DMT) plus β-carboline alkaloids with monoamine-oxidase (MAO)-inhibiting properties. Although the psychoactive effects of ayahuasca have commonly been attributed solely to agonism at the 5-HT2A receptor, the molecular target of classical psychedelics, this has not been tested experimentally. Here we wished to study the contribution of the 5-HT2A receptor to the neurophysiological and psychological effects of ayahuasca in humans. We measured drug-induced changes in spontaneous brain oscillations and subjective effects in a double-blind randomized placebo-controlled study involving the oral administration of ayahuasca (0.75mg DMT/kg body weight) and the 5-HT2A antagonist ketanserin (40mg). Twelve healthy, experienced psychedelic users (5 females) participated in four experimental sessions in which they received the following drug combinations: placebo+placebo, placebo+ayahuasca, ketanserin+placebo and ketanserin+ayahuasca. Ayahuasca induced EEG power decreases in the delta, theta and alpha frequency bands. Current density in alpha-band oscillations in parietal and occipital cortex was inversely correlated with the intensity of visual imagery induced by ayahuasca. Pretreatment with ketanserin inhibited neurophysiological modifications, reduced the correlation between alpha and visual effects, and attenuated the intensity of the subjective experience. These findings suggest that despite the chemical complexity of ayahuasca, 5-HT2A activation plays a key role in the neurophysiological and visual effects of ayahuasca in humans. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  8. Cdc25A promotes cell survival by stimulating NF-{kappa}B activity through I{kappa}B-{alpha} phosphorylation and destabilization

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Hey-Young; Choi, Jiyeon [Department of Biochemistry, College of Natural Sciences, Kangwon National University, 192-1 Hyoja-2-dong, Chuncheon 200-701 (Korea, Republic of); Cho, Young-Wook [Korea Basic Science Institute, Chuncheon Center, Gangwondaehak-gil 1, Chuncheon 200-701 (Korea, Republic of); Kim, Byung-Chul, E-mail: bckim@kangwon.ac.kr [Department of Biochemistry, College of Natural Sciences, Kangwon National University, 192-1 Hyoja-2-dong, Chuncheon 200-701 (Korea, Republic of)

    2012-04-06

    Highlights: Black-Right-Pointing-Pointer We examine the antiapoptotic mechanisms of Cdc25A. Black-Right-Pointing-Pointer Smad7 decreases the phosphorylation of I{kappa}B-alpha at Ser-32. Black-Right-Pointing-Pointer Smad7 positively regulates NF-{kappa}B activity through I{kappa}B-alpha ubiquitination. -- Abstract: Cell division cycle 25A (Cdc25A), a dual specificity protein phosphatase, exhibits anti-apoptotic activity, but the underlying molecular mechanisms are poorly characterized. Here we report that Cdc25A inhibits cisplatin-induced apoptotic cell death by stimulating nuclear factor-kappa B (NF-{kappa}B) activity. In HEK-293 cells, Cdc25A decreased protein level of inhibitor subunit kappa B alpha (I{kappa}-B{alpha}) in association with increased serine 32-phosphorylation, followed by stimulation of transcriptional activity of NF-{kappa}B. Inhibition of NF-{kappa}B activity by chemical inhibitor or overexpression of I{kappa}-B{alpha} in Cdc25A-elevated cancer cells resistant to cisplatin improved their sensitivity to cisplatin-induced apoptosis. Our data show for the first time that Cdc25A has an important physiological role in NF-{kappa}B activity regulation and it may be an important survival mechanism of cancer cells.

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

    International Nuclear Information System (INIS)

    Tachibana, Keisuke; Takeuchi, Kentaro; Inada, Hirohiko; Yamasaki, Daisuke; Ishimoto, Kenji; Tanaka, Toshiya; Hamakubo, Takao; Sakai, Juro; Kodama, Tatsuhiko; Doi, Takefumi

    2009-01-01

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

  10. Voltage dependence of a stochastic model of activation of an alpha helical S4 sensor in a K channel membrane

    Science.gov (United States)

    Vaccaro, S. R.

    2011-09-01

    The voltage dependence of the ionic and gating currents of a K channel is dependent on the activation barriers of a voltage sensor with a potential function which may be derived from the principal electrostatic forces on an S4 segment in an inhomogeneous dielectric medium. By variation of the parameters of a voltage-sensing domain model, consistent with x-ray structures and biophysical data, the lowest frequency of the survival probability of each stationary state derived from a solution of the Smoluchowski equation provides a good fit to the voltage dependence of the slowest time constant of the ionic current in a depolarized membrane, and the gating current exhibits a rising phase that precedes an exponential relaxation. For each depolarizing potential, the calculated time dependence of the survival probabilities of the closed states of an alpha helical S4 sensor are in accord with an empirical model of the ionic and gating currents recorded during the activation process.

  11. Receptor protein tyrosine phosphatase alpha activates Src-family kinases and controls integrin-mediated responses in fibroblasts

    DEFF Research Database (Denmark)

    Su, J; Muranjan, M; Sap, J

    1999-01-01

    of tyrosine kinases, the activity of which is tightly controlled by inhibitory phosphorylation of a carboxyterminal tyrosine residue (Tyr527 in chicken c-Src); this phosphorylation induces the kinases to form an inactive conformation. Whereas the identity of such inhibitory Tyr527 kinases has been well...... established, no corresponding phosphatases have been identified that, under physiological conditions, function as positive regulators of c-Src and Fyn in fibroblasts. RESULTS: Receptor protein tyrosine phosphatase alpha (RPTPalpha) was inactivated by homologous recombination. Fibroblasts derived from...... these RPTPalpha-/- mice had impaired tyrosine kinase activity of both c-Src and Fyn, and this was accompanied by a concomitant increase in c-Src Tyr527 phosphorylation. RPTPalpha-/- fibroblasts also showed a reduction in the rate of spreading on fibronectin substrates, a trait that is a phenocopy of the effect...

  12. Evaluation of a rapid radiometric differentiation test for the Mycobacterium tuberculosis complex by selective inhibition with p-nitro-alpha-acetylamino-beta-hydroxypropiophenone

    International Nuclear Information System (INIS)

    Laszlo, A.; Siddiqi, S.H.

    1984-01-01

    This study is an evaluation of a rapid technique for the differentiation of the Mycobacterium tuberculosis complex from other mycobacteria, using p-nitro-alpha-acetylamino-beta- hydroxypropiophenone (NAP) as a selective inhibitory agent. A total of 416 coded cultures, 234 cultures belonging to the M. tuberculosis complex and 182 cultures belonging to 35 other mycobacterial species, were tested in two laboratories for p-nitro-alpha-acetylamino-beta- hydroxypropiophenone inhibition to concentrations of 5 and 10 micrograms of NAP per ml in Middlebrook 7H12 liquid medium. Two testing modes were compared: the indirect, in which a large bacterial inoculum was used from an isolated culture on a solid medium, and the direct, which used a small inoculum from 7H12 medium. A decrease or no increase in daily 14 CO 2 output as measured by a BACTEC system was considered evidence of inhibition. The data presented show that a concentration of 5 micrograms of NAP per ml can effectively separate the M. tuberculosis complex from other mycobacterial species in 4 to 6 days. The direct test data show that, unlike other conventional biochemical tests, it does not require a heavy inoculum of mycobacteria and can therefore be performed soon after growth is detected by the radiometric method

  13. Selective activation of neuromuscular compartments within the human trapezius muscle

    DEFF Research Database (Denmark)

    Holtermann, A; Roeleveld, K; Mork, P J

    2009-01-01

    of the human trapezius muscle can be independently activated by voluntary command, indicating neuromuscular compartmentalization of the trapezius muscle. The independent activation of the upper and lower subdivisions of the trapezius is in accordance with the selective innervation by the fine cranial and main...... branch of the accessory nerve to the upper and lower subdivisions. These findings provide new insight into motor control characteristics, learning possibilities, and function of the clinically relevant human trapezius muscle....

  14. Three phase active power filter with selective harmonics elimination

    Directory of Open Access Journals (Sweden)

    Sozański Krzysztof

    2016-03-01

    Full Text Available This paper describes a three phase shunt active power filter with selective harmonics elimination. The control algorithm is based on a digital filter bank. The moving Discrete Fourier Transformation is used as an analysis filter bank. The correctness of the algorithm has been verified by simulation and experimental research. The paper includes exemplary results of current waveforms and their spectra from a three phase active power filter.

  15. 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.

  16. Classification of alpha 1-adrenoceptor subtypes

    NARCIS (Netherlands)

    Michel, M. C.; Kenny, B.; Schwinn, D. A.

    1995-01-01

    Two alpha 1-adrenoceptor subtypes (alpha 1A and alpha 1B) have been detected in various tissues by pharmacological techniques, and three distinct cDNAs encoding alpha 1-adrenoceptor subtypes have been cloned. The profile of an increasing number of subtype-selective compounds at cloned and endogenous

  17. Antiulcerogenic activity of fractions and 3,15-dioxo-21alpha-hydroxy friedelane isolated from Maytenus robusta (Celastraceae).

    Science.gov (United States)

    de Andrade, Sérgio Faloni; Comunello, Eros; Noldin, Vânia Floriani; Monache, Franco Delle; Cechinel Filho, Valdir; Niero, Rivaldo

    2008-01-01

    The hexane, chloroform, ethyl acetate and aqueous-soluble fractions from leaves of Maytenus robusta (Celastraceae) were evaluated for their protective actions against ethanol-induced gastric lesions in rats. The treatment with all fractions (150 mg/kg) and omeprazol (30 mg/kg) significantly reduced the lesion index, the total lesion area, and the percentage of lesion, in comparison with the control group (p<0.05). Since the ethyl acetate-soluble fraction was found to be most active in the pylorus ligated model, this fraction was further investigated and resulted in the isolation of triterpene 3,15-dioxo-21alpha-hydroxy friedelane. The triterpene was evaluated in the HCl/ethanol-induced ulcer model in mice. In this assay, both the groups treated with 3,15-dioxo-21alpha-hydroxy friedelane and omeprazol, at a dose of 30 mg/kg, presented a significant reduction in lesion index, total lesion area, and in the percentage of the lesion, when compared with the control group (p<0.05). The result suggests that the antiulcer effect observed in the extract and fractions may be attributed, at least in part, to this compound. Further experiments are underway to determine which antiulcer mechanisms involved in gastroprotection.

  18. Alpha-PVP as an active component of herbal highs in Poland between 2013 and 2015.

    Science.gov (United States)

    Byrska, Bogumiła; Stanaszek, Roman; Zuba, Dariusz

    2017-08-01

    Alpha-PVP (alpha-pyrrolidinovalerophenone, α-PVP) is a synthetic derivative of cathinone. It has been one of the most frequently detected new psychoactive substances (NPS) available on the drug market in recent years in Poland. The usual routes of administration of the drug include oral, insufflation, and injection. Unexpectedly, we dealt with a great number of herbal samples that turned out to contain α-PVP. A total number of 352 herbal samples from 19 cases in which we detected synthetic cathinones, were investigated in the Institute of Forensic Research (IFR) from 2013 to 2015. The seized products that were received by our laboratory were first screened by gas chromatography coupled to mass spectrometry (GC-MS). Quantification of α-PVP and other cathinones was performed by ultra-performance liquid chromatography with photodiode array detection (UPLC-PDA). Of the samples, 84% contained only α-PVP. Other groups of products were those containing only α-PVT, α-PVP and α-PVT, α-PVP and synthetic cannabinoid A-834, 735, and α-PVP and cannabis. In one herbal sample, α-PVP was detected along with caffeine and tadalafil. The herbal products present on the market containing only α-PVP usually had a mass of 0.3 to 0.6 g, and concentration range in this group of samples was 3.0-44.0% (content: 13.0-222.0 mg per package). The amount of α-PVP in samples below 0.30 g was in a range 9-18 mg whiles in samples above 0.60 g it was in the range 30-716 mg. There were also products containing a mixture of α-PVP and α-PVT. In those samples, α-PVP concentrations were: 3.0-6.0% (amount: 15.0-34.0 mg). Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  19. Pharmacological characterisation of strychnine and brucine analogues at glycine and alpha7 nicotinic acetylcholine receptors

    DEFF Research Database (Denmark)

    Jensen, Anders A.; Gharagozloo, Parviz; Birdsall, Nigel J M

    2006-01-01

    of tertiary and quaternary analogues as well as bisquaternary dimers of strychnine and brucine at human alpha1 and alpha1beta glycine receptors and at a chimera consisting of the amino-terminal domain of the alpha7 nicotinic receptor (containing the orthosteric ligand binding site) and the ion channel domain...... of strychnine and brucine, none of the analogues displayed significant selectivity between the alpha1 and alpha1beta subtypes. The structure-activity relationships for the compounds at the alpha7/5-HT3 chimera were significantly different from those at the glycine receptors. Most strikingly, quaternization...... of strychnine and brucine with substituents possessing different steric and electronic properties completely eliminated the activity at the glycine receptors, whereas binding affinity to the alpha7/5-HT3 chimera was retained for the majority of the quaternary analogues. This study provides an insight...

  20. Standardization and estimation of gross alpha and beta activities for potable water samples in presence of TDS using TDCR based LSA (Hidex 300SL)

    International Nuclear Information System (INIS)

    Gupta, Anil; Lenka, P.; Sahoo, S.K.; Patra, A.C.; Jha, S.K.; Tripathi, R.M.

    2018-01-01

    Quality of water is important in environmental studies because of its daily use for human consumption and an important route of intake for various elements and radionuclides. Therefore radiological quality of drinking water must be ensured. The screening parameter to evaluate the radiological safety of potable water is by estimating gross alpha and gross beta activities with a limit of 0.5 Bq/l and 1 Bq/l respectively. These have been traditionally being done by radiochemical co-precipitation of alpha and beta emitters followed by counting by ZnS(Ag) counter for alpha and gas flow proportional counter for beta. Gross alpha estimation in water samples with high TDS by ZnS(Ag) is difficult and often leads to underestimation of result due to self-absorption of alpha within the residue. This study was carried out to standardize a method to provide rapid results by simultaneously estimating both gross alpha and gross beta activity in the presence of TDS with adequate sensitivity, minimum sample processing

  1. Reduced auditory efferent activity in childhood selective mutism.

    Science.gov (United States)

    Bar-Haim, Yair; Henkin, Yael; Ari-Even-Roth, Daphne; Tetin-Schneider, Simona; Hildesheimer, Minka; Muchnik, Chava

    2004-06-01

    Selective mutism is a psychiatric disorder of childhood characterized by consistent inability to speak in specific situations despite the ability to speak normally in others. The objective of this study was to test whether reduced auditory efferent activity, which may have direct bearings on speaking behavior, is compromised in selectively mute children. Participants were 16 children with selective mutism and 16 normally developing control children matched for age and gender. All children were tested for pure-tone audiometry, speech reception thresholds, speech discrimination, middle-ear acoustic reflex thresholds and decay function, transient evoked otoacoustic emission, suppression of transient evoked otoacoustic emission, and auditory brainstem response. Compared with control children, selectively mute children displayed specific deficiencies in auditory efferent activity. These aberrations in efferent activity appear along with normal pure-tone and speech audiometry and normal brainstem transmission as indicated by auditory brainstem response latencies. The diminished auditory efferent activity detected in some children with SM may result in desensitization of their auditory pathways by self-vocalization and in reduced control of masking and distortion of incoming speech sounds. These children may gradually learn to restrict vocalization to the minimal amount possible in contexts that require complex auditory processing.

  2. Antifungal activity of epithelial secretions from selected frog species ...

    African Journals Online (AJOL)

    This study aimed to investigate the antifungal activity of skin secretions from selected frogs (Amietia fuscigula, Strongylopus grayi and Xenopus laevis) and one toad (Amietophrynus pantherinus) of the south Western Cape Province of South Africa. Initially, different extraction techniques for the collection of skin secretions ...

  3. Stroop interference and the timing of selective response activation.

    NARCIS (Netherlands)

    Lansbergen, M.M.; Kenemans, J.L.

    2008-01-01

    OBJECTIVE: To examine the exact timing of selective response activation in a manual color-word Stroop task. METHODS: Healthy individuals performed two versions of a manual color-word Stroop task, varying in the probability of incongruent color-words, while EEG was recorded. RESULTS: Stroop

  4. Electroless Plating on Plastic Induced by Selective Laser Activation

    DEFF Research Database (Denmark)

    Zhang, Yang; Tang, Peter Torben; Hansen, Hans Nørgaard

    2009-01-01

    This paper presents a new method for selective micro metallization of polymers. A Nd:YAG laser is employed to draw patterns on polymer surfaces that are submerged in a liquid (usually water). After subsequent activation with palladium chloride and followed by auto-catalytic electroless plating, c...

  5. Antibacterial activity of some selected plants traditionally used as ...

    African Journals Online (AJOL)

    Antibacterial activity of some selected plants traditionally used as medicine in Manipur. ... Hence these plants can be used to discover bioactive natural products that may serve as leads in the development of the new pharmaceuticals. Keywords: Antibacterial, human pathogens, methanolic extract, traditional medicine

  6. 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

  7. Hepatitis B spliced protein (HBSP) promotes the carcinogenic effects of benzo [alpha] pyrene by interacting with microsomal epoxide hydrolase and enhancing its hydrolysis activity

    International Nuclear Information System (INIS)

    Chen, Jin-Yan; Chen, Wan-Nan; Jiao, Bo-Yan; Lin, Wan-Song; Wu, Yun-Li; Liu, Ling-Ling; Lin, Xu

    2014-01-01

    The risk of hepatocellular carcinoma (HCC) increases in chronic hepatitis B surface antigen (HBsAg) carriers who often have concomitant increase in the levels of benzo[alpha]pyrene-7,8-diol-9,10-epoxide(±) (BPDE)-DNA adduct in liver tissues, suggesting a possible co-carcinogenesis of Hepatitis B virus (HBV) and benzo[alpha]pyrene in HCC; however the exact mechanisms involved are unclear. The interaction between hepatitis B spliced protein (HBSP) and microsomal epoxide hydrolase (mEH) was confirmed using GST pull-down, co-immunoprecipitation and mammalian two-hybrid assay; the effects of HBSP on mEH-mediated B[alpha]P metabolism was examined by high performance liquid chromatography (HPLC); and the influences of HBSP on B[alpha]P carcinogenicity were evaluated by bromodeoxyuridine cell proliferation, anchorage-independent growth and tumor xenograft. HBSP could interact with mEH in vitro and in vivo, and this interaction was mediated by the N terminal 47 amino acid residues of HBSP. HBSP could greatly enhance the hydrolysis activity of mEH in cell-free mouse liver microsomes, thus accelerating the metabolism of benzo[alpha]pyrene to produce more ultimate carcinnogen, BPDE, and this effect of HBSP requires the intact HBSP molecule. Expression of HBSP significantly increased the formation of BPDE-DNA adduct in benzo[alpha]pyrene-treated Huh-7 hepatoma cells, and this enhancement was blocked by knockdown of mEH. HBSP could enhance the cell proliferation, accelerate the G1/S transition, and promote cell transformation and tumorigenesis of B[alpha]P-treated Huh-7 hepatoma cells. Our results demonstrated that HBSP could promote carcinogenic effects of B[alpha]P by interacting with mEH and enhancing its hydrolysis activity

  8. Impact of exercise selection on hamstring muscle activation.

    Science.gov (United States)

    Bourne, Matthew N; Williams, Morgan D; Opar, David A; Al Najjar, Aiman; Kerr, Graham K; Shield, Anthony J

    2017-07-01

    To determine which strength training exercises selectively activate the biceps femoris long head (BF LongHead ) muscle. We recruited 24 recreationally active men for this two-part observational study . Part 1: We explored the amplitudes and the ratios of lateral (BF) to medial hamstring (MH) normalised electromyography (nEMG) during the concentric and eccentric phases of 10 common strength training exercises. Part 2: We used functional MRI (fMRI) to determine the spatial patterns of hamstring activation during two exercises which (1) most selectively and (2) least selectively activated the BF in part 1. Eccentrically, the largest BF/MH nEMG ratio occurred in the 45° hip-extension exercise; the lowest was in the Nordic hamstring (Nordic) and bent-knee bridge exercises. Concentrically, the highest BF/MH nEMG ratio occurred during the lunge and 45° hip extension; the lowest was during the leg curl and bent-knee bridge. fMRI revealed a greater BF (LongHead) to semitendinosus activation ratio in the 45° hip extension than the Nordic (phamstring muscles (p≤0.002). We highlight the heterogeneity of hamstring activation patterns in different tasks. Hip-extension exercise selectively activates the long hamstrings, and the Nordic exercise preferentially recruits the semitendinosus. These findings have implications for strategies to prevent hamstring injury as well as potentially for clinicians targeting specific hamstring components for treatment (mechanotherapy). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  9. Photometric assay of maltose and maltose-forming enzyme activity by using 4-alpha-glucanotransferase (DPE2) from higher plants.

    Science.gov (United States)

    Smirnova, Julia; Fernie, Alisdair R; Spahn, Christian M T; Steup, Martin

    2017-09-01

    Maltose frequently occurs as intermediate of the central carbon metabolism of prokaryotic and eukaryotic cells. Various mutants possess elevated maltose levels. Maltose exists as two anomers, (α- and β-form) which are rapidly interconverted without requiring enzyme-mediated catalysis. As maltose is often abundant together with other oligoglucans, selective quantification is essential. In this communication, we present a photometric maltose assay using 4-alpha-glucanotransferase (AtDPE2) from Arabidopsis thaliana. Under in vitro conditions, AtDPE2 utilizes maltose as glucosyl donor and glycogen as acceptor releasing the other hexosyl unit as free glucose which is photometrically quantified following enzymatic phosphorylation and oxidation. Under the conditions used, DPE2 does not noticeably react with other di- or oligosaccharides. Selectivity compares favorably with that of maltase frequently used in maltose assays. Reducing end interconversion of the two maltose anomers is in rapid equilibrium and, therefore, the novel assay measures total maltose contents. Furthermore, an AtDPE2-based continuous photometric assay is presented which allows to quantify β-amylase activity and was found to be superior to a conventional test. Finally, the AtDPE2-based maltose assay was used to quantify leaf maltose contents of both Arabidopsis wild type and AtDPE2-deficient plants throughout the light-dark cycle. These data are presented together with assimilatory starch levels. Copyright © 2017. Published by Elsevier Inc.

  10. The role and regulation of the peroxisome proliferator activated receptor alpha in human liver

    NARCIS (Netherlands)

    Kersten, Sander; Stienstra, Rinke

    2017-01-01

    The peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that is abundantly expressed in liver. PPARα is activated by fatty acids and various other lipid species, as well as by a class of chemicals referred to as peroxisome proliferators. Studies in mice

  11. Electrocatalytic Activity and Selectivity - a Density Functional Theory Study

    DEFF Research Database (Denmark)

    Karamad, Mohammadreza

    -catalysts towards two appealing electrochemical reactions: 1)electroreduction of CO2 to hydrocarbons and alcohols, and 2) electrochemical production of hydrogen peroxide, i.e. H2O2, from its elements i.e. H2 and O2. The thesis is divided into three parts: In the first part, electro-catalytic activity of different...... metallic and functionalized graphene catalysts. Secondly, we considered CO2 reduction on RuO2, which has a distinctive catalytic activity and selectivity compared to Cu to get insight into mechanistic pathway of the CO2 reduction. Finally, in the last part, we have taken advantage of the isolated active...

  12. 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...

  13. Whole blood assay for NK activity in splenectomized and non-splenectomized hairy cell leukemia patients during IFN-alpha-2b treatment

    DEFF Research Database (Denmark)

    Nielsen, B; Hokland, P; Ellegaard, J

    1989-01-01

    Natural killer cell (NK) activity in peripheral blood (PB) was followed longitudinally for up to 2 yr after initiation of low-dose IFN-alpha-2b therapy in nine hairy cell leukemia (HCL) patients. A whole blood NK (WB-NK) assay was employed in order to measure the NK activity per unit blood. The p...

  14. Elafibranor, an Agonist of the Peroxisome Proliferator-Activated Receptor-alpha and -delta, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening

    NARCIS (Netherlands)

    Ratziu, V.; Harrison, S.A.; Francque, S.; Bedossa, P.; Lehert, P.; Serfaty, L.; Romero-Gomez, M.; Boursier, J.; Abdelmalek, M.; Caldwell, S.; Drenth, J.P.; Anstee, Q.M.; Hum, D.; Hanf, R.; Roudot, A.; Megnien, S.; Staels, B.; Sanyal, A.

    2016-01-01

    BACKGROUND & AIMS: Elafibranor is an agonist of the peroxisome proliferator-activated receptor-alpha and peroxisome proliferator-activated receptor-delta. Elafibranor improves insulin sensitivity, glucose homeostasis, and lipid metabolism and reduces inflammation. We assessed the safety and efficacy

  15. Effect of antitumour necrosis factor-alpha therapy on bone turnover in patients with active Crohn's disease: a prospective study.

    Science.gov (United States)

    Ryan, B M; Russel, M G V M; Schurgers, L; Wichers, M; Sijbrandij, J; Stockbrugger, R W; Schoon, E

    2004-10-15

    Patients with Crohn's disease are at increased risk of osteoporosis. Disease activity and circulating proinflammatory cytokines are thought to play a role in this process. Infliximab, a chimaeric antitumour necrosis factor-alpha antibody is effective in the treatment of Crohn's disease. The aim of this study was to investigate the impact of treatment with infliximab on bone turnover in Crohn's disease patients. This was a prospective trial. Twenty-four patients with active Crohn's disease were treated with infliximab (5 mg/kg). Bone markers were assayed pre- and post-treatment. Bone formation was measured using serum bone-specific alkaline phosphatase and total osteocalcin and bone resorption using serum N-telopeptide cross-linked type 1 collagen. Infliximab therapy caused a significant increase in both markers of bone formation in patients with active Crohn's disease. No significant change in the bone resorption marker serum N-telopeptide cross-linked type 1 was found. Infliximab therapy had a significant beneficial effect on bone metabolism in patients with active Crohn's disease. These findings further support the theory that active ongoing inflammation and high levels of circulating cytokines play a pivotal role in the pathogenesis of bone loss in patients with Crohn's disease.

  16. Minimum detectable activity and false alarm rate relationships for alpha continuous air monitors

    International Nuclear Information System (INIS)

    Hoover, M.D.; Newton, G.J.

    1994-01-01

    The U.S. Department of Energy rule for Occupational Radiation Protection (10 CFR Part 835, December 1993) and the DOE Radiological Control Manual (the RCM) (DOE/EH-0256T, Rev. 1, April 1994) require the use of continuous air monitors (CAMs) in normally occupied areas where an individual is likely to be exposed to a concentration of airborne radioactivity exceeding the derived air concentration (DAC) or where there is a need to alert potentially exposed individuals to unexpected increases in airborne radioactivity levels. The DAC is the airborne concentration that equals the annual limit on intake divided by the volume of air breathed by an average worker for a working year of 2000 h (assuming a breathing volume of 2400 m 3 ). It is equivalent to the airborne concentration to which a worker could be exposed for an entire working year (2000 h) without exceeding the allowable annual limit on intake. The rule and the RCM further require that real-time air monitors have an alarm capability and sufficient sensitivity to alert potentially exposed individuals that immediate action is necessary in order to minimize or terminate inhalation exposures. The RCM also recommends that real-time air monitors should be capable of measuring 1 DAC when averaged over 8 h (8 DAC-h) under laboratory conditions. In response to these recommendations, we are developing procedures for determining the basic sensitivity of alpha CAMs under laboratory conditions and for documenting practical alarm set points for routine use of CAMs under a range of radon and thoron concentrations

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

    Directory of Open Access Journals (Sweden)

    Iuliia Vitko

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

  18. 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.

  19. Determination of specific activity of americium and plutonium in selected environmental samples

    International Nuclear Information System (INIS)

    Trebunova, T.

    1999-01-01

    The aim of this work was development of method for determination of americium and plutonium in environmental samples. Developed method was evaluated on soil samples and after they was applied on selected samples of fishes (smoked mackerel, herring and fillet from Alaska hake). The method for separation of americium is based on liquid separation with Aliquate-336, precipitation with oxalic acid and using of chromatographic material TRU-Spec TM .The intervals of radiochemical yields were from 13.0% to 80.9% for plutonium-236 and from 10.5% to 100% for americium-241. Determined specific activities of plutonium-239,240 were from (2.3 ± 1.4) mBq/kg to (82 ± 29) mBq/kg, the specific activities of plutonium-238 were from (14.2 ± 3.7) mBq/kg to (708 ± 86) mBq/kg. The specific activities of americium-241 were from (1.4 ± 0.9) mBq/kg to (3360 ± 210) mBq/kg. The fishes from Baltic Sea as well as from North Sea show highest specific activities then fresh-water fishes from Slovakia. Therefore the monitoring of alpha radionuclides in foods imported from territories with nuclear testing is recommended

  20. Induction of osteoblast differentiation by selective activation of kinase-mediated actions of the estrogen receptor.

    Science.gov (United States)

    Kousteni, Stavroula; Almeida, Maria; Han, Li; Bellido, Teresita; Jilka, Robert L; Manolagas, Stavros C

    2007-02-01

    Estrogens control gene transcription by cis or trans interactions of the estrogen receptor (ER) with target DNA or via the activation of cytoplasmic kinases. We report that selective activation of kinase-mediated actions of the ER with 4-estren-3alpha,17beta-diol (estren) or an estradiol-dendrimer conjugate, each a synthetic compound that stimulates kinase-mediated ER actions 1,000 to 10,000 times more potently than direct DNA interactions, induced osteoblastic differentiation in established cell lines of uncommitted osteoblast precursors and primary cultures of osteoblast progenitors by stimulating Wnt and BMP-2 signaling in a kinase-dependent manner. In sharp contrast, 17beta-estradiol (E(2)) suppressed BMP-2-induced osteoblast progenitor commitment and differentiation. Consistent with the in vitro findings, estren, but not E(2), stimulated Wnt/beta-catenin-mediated transcription in T-cell factor-lacZ transgenic mice. Moreover, E(2) stimulated BMP signaling in mice in which ERalpha lacks DNA binding activity and classical estrogen response element-mediated transcription (ERalpha(NERKI/-)) but not in wild-type controls. This evidence reveals for the first time the existence of a large signalosome in which inputs from the ER, kinases, bone morphogenetic proteins, and Wnt signaling converge to induce differentiation of osteoblast precursors. ER can either induce it or repress it, depending on whether the activating ligand (and presumably the resulting conformation of the receptor protein) precludes or accommodates ERE-mediated transcription.

  1. Buffett's Alpha

    DEFF Research Database (Denmark)

    Frazzini, Andrea; Kabiller, David; Heje Pedersen, Lasse

    Berkshire Hathaway has realized a Sharpe ratio of 0.76, higher than any other stock or mutual fund with a history of more than 30 years, and Berkshire has a significant alpha to traditional risk factors. However, we find that the alpha becomes insignificant when controlling for exposures to Betting...

  2. Alpha Blockers

    Science.gov (United States)

    ... quickly, but their effects last only a few hours. Long-acting medications take longer to work, but their effects last longer. Which alpha blocker is best for you depends on your health and the condition being treated. Alpha blockers are ...

  3. Differences in genotoxic activity of alpha-Ni3S2 on human lymphocytes from nickel-hypersensitized and nickel-unsensitized donors.

    Science.gov (United States)

    Arrouijal, F Z; Marzin, D; Hildebrand, H F; Pestel, J; Haguenoer, J M

    1992-05-01

    The genotoxic activity of alpha-Ni3S2 was assessed on human lymphocytes from nickel-hypersensitized (SSL) and nickel-unsensitized (USL) subjects. Three genotoxicity tests were performed: the sister chromatid exchange (SCE) test, the metaphase analysis test and the micronucleus test. (i) The SCE test (3-100 micrograms/ml) showed a weak but statistically significant increase in the number of SCE in both lymphocyte types with respect to controls, USL presenting a slightly higher SCE incidence but only at one concentration. (ii) The metaphase analysis test demonstrated a high dose-dependent clastogenic activity of alpha-Ni3S2 in both lymphocyte types. The frequency of chromosomal anomalies was significantly higher in USL than in SSL for all concentrations applied. (iii) The micronucleus test confirmed the dose-dependent clastogenic activity of alpha-Ni3S2 and the differences already observed between USL and SSL, i.e. the number of cells with micronuclei was statistically higher in USL. Finally, the incorporation study with alpha-63Ni3S2 showed a higher uptake of its solubilized fraction by USL. This allows an explanation of the different genotoxic action of nickel on the two cell types. In this study we demonstrated that hypersensitivity has an influence on the incorporation of alpha-Ni3S2 and subsequently on the different induction of chromosomal aberrations in human lymphocytes.

  4. Ratio of Circulating Estrogen Receptors Beta and Alpha (ERβ/ERα) Indicates Endoscopic Activity in Patients with Crohn's Disease.

    Science.gov (United States)

    Linares, Pablo M; Algaba, Alicia; Urzainqui, Ana; Guijarro-Rojas, Mercedes; González-Tajuelo, Rafael; Garrido, Jesús; Chaparro, María; Gisbert, Javier P; Bermejo, Fernando; Guerra, Iván; Castellano, Víctor; Fernández-Contreras, María-Encarnación

    2017-10-01

    Data supporting a role of female hormones and/or their receptors in inflammatory bowel disease (IBD) are increasing, but most of them are derived from animal models. Estrogen receptors alpha (ERα) and beta (ERβ) participate in immune and inflammatory response, among a variety of biological processes. Their effects are antagonistic, and the net action of estrogens may depend on their relative proportions. To determine the possible association between the balance of circulating ERβ and ERα (ERβ/ERα) and IBD risk and activity. Serum samples from 145 patients with IBD (79 Crohn's disease [CD] and 66 ulcerative colitis [UC]) and 39 controls were retrospectively studied. Circulating ERα and ERβ were measured by ELISA. Disease activities were assessed by clinical and endoscopic indices specific for CD and UC. Low values of ERβ/ERα ratio were directly associated with clinical (p = 0.019) and endoscopic (p = 0.002) disease activity. Further analyses by type of IBD confirmed a strong association between low ERβ/ERα ratio and CD clinical (p = 0.011) and endoscopic activity (p = 0.002). The receiver operating curve (ROC) analysis showed that an ERβ/ERα ratio under 0.85 was a good marker of CD endoscopic activity (area under the curve [AUC]: 0.84; p = 0.002; sensitivity: 70%; specificity: 91%). ERβ/ERα ratio was not useful to predict UC activity. An ERβ/ERα ratio under 0.85 indicated CD endoscopic activity. The determination of serum ERβ/ERα might be a useful noninvasive screening tool for CD endoscopic activity.

  5. Relative left frontal activity in reappraisal and suppression of negative emotion: Evidence from frontal alpha asymmetry (FAA).

    Science.gov (United States)

    Choi, Damee; Sekiya, Takahiro; Minote, Natsumi; Watanuki, Shigeki

    2016-11-01

    Previous studies have shown that reappraisal (changing the way that one thinks about emotional events) is an effective strategy for regulating emotion, compared with suppression (reducing emotion-expressive behavior). In the present study, we investigated relative left frontal activity when participants were instructed to use reappraisal and suppression of negative emotion, by measuring frontal alpha asymmetry (FAA). Two electroencephalography (EEG) experiments were conducted; FAA was analyzed while 102 healthy participants (59 men, 43 women) watched negative images after being instructed to perform reappraisal (Experiment 1) and suppression (Experiment 2). Habitual use of reappraisal and suppression was also assessed using the emotion regulation questionnaire (ERQ). The results of Experiment 1 showed that relative left frontal activity was greater when instructed to use reappraisal of negative images than when normally viewing negative images. In contrast, we observed no difference between conditions of instructed suppression and normal viewing in Experiment 2. In addition, in male participants, habitual use of reappraisal was positively correlated with increased relative left frontal activity for instructed reappraisal, while habitual use of suppression did not show a significant correlation with changes in relative left frontal activity for instructed suppression. These results suggest that emotional responses to negative images might be decreased for instructed reappraisal, but not suppression. These findings support previous reports that reappraisal is an effective emotion regulation strategy, compared with suppression. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Acute cadmium intoxication induces alpha-class glutathione S-transferase protein synthesis and enzyme activity in rat liver

    International Nuclear Information System (INIS)

    Casalino, Elisabetta; Sblano, Cesare; Calzaretti, Giovanna; Landriscina, Clemente

    2006-01-01

    Acute cadmium intoxication affects glutathione S-transferase (GST) in rat liver. It has been found that 24 h after i.p. cadmium administration to rats, at a dose of 2.5 mg CdCl 2 kg -1 body weight, the activity of this enzyme in liver cytosol increased by 40%. A less stimulatory effect persisted till 48 h and thereafter the enzyme activity normalized. Since, GST isoenzymes belong to different classes in mammalian tissues, we used quantitative immunoassays to verify which family of GST isoenzymes is influenced by this intoxication. Only alpha-class glutathione S-transferase (α-GST) proteins were detected in rat liver cytosol and their level increased by about 25%, 24 h after cadmium treatment. No pi-GST isoforms were found in liver cytosol from either normal or cadmium-treated rats. Co-administration of actinomycin D with cadmium normalized both the protein level and the activity of α-GST, suggesting that some effect occurs on enzyme transcription of these isoenzymes by this metal. On the other hand, it seems unlikely that the stimulatory effect is due to the high level of peroxides caused by lipid peroxidation, since Vitamin E administration strongly reduced the TBARS level, but did not cause any GST activity decrease

  7. Stabilization and activation of alpha-chymotrypsin in water-organic solvent systems by complex formation with oligoamines.

    Science.gov (United States)

    Kudryashova, Elena V; Artemova, Tatiana M; Vinogradov, Alexei A; Gladilin, Alexander K; Mozhaev, Vadim V; Levashov, Andrey V

    2003-04-01

    Formation of enzyme-oligoamine complexes was suggested as an approach to obtain biocatalysts with enhanced resistance towards inactivation in water-organic media. Complex formation results in broadening (by 20-40% v/v ethanol) of the range of cosolvent concentrations where the enzyme retains its catalytic activity (stabilization effect). At moderate cosolvent concentrations (20-40% v/v) complex formation activates the enzyme (by 3-6 times). The magnitude of activation and stabilization effects increases with the number of possible electrostatic contacts between the protein surface and the molecules of oligoamines (OA). Circular dichroism spectra in the far-UV region show that complex formation stabilizes protein conformation and prevents aggregation in water-organic solvent mixtures. Two populations of the complexes with different thermodynamic stabilities were found in alpha-chymotrypsin (CT)-OA systems depending on the CT/OA ratio. The average dissociation constants and stoichiometries of both low- and high-affinity populations of the complexes were estimated. It appears that it is the low-affinity sites on the CT surface that are responsible for the activation effect.

  8. Observations of the distribution and the nature of alpha-active particulate material in a HEPA filter used for plutonium-containing dust

    International Nuclear Information System (INIS)

    Ryan, M.T.; McDowell, W.J.

    1977-02-01

    Autoradiography has been used to determine the distribution and the nature of plutonium particulate material on a high-efficiency particulate air (HEPA) filter used to filter 239 Pu-containing dust. Higher concentrations of alpha-active material on upstream and downstream folds of the filter indicate uneven airflow through the filter. Observations of aggregate recoil particles on the downstream face of the filter suggest that aggregate recoil transfer, a mechanism which may reduce long-term HEPA filter efficiency, may be occurring. Amounts of alpha activity found on downstream filters confirm this supposition

  9. Prediction for the high-level alpha-active waste to be generated by nuclear power stations in the Member States of the European Communities

    International Nuclear Information System (INIS)

    Schmidt, E.

    1977-04-01

    Starting with a forecast for the nuclear power generating capacity to be installed in the Member States of the European Communities before the end of this century, a prediction is made of the annual production of high-level alpha-active waste from reprocessing plants and the corresponding accumulation up to the year 2000. The isotopic composition of the alpha-active waste from individual reactor types was calculated and an estimation of the influence of recycling plutonium through light water reactors on the produced quantity of higher actinides is made

  10. 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...

  11. Dimerization inhibits the activity of receptor-like protein-tyrosine phosphatase-alpha

    DEFF Research Database (Denmark)

    Jiang, G; den Hertog, J; Su, J

    1999-01-01

    that dimerization can negatively regulate activity, through the interaction of an inhibitory 'wedge' on one monomer with the catalytic cleft of domain 1 in the other monomer. Here we show that dimerization inhibits the activity of a full-length RPTP in vivo. We generated stable disulphide-bonded full...

  12. Effects of a dietary Aspergillus oryzae extract containing alpha-amylase activity on performance and carcass characteristics of finishing beef cattle.

    Science.gov (United States)

    Tricarico, J M; Abney, M D; Galyean, M L; Rivera, J D; Hanson, K C; McLeod, K R; Harmon, D L

    2007-03-01

    Three experiments were conducted to examine the effects of an Aspergillus oryzae extract containing alpha-amylase activity on performance and carcass characteristics of finishing beef cattle. In Exp. 1, 120 crossbred steers were used in a randomized complete block design to evaluate the effects of roughage source (alfalfa hay vs. cottonseed hulls) and supplemental alpha-amylase at 950 dextrinizing units (DU)/kg of DM. Significant roughage source x alpha-amylase interactions (P < 0.05) were observed for performance. In steers fed cottonseed hulls, supplemental alpha-amylase increased ADG through d 28 and 112 and tended (P < 0.15) to increase ADG in all other periods. The increases in ADG were related to increased DMI and efficiency of gain during the initial 28-d period but were primarily related to increased DMI as the feeding period progressed. Supplemental alpha-amylase increased (P = 0.02) the LM area across both roughage sources. In Exp. 2, 96 crossbred heifers were used in a randomized complete block design with a 2 x 3 factorial arrangement of treatments to evaluate the effects of corn processing (dry cracked vs. high moisture) and supplemental alpha-amylase concentration (0, 580, or 1,160 DU/kg of DM). Alpha-amylase supplementation increased DMI (P = 0.05) and ADG (P = 0.03) during the initial 28 d on feed and carcass-adjusted ADG (P = 0.04) across corn processing methods. Longissimus muscle area was greatest (quadratic effect, P = 0.04), and yield grade was least (quadratic effect, P = 0.02) in heifers fed 580 DU of alpha-amylase/kg of DM across corn processing methods. In Exp. 3, 56 crossbred steers were used in a randomized complete block design to evaluate the effects of supplemental alpha-amylase (930 DU/kg of DM) on performance when DMI was restricted to yield a programmed ADG. Alpha-amylase supplementation did not affect performance when DMI was restricted. We conclude that dietary alpha-amylase supplementation of finishing beef diets may result in

  13. A Quantitative Electrochemiluminescence Assay for Clostridium perfringens alpha toxin

    National Research Council Canada - National Science Library

    Merrill, Gerald A; Rivera, Victor R; Neal, Dwayne D; Young, Charles; Poli, Mark A

    2006-01-01

    .... Biotinylated antibodies to C. perfringens alpha toxin bound to streptavidin paramagnetic beads specifically immunoadsorbed soluble sample alpha toxin which subsequently selectively immunoadsorbed ruthenium (Ru...

  14. Structure-activity relationship of 9-methylstreptimidone, a compound that induces apoptosis selectively in adult T-cell leukemia cells.

    Science.gov (United States)

    Takeiri, Masatoshi; Ota, Eisuke; Nishiyama, Shigeru; Kiyota, Hiromasa; Umezawa, Kazuo

    2012-01-01

    We previously reported that 9-methylstreptimidone, a piperidine compound isolated from a culture filtrate of Streptomyces, induces apoptosis selectively in adult T-cell leukemia cells. It was screened for a compound that inhibits LPS-induced NF-kappaB and NO production in mouse macrophages. However, 9-methystreptimidone is poorly obtained from the producing microorganism and difficult to synthesize. Therefore, in the present research, we studied the structure-activity relationship to look for new selective inhibitors. We found that the structure of the unsaturated hydrophobic portion of 9-methylstreptimidone was essential for the inhibition of LPS-induced NO production. Among the 9-methylstreptimidone-related compounds tested, (+/-)-4,alpha-diepi-streptovitacin A inhibited NO production in macrophage-like cells as potently as 9-methylstreptimidone and without cellular toxicity. Moreover, this compound selectively induced apoptosis in adult T-cell leukemia MT-1 cells.

  15. Communication activities for NUMO's site selection process

    International Nuclear Information System (INIS)

    Takeuchi, Mitsuo; Okuyama, Shigeru; Kitayama, Kazumi; Kuba, Michiyoshi

    2004-01-01

    A siting program for geological disposal of high-level radioactive waste (HLW) in Japan has just started and is moving into a new stage of communication with the public. A final repository site will be selected via a stepwise process, as stipulated in the Specified Radioactive Waste Final Disposal Act promulgated in June 2000. Based on the Act, the site selection process of the Nuclear Waste Management Organization of Japan (NUMO, established in October 2000) will be carried out in the three steps: selection of Preliminary Investigation Areas (PIAs), selection of Detailed Investigation Areas (DIAs) and selection of the Repository Site. The Act also defines NUMO's responsibilities in terms of implementing the HLW disposal program in an open and transparent manner. NUMO fully understands the importance of public participation in its activities and is aiming to promote public involvement in the process of site selection based on a fundamental policy, which consists of 'adopting a stepwise approach', 'respecting the initiative of municipalities' and 'ensuring transparency in information disclosure'. This policy is clearly reflected in the adoption of an open solicitation approach for volunteer municipalities for Preliminary Investigation Areas (PIAs). NUMO made the official announcement of the start of its open solicitation program on 19 December 2002. This paper outlines how NUMO's activities are currently carried out with a view to encouraging municipalities to volunteer as PIAs and how public awareness of the safety of the HLW disposal is evaluated at this stage

  16. Activity modes selection for project crashing through deterministic simulation

    Directory of Open Access Journals (Sweden)

    Ashok Mohanty

    2011-12-01

    Full Text Available Purpose: The time-cost trade-off problem addressed by CPM-based analytical approaches, assume unlimited resources and the existence of a continuous time-cost function. However, given the discrete nature of most resources, the activities can often be crashed only stepwise. Activity crashing for discrete time-cost function is also known as the activity modes selection problem in the project management. This problem is known to be NP-hard. Sophisticated optimization techniques such as Dynamic Programming, Integer Programming, Genetic Algorithm, Ant Colony Optimization have been used for finding efficient solution to activity modes selection problem. The paper presents a simple method that can provide efficient solution to activity modes selection problem for project crashing.Design/methodology/approach: Simulation based method implemented on electronic spreadsheet to determine activity modes for project crashing. The method is illustrated with the help of an example.Findings: The paper shows that a simple approach based on simple heuristic and deterministic simulation can give good result comparable to sophisticated optimization techniques.Research limitations/implications: The simulation based crashing method presented in this paper is developed to return satisfactory solutions but not necessarily an optimal solution.Practical implications: The use of spreadsheets for solving the Management Science and Operations Research problems make the techniques more accessible to practitioners. Spreadsheets provide a natural interface for model building, are easy to use in terms of inputs, solutions and report generation, and allow users to perform what-if analysis.Originality/value: The paper presents the application of simulation implemented on a spreadsheet to determine efficient solution to discrete time cost tradeoff problem.

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

  18. Microglia acquire distinct activation profiles depending on the degree of alpha-synuclein neuropathology in a rAAV based model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Vanesa Sanchez-Guajardo

    Full Text Available Post-mortem analysis of brains from Parkinson's disease (PD patients strongly supports microglia activation and adaptive immunity as factors contributing to disease progression. Such responses may be triggered by alpha-synuclein (alpha-syn, which is known to be the main constituent of the aggregated proteins found in Lewy bodies in the brains of PD patients. To investigate this we used a recombinant viral vector to express human alpha-syn in rat midbrain at levels that induced neuronal pathology either in the absence or the presence of dopaminergic cell death, thereby mimicking early or late stages of the disease. Microglia activation was assessed by stereological quantification of Mac1+ cells, as well as the expression patterns of CD68 and MCH II. In our study, when alpha-syn induced neuronal pathology but not cell death, a fast transient increase in microglia cell numbers resulted in the long-term induction of MHC II+ microglia, denoting antigen-presenting ability. On the other hand, when alpha-syn induced both neuronal pathology and cell death, there was a delayed increase in microglia cell numbers, which correlated with long-lasting CD68 expression and a morphology reminiscent of peripheral macrophages. In addition T-lymphocyte infiltration, as judged by the presence of CD4+ and CD8+ cells, showed distinct kinetics depending on the degree of neurodegeneration, and was significantly higher when cell death occurred. We have thus for the first time shown that the microglial response differs depending on whether alpha-syn expression results on cell death or not, suggesting that microglia may play different roles during disease progression. Furthermore, our data suggest that the microglial response is modulated by early events related to alpha-syn expression in substantia nigra and persists at the long term.

  19. Effect of the glass transition temperature on alpha-amylase activity in a starch matrix.

    Science.gov (United States)

    Chaudhary, Vinita; Panyoyai, Naksit; Small, Darryl M; Shanks, Robert A; Kasapis, Stefan

    2017-02-10

    This study optimises a protocol for the estimation of α-amylase activity in a condensed starch matrix in the vicinity of the glass transition region. Enzymatic activity on the vitrified starch system was compared with that of a reference substrate, maltodextrin. The activity was assayed as the rate of release of reducing sugar using a dinitrosalicylic acid procedure. The condensed carbohydrate matrices served the dual purpose of acting as a substrate as well as producing a pronounced effect on the ability to enzymatic hydrolysis. Activation energies were estimated throughout the glass transition region of condensed carbohydrate preparations based on the concept of the spectroscopic shift factor. Results were used to demonstrate a considerable moderation by the mechanical glass transition temperature, beyond the expected linear effect of the temperature dependence, on the reaction rate of starch hydrolysis by α-amylase in comparison with the low-molecular weight chain of maltodextrin. Copyright © 2016. Published by Elsevier Ltd.

  20. PPARgamma-PGC-1alpha activity is determinant of alcohol related breast cancer

    DEFF Research Database (Denmark)

    Koefoed Petersen, Rasmus; Benzon Larsen, Signe; Jensen, Ditte Marie

    2012-01-01

    Alcohol is a risk factor for postmenopausal breast cancer. One of several proposed mechanisms is that alcohol-related breast cancer is caused by increased sex hormone levels. PPARγ inhibits aromatase transcription in breast adipocytes. We reproduced previously found allele-specific effects...... of the wildtype Pro-allele of PPARG Pro12Ala in alcohol related breast cancer. In transiently transfected cells, transcriptional activation by PPARγ and the PPARγ-PGC-1α complex was inhibited by ethanol. PPARγ 12Ala-mediated transcription activation was not enhanced by PGC-1α, resulting in allele......-specific transcription activation by the PPARγ 12Pro-PGC-1α complex. Our results suggest that PPARγ and PGC-1α activity is an important determinant of alcohol related breast cancer....

  1. Selecting activated carbon for water and wastewater treatability studies

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, W.; Chang, Q.G.; Liu, W.D.; Li, B.J.; Jiang, W.X.; Fu, L.J.; Ying, W.C. [East China University of Chemical Technology, Shanghai (China)

    2007-10-15

    A series of follow-up investigations were performed to produce data for improving the four-indicator carbon selection method that we developed to identify high-potential activated carbons effective for removing specific organic water pollutants. The carbon's pore structure and surface chemistry are dependent on the raw material and the activation process. Coconut carbons have relatively more small pores than large pores; coal and apricot nutshell/walnut shell fruit carbons have the desirable pore structures for removing adsorbates of all sizes. Chemical activation, excessive activation, and/or thermal reactivation enlarge small pores, resulting in reduced phenol number and higher tannic acid number. Activated carbon's phenol, iodine, methylene blue, and tannic acid numbers are convenient indicators of its surface area and pore volume of pore diameters < 10, 10-15, 15-28, and > 28 angstrom, respectively. The phenol number of a carbon is also a good indicator of its surface acidity of oxygen-containing organic functional groups that affect the adsorptive capacity for aromatic and other small polar organics. The tannic acid number is an indicator of carbon's capacity for large, high-molecular-weight natural organic precursors of disinfection by-products in water treatment. The experimental results for removing nitrobenzene, methyl-tert-butyl ether, 4,4-bisphenol, humic acid, and the organic constituents of a biologically treated coking-plant effluent have demonstrated the effectiveness of this capacity-indicator-based method of carbon selection.

  2. 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.

  3. Selective T-cell Ablation with Bismuth-213 Labeled Anti-TCR Alpha Beta as Nonmyeloablative Conditioning for Allogeneic Canine Marrow Transplantion

    International Nuclear Information System (INIS)

    Bethge, W. A.; Wilbur, D. Scott; Storb, R.; Hamlin, Donald K.; Santos, E. B.; Brechbiel, M. W.; Fisher, Darrell R.; Sandmaier, B. M.

    2003-01-01

    Two major immunological barriers, the host versus graft (HVG) and the graft versus host (GVH) reaction, must be overcome for successful allogeneic hematopoietic stem cell transplantation. T-cells are involved in these barriers in the major histocompatibility complex-identical settings. We hypothesized that selective ablation of T-cells using radioimmunotherapy, together with postgrafting immunosuppression, would ensure stable allogeneic engraftment. We developed a canine model of nonmyeloablative marrow transplantation in which host immune reactions are impaired by a single dose of 2 Gy total body irradiation (TBI), and where both GVH and residual HVG reactions are controlled by postgrafting immunosuppression with mycophenolate mofetil (MMF) and cyclosporine (CSP). We substituted the alpha-emitter bismuth-213 linked to a monoclonal antibody against TCR(alpha,beta)using the metal-binding chelate CHX-A-DTPA, for 2 Gy TBI. Biodistribution studies using a gamma-emitting indium-111-labeled anti-TCR mAb showed uptake primarily in blood, marrow, lymph nodes, spleen and liver. In a dosimetry study, 4 dogs were treated with 0.13-0.46 mg/kg TCR mAb labeled with 3.7-5.6 mCi/kg (137-207 MBq/kg) Bi-213. The treatment was administered in 6 injections on days -3 and -2 followed by transplantion of dog leukocyte antigen-identical marrow on day 0 and postgrafting immunosuppression with MMF and CSP. Therapy was well tolerated except for elevations of transaminases, which were transient in all but one dog. No other organ toxicities or signs of graft-versus-host-disease were noted. The dogs had prompt allogeneic hematopoietic engraftment and achieved stable mixed donor-host hematopoietic chimerism with donor contributions ranging from 5-55 % with >30 weeks follow up

  4. Selective T-cell Ablation with Bismuth-213 Labeled Anti-TCR Alpha Beta as Nonmyeloablative Conditionaing for Allogeneic Canine Marrow Transplantion

    Energy Technology Data Exchange (ETDEWEB)

    Bethge, W. A.; Wilbur, D. Scott; Storb, R.; Hamlin, Donald K.; Santos, E. B.; Brechbiel, M. W.; Fisher, Darrell R.; Sandmaier, B. M.

    2003-06-15

    Two major immunological barriers, the host versus graft (HVG) and the graft versus host (GVH) reaction, must be overcome for successful allogeneic hematopoietic stem cell transplantation. T-cells are involved in these barriers in the major histocompatibility complex-identical settings. We hypothesized that selective ablation of T-cells using radioimmunotherapy, together with postgrafting immunosuppression, would ensure stable allogeneic engraftment. We developed a canine model of nonmyeloablative marrow transplantation in which host immune reactions are impaired by a single dose of 2 Gy total body irradiation (TBI), and where both GVH and residual HVG reactions are controlled by postgrafting immunosuppression with mycophenolate mofetil (MMF) and cyclosporine (CSP). We substituted the alpha-emitter bismuth-213 linked to a monoclonal antibody against TCR(alpha,beta)using the metal-binding chelate CHX-A”-DTPA, for 2 Gy TBI. Biodistribution studies using a gamma-emitting indium-111-labeled anti-TCR mAb showed uptake primarily in blood, marrow, lymph nodes, spleen and liver. In a dosimetry study, 4 dogs were treated with 0.13-0.46 mg/kg TCR mAb labeled with 3.7-5.6 mCi/kg (137-207 MBq/kg) Bi-213. The treatment was administered in 6 injections on days -3 and -2 followed by transplantion of dog leukocyte antigen-identical marrow on day 0 and postgrafting immunosuppression with MMF and CSP. Therapy was well tolerated except for elevations of transaminases, which were transient in all but one dog. No other organ toxicities or signs of graft-versus-host-disease were noted. The dogs had prompt allogeneic hematopoietic engraftment and achieved stable mixed donor-host hematopoietic chimerism with donor contributions ranging from 5-55 % with >30 weeks follow up.

  5. UK equity mutual fund alphas make a comeback

    OpenAIRE

    Mateus, Irina B.; Mateus, Cesario; Todorovic, Natasa

    2016-01-01

    In this study, we re-visit the performance of 887 active UK equity mutual funds using a new approach proposed by Angelidis, Giamouridis, and Tessaromatis. The authors argue that mutual funds stock selection is driven by the benchmark index, so if the benchmark generates alpha, there will be a bias in interpretation of manager's stock-picking ability. In their model, the alpha of a fund is adjusted by the benchmark's alpha. By applying this method, we eliminate bias inflicted by the persistent...

  6. Real-time fMRI neurofeedback of the mediodorsal and anterior thalamus enhances correlation between thalamic BOLD activity and alpha EEG rhythm.

    Science.gov (United States)

    Zotev, Vadim; Misaki, Masaya; Phillips, Raquel; Wong, Chung Ki; Bodurka, Jerzy

    2018-02-01

    Real-time fMRI neurofeedback (rtfMRI-nf) with simultaneous EEG allows volitional modulation of BOLD activity of target brain regions and investigation of related electrophysiological activity. We applied this approach to study correlations between thalamic BOLD activity and alpha EEG rhythm. Healthy volunteers in the experimental group (EG, n = 15) learned to upregulate BOLD activity of the target region consisting of the mediodorsal (MD) and anterior (AN) thalamic nuclei using rtfMRI-nf during retrieval of happy autobiographical memories. Healthy subjects in the control group (CG, n = 14) were provided with a sham feedback. The EG participants were able to significantly increase BOLD activities of the MD and AN. Functional connectivity between the MD and the inferior precuneus was significantly enhanced during the rtfMRI-nf task. Average individual changes in the occipital alpha EEG power significantly correlated with the average MD BOLD activity levels for the EG. Temporal correlations between the occipital alpha EEG power and BOLD activities of the MD and AN were significantly enhanced, during the rtfMRI-nf task, for the EG compared to the CG. Temporal correlations with the alpha power were also significantly enhanced for the posterior nodes of the default mode network, including the precuneus/posterior cingulate, and for the dorsal striatum. Our findings suggest that the temporal correlation between the MD BOLD activity and posterior alpha EEG power is modulated by the interaction between the MD and the inferior precuneus, reflected in their functional connectivity. Our results demonstrate the potential of the rtfMRI-nf with simultaneous EEG for noninvasive neuromodulation studies of human brain function. © 2017 Wiley Periodicals, Inc.

  7. Interferon-alpha administration enhances CD8+ T cell activation in HIV infection.

    Directory of Open Access Journals (Sweden)

    Maura Manion

    Full Text Available Type I interferons play important roles in innate immune defense. In HIV infection, type I interferons may delay disease progression by inhibiting viral replication while at the same time accelerating disease progression by contributing to chronic immune activation.To investigate the effects of type I interferons in HIV-infection, we obtained cryopreserved peripheral blood mononuclear cell samples from 10 subjects who participated in AIDS Clinical Trials Group Study 5192, a trial investigating the activity of systemic administration of IFNα for twelve weeks to patients with untreated HIV infection. Using flow cytometry, we examined changes in cell cycle status and expression of activation antigens by circulating T cells and their maturation subsets before, during and after IFNα treatment.The proportion of CD38+HLA-DR+CD8+ T cells increased from a mean of 11.7% at baseline to 24.1% after twelve weeks of interferon treatment (p = 0.006. These frequencies dropped to an average of 20.1% six weeks after the end of treatment. In contrast to CD8+ T cells, the frequencies of activated CD4+ T cells did not change with administration of type I interferon (mean percentage of CD38+DR+ cells = 2.62% at baseline and 2.17% after 12 weeks of interferon therapy. As plasma HIV levels fell with interferon therapy, this was correlated with a "paradoxical" increase in CD8+ T cell activation (p<0.001.Administration of type I interferon increased expression of the activation markers CD38 and HLA DR on CD8+ T cells but not on CD4+ T cells of HIV+ persons. These observations suggest that type I interferons may contribute to the high levels of CD8+ T cell activation that occur during HIV infection.

  8. 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

    . Phosphorylation had returned to resting levels at 3 h of exercise only in the control trial. Thus, an inverse association between PDH-E1a phosphorylation and PDHa activity exists. Short-term elevation in plasma FFA at rest increases PDH-E1a phosphorylation, but exercise overrules this effect of FFA on PDH-E1a...... extensor exercise at moderate intensity. During the 4-h resting period, activity of PDH in the active form (PDHa) did not change in either trial, yet phosphorylation of PDH-E1a site 1 (PDH-P1) and site 2 (PDH-P2) was elevated in the intralipid compared with the control trial. PDHa activity increased during...... exercise similarly in the two trials. After 3 h of exercise, PDHa activity remained elevated in the intralipid trial but returned to resting levels in the control trial. Accordingly, in both trials PDH-P1 and PDH-P2 decreased during exercise, and the decrease was more marked during intralipid infusion...

  9. Predominant alpha2/beta2/gamma3 AMPK activation during exercise in human skeletal muscle

    DEFF Research Database (Denmark)

    Birk, Jesper Bratz; Wojtaszewski, Jørgen

    2006-01-01

    -Thr-172 AMPK phosphorylation (r2 = 0.84, P important actor in exercise-regulated AMPK signalling in human skeletal muscle, probably mediating phosphorylation of ACCß.......5'AMP-activated protein kinase (AMPK) is a key regulator of cellular metabolism and is regulated in muscle during exercise. We have previously established that only three of 12 possible AMPK a/ß/¿-heterotrimers are present in human skeletal muscle. Previous studies describe discrepancies between...... total AMPK activity and regulation of its target acetyl-CoA-carboxylase (ACC)ß. Also, exercise training decreases expression of the regulatory ¿3 AMPK subunit and attenuates a2 AMPK activity during exercise. We hypothesize that these observations reflect a differential regulation of the AMPK...

  10. The radiological evaluation of a prototype posting-in hatch under conditions of high alpha activity

    International Nuclear Information System (INIS)

    Smith, D.I.; Hollick, R.C.

    1987-07-01

    A prototype posting-in hatch, mounted vertically in the top panel of a highly active glovebox has been radiologically evaluated in the Fuels Laboratory, AEEW. This simple, air-lock type system of 100 mm diameter has pneumatically operated and interlocked lids and a low velocity, inward purge, supplied by the glovebox depression. The hatch proved extremely reliable and very easy to operate. More than 1200 simulated posting movements were carried out and a > 8 order of magnitude reduction in aerosol concentration was recorded from the active glovebox to the monitoring environment. (author)

  11. Synthesis and evaluation of alpha-[[(2-haloethyl)amino]methyl]-2- nitro-1H-imidazole-1-ethanols as prodrugs of alpha-[(1-aziridinyl)methyl]-2- nitro-1H-imidazole-1-ethanol (RSU-1069) and its analogues which are radiosensitizers and bioreductively activated cytotoxins

    International Nuclear Information System (INIS)

    Jenkins, T.C.; Naylor, M.A.; O'Neill, P.; Threadgill, M.D.; Cole, S.; Stratford, I.J.; Adams, G.E.; Fielden, E.M.; Suto, M.J.; Stier, M.A.

    1990-01-01

    alpha-[(1-Aziridinyl)methyl]-2-nitro-1H-imidazole-1-ethanols, of general formula ImCH2CH(OH)CH2NCR1R2CR3R4, where Im = 2-nitroimidazole and R1, R2, R3, R4 = H, Me, are radiosensitizers and selective bioreductively activated cytotoxins toward hypoxic tumor cells in vitro and in vivo. Treatment of the aziridines with hydrogen halide in acetone or aqueous acetone gave the corresponding 2-haloethylamines of general formula ImCH2CH(OH)CH2(+)-NH2CR1R2CR3R4X X-, where R1, R2, R3, R4 = H, Me, and X = F, Cl, Br, I. These 2-haloethylamines were evaluated as prodrugs of the parent aziridines. The rates of ring closure in aqueous solution at pH approximately 6 were found to increase with increasing methyl substitution and to depend on the nature of the leaving group (I approximately Br greater than Cl much greater than F). A competing reaction of ImCH2CH(OH)CH2+NH2CH2CH2X X- (X = Cl, Br) with aqueous HCO3- ions gives 3-[2-hyroxy-3-(2-nitro-1H-imidazol-1-yl)propyl]-2-oxazolidinone. The activities of these prodrugs as radiosensitizers or as bioreductively activated cytotoxins were consistent with the proportion converted to the parent aziridine during the course of the experiment. alpha-[[(2-Bromoethyl)amino]methyl]-2-nitro-1H-imidazole-1- ethanol (RB 6145, 10), the prodrug of alpha-[(1-aziridinyl)methyl]-2-nitro-1H-imidazole-1-ethanol (RSU-1069, 3), is identified as the most useful compound in terms of biological activity and rate of ring closure under physiological conditions

  12. Screening of selected indigenous plants of Cambodia for antiplasmodial activity.

    Science.gov (United States)

    Hout, Sotheara; Chea, Aun; Bun, Sok-Siya; Elias, Riad; Gasquet, Monique; Timon-David, Pierre; Balansard, Guy; Azas, Nadine

    2006-08-11

    The in vitro antiplasmodial activity of 117 aqueous, methanol and dichloromethane extracts derived from different parts of 28 indigenous wild plant species was studied. These plants are commonly used in Cambodian traditional medicine. The plant extracts were tested for in vitro activity against a chloroquine resistant Plasmodium falciparum strain (W2). Nine extracts were moderately active with IC(50) values ranging between 5 and 10 microg/ml, 17 extracts were active with IC(50) values ranging between 1 and 5 microg/ml. These 26 extracts derived from eight plants belong to six families. The most active extracts were dichloromethane and came from Stephania rotunda and Brucea javanica with IC(50) values of 1 microg/ml and a selectivity index > or = 25. It is interesting to note that some aqueous extracts were as active as dichloromethane extracts especially aqueous extracts of Stephania rotunda, Brucea javanica, Phyllanthus urinaria and Eurycoma longifolia with IC(50) values of uses of these plants for the treatment of malaria and/or fever. In this study, we report the antiplasmodial potential activity of eight plant species from Cambodia. Among them four are tested for the first time.

  13. The Determination of Thorium Contents in Urine With Neutron Activation Analysis and Alpha Spectrometry

    International Nuclear Information System (INIS)

    Mukh-Syaifudin

    2007-01-01

    Internal contamination by a radionuclide that entered into body through inhalation is most conveniently determined by using urine as sample. The aim of this research was developing a fast and simple method to determine thorium content in urine. The method was based on comparison of the activities between the sample added with and without standard thorium. Urine sample was divided into two parts, one of which was added with Th-232 standard, and then both were simultaneously proceed which was consist of decomposition of organic materials, precipitation of thorium by adding ammonium hydroxide, wash with aquadest, and then dissolution in nitric acid. The solution was then activated for 15 minutes with neutron flux of 10 12 ncm -2 second -1 and the activated product was co-precipitated two times with lanthanum carrier and sodium chloride by addition of ammonium hydroxide. Finally, the precipitate was dissolved in nitric acid and the gamma emission of Th-233 was analyzed with gamma spectrometry. The results of analysis showed that the concentration of four urine samples analyzed was below detection limit (BDL); 200.40; 273.88 and 22.03 pg/l, respectively. With the simple procedure, neutron activation analysis can be used in the determining the actinide contents in several types of biological sample. (author)

  14. Melatonin suppresses activation of hepatic stellate cells through ROR alpha-mediated inhibition of 5-lipoxygenase

    NARCIS (Netherlands)

    Shajari, Shiva; Laliena, Almudena; Heegsma, Janette; Jesus Tunon, Maria; Moshage, Han; Faber, Klaas Nico

    2015-01-01

    Liver fibrosis is scar tissue resulting from an uncontrolled wound-healing process in response to chronic liver injury. Liver damage generates an inflammatory reaction that activates hepatic stellate cells (HSC) that transdifferentiate from quiescent cells that control retinol metabolism to

  15. Solvated States of Poly-L-alanine alpha-Helix Explored by Raman Optical Activity

    Czech Academy of Sciences Publication Activity Database

    Yamamoto, S.; Furukawa, T.; Bouř, Petr; Ozaki, Y.

    2014-01-01

    Roč. 118, č. 20 (2014), s. 3655-3662 ISSN 1089-5639 R&D Projects: GA ČR GAP208/11/0105 Grant - others:AV ČR(CZ) M200550902 Institutional support: RVO:61388963 Keywords : molecular property tensors * nuclear magnetic resonance * activity spectra Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.693, year: 2014

  16. Transcriptome profiling reveals bisphenol A alternatives activate estrogen receptor alpha in human breast cancer cells

    Science.gov (United States)

    Plasticizers with estrogenic activity, such as bisphenol A (BPA), have potential adverse health effects in humans. Due to mounting evidence of these health effects, BPA is being phased out and replaced by other bisphenol variants in “BPA-free” products. We have compared estrogeni...

  17. In-vitro alpha amylase inhibitory activity of the leaf extracts of Adenanthera pavonina.

    Science.gov (United States)

    Wickramaratne, M Nirmali; Punchihewa, J C; Wickramaratne, D B M

    2016-11-15

    Diabetes has caused a major burden to the health sector in the developing countries and has shown an increasing trend among the urban population. It is estimated that most patients are with type II diabetes which could be easily treated with dietary changes, exercise, and medication. Sri Lanka carries a long history ayurvedic medicine where it uses the plant for treating many diseases. Therefore it is important to screen medicinal plants scientifically so they could be used safely and effectively in the traditional medical system and also be used for further investigations. Adenanthera pavonina is a plant used in the Ayurvedic medical system in Sri Lanka for treating many diseases including diabetics. We evaluated the anti-diabetic properties and the antioxidant properties of Adenanthera pavonina leaves. The methanol extract of the leaves was sequentially extracted with petroleum ether and thereafter was partitioned between EtOAc, and water. The α-amylase inhibition assay was performed using the 3,5- dinitrosalicylic acid method. The antioxidant activities were measured using the DPPH free radical scavenging activity and the total phenolic content using Folin-Ciocalteu's reagent. The cytotoxicity of the extract was evaluated using the Brine shrimp bioassay. The IC 50 values of α amylase inhibitory activity of MeOH, EtOAc, petroleum ether, and water were 16.16 ± 2.23, 59.93 ± 0.25, 145.49 ± 4.86 and 214.85 ± 9.72 μg/ml respectively and was similar to that of Acarbose (18.63 ± 1.21 (μg/ml). Antioxidant activities were also determined and the EtOAc fraction showed the highest total phenolic content (34. 62 ± 1.14 mg/g extract) and the highest DPPH scavenging activity with an IC 50 of 249.92 ± 3.35 μg/ml. The leaf extracts of Adenanthera pavonina exhibit remarkable α-amylase inhibitory activity in the crude methanolic extract. Hence leaves of Adenanthera pavonina has a potential to be used as a regular green vegetable and

  18. Habitat Selection and Activity Pattern of GPS Collared Sumateran Tigers

    Directory of Open Access Journals (Sweden)

    Dolly Priatna

    2012-12-01

    Full Text Available Although translocation has been used in mitigating human-carnivore conflict for decades, few studies have been conducted on the behavioral ecology of released animals. Such information is necessary in the context of sustainable forest management. In this study we determine the type of land cover used as main habitat and examine the activity pattern of translocated tigers. Between 2008 and 2010 we captured six conflict tigers and translocated them 74-1,350 km from their capture sites in Sumatera. All tigers were fitted with global positioning system (GPS collars. The collars were set to fix 24-48 location coordinates per day.  All translocated tigers showed a preference for a certain habitat type within their new home range, and tended to select the majority of natural land cover type within the landscape as their main habitat, but the availability of natural forest habitat within the landscape remains essensial for their survival. The activity of male translocated tigers differed significantly between the six time intervals of 24 hours, and their most active periods were in the afternoon (14:00-18:00 hours and in the evening (18:00-22:00 hours. Despite being preliminary, the findings of this study-which was the first such study conducted in Sumatera-highlight the conservation value of tiger translocation and provide valuable information for improving future management of conflict tigers.Keywords: activity pattern, GPS collars, habitat selection, sumateran tiger, translocation

  19. Pharmacologically relevant receptor binding characteristics and 5alpha-reductase inhibitory activity of free Fatty acids contained in saw palmetto extract.

    Science.gov (United States)

    Abe, Masayuki; Ito, Yoshihiko; Oyunzul, Luvsandorj; Oki-Fujino, Tomomi; Yamada, Shizuo

    2009-04-01

    Saw palmetto extract (SPE), used widely for the treatment of benign prostatic hyperplasia (BPH) has been shown to bind alpha(1)-adrenergic, muscarinic and 1,4-dihydropyridine (1,4-DHP) calcium channel antagonist receptors. Major constituents of SPE are lauric acid, oleic acid, myristic acid, palmitic acid and linoleic acid. The aim of this study was to investigate binding affinities of these fatty acids for pharmacologically relevant (alpha(1)-adrenergic, muscarinic and 1,4-DHP) receptors. The fatty acids inhibited specific [(3)H]prazosin binding in rat brain in a concentration-dependent manner with IC(50) values of 23.8 to 136 microg/ml, and specific (+)-[(3)H]PN 200-110 binding with IC(50) values of 24.5 to 79.5 microg/ml. Also, lauric acid, oleic acid, myristic acid and linoleic acid inhibited specific [(3)H]N-methylscopolamine ([(3)H]NMS) binding in rat brain with IC(50) values of 56.4 to 169 microg/ml. Palmitic acid had no effect on specific [(3)H]NMS binding. The affinity of oleic acid, myristic acid and linoleic acid for each receptor was greater than the affinity of SPE. Scatchard analysis revealed that oleic acid and lauric acid caused a significant decrease in the maximal number of binding sites (B(max)) for [(3)H]prazosin, [(3)H]NMS and (+)-[(3)H]PN 200-110. The results suggest that lauric acid and oleic acid bind noncompetitively to alpha(1)-adrenergic, muscarinic and 1,4-DHP calcium channel antagonist receptors. We developed a novel and convenient method of determining 5alpha-reductase activity using LC/MS. With this method, SPE was shown to inhibit 5alpha-reductase activity in rat liver with an IC(50) of 101 microg/ml. Similarly, all the fatty acids except palmitic acid inhibited 5alpha-reductase activity, with IC(50) values of 42.1 to 67.6 microg/ml. In conclusion, lauric acid, oleic acid, myristic acid, and linoleic acid, major constituents of SPE, exerted binding activities of alpha(1)-adrenergic, muscarinic and 1,4-DHP receptors and inhibited 5

  20. Evaluation of estrogen receptor alpha activation by glyphosate-based herbicide constituents.

    Science.gov (United States)

    Mesnage, Robin; Phedonos, Alexia; Biserni, Martina; Arno, Matthew; Balu, Sucharitha; Corton, J Christopher; Ugarte, Ricardo; Antoniou, Michael N

    2017-10-01

    The safety, including the endocrine disruptive capability, of glyphosate-based herbicides (GBHs) is a matter of intense debate. We evaluated the estrogenic potential of glyphosate, commercial GBHs and polyethoxylated tallowamine adjuvants present as co-formulants in GBHs. Glyphosate (≥10,000 μg/L or 59 μM) promoted proliferation of estrogen-dependent MCF-7 human breast cancer cells. Glyphosate also increased the expression of an estrogen response element-luciferase reporter gene (ERE-luc) in T47D-KBluc cells, which was blocked by the estrogen antagonist ICI 182,780. Commercial GBH formulations or their adjuvants alone did not exhibit estrogenic effects in either assay. Transcriptomics analysis of MCF-7 cells treated with glyphosate revealed changes in gene expression reflective of hormone-induced cell proliferation but did not overlap with an ERα gene expression biomarker. Calculation of glyphosate binding energy to ERα predicts a weak and unstable interaction (-4.10 kcal mol -1 ) compared to estradiol (-25.79 kcal mol -1 ), which suggests that activation of this receptor by glyphosate is via a ligand-independent mechanism. Induction of ERE-luc expression by the PKA signalling activator IBMX shows that ERE-luc is responsive to ligand-independent activation, suggesting a possible mechanism of glyphosate-mediated activation. Our study reveals that glyphosate, but not other components present in GBHs, can activate ERα in vitro, albeit at relatively high concentrations. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Measurement of the absolute activity of alpha or beta emitters by measuring product nuclei (daughter) activity increase or by studing its radioactive decay

    International Nuclear Information System (INIS)

    Campos, L.C. de.

    1981-01-01

    A new method for determining absolute activity of alpha or beta emitters by measuring daughter product radioactive decay is presented. The separation method of UX from hexahydrated uranyl nitrate UO 2 (NO 3 ) 2 6H 2 O based on its dissolution in ethyl ether is described and the accuracy of this method is shown. The factors which accuate on total efficiency of a Geiger Mueller detector for beta particles are determined. The possibility to determine the mass of precursor element by daughter nuclei activity is shown. The results are compared with the one obtained by direct measurement of the mass (or number of atoms) of precursor radioactive substance and with theoretical values calculated for isotopes in secular equilibrium. (Author) [pt

  2. Selection of Activities in Dynamic Business Process Simulation

    Directory of Open Access Journals (Sweden)

    Toma Rusinaitė

    2016-06-01

    Full Text Available Maintaining dynamicity of business processes is one of the core issues of today's business as it enables businesses to adapt to constantly changing environment. Upon changing the processes, it is vital to assess possible impact, which is achieved by using simulation of dynamic processes. In order to implement dynamicity in business processes, it is necessary to have an ability to change components of the process (a set of activities, a content of activity, a set of activity sequences, a set of rules, performers and resources or dynamically select them during execution. This problem attracted attention of researches over the past few years; however, there is no proposed solution, which ensures the business process (BP dynamicity. This paper proposes and specifies dynamic business process (DBP simulation model, which satisfies all of the formulated DBP requirements.

  3. Triclocarban mediates induction of xenobiotic metabolism through activation of the constitutive androstane receptor and the estrogen receptor alpha.

    Directory of Open Access Journals (Sweden)

    Mei-Fei Yueh

    Full Text Available Triclocarban (3,4,4'-trichlorocarbanilide, TCC is used as a broad-based antimicrobial agent that is commonly added to personal hygiene products. Because of its extensive use in the health care industry and resistance to degradation in sewage treatment processes, TCC has become a significant waste product that is found in numerous environmental compartments where humans and wildlife can be exposed. While TCC has been linked to a range of health and environmental effects, few studies have been conducted linking exposure to TCC and induction of xenobiotic metabolism through regulation by environmental sensors such as the nuclear xenobiotic receptors (XenoRs. To identify the ability of TCC to activate xenobiotic sensors, we monitored XenoR activities in response to TCC treatment using luciferase-based reporter assays. Among the XenoRs in the reporter screening assay, TCC promotes both constitutive androstane receptor (CAR and estrogen receptor alpha (ERα activities. TCC treatment to hUGT1 mice resulted in induction of the UGT1A genes in liver. This induction was dependent upon the constitutive active/androstane receptor (CAR because no induction occurred in hUGT1Car(-/- mice. Induction of the UGT1A genes by TCC corresponded with induction of Cyp2b10, another CAR target gene. TCC was demonstrated to be a phenobarbital-like activator of CAR in receptor-based assays. While it has been suggested that TCC be classified as an endocrine disruptor, it activates ERα leading to induction of Cyp1b1 in female ovaries as well as in promoter activity. Activation of ERα by TCC in receptor-based assays also promotes induction of human CYP2B6. These observations demonstrate that TCC activates nuclear xenobiotic receptors CAR and ERα both in vivo and in vitro and might have the potential to alter normal physiological homeostasis. Activation of these xenobiotic-sensing receptors amplifies gene expression profiles that might represent a mechanistic base for

  4. Effect of diclofenac alone or in combination with alpha-tocopherol on the oxidative activity of polymorphonuclear leukocytes in healthy and osteoartheritic individuals

    International Nuclear Information System (INIS)

    Al-Arfaj, Abdurahman S.; Alballa, Sulaiman R.; Mustafa, Ali A.; Al-Tuwajiri, Ali S.; Al-Humayyad, M.S.; Al-Dalaan, Abdullah N.

    2004-01-01

    To ivestigate the effects of diclofenac alone or when combined with alpha-tocopherol on the oxidative activity of polymorphonuclear leukocytes (PMNs) in healthy and osteoartheritic (OA) patients. The study was carried out at the College of Medicine, King Saud University, Riyadh, KIgdom of Saudi Arabia, over the period 1999 to 2000. 12 healthy controls and 12 osteoartheritic patients were recruited to the study. They were given diclofenac 50mg thricedaily orally, initially for 5 days then alpha-tocopherol at 200mg thrice daily orally, was added for another 5 days. Blood samples were drawn before the start of study and at 5 days following treatmentwith diclofenac alone and 10 days following treatment with diclophenac and alpha-tocopherol. Chemiluminescence (CL)reponse was measured for wohle blood and isolated (PMNs) on all samples. Diclofenac enhanced CL response of whole blood and PMNs of healthy controls when stimulated with phorbol myristate acetate (PMA) and opsonized zymosan (OPZ). Cotreatment with alpha-tocopherol resulted in no appreciable change in the CL response of whole blood when stimulated with PMA or OPZ but a further significant enhancement of CL response of isolated PMNs when these cells were stimulated by either PMA or OPZ. In osteoartheritic patients, diclofenac alone and when combined with alpha-tocopherol showed no significant change in CL response of the whole blood.The CL response of PMNs from OA patients was decreased by diclofenac alone. However the inhibitory effect was not observed when alpha-tocopherol was used together with diclofenac. The effect of diclofenac alone or in combination with alpha-tocopherol did not produce a consistent effect on the CL response of whole blood or isolated PMNs of healthy or osteoartheritic patients. (author)

  5. Inhibitory Effect of Capparis spinosa Extract on Pancreatic Alpha-Amylase Activity

    Directory of Open Access Journals (Sweden)

    Mostafa Selfayan

    2016-04-01

    Full Text Available Background Diabetes mellitus is a metabolic disorder characterized by high blood glucose level caused due to deficiency of insulin secretion or insulin function. The inhibition of carbohydrate hydrolyzing enzymes such as α-amylase can be an important strategy for decrease postprandial blood glucose level in patients with type II diabetes. Plants contains different chemical constituents with potential for inhibition of α-amylase and hence maybe used as therapeutic. Objectives The aim of the present study is to investigate the effect of the ethanolic extract of Capparis spinosa on pancreatic α-amylase activities to find out the relevance of the plant in controlling blood sugar. Materials and Methods In this experimental study, root and leaves of C. spinosa were tested for α-amylase inhibition. Different concentrations (1.56, 3.12, 6.25, 12.5 and 25 mg/mL of extracts were incubated with enzyme substrate solution and the spectrometric method used for measure enzyme activity. Also acarbose was used as the standard inhibitor. Results Both root and leaves extracts showed inhibition of α-amylase (root = 97.31% and leaves = 98.92%. The root and leaves extracts of C. spinosa exhibited appreciable α-amylase inhibitory activity with an IC50 values 5.93 mg/mL and 3.89 mg/mL respectively, when compared with acarbose (IC50 value 0.038 mg/mL. Conclusions This study supports that root and leaves extracts of C. spinosa exhibit considerable α-amylase inhibitory activities. These results could be useful for developing functional foods by combination of plant-based foods for treatment of diabetes mellitus.

  6. Increased renal alpha-epithelial sodium channel (ENAC) protein and increased ENAC activity in normal pregnancy.

    Science.gov (United States)

    West, Crystal; Zhang, Zheng; Ecker, Geoffrey; Masilamani, Shyama M E

    2010-11-01

    Pregnancy-mediated sodium (Na) retention is required to provide an increase in plasma volume for the growing fetus. The mechanisms responsible for this Na retention are not clear. We first used a targeted proteomics approach and found that there were no changes in the protein abundance compared with virgin rats of the β or γ ENaC, type 3 Na(+)/H(+) exchanger (NHE3), bumetanide-sensitive cotransporter (NKCC2), or NaCl cotransporter (NCC) in mid- or late pregnancy. In contrast, we observed marked increases in the abundance of the α-ENaC subunit. The plasma volume increased progressively during pregnancy with the greatest plasma volume being evident in late pregnancy. ENaC inhibition abolished the difference in plasma volume status between virgin and pregnant rats. To determine the in vivo activity of ENaC, we conducted in vivo studies of rats in late pregnancy (days 18-20) and virgin rats to measure the natriuretic response to ENaC blockade (with benzamil). The in vivo activity of ENaC (U(Na)V postbenzamil-U(Na)V postvehicle) was markedly increased in late pregnancy, and this difference was abolished by pretreatment with the mineralocorticoid receptor antagonist, eplerenone. These findings demonstrate that the increased α-ENaC subunit of pregnancy is associated with an mineralocorticoid-dependent increase in ENaC activity. Further, we show that ENaC activity is a major contributor of plasma volume status in late pregnancy. These changes are likely to contribute to the renal sodium retention and plasma volume expansion required for an optimal pregnancy.

  7. Fibroblast Activation Protein-Alpha, a Serine Protease that Facilitates Metastasis by Modification of Diverse Microenvironments

    Science.gov (United States)

    2011-10-01

    diabetes and hematopoietic stem cell engraftment [21]. Sitagliptin is a DPPIV inhibitor already approved for type 2 diabetes because it has...activation protein (FAP) in hepatitis C virus infection. Adv Exp Med Biol 524:235–243 12. Levy MT, McCaughan GW, Abbott CA, Park JE, Cunningham AM...kb ( Abbott et al., 1994). Three different splice variants of FAP have been observed in mouse embryonic tissues, with all three predicted to encode

  8. Experimental system using an active method for the measurement of low alpha emitter grades

    International Nuclear Information System (INIS)

    Bernard, P.; Cance, M.

    1986-06-01

    The diversity of waste produced in France, the limitations of passive neutron measurements, the new safety requirements in the field of low level waste disposal have induced us to develop active neutron techniques. Two experimental pulsed neutron interrogation systems are described giving a sensitivity lower than 10 mg Pu 239 in 200 l drums. This project is the result of a close cooperation between the CEA, SGN and SODERN

  9. Thorium: one of the analytical techniques in neutronic activation and alpha spectrometry of the CDTN (Brazilian Nuclear Technology Development Center) in the last three decades

    International Nuclear Information System (INIS)

    Menezes, M.A.B.C.; Sabino, C.V.S.

    1994-01-01

    For long years, the CDTN (Brazilian Nuclear Technology Development Center ) has applied several analytical techniques in the thorium determination. This work is about the evolution of the neutronic activation in the thorium 232 analysis from the 1960's to now. The importance of the analysis request and alpha spectrometry for the thorium 228 and thorium 232 determination is emphasized. (J.A.M.M.)

  10. Influence of storage period of gamma-irradiated seeds on the catalase activity and the sinthesis of alpha-amilase in maize

    International Nuclear Information System (INIS)

    Velichkov, D.; Antonov, M.; Spasov, S.

    1983-10-01

    It was established that irradiation of the maize hybrid Knezha 2L-611 seeds with the dose 5 Gy showed the most constant and the best expressed stimulation effect. The activity of catalase and synthesis of alpha-amylase showed that the most convenient time for sowing of seeds irradiated with 5 Gy was 2 days after the treatment

  11. Rhodocytin (aggretin) activates platelets lacking alpha(2)beta(1) integrin, glycoprotein VI, and the ligand-binding domain of glycoprotein Ibalpha

    DEFF Research Database (Denmark)

    Bergmeier, W; Bouvard, D; Eble, J A

    2001-01-01

    Although alpha(2)beta(1) integrin (glycoprotein Ia/IIa) has been established as a platelet collagen receptor, its role in collagen-induced platelet activation has been controversial. Recently, it has been demonstrated that rhodocytin (also termed aggretin), a snake venom toxin purified from the v...

  12. Interferon-alpha subtype 11 activates NK cells and enables control of retroviral infection.

    Directory of Open Access Journals (Sweden)

    Kathrin Gibbert

    Full Text Available The innate immune response mediated by cells such as natural killer (NK cells is critical for the rapid containment of virus replication and spread during acute infection. Here, we show that subtype 11 of the type I interferon (IFN family greatly potentiates the antiviral activity of NK cells during retroviral infection. Treatment of mice with IFN-α11 during Friend retrovirus infection (FV significantly reduced viral loads and resulted in long-term protection from virus-induced leukemia. The effect of IFN-α11 on NK cells was direct and signaled through the type I IFN receptor. Furthermore, IFN-α11-mediated activation of NK cells enabled cytolytic killing of FV-infected target cells via the exocytosis pathway. Depletion and adoptive transfer experiments illustrated that NK cells played a major role in successful IFN-α11 therapy. Additional experiments with Mouse Cytomegalovirus infections demonstrated that the therapeutic effect of IFN-α11 is not restricted to retroviruses. The type I IFN subtypes 2 and 5, which bind the same receptor as IFN-α11, did not elicit similar antiviral effects. These results demonstrate a unique and subtype-specific activation of NK cells by IFN-α11.

  13. Nitric oxide mediates angiogenesis induced in vivo by platelet-activating factor and tumor necrosis factor-alpha.

    Science.gov (United States)

    Montrucchio, G.; Lupia, E.; de Martino, A.; Battaglia, E.; Arese, M.; Tizzani, A.; Bussolino, F.; Camussi, G.

    1997-01-01

    We evaluated the role of an endogenous production of nitric oxide (NO) in the in vitro migration of endothelial cells and in the in vivo angiogenic response elicited by platelet-activating factor (PAF), tumor necrosis factor-alpha (TNF), and basic fibroblast growth factor (bFGF). The NO synthase inhibitor, N omega-nitro-L-arginine-methyl ester (L-NAME), but not its enantiomer D-NAME, prevented chemotaxis of endothelial cells induced in vitro by PAF and by TNF. The motogenic activity of TNF was also inhibited by WEB 2170, a specific PAF-receptor antagonist. In contrast, chemotaxis induced by bFGF was not prevented by L-NAME or by WEB 2170. Angiogenesis was studied in vivo in a murine model in which Matrigel was used as a vehicle for the delivery of mediators. In this model, the angiogenesis induced by PAF and TNF was inhibited by WEB 2170 and L-NAME but not by D-NAME. In contrast, angiogenesis induced by bFGF was not affected by L-NAME or by WEB 2170. TNF, but not bFGF, induced PAF synthesis within Matrigel. These results suggest that NO mediates the angiogenesis induced by PAF as well as that induced by TNF, which is dependent on the production of PAF. In contrast, the angiogenic effect of bFGF appears to be both PAF and NO independent. Images Figure 3 Figure 4 PMID:9250168

  14. Effect of 17alpha-ethinylestradiol on activity of rat liver enzymes for synthesis and hydrolysis of cholesterol esters

    International Nuclear Information System (INIS)

    Nikitin, Yu.P.; Dushkin, M.I.; Dolgov, A.V.; Gordienko, I.A.

    1987-01-01

    Administration of estrogens is known to lower the concentration of cholesterol esters in the blood vessel wall and may delay the development of arteriosclerosis. It is also known that under the influence of estrogens the redistribution of concentrations of free cholesterol and cholesterol esters takes place in rats between the blood and liver as a result of the intensification of receptor-dependent uptake of low-density lipoproteins by the hepatocytes. The mechanisms of this intracellular redistribution, however, have been inadequately studied. The purpose of this paper is to study the effects of 17alpha-ethinylestradiol on the activity of lysosomal and cytoplasmic cholesterol esterases, acyl-CoA-cholesterol-O-acyltransferase, lysosomal acid phosphatase, and beta-D-galactosidase. The activity was measured by using cholesterol [1-C 14]-oleate as the substrate. The influence of the estradiol is found to be based on cholesterol redistribution between the blood and liver. Accumulation of free cholesterol in the liver under these conditions stimulates bile acid formation. Depression of cholesterol ester synthesis as a result of direct inhibition of the acyltransferase by the estradiol is found to possibly contribute to the fall in the cholesterol level in the body. Liquid scintillation counting was used to measure distribution and accumulation

  15. 16 alpha-[77Br]bromoestradiol-17 beta: a high specific-activity, gamma-emitting tracer with uptake in rat uterus and uterus and induced mammary tumors

    International Nuclear Information System (INIS)

    Katzenellenbogen, J.A.; Senderoff, S.G.; McElvany, K.D.; O'Brien, H.A. Jr.; Welch, M.J.

    1981-01-01

    16 alpha-[77Br]bromoestradiol-17 beta (Compound 1) has been synthesized by radiobromination of estrone enoldiacetate. Tissue uptake studies performed 1 h after administration of Compound 1 to immature or mature female rats showed uterus-to-blood ratios of 13, with nontarget issue-to-blood ratios ranging from 0.6 to 2. Co-administration of unlabelled estradiol caused a selective depression in the uterine uptake with no effect on nontarget tissue uptake. In adult animals bearing adenocarcinomas induced by DMBA (7,12-dimethylbenz(a)anthracene), tumor-to-blood ratios of 6.3 were obtained, this uptake also being depressed in animals treated with unlabeled estradiol. The studies demonstrate that Compound 1 has suitable binding properties and sufficiently high specific activity so that its uptake in estrogen target tissues in vivo is mediated primarily by the estrogen receptor. Furthermore, they suggest that this compound may be suitable for imaging human breast tumors that contain estrogen receptors

  16. Antioxidant and antimicrobial activities of selected medicinal plants from Algeria

    Institute of Scientific and Technical Information of China (English)

    Krimat Soumia; Dob Tahar; Lamari Lynda; Boumeridja Saida; Chelghoum Chabane; Metidji Hafidha

    2014-01-01

    Objective:To evaluate the antioxidant and antimicrobial activity of methanolic extract extracts of selected Algerian medicinal plants. Methods:Antioxidant activity of extracts was evaluated in terms of radical scavenging potential (2,2-diphenyl-1-picrylhydrazyl) and β-carotene bleaching assay. Total phenolic contents and flavonoid contents were also measured. Antimicrobial activity of these plants was examined against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans. Results:The values of IC50 ranged from 4.30 μg/mL to 486.6 μg/mL for the DPPH method, while total antioxidant activity using β-carotene/linoleic acid bleaching assay ranged from 17.03%to 86.13%. It was found that Pistacia lentiscus showed the highest antioxidant capacities using DPPH assay (IC50=4.30 μg/mL), while Populus trimula, Origanum glandulosum, Centaurea calcitrapa, Sysimbrium officinalis and Rhamnus alaternus showed the highest percent of total antioxidant activity inβ-carotene/linoleic acid bleaching assay. Total phenolic and flavonoid contents ranged from 3.96 to 259.65 mg GAE/g extract and from 1.13 to 26.84 mg QE/g extract, respectively. The most interesting antimicrobial activity was obtained from Sysimbrium officinalis, Rhamnus alaternus, Origanum glandulosum, Cupressus sempervirens, Pinus halipensis and Centaurea calcitrapa. Conclusions:The results indicated that the plants tested may be potential sources for isolation of natural antioxidant and antimicrobial compounds.

  17. Non-destructive alpha-particle activation analysis of P, Cl, K and Ca in marine macro-alga samples using synthetic multielement reference material as comparative standard

    International Nuclear Information System (INIS)

    Iwata, Y.; Naitoh, H.; Suzuki, N.

    1992-01-01

    A Synthetic Reference Material (SyRM) composed with accurately known amounts of 12 elements has been prepared. The elemental composition of the SyRM is closely similar to that of marine macro-algae sample. The elemental composition of the SyRM was regulated by the starting materials used for the synthesis. The SyRM was used as a comparative standard for non-destructive alpha-particle activation analysis of marine macro-alga samples. P, Cl, K and Ca were determined simultaneously without correction for alpha range due to difference in the elemental composition between the analytical samples and the comparative standard. (author) 19 refs.; 4 tabs

  18. Fibrates suppress bile acid synthesis via peroxisome proliferator-activated receptor-alpha-mediated downregulation of cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase expression

    NARCIS (Netherlands)

    Post, SM; Duez, H; Gervois, PP; Staels, B; Kuipers, F; Princen, HMG

    2001-01-01

    Fibrates are hypolipidemic drugs that affect the expression of genes involved in lipid metabolism by activating peroxisome proliferator-activated receptors (PPARs). Fibrate treatment causes adverse changes in biliary lipid composition and decreases bile acid excretion, leading to an increased

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

    CERN Document Server

    Singh, N L; Chintalapudi, S N

    2000-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2000-05-01

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

  1. Proposed development programme for a temporary containment system for alpha active decommissioning

    International Nuclear Information System (INIS)

    Pengelly, M.G.A.; Burnett, R.C.

    1983-06-01

    This report makes a proposal to design, develop and test a containment of modular construction under plutonium active conditions. While this proposal contemplates work with plutonium, the system, when fully developed, has obvious applications wherever a temporary containment of radioactive or toxic materials is required. The fundamental feature of the proposal is that strippable coatings are used to prevent the inner surfaces of the working area from becoming contaminated. It is envisaged that this method of protecting the surfaces will enable the modular containment structure to be disassembled and re-used. (author)

  2. Parkinson's disease: acid-glucocerebrosidase activity and alpha-synuclein clearance.

    Science.gov (United States)

    Blanz, Judith; Saftig, Paul

    2016-10-01

    The role of mutations in the gene GBA1 encoding the lysosomal hydrolase β-glucocerebrosidase for the development of synucleinopathies, such as Parkinson's disease and dementia with Lewy bodies, was only very recently uncovered. The knowledge obtained from the study of carriers or patients suffering from Gaucher disease (a common lysosomal storage disorder because of GBA1 mutations) is of particular importance for understanding the role of the enzyme and its catabolic pathway in the development of synucleinopathies. Decreased activity of β-glucocerebrosidase leads to lysosomal dysfunction and the accumulation of its substrate glucosylceramide and related lipid derivatives. Glucosylceramide is suggested to stabilize toxic oligomeric forms of α-synuclein that negatively influence the activity of β-glucocerebrosidase and to partially block export of newly synthesized β-glucocerebrosidase from the endoplasmic reticulum to late endocytic compartments, amplifying the pathological effects of α-synuclein and ultimately resulting in neuronal cell death. This pathogenic molecular feedback loop and most likely other factors (such as impaired endoplasmic reticulum-associated degradation, activation of the unfolded protein response and dysregulation of calcium homeostasis induced by misfolded GC mutants) are involved in shifting the cellular homeostasis from monomeric α-synuclein towards oligomeric neurotoxic and aggregated forms, which contribute to Parkinson's disease progression. From a therapeutic point of view, strategies aiming to increase either the expression, stability or delivery of the β-glucocerebrosidase to lysosomes are likely to decrease the α-synuclein burden and may be useful for an in depth evaluation at the organismal level. Lysosomes are critical for protein and lipid homeostasis. Recent research revealed that dysfunction of this organelle contributes to the development of neurodegenerative diseases such as Parkinson's disease (PD). Mutations in the

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    is dependent on the length and position of the lipid element(s). The resulting lead compound, Pam-(Lys-beta NSpe)(6)-NH2, blocks LPS-induced cytokine secretion with a potency comparable to that of polymyxin B. The mode of action of this HDP mimic appears not to involve direct LPS interaction since it......, in contrast to polymyxin B, displayed only minor activity in the Limulus amebocyte lysate assay. Flow cytometry data showed specific interaction of a fluorophore-labeled lipidated a-peptide/beta-peptoid hybrid with monocytes and granulocytes indicating a cellular target expressed by these leukocyte subsets....

  4. Role of tumor necrosis factor-alpha and platelet-activating factor in neoangiogenesis induced by synovial fluids of patients with rheumatoid arthritis.

    Science.gov (United States)

    Lupia, E; Montrucchio, G; Battaglia, E; Modena, V; Camussi, G

    1996-08-01

    The aim of the present study was to investigate in vivo in a mouse model the stimulation of neoangiogenesis by synovial fluids of patients with rheumatoid arthritis (RA) and to determine the role of tumor necrosis factor (TNF)-alpha and platelet-activating factor (PAF) in the formation of new vessels. Angiogenesis was studied in a mouse model in which Matrigel, injected subcutaneously, was used as a vehicle for the delivery of potential angiogenic stimuli. Synovial fluids of patients with RA but not with osteoarthritis (OA) were shown to induce neoangiogenesis. Since synovial fluid of patients with RA contained significantly higher levels of TNF-alpha-like bioactivity and of PAF than that of patients with OA, the role of these mediators was evaluated by using an anti-TNF-alpha neutralizing monoclonal antibody (mAb) and a PAF receptor antagonist, WEB 2170. When added to Matrigel, anti-TNF-alpha mAb and particularly WEB 2170 significantly reduced neoangiogenesis induced by synovial fluids of RA patients. Moreover, PAF extracted and purified from synovial fluid induced angiogenesis. These results suggest that the neoangiogenesis observed in rheumatoid synovitis may be due, at least in part, to the angiogenic effect of locally produced TNF-alpha and PAF.

  5. Effect of efferent activation on binaural frequency selectivity.

    Science.gov (United States)

    Verhey, Jesko L; Kordus, Monika; Drga, Vit; Yasin, Ifat

    2017-07-01

    Binaural notched-noise experiments indicate a reduced frequency selectivity of the binaural system compared to monaural processing. The present study investigates how auditory efferent activation (via the medial olivocochlear system) affects binaural frequency selectivity in normal-hearing listeners. Thresholds were measured for a 1-kHz signal embedded in a diotic notched-noise masker for various notch widths. The signal was either presented in phase (diotic) or in antiphase (dichotic), gated with the noise. Stimulus duration was 25 ms, in order to avoid efferent activation due to the masker or the signal. A bandpass-filtered noise precursor was presented prior to the masker and signal stimuli to activate the efferent system. The silent interval between the precursor and the masker-signal complex was 50 ms. For comparison, thresholds for detectability of the masked signal were also measured in a baseline condition without the precursor and, in addition, without the masker. On average, the results of the baseline condition indicate an effectively wider binaural filter, as expected. For both signal phases, the addition of the precursor results in effectively wider filters, which is in agreement with the hypothesis that cochlear gain is reduced due to the presence of the precursor. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. K- and M-type dwarf stars within 25 parsecs of the sun. I. The age-chromospheric activity relations from H-alpha equivalent widths

    Energy Technology Data Exchange (ETDEWEB)

    Eggen, O.J. (Observatorio Interamericano de Cerro Totolo, La Serena (Chile))

    1990-02-01

    The available equivalent-width measurements of H-alpha in dwarf K and M stars within 25 pc of the sun indicate that, as a chromospheric diagnostic, the H-alpha decay rate is about t exp 0.5. The decay rate of line emission in Mg II h and k (Ca II H and K) is about t exp 0.3. The decay rates are derived from observations of members of a few stellar superclusters and groups, for which the consistency of results argues strongly for the importance of more data. The only major inconsistency encountered is for the unique HR 1614 group which, in the age/chromospheric-activity progression, gives different results from Mg II h and k and from WH-alpha. 63 refs.

  7. Simultaneous measurement of cholesterol 7 alpha-hydroxylase activity by reverse-phase high-performance liquid chromatography using both endogenous and exogenous [4-14C]cholesterol as substrate

    International Nuclear Information System (INIS)

    Hylemon, P.B.; Studer, E.J.; Pandak, W.M.; Heuman, D.M.; Vlahcevic, Z.R.; Chiang, J.Y.

    1989-01-01

    The HPLC-spectrophotometric method for measuring cholesterol 7 alpha-hydroxylase activity was modified by using a C-18 reverse-phase column to separate 7 alpha-hydroxy-4-cholesten-3-one and 4-cholesten-3-one and by adding 7 beta-hydroxycholesterol to each reaction mixture as an internal recovery standard. With this method, we were able to simultaneously measure cholesterol 7 alpha-hydroxylase activity using endogenous cholesterol and exogenous [4- 14 C]cholesterol as substrate. Rat liver cytosol differentially stimulated (286%) the 7 alpha-hydroxylation of exogenous [4- 14 C]-cholesterol. In contrast, total cholesterol 7 alpha-hydroxylase activity was stimulated only 35% by cytosol. This method should prove useful for studying mechanisms of cholesterol delivery to cholesterol 7 alpha-hydroxylase

  8. Determination of oxygen impurity in high purity materials by charged particle activation analysis using alpha projectiles

    International Nuclear Information System (INIS)

    Chowdhury, D.P.; Pal, S.; Arunachalam, J.; Verma R.; Gangadharan, S.

    1992-01-01

    40 MeV α-particles have been used to determine oxygen impurity at ppm levels in silicon, copper, and stainless steel, through the radiochemical separation of 18 F from the matrix. The separation of 18 F has been carried out by two techniques, viz. distillation of H 2 SiF 6 and precipitation of KBF 4 and some modification has been applied in the separation, depending on the nature of interferences from the matrix. Instrumental approach was also carried o