Sample records for alpha activity localisation

  1. Slower resting alpha frequency is associated with superior localisation of moving targets. (United States)

    Howard, Christina J; Arnold, Craig P A; Belmonte, Matthew K


    We examined the neurophysiological underpinnings of individual differences in the ability to maintain up-to-date representations of the positions of moving objects. In two experiments similar to the multiple object tracking (MOT) task, we asked observers to monitor continuously one or several targets as they moved unpredictably for a semi-random period. After all objects disappeared, observers were immediately prompted to report the perceived final position of one queried target. Precision of these position reports declined with attentional load, and reports tended to best resemble positions occupied by the queried target between 0 and 30ms in the past. Measurement of event-related potentials showed a contralateral delay activity over occipital scalp, maximal in the right hemisphere. The peak power-spectral frequency of observers' eyes-closed resting occipital alpha oscillations reliably predicted performance, such that lower-frequency alpha was associated with superior spatial localisation. Slower resting alpha might be associated with a cognitive style that depends less on memory-related processing and instead emphasises attention to changing stimuli. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  2. Active surveillance strategy for patients with localised prostate cancer

    DEFF Research Database (Denmark)

    Thomsen, Frederik Birkebæk


    BACKGROUND: Active surveillance - an initial observational strategy - offers a tailored management of patients with localised prostate cancer. The aim of the strategy is to appoint patients with potentially lethal prostate cancer to curatively intended treatment, while patients with slowly evolving...... measurements, repeated biopsies, and regular digital rectal examinations. The programme recommended change of management from active surveillance to curatively intended treatment based on PSA doubling time, deteriorating histopathology in repeated prostatic biopsies, and increased clinical tumour category...... with defined final histopathological findings at radical prostatectomy that was perceived as unacceptable for a continued observational strategy. CONCLUSION: The thesis has demonstrated that active surveillance is feasible and reduces the number of patients undergoing curative intended treatment. However...

  3. Bi209 alpha activity

    International Nuclear Information System (INIS)

    Araujo Penna, M.M. de.


    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

  4. How active ingredient localisation in plant tissues determines the targeted pest spectrum of different chemistries

    DEFF Research Database (Denmark)

    Buchholz, Anke; Trapp, Stefan


    information sets revealed that the intracellular localisation of active ingredients determines the performance of test compounds against different target pests because of different feeding behaviours: mites feed on mesophyll, and aphids and whiteflies mostly in the vascular system. Polar compounds have a slow...

  5. Resting alpha activity predicts learning ability in alpha neurofeedback

    Directory of Open Access Journals (Sweden)

    Wenya eNan


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

  6. Control of ADAM17 activity by regulation of its cellular localisation (United States)

    Lorenzen, Inken; Lokau, Juliane; Korpys, Yvonne; Oldefest, Mirja; Flynn, Charlotte M.; Künzel, Ulrike; Garbers, Christoph; Freeman, Matthew; Grötzinger, Joachim; Düsterhöft, Stefan


    An important, irreversible step in many signalling pathways is the shedding of membrane-anchored proteins. A Disintegrin And Metalloproteinase (ADAM) 17 is one of the major sheddases involved in a variety of physiological and pathophysiological processes including regeneration, differentiation, and cancer progression. This central role in signalling implies that ADAM17 activity has to be tightly regulated, including at the level of localisation. Most mature ADAM17 is localised intracellularly, with only a small amount at the cell surface. We found that ADAM17 is constitutively internalised by clathrin-coated pits and that physiological stimulators such as GPCR ligands induce ADAM17-mediated shedding, but do not alter the cell-surface abundance of the protease. In contrast, the PKC-activating phorbol ester PMA, often used as a strong inducer of ADAM17, causes not only proteolysis by ADAM17 but also a rapid increase of the mature protease at the cell surface. This is followed by internalisation and subsequent degradation of the protease. Eventually, this leads to a substantial downregulation of mature ADAM17. Our results therefore imply that physiological activation of ADAM17 does not rely on its relocalisation, but that PMA-induced PKC activity drastically dysregulates the localisation of ADAM17. PMID:27731361

  7. Automaticity and localisation of concurrents predicts colour area activity in grapheme-colour synaesthesia. (United States)

    Gould van Praag, Cassandra D; Garfinkel, Sarah; Ward, Jamie; Bor, Daniel; Seth, Anil K


    In grapheme-colour synaesthesia (GCS), the presentation of letters or numbers induces an additional 'concurrent' experience of colour. Early functional MRI (fMRI) investigations of GCS reported activation in colour-selective area V4 during the concurrent experience. However, others have failed to replicate this key finding. We reasoned that individual differences in synaesthetic phenomenology might explain this inconsistency in the literature. To test this hypothesis, we examined fMRI BOLD responses in a group of grapheme-colour synaesthetes (n=20) and matched controls (n=20) while characterising the individual phenomenology of the synaesthetes along dimensions of 'automaticity' and 'localisation'. We used an independent functional localiser to identify colour-selective areas in both groups. Activations in these areas were then assessed during achromatic synaesthesia-inducing, and non-inducing conditions; we also explored whole brain activations, where we sought to replicate the existing literature regarding synaesthesia effects. Controls showed no significant activations in the contrast of inducing > non-inducing synaesthetic stimuli, in colour-selective ROIs or at the whole brain level. In the synaesthete group, we correlated activation within colour-selective ROIs with individual differences in phenomenology using the Coloured Letters and Numbers (CLaN) questionnaire which measures, amongst other attributes, the subjective automaticity/attention in synaesthetic concurrents, and their spatial localisation. Supporting our hypothesis, we found significant correlations between individual measures of synaesthetic phenomenology and BOLD responses in colour-selective areas, when contrasting inducing against non-inducing stimuli. Specifically, left-hemisphere colour area responses were stronger for synaesthetes scoring high on phenomenological localisation and automaticity/attention, while right-hemisphere colour area responses showed a relationship with localisation

  8. Naturally-occurring alpha activity

    Energy Technology Data Exchange (ETDEWEB)

    Mayneord, W V


    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.

  9. Localisation of malignant germ-cell tumours by external scanning after injection of radiolabelled anti-alpha-fetoprotein

    International Nuclear Information System (INIS)

    Halsall, A.K.; Fairweather, D.S.; Bradwell, A.R.; Blackburn, J.C.; Howell, A.; Dykes, P.W.; Reeder, A.; Hine, K.R.


    Sheep IgG antibody to alpha-fetoprotein was labelled with 131 I and used to identify human germ-cell tumours by emission scanning. Eleven patients were studied after resection of their primary tumours. Ten had malignant teratoma and one an endodermal sinus tumour. All eight patients with raised serum alpha-fetoprotein concentrations had metastases apparent in the antibody scans. Of the remaining three patients with normal serum alpha-fetoprotein concentrations, two had positive scans. Three of the patients with positive results were scanned twice; the second scans were negative after treatment, when the alpha-fetoprotein concentrations had returned to normal. These results suggest that antibody scans are useful in the clinical management of patients with germ-cell tumours. (author)

  10. Tissue level, activation and cellular localisation of TGF-β1 and association with survival in gastric cancer patients

    NARCIS (Netherlands)

    Hawinkels, L.J.A.C.; Verspaget, H.W.; Duijn, W. van; Zon, J.M. van der; Zuidwijk, K.; Kubben, F.J.G.M.; Verheijen, J.H.; Hommes, D.W.; Lamers, C.B.H.W.; Sier, C.F.M.


    Transforming growth factor-β1 (TGF-β1), a tumour suppressing as well as tumour-promoting cytokine, is stored as an extracellular matrix-bound latent complex. We examined TGF-β1 activation and localisation of TGF-β1 activity in gastric cancer. Gastric tumours showed increased stromal and epithelial

  11. Activation of multiple chemotherapeutic prodrugs by the natural enzymolome of tumour-localised probiotic bacteria. (United States)

    Lehouritis, Panos; Stanton, Michael; McCarthy, Florence O; Jeavons, Matthieu; Tangney, Mark


    Some chemotherapeutic drugs (prodrugs) require activation by an enzyme for efficacy. We and others have demonstrated the ability of probiotic bacteria to grow specifically within solid tumours following systemic administration, and we hypothesised that the natural enzymatic activity of these tumour-localised bacteria may be suitable for activation of certain such chemotherapeutic drugs. Several wild-type probiotic bacteria; Escherichia coli Nissle, Bifidobacterium breve, Lactococcus lactis and Lactobacillus species, were screened against a panel of popular prodrugs. All strains were capable of activating at least one prodrug. E. coli Nissle 1917 was selected for further studies because of its ability to activate numerous prodrugs and its resistance to prodrug toxicity. HPLC data confirmed biochemical transformation of prodrugs to their toxic counterparts. Further analysis demonstrated that different enzymes can complement prodrug activation, while simultaneous activation of multiple prodrugs (CB1954, 5-FC, AQ4N and Fludarabine phosphate) by E. coli was confirmed, resulting in significant efficacy improvement. Experiments in mice harbouring murine tumours validated in vitro findings, with significant reduction in tumour growth and increase in survival of mice treated with probiotic bacteria and a combination of prodrugs. These findings demonstrate the ability of probiotic bacteria, without the requirement for genetic modification, to enable high-level activation of multiple prodrugs specifically at the site of action. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Cortical Alpha Activity in Schizoaffective Patients. (United States)

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


    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.

  13. Activity monitoring of alpha-bearing wastes

    International Nuclear Information System (INIS)

    Birkhoff, G.; Bondar, L.


    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

  14. Plasma levels of intact and cleaved urokinase plasminogen activator receptor (uPAR) in men with clinically localised prostate cancer

    DEFF Research Database (Denmark)

    Kristensen, Gitte; Berg, Kasper Drimer; Lippert, Solvej


    Aims: Lymph node metastasis (N1) is an adverse prognostic factor for men with clinically localised prostate cancer (PCa), but the prediction of N1 disease remains difficult. Urokinase plasminogen activator receptor (uPAR) plays an important role in angiogenesis and tumorigenesis. We analysed...... analysis and quantified using the areas under the ROC curve (AUC).Results: All soluble uPAR levels were significantly (p=0.03) higher in patients with N1 disease compared with patients with N0/x disease. ROC curves including clinical tumour stage, biopsy Gleason score, prostate-specific antigen and percent...

  15. Miniature Neutron-Alpha Activation Spectrometer (United States)

    Rhodes, E.; Goldsten, J.


    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.

  16. Miniature neutron-alpha activation spectrometer

    International Nuclear Information System (INIS)

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


    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

  17. 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


    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.

  18. 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

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

    DEFF Research Database (Denmark)

    Elgqvist, Jörgen; Andersson, Håkan; Haglund, Elin


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

  20. In normal human fibroblasts variation in DSB repair capacity cannot be ascribed to radiation-induced changes in the localisation, expression or activity of major NHEJ proteins

    DEFF Research Database (Denmark)

    Kasten-Pisula, Ulla; Vronskaja, Svetlana; Overgaard, Jens


    in the activity of the DNA-PK complex induced upon irradiation. CONCLUSIONS: For normal human fibroblasts, the level or activity of NHEJ proteins measured prior to or after irradiation cannot be used to predict the DSB repair capacity or cellular radiosensitivity. Udgivelsesdato: 2008-Mar......BACKGROUND AND PURPOSE: The aim of the present study was to test whether for normal human fibroblasts the variation in double-strand break (DSB) repair capacity results from radiation-induced differences in localisation, expression or activity of major non-homologous end-joining (NHEJ) proteins....... MATERIALS AND METHODS: Experiments were performed with 11 normal human fibroblast strains AF01-11. NHEJ proteins were determined by Western blot and DNA-PK activity by pulldown-assay. RESULTS: The four NHEJ proteins tested (Ku70, Ku80, XRCC4 and DNA-PKcs) were found to be localised almost exclusively...

  1. Automatic reference selection for quantitative EEG interpretation: identification of diffuse/localised activity and the active earlobe reference, iterative detection of the distribution of EEG rhythms. (United States)

    Wang, Bei; Wang, Xingyu; Ikeda, Akio; Nagamine, Takashi; Shibasaki, Hiroshi; Nakamura, Masatoshi


    EEG (Electroencephalograph) interpretation is important for the diagnosis of neurological disorders. The proper adjustment of the montage can highlight the EEG rhythm of interest and avoid false interpretation. The aim of this study was to develop an automatic reference selection method to identify a suitable reference. The results may contribute to the accurate inspection of the distribution of EEG rhythms for quantitative EEG interpretation. The method includes two pre-judgements and one iterative detection module. The diffuse case is initially identified by pre-judgement 1 when intermittent rhythmic waveforms occur over large areas along the scalp. The earlobe reference or averaged reference is adopted for the diffuse case due to the effect of the earlobe reference depending on pre-judgement 2. An iterative detection algorithm is developed for the localised case when the signal is distributed in a small area of the brain. The suitable averaged reference is finally determined based on the detected focal and distributed electrodes. The presented technique was applied to the pathological EEG recordings of nine patients. One example of the diffuse case is introduced by illustrating the results of the pre-judgements. The diffusely intermittent rhythmic slow wave is identified. The effect of active earlobe reference is analysed. Two examples of the localised case are presented, indicating the results of the iterative detection module. The focal and distributed electrodes are detected automatically during the repeating algorithm. The identification of diffuse and localised activity was satisfactory compared with the visual inspection. The EEG rhythm of interest can be highlighted using a suitable selected reference. The implementation of an automatic reference selection method is helpful to detect the distribution of an EEG rhythm, which can improve the accuracy of EEG interpretation during both visual inspection and automatic interpretation. Copyright © 2013 IPEM

  2. Development of a new technique of localised analysis of electrically active defects in semiconductors

    International Nuclear Information System (INIS)

    Heiser, T.


    An analysis technique derived from minority carrier transient spectroscopy (MCTS) was developed. By giving this technique spatial resolution via a focused optical beam, it is possible to exploit the high sensitivity and the spectroscopic nature of the technique to develop a method called scanning MCTS (SMCTS) which can be used to acquire information on lateral distribution of electrically active flaws in semiconductors or associated chemical impurities. The optimum conditions, corresponding to the maximum signal for the highest resolution, can be expressed by the value of a signal parameter. The transients system was digitized, considerably reducing background noise. In order to link the SMCTS to a given flaw, two methods for exploiting the transients are used. The method was verified in tests with artificial defects created by laser and on real cases, arising in industrial processes [fr

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

    Energy Technology Data Exchange (ETDEWEB)

    Serafini, P.; Lobo, R.A.


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

  4. 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


    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.

  5. Expression and Immunohistochemical Localisation of the G beta gamma activated and Calcineurin-inhibited Adenylyl Cyclase Isoforms in Rat Articular Chondrocytes

    International Nuclear Information System (INIS)

    Memon, I.; Khan, K.M.; Siddiqui, S.; Perveen, S.; Ishaq, M.


    Objective: To determine the expression and localisation of the Gβγ-activated adenylyl cyclase (AC) isoforms 2, 4, and 7 and calcineurin-inhibited AC isoform 9 in rat articular chondrocytes. Study Design: Experimental study. Place and Duration of Study: Jumma Research Laboratory and Histology Laboratory, The Aga Khan University, Karachi, from 2009 to 2011. Methodology: Fresh slices of articular cartilage were taken from various synovial joints of rats of different age groups. The expression of AC isoforms was determined by RT-PCR and immunohistochemistry was performed to localise these isoforms in articular chondrocytes. Tissue sections were processed for immunostaining with respective antibodies. The color was developed by diaminobenzidine. Results: All the studied AC isoforms were found to be differentially expressed in different zones of the rat articular cartilage. Generally, expression of all AC isoforms studied increased with age. The expression of the AC isoforms through PCR was almost consistent with the localisation of these isoforms by immunohistochemistry. Conclusion: These data add to the information about signalling cascades possibly involved in articular chondrocytes. Variable expression of AC isoforms 2, 4, 7, and 9 suggest a role for the signalling cascades regulated by the AC isoforms in articular chondrocytes. (author)

  6. Alpha particle losses during sawtooth activity in Tokamaks

    International Nuclear Information System (INIS)

    Anderson, D.; Lisak, M.


    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)

  7. [Acetylcholine activation of alpha-ketoglutarate oxidation in liver mitochondria]. (United States)

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


    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.

  8. Alpha-mannosidase activity in goats fed with Sida carpinifolia. (United States)

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


    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.

  9. 5alphaDH-DOC (5alpha-dihydro-deoxycorticosterone) activates androgen receptor in castration-resistant prostate cancer. (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


    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.

  10. 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.

  11. Localisation for industrial development

    CSIR Research Space (South Africa)

    Bhugwandin, Ashley


    Full Text Available This presentation focuses on localisation for industrial development, and is presented by Ashley Bhugwandin at The 6th CSIR Conference: Ideas that work for industrial development, 5-6 October 2017, CSIR International Convention Centre, Pretoria...

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

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


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

  13. Gross alpha and beta activities in Tunisian mineral water

    International Nuclear Information System (INIS)

    Hamrouni Benbelgacem, Samar


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

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


    Reka Palanivel; Thahira Banu Azeez; Seethalakshmi Muthaya


    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...

  16. Localization of alpha emitters by damage production in a thin film. Application to the study of alpha emitter diffusion in irradiated samples; Localisation des emetteurs alpha par creation de dommages dans un film mince. Application a l'etude de la diffusion des emetteurs alpha dans des echantillons irradies

    Energy Technology Data Exchange (ETDEWEB)

    Houdaille, B; Perrot, M [Commissariat a l' Energie Atomique, 91 - Saclay (France). Centre d' Etudes Nucleaires


    The process of recording {alpha} particles on cellulose nitrate films, called alpha-graphy, is applied to the study of the diffusion of {alpha}-emitting elements in irradiated alloys. The existence of diffusion is shown by attacking the film with concentrated caustic soda after exposition. The insensitivity of the recorder to {beta} {gamma} radiation emitted by the sample after passing in the reactor makes it possible to operate with long exposure times and to detect small diffusions. The concentration-penetration curves are drawn up after carrying out a densitometric analysis of the alpha-graphies. - As the cellulose nitrate is affected only by {alpha} particles of energies of between 0.5 and 4 MeV, it was first necessary to determine the yield of the recorder for {alpha} particles emitted by a thick source, i.e. whose energy varies between 0 and E{sub 0}, E{sub 0} being the energy of the alpha emitter. - The concentration C of the {alpha}-emitter, as a function of the optical density D of the alpha-graphy, and of the exposure time t is given by a simple relationship: C = D/at where a is an experimental constant determined by calibration. It depends on the nature of the cellulose nitrate, of the {alpha}-emitting element and of the alloy studied. (authors) [French] Le procede d'enregistrement des particules alpha sur film de nitrate de cellulose, ou alphagraphie, est applique a l'etude de la diffusion d'elements emetteurs alpha dans des alliages irradies. La diffusion est mise en evidence par une attaque du film de nitrate, apres exposition, dans de la soude concentree. L'insensibilite de l'enregistreur au rayonnement {beta} {gamma}, emis par l'echantillon apres son sejour en pile, permet d'operer sur de longs temps de pose et de detecter des diffusions faibles. Les courbes concentration - penetration sont etablies par exploitation densitometrique des alphagraphies. - Comme le nitrate de cellulose n'est impressionne que par des particules alpha dont l'energie est

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

    Directory of Open Access Journals (Sweden)

    Freya M Mowat


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

  18. Design of a randomised controlled trial of adapted physical activity during adjuvant treatment for localised breast cancer: the PASAPAS feasibility study (United States)

    Touillaud, M; Foucaut, A-M; Berthouze, S E; Reynes, E; Kempf-Lépine, A-S; Carretier, J; Pérol, D; Guillemaut, S; Chabaud, S; Bourne-Branchu, V; Perrier, L; Trédan, O; Fervers, B; Bachmann, P


    Introduction After a diagnosis of localised breast cancer, overweight, obesity and weight gain are negatively associated with prognosis. In contrast, maintaining an optimal weight through a balanced diet combined with regular physical activity appears to be effective protective behaviour against comorbidity or mortality after a breast cancer diagnosis. The primary aim of the Programme pour une Alimentation Saine et une Activité Physique Adaptée pour les patientes atteintes d'un cancer du Sein (PASAPAS) randomised controlled trial is to evaluate the feasibility of implementing an intervention of adapted physical activity (APA) for 6 months concomitant with the prescription of a first line of adjuvant chemotherapy. Secondary aims include assessing the acceptability of the intervention, compliance to the programme, process implementation, patients’ satisfaction, evolution of biological parameters and the medicoeconomic impact of the intervention. Methods and analysis The study population consists of 60 women eligible for adjuvant chemotherapy after a diagnosis of localised invasive breast cancer. They will be recruited during a 2-year inclusion period and randomly allocated between an APA intervention arm and a control arm following a 2:1 ratio. All participants should benefit from personalised dietetic counselling and patients allocated to the intervention arm will be offered an APA programme of two to three weekly sessions of Nordic walking and aerobic fitness. During the 6-month intervention and 6-month follow-up, four assessments will be performed including blood draw, anthropometrics and body composition measurements, and questionnaires about physical activity level, diet, lifestyle factors, psychological criteria, satisfaction with the intervention and medical data. Ethics and dissemination The study was approved by the French Ethics Committee (Comité de Protection des Personnes Sud-Est IV) and the national agencies for biomedical studies and for privacy

  19. 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


    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.

  20. 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


    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

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

    International Nuclear Information System (INIS)

    Mukherjee, B.; Manzoor, S.


    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

  2. 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,

  3. 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



    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 ...

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

    International Nuclear Information System (INIS)

    Blanchis, P.


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

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

    International Nuclear Information System (INIS)

    Labarre, S.; Bardy, N.


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

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

    DEFF Research Database (Denmark)

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


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

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

    Directory of Open Access Journals (Sweden)

    Reka Palanivel


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

  8. Peroxisome Proliferator-Activated Receptor Alpha Target Genes

    Directory of Open Access Journals (Sweden)

    Maryam Rakhshandehroo


    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.

  9. 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.


    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)

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

    NARCIS (Netherlands)

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


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

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

    NARCIS (Netherlands)

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


    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,

  12. The brain smell centres - comparison of localisation and activation in male and female subjects using functional MR imaging

    International Nuclear Information System (INIS)

    Marchwicka-Wasiak, M.; Goraj, B.


    The study was conducted in order to determine and to compare the location and activation of smell brain centres in females and males brains using olfactory nerve-mediated (geraniol) and combined olfactory and trigeminal nerve-mediated (patchouli) stimulants. 10 normal volunteers (five women and five men), right-handed, non-smokers, without any CNS diseases were examined to determine the activated cortex areas during stimulation by geraniol and patchouli. MR brain scans were obtained using a 1.5 T clinical scanner, with the head-neck coil. The imaging was performed in each subject using SE and EPI sequences with a blood-oxygen-level-dependent (BOLD) effect. The individual inhaled odorized air during the 30 seconds period and alternating room air over the same period. The mean pixel intensity of activated images was substracted from the mean pixel intensity of preactivated images. The olfactory system-mediated stimuli (geraniol) evoked bilateral activation of female brains smell centres and right hemisphere centres activation in male brains. The exposure to the olfactory and trigeminal nerve-mediated stimuli (patchouli) showed more activated regions in both sexes than to the olfactory nerve-ediated stimuli. fMRI proved to be a useful method to compare the location and activation of male and female brain smell centres. (author)

  13. Localisation of the subthalamic nucleus in Parkinson's disease with neural beta and gamma activity of local field potentials

    NARCIS (Netherlands)

    Verhagen, R.; Zwartjes - de Klerk, D.G.M; Heida, Tjitske; Contarino, M.F.; de Bie, R.M.A.; van den Munckhof, P; Schuurman, P.R.; Martens, H.C.F.; Veltink, Petrus H.; Bour, L.J.


    To evaluate the nature of oscillatory activity in the subthalamic nucleus (STN) by means of intraoperative local field potential (LFP) recordings, its relationship with microelectrode recordings (MER) and its potential use to locate the STN and its sensorimotor sub-area in patients with Parkinson’s

  14. Localisation and identification of radioactive particles in solid samples by means of a nuclear track technique

    International Nuclear Information System (INIS)

    Boehnke, Antje; Treutler, Hanns-Christian; Freyer, Klaus; Schubert, Michael; Holger Weiss


    This study is aimed to develop a generally applicable methodology of investigation that can be used for the localisation of single alpha-active particles in solid samples, such as industrial dust or natural soils, sediments and rocks by autoradiography using solid-state nuclear track detectors. The developed technique allows the detection of local enrichments of alpha-emitters in any solid material. The results of such an investigation are of interest from technical, biological and environmental points of view. The idea behind the methodology is to locate the position of alpha-active spots in a sample by attaching the track detector to the sample in a defined manner, thoroughly described in the paper. The located alpha-active particles are subsequently analysed by an electron microscope and an electron microprobe. An example of the application of this methodology is also given. An ultra-fine -grained ore-processing residue, which causes serious environmental pollution in the respective mining district and thus limits possible land use and affects quality of life in the area, was examined using the described technique. The investigation revealed considerable amounts of alpha-active particles in this material

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

    International Nuclear Information System (INIS)

    Krejbichova, Z.


    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.)

  17. Small and intermediate conductance Ca(2+)-activated K+ channels confer distinctive patterns of distribution in human tissues and differential cellular localisation in the colon and corpus cavernosum. (United States)

    Chen, Mao Xiang; Gorman, Shelby A; Benson, Bill; Singh, Kuljit; Hieble, J Paul; Michel, Martin C; Tate, Simon N; Trezise, Derek J


    The SK/IK family of small and intermediate conductance calcium-activated potassium channels contains four members, SK1, SK2, SK3 and IK1, and is important for the regulation of a variety of neuronal and non-neuronal functions. In this study we have analysed the distribution of these channels in human tissues and their cellular localisation in samples of colon and corpus cavernosum. SK1 mRNA was detected almost exclusively in neuronal tissues. SK2 mRNA distribution was restricted but more widespread than SK1, and was detected in adrenal gland, brain, prostate, bladder, liver and heart. SK3 mRNA was detected in almost every tissue examined. It was highly expressed in brain and in smooth muscle-rich tissues including the clitoris and the corpus cavernosum, and expression in the corpus cavernosum was upregulated up to 5-fold in patients undergoing sex-change operations. IK1 mRNA was present in surface-rich, secretory and inflammatory cell-rich tissues, highest in the trachea, prostate, placenta and salivary glands. In detailed immunohistochemical studies of the colon and the corpus cavernosum, SK1-like immunoreactivity was observed in the enteric neurons. SK3-like immunoreactivity was observed strongly in smooth muscle and vascular endothelium. IK1-like immunoreactivity was mainly observed in inflammatory cells and enteric neurons of the colon, but absent in corpus cavernosum. These distinctive patterns of distribution suggest that these channels are likely to have different biological functions and could be specifically targeted for a number of human diseases, such as irritable bowel syndrome, hypertension and erectile dysfunction.

  18. Variability of the Lyman alpha flux with solar activity

    International Nuclear Information System (INIS)

    Lean, J.L.; Skumanich, A.


    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

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

    Directory of Open Access Journals (Sweden)

    Marie-Pierre eDeiber


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

  20. Strain localisation in granular media


    Desrues , Jacques


    This study is devoted to strain localisation in Granular materials. Both experimental and theoretical results have been obtained.The first part of the thesis is a review of the methods and theories about rupture in sols mechanics and more generally, in solid mechanics. The classical framework of Shear Band analysis is presented, and the main results available for different classes of materials are discussed.The second part describes an experimental study of strain localisation in sand specime...

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

    NARCIS (Netherlands)

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


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

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

    International Nuclear Information System (INIS)

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


    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

  3. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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


    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

  5. A Localised Corrosion Cell for Industrial Applications

    DEFF Research Database (Denmark)

    Andersen, A.; Hilbert, Lisbeth Rischel; Jansen, P.


    The LOCORR-CELL™ developed by FORCE TECHNOLOGY is an electrochemical cell for industrial applications estimating localised corrosion. The cell is constructed in a carbon steel casing for direct mounting into the system. It is based on an oxygen concentration element reflecting the interaction...... between the environment formed under a deposit or in a crevice. The essential feature of the method is that it reflects the influence of oxygen content, conductivity and temperature as well as the influence of corrosion inhibitors, MIC and other effects that have an effect on localised corrosion under...... deposits and in crevices. The measuring principle in the cell is based on measurements of the galvanic current flow between the steel anode covered by a porous glass frit and the surrounding steel casing. The current is measured by a zero-resistance circuit-instrument and the activity can be presented...

  6. Problems associated with localised skin exposures

    International Nuclear Information System (INIS)

    Wells, J.


    The possible sources of localised skin exposure include small commercial sources (for radiotherapy, for example), radiopharmaceuticals, collimated microbeams, and both fission and activation products from nuclear reactors, neutron generators and associated facilities. Each of these sources has its own particular characteristics and associated problems. Recommendations and regulations relating to limits on skin dose for such exposures have been constrained by inadequate radiobiological data and the limitations inherent in personal dosimetric techniques. A growing body of data is now available for beta-emitters which allows a preliminary reassessment of some aspects of the currently recommended dose limits for localised skin exposures. How the skin dose is measured is particularly important for such exposures, as doses often have to be averaged over a specific area. The area chosen for dose measurement and the depth at which the measurement is made are crucial to understanding the possible biological consequences and for formulating appropriate protection criteria. (author)

  7. 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:; 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)


    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.

  8. 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


    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

  9. 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.


    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.

  10. Activation of the skeletal alpha-actin promoter during muscle regeneration. (United States)

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


    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.

  11. 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.


    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

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

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


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

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

    DEFF Research Database (Denmark)

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


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

  14. 6-Mercaptopurine, an activator of Nur77, enhances transcriptional activity of HIF-1alpha resulting in new vessel formation. (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


    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.

  15. 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.


    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)

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

    DEFF Research Database (Denmark)

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


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

  17. Measurement of very low alpha activity in water

    International Nuclear Information System (INIS)

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


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

  18. Different responses of spontaneous and stimulus-related alpha activity to ambient luminance changes. (United States)

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


    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.

  19. Rare localisations of osteochondrosis juvenilis

    Energy Technology Data Exchange (ETDEWEB)

    Schumacher, R; Schuster, W; Mueller, U


    A survey of rare localisations of osteochondrosis juvenilis is given and illustrated by cases of Morbus Friedrich, Morbus Panner, Vertebra plana Calve, Morbus Blount, Morbus Iselin, Morbus Hegemann and Morbus Thiemann. This is followed by discussion of etiology and differential diagnosis.

  20. Alpha-mannosidosis

    DEFF Research Database (Denmark)

    Borgwardt, Line; Stensland, Hilde Monica Frostad Riise; Olsen, Klaus Juul


    of the three subgroups of genotype/subcellular localisation and the clinical and biochemical data were done to investigate the potential relationship between genotype and phenotype in alpha-mannosidosis. Statistical analyses were performed using the SPSS software. Analyses of covariance were performed...

  1. 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.


    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)

  2. 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.


    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)

  3. Evidence for a prolonged role of alpha 4 integrin throughout active experimental allergic encephalomyelitis. (United States)

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


    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.

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

    DEFF Research Database (Denmark)

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


    Like other adipocyte genes that are transcriptionally activated by CCAAT/enhancer binding protein alpha (C/EBP alpha) during preadipocyte differentiation, expression of the mouse obese (ob) gene is immediately preceded by the expression of C/EBP alpha. While the 5' flanking region of the mouse ob...... 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...

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

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


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

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

    Directory of Open Access Journals (Sweden)

    Rakita Slađana M.


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

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

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


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

  8. 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


    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

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

    International Nuclear Information System (INIS)

    Tobias, C.C.B.


    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

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


    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.

  11. 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.


    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

  12. Periostitis and localised myositis in polyarteritis nodosa

    International Nuclear Information System (INIS)

    Macdonald, W.B.G.; Blake, M.P.


    Full text: A 20-year-old man with previously diagnosed polyarteritis nodosa was referred for a bone scan to investigate longstanding knee and lower leg pain. The patient's symptoms worsened with any reduction of steroid dose and his physician was concerned about avascular necrosis of the hips. Plain x-rays of the lower limbs were normal. The blood pool images showed bilaterally increased activity in the anterior muscle compartments of the lower legs, suggestive of localised myositis. Three-hour delayed images showed widespread, increased subperiosteal activity with no evidence of avascular necrosis. Subsequent MRI scanning showed patchy muscle enhancement in both lower legs, also typical of myositis. A muscle biopsy was performed which demonstrated features of both myositis and vasculitis. The patient remains dependent on high-dose steroids for symptom relief. Localised myositis has previously been reported in polyarteritis nodosa and is a recognised, albeit rare, complication of the disorder, the basis of which is not well understood. Diagnostic muscle biopsy should be directed at involved muscle groups, which are best detected with MRI. Lower limb periostitis is well described in polyarteritis nodosa and may result in gross deformity. Several cases have previously been reported in the literature based on radiographic abnormalities, which were not present in our patient. Bone scanning demonstrated the sub-periosteal activity well in our subject and is suggested as a useful investigation in patients with polyarteritis nodosa who complain of lower limb pain. Copyright (2003) The Australian and New Zealand Society of Nuclear Medicine Inc

  13. [G-protein potentiates the activation of TNF-alpha on calcium-activated potassium channel in ECV304]. (United States)

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


    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.

  14. 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)


    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)

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

    DEFF Research Database (Denmark)

    Nielsen, M; Nordahl, M; Svejgaard, A


    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...

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

    International Nuclear Information System (INIS)

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


    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

  17. Reactivation of the chloroplast CF1-ATPase beta subunit by trace amounts of the CF1 alpha subunit suggests a chaperonin-like activity for CF1 alpha. (United States)

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


    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.

  18. 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.


    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)

  19. 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.


    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)

  20. 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.


    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

  1. 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.

  2. 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.


    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)

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

    Directory of Open Access Journals (Sweden)

    Hironori eNakatani


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

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

    International Nuclear Information System (INIS)

    Bains, M.E.D.


    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)

  5. 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.


    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)

  6. Blocking of irrelevant memories by posterior alpha activity boosts memory encoding. (United States)

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


    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.

  7. Correlation between protein kinase C alpha activity and membrane phase behavior. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Paul eSauseng


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

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

    Directory of Open Access Journals (Sweden)

    Sugawara A.M.


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

  11. Frontal alpha EEG asymmetry before and after behavioral activation treatment for depression. (United States)

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


    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.

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

    DEFF Research Database (Denmark)

    Olsen, Jørgen; Laustsen, Lotte; Troelsen, J


    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....

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

    International Nuclear Information System (INIS)

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


    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

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

    NARCIS (Netherlands)

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


    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

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

    International Nuclear Information System (INIS)

    Galicia C, F. J.


    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

  16. 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.


    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

  17. 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


    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.

  18. Prediction of Active Site and Distal Residues in E. coli DNA Polymerase III alpha Polymerase Activity. (United States)

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


    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.

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

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


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

  20. Localisation of RNAs into the germ plasm of vitellogenic Xenopus oocytes.

    Directory of Open Access Journals (Sweden)

    Sarbjit Nijjar

    Full Text Available We have studied the localisation of mRNAs in full-grown Xenopus laevis oocytes by injecting fluorescent RNAs, followed by confocal microscopy of the oocyte cortex. Concentrating on RNA encoding the Xenopus Nanos homologue, nanos1 (formerly Xcat2, we find that it consistently localised into aggregated germ plasm ribonucleoprotein (RNP particles, independently of cytoskeletal integrity. This implies that a diffusion/entrapment-mediated mechanism is active, as previously reported for previtellogenic oocytes. Sometimes this was accompanied by localisation into scattered particles of the "late", Vg1/VegT pathway; occasionally only late pathway localisation was seen. The Xpat RNA behaved in an identical fashion and for neither RNA was the localisation changed by any culture conditions tested. The identity of the labelled RNP aggregates as definitive germ plasm was confirmed by their inclusion of abundant mitochondria and co-localisation with the germ plasm protein Hermes. Further, the nanos1/Hermes RNP particles are interspersed with those containing the germ plasm protein Xpat. These aggregates may be followed into the germ plasm of unfertilized eggs, but with a notable reduction in its quantity, both in terms of injected molecules and endogenous structures. Our results conflict with previous reports that there is no RNA localisation in large oocytes, and that during mid-oogenesis even germ plasm RNAs localise exclusively by the late pathway. We find that in mid oogenesis nanos1 RNA also localises to germ plasm but also by the late pathway. Late pathway RNAs, Vg1 and VegT, also may localise into germ plasm. Our results support the view that mechanistically the two modes of localisation are extremely similar, and that in an injection experiment RNAs might utilise either pathway, the distinction in fates being very subtle and subject to variation. We discuss these results in relation to their biological significance and the results of others.

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

    DEFF Research Database (Denmark)

    Schmidt, Søren F; Mandrup, Susanne


    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...

  2. FcepsilonRI-alpha siRNA inhibits the antigen-induced activation of mast cells. (United States)

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


    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

  3. 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 ...

  4. Epigenetic Basis for the Regulation of Estrogen Receptor Alpha Activity in Breast Cancer Cells (United States)


    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

  5. 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.


    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)

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


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


    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 ...

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


    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

  8. Reaction-Diffusion Automata Phenomenology, Localisations, Computation

    CERN Document Server

    Adamatzky, Andrew


    Reaction-diffusion and excitable media are amongst most intriguing substrates. Despite apparent simplicity of the physical processes involved the media exhibit a wide range of amazing patterns: from target and spiral waves to travelling localisations and stationary breathing patterns. These media are at the heart of most natural processes, including morphogenesis of living beings, geological formations, nervous and muscular activity, and socio-economic developments.   This book explores a minimalist paradigm of studying reaction-diffusion and excitable media using locally-connected networks of finite-state machines: cellular automata and automata on proximity graphs. Cellular automata are marvellous objects per se because they show us how to generate and manage complexity using very simple rules of dynamical transitions. When combined with the reaction-diffusion paradigm the cellular automata become an essential user-friendly tool for modelling natural systems and designing future and emergent computing arch...

  9. 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.


    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

  10. Low level alpha activity measurements with pulse shape discrimination

    International Nuclear Information System (INIS)

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


    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)

  11. Multimodal Localisation: Analysis, Algorithms and Experimental Evaluation

    NARCIS (Netherlands)

    Kavitha Muthukrishnan, K.


    The term localisation is derived from the word locale, which traditionally means a small area or vicinity. In ancient days, localisation meant navigation -- an art of finding the way from one place to another. Tremendous advancement in the science of navigation dates back to the sixteenth century,

  12. 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.


    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

  13. Quantum localisation on the circle (United States)

    Fresneda, Rodrigo; Gazeau, Jean Pierre; Noguera, Diego


    Covariant integral quantisation using coherent states for semi-direct product groups is implemented for the motion of a particle on the circle. In this case, the phase space is the cylinder, which is viewed as a left coset of the Euclidean group E(2). Coherent states issued from fiducial vectors are labeled by points in the cylinder and depend also on extra parameters. We carry out the corresponding quantisations of the basic classical observables, particularly the angular momentum and the 2π-periodic discontinuous angle function. We compute their corresponding lower symbols. The quantum localisation on the circle is examined through the properties of the angle operator yielded by our procedure, its spectrum and lower symbol, its commutator with the quantum angular momentum, and the resulting Heisenberg inequality. Comparison with other approaches to the long-standing question of the quantum angle is discussed.

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

    International Nuclear Information System (INIS)


    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

  15. 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.


    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

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


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


    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....

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

    Li, Minyong; Xia, Lin


    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.

  18. Cell motility in chronic lymphocytic leukemia: defective Rap1 and alphaLbeta2 activation by chemokine. (United States)

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


    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.

  19. Radioactive probes for human gene localisation by in situ hybridisation

    International Nuclear Information System (INIS)

    Fennell, S.J.


    Radioactive probes of high specific activity have been used for human gene localisation on metaphase chromosome preparations. Human 5S ribosomal RNA was used as a model system, as a probe for the localisation of human 5S ribosomal genes. 125 I-labelled mouse 5S ribosomal RNA was used to study the 5S ribosomal gene content and arrangement in families with translocations on the long arm of chromosome 1 close to or containing the 5S ribosomal RNA locus, by in situ hybridisation to human metaphase chromosomes from peripheral blood cultures. This confirmed the chromosomal assignment of 5S ribosomal genes to 1q 42-43. In situ hybridisation probes were also prepared from recombinant plasmids containing Xenopus laevis oocyte 5S or 28S/18S gene sequences to give [ 3 H]-labelled cRNA and [ 3 H]-labelled nick-translated plasmid DNA. Studies on the kinetics of hybridisation of plasmid probes with and without ribosomal gene sequences questioned the role of plasmid DNA for amplification of signal during gene localisation. Gene localisation was obtained with nick-translated plasmid DNA containing the 28S/18S ribosomal DNA insert after short exposure times, but poor results were obtained using a [ 3 H]-labelled cRNA probe transcribed from the plasmid with the 5S gene insert. (author)

  20. Thioesterase activity and acyl-CoA/fatty acid cross-talk of hepatocyte nuclear factor-4{alpha}. (United States)

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


    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.

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

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


    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.

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

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

    International Nuclear Information System (INIS)

    Warburton, W.K.


    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

  4. 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.


    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)

  5. Experiences with a new breast localisation needle

    International Nuclear Information System (INIS)

    Hergan, K.; Amann, T.; Doringer, W.; Hollenstein, P.


    In view of the increasing number of biopsies of non-palpable lesions of the female breast we found an ideal localisation system in the Hawkins breast localisation needle. Localisation was successful without technical problems in 31 out of 34 patients. The special advantages of the needle are its stability in position and excellent manoeverability due to the construction of the needle. The very simple handling of the needle is an advantage not only for the radiologist but also for the surgeon. (orig.) [de

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


    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.

  7. 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.


    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.)

  8. 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:, E-mail:, E-mail: [Centro Regional de Ciencias Nucleares do Centro-Oeste (CRCN-CO/CNEN), Abadia de Goias, GO (Brazil). Parque Estadual Telma Ortegal


    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)

  9. A role for 5alpha-reductase activity in the development of male homosexuality? (United States)

    Alias, A G


    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.

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


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

    International Nuclear Information System (INIS)

    Terini, R.A.


    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)

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

    DEFF Research Database (Denmark)

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


    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)....

  14. Testosterone 5alpha-reductase inhibitory active constituents of Piper nigrum leaf. (United States)

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


    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


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


    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


    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 (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


    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.


    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. (United States)

    Saher, G; Hildt, E


    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. Implementing localisation programmes in South Africa

    CSIR Research Space (South Africa)

    Strachan, Garth


    Full Text Available challenges – from job creation and poverty reduction to participating in the technological revolution and global value chains, from promoting efficient and clean energy to mitigating climate change and greening the economy – without using some kind... sector value chains where the public sector supports supplier development – e.g. automotives, retail, clothing and textiles etc. Support for technology localisation and diffusion – The Technology Localisation and Implementation Unit [TLIU...

  1. 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.


    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

  2. Negative feedback regulation of human platelets via autocrine activation of the platelet-derived growth factor alpha-receptor. (United States)

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


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  4. 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

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

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


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

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

    Directory of Open Access Journals (Sweden)

    Reini F Luco


    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.

  7. [Cost-effectiveness of drotrecogin alpha [activated] in the treatment of severe sepsis in Spain]. (United States)

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


    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

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

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


    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.

  9. 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.


    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

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

    DEFF Research Database (Denmark)

    Chouin, N; Lindegren, S; Jensen, Holger


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

  11. Small and intermediate conductance Ca2+-activated K+ channels confer distinctive patterns of distribution in human tissues and differential cellular localisation in the colon and corpus cavernosum

    NARCIS (Netherlands)

    Chen, Mao Xiang; Gorman, Shelby A.; Benson, Bill; Singh, Kuljit; Hieble, J. Paul; Michel, Martin C.; Tate, Simon N.; Trezise, Derek J.


    The SK/IK family of small and intermediate conductance calcium-activated potassium channels contains four members, SK1, SK2, SK3 and IK1, and is important for the regulation of a variety of neuronal and non-neuronal functions. In this study we have analysed the distribution of these channels in

  12. 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.

  13. 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))


    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).

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

    International Nuclear Information System (INIS)



    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.

  15. An isozyme of acid alpha-glucosidase with reduced catalytic activity for glycogen. (United States)

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


    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.

  16. 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.


    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


    Directory of Open Access Journals (Sweden)

    A. S. Yanina


    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. 

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

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


    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.

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


    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


    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...

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  1. Locus coeruleus alpha-adrenergic-mediated activation of cortical astrocytes in vivo. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Navarrete Erika


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

  3. 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


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

    International Nuclear Information System (INIS)

    Romero, L.; Travesi, A.


    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

  5. 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

  6. 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


    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

  7. Activation of peroxisome proliferator-activated receptor-alpha and -gamma in auricular tissue from heart failure patients. (United States)

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


    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.

  8. Weak Localisation in Clean and Highly Disordered Graphene

    International Nuclear Information System (INIS)

    Hilke, Michael; Massicotte, Mathieu; Whiteway, Eric; Yu, Victor


    We look at the magnetic field induced weak localisation peak of graphene samples with different mobilities. At very low temperatures, low mobility samples exhibit a very broad peak as a function of the magnetic field, in contrast to higher mobility samples, where the weak localisation peak is very sharp. We analyze the experimental data in the context of the localisation length, which allows us to extract, both the localisation length and the phase coherence length of the samples, regardless of their mobilities. This analysis is made possible by the observation that the localisation length undergoes a generic weak localisation dependence with striking universal properties

  9. 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.


    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

  10. 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)


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Takács, S., E-mail: [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)


    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.

  12. The anti-apoptotic activity associated with phosphatidylinositol transfer protein alpha activates the MAPK and Akt/PKB pathway. (United States)

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


    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.

  13. 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


    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.

  14. 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


    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)

  15. Increase in posterior alpha activity during rehearsal predicts successful long-term memory formation of word sequences. (United States)

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


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  17. Glycogen synthase kinase 3 alpha phosphorylates and regulates the osteogenic activity of Osterix. (United States)

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


    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.

  18. 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


    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...

  19. 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.


    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

  20. [Activity of alpha-amylase and concentration of protein in saliva of pregnant women]. (United States)

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


    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.

  1. Primary localised cutaneous amyloidosis - a systematic review

    DEFF Research Database (Denmark)

    Kaltoft, Britta; Schmidt, Grethe; Lauritzen, Anne Falensteen


    Amyloidosis is defined as extracellular deposits of heterogenic, misfolded proteins, amyloid fibrils, in various tissues. The aim of our study was to review the literature and to evaluate the risk of developing systemic amyloidosis (SA) and the risk of local recurrence of primary localised...

  2. Comparing mobile robot localisation algorithms using Kalmtool

    DEFF Research Database (Denmark)

    Mogensen, Lars Valdemar; Hansen, Søren; Ravn, Ole


    In this paper we present an estimation platform with simulation capabilities to evaluate methods for localisation of a mobile robot using a feature map. The platform is based on the Kalmtool 4 toolbox which is a set of MATLAB tools for state estimation of nonlinear systems. The toolbox contains...

  3. Search and localisation of CERN buildings

    CERN Multimedia

    TS/FM - Patrimony and Site Information Section


    A new, updated version of the web application allowing search and localisation of CERN buildings has been available since 20 May 2005. You can now find a specific building, road, car-park and other information regarding the CERN sites. For comments or enquiries please contact TS/FM - Patrimony and Site Information Section (ISP)

  4. Neuronal NOS localises to human airway cilia. (United States)

    Jackson, Claire L; Lucas, Jane S; Walker, Woolf T; Owen, Holly; Premadeva, Irnthu; Lackie, Peter M


    Airway NO synthase (NOS) isoenzymes are responsible for rapid and localised nitric oxide (NO) production and are expressed in airway epithelium. We sought to determine the localisation of neuronal NOS (nNOS) in airway epithelium due to the paucity of evidence. Sections of healthy human bronchial tissue in glycol methacrylate resin and human nasal polyps in paraffin wax were immunohistochemically labelled and reproducibly demonstrated nNOS immunoreactivity, particularly at the proximal portion of cilia; this immunoreactivity was blocked by a specific nNOS peptide fragment. Healthy human epithelial cells differentiated at an air-liquid interface (ALI) confirmed the presence of all three NOS isoenzymes by immunofluorescence labelling. Only nNOS immunoreactivity was specific to the ciliary axonemeand co-localised with the cilia marker β-tubulin in the proximal part of the ciliary axoneme. We report a novel localisation of nNOS at the proximal portion of cilia in airway epithelium and conclude that its independent and local regulation of NO levels is crucial for normal cilia function. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

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


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

  6. Correlated alpha activity with the facial expression processing network in a simultaneous EEG-fMRI experiment. (United States)

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


    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.

  7. Structural (operational) synchrony of EEG alpha activity during an auditory memory task. (United States)

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


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

    International Nuclear Information System (INIS)

    Tobias, C.C.B.


    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

  10. Generalised two target localisation using passive monopulse radar

    KAUST Repository

    Jardak, Seifallah; Ahmed, Sajid; Alouini, Mohamed-Slim


    The simultaneous lobing technique, also known as monopulse technique, has been widely used for fast target localisation and tracking purposes. Many works focused on accurately localising one or two targets lying within a narrow beam centred around

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

    Directory of Open Access Journals (Sweden)

    Cristina Di Donato


    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.

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

    Directory of Open Access Journals (Sweden)

    Mahmoud M. Mansour


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

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

    Directory of Open Access Journals (Sweden)

    Robert C McDermid


    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.

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

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


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

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

    International Nuclear Information System (INIS)

    Chakravarti, S.K.


    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

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

    LENUS (Irish Health Repository)

    Carroll, Tomás P


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

  17. 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.


    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)

  18. 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.


    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.

  19. Channelrhodopsin-2 localised to the axon initial segment.

    Directory of Open Access Journals (Sweden)

    Matthew S Grubb


    Full Text Available The light-gated cation channel Channelrhodopsin-2 (ChR2 is a powerful and versatile tool for controlling neuronal activity. Currently available versions of ChR2 either distribute uniformly throughout the plasma membrane or are localised specifically to somatodendritic or synaptic domains. Localising ChR2 instead to the axon initial segment (AIS could prove an extremely useful addition to the optogenetic repertoire, targeting the channel directly to the site of action potential initiation, and limiting depolarisation and associated calcium entry elsewhere in the neuron. Here, we describe a ChR2 construct that we localised specifically to the AIS by adding the ankyrinG-binding loop of voltage-gated sodium channels (Na(vII-III to its intracellular terminus. Expression of ChR2-YFP-Na(vII-III did not significantly affect the passive or active electrical properties of cultured rat hippocampal neurons. However, the tiny ChR2 currents and small membrane depolarisations resulting from AIS targeting meant that optogenetic control of action potential firing with ChR2-YFP-Na(vII-III was unsuccessful in baseline conditions. We did succeed in stimulating action potentials with light in some ChR2-YFP-Na(vII-III-expressing neurons, but only when blocking KCNQ voltage-gated potassium channels. We discuss possible alternative approaches to obtaining precise control of neuronal spiking with AIS-targeted optogenetic constructs and propose potential uses for our ChR2-YFP-Na(vII-III probe where subthreshold modulation of action potential initiation is desirable.

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

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Hara Lim


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

  2. Oridonin stabilizes retinoic acid receptor alpha through ROS-activated NF-κB signaling. (United States)

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


    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

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

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


    The present studies were designed to determine effects of microgravity upon lipopolysaccharide (LPS) stimulated tumor necrosis factor alpha (TNF - alpha) activity and indices of insulin and fuel homeostasis of pancreatic islets of Langerhans. Islets (1726+/-117,150 u IEU) from Wistar Furth rats were treated as: 1) HARV (High Aspect Ratio Vessel cell culture) , 2) HARV plus LPS 3) static culture, 4) static culture plus LPS TNF-alpha (L929 cytotoxicity assay) was significantly increased in LPS-induced HARV and static cultures, yet the increase was more pronounced in the static culture group (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.

  4. 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:; Silva, Antonio A. [Universidade Federal de Vicosa (UFV), MG (Brazil). Dept. de Fitotecnia


    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)

  5. Localised Microwave Bursts During ELMs on MAST

    Directory of Open Access Journals (Sweden)

    Freethy Simon


    Full Text Available Bursts of microwave emission are observed during ELM events on the Mega Ampère Spherical Tokamak. In agreement with observations on other machines, these bursts are up to 3 orders of magnitude more intense than the thermal background, but are electron cyclotron in nature. The peak in microwave emission is ~20μ before the peak in midplane Dα emission. Using the Synthetic Aperture Microwave Imaging radiometer, we are able to demonstrate that these bursts are often highly spatially localised and preferentially occur at the tokamak midplane. It is hypothesised that the localisation is a result of Doppler resonance broadening for electron Bernstein waves and the high perpendicular electron energies could be the result of pitch angle scattering in high collisionality regions of the plasma.

  6. The Role of Localisation in Advertising Translation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ying


    Today, a growing number of international corporations have been seeking to boost their sales on the global scale. To achieve this, adverting, one of the most common way to stimulate consumption, is widely used in which translation is involved because of diverse languages. Thus, how to translate a source advertising in a target culture has a decisive influence on a compa-ny’s marketing. The aim of the target advertising is to sell products to the locals. In this sense, localisation plays a significant role in the translation of advertising. This essay will discuss the importance of localisation in the translation of advertising and analyse cases of English-Chinese advertising translation based on the purpose of advertising and advertising translation.

  7. Kinesthetic and vestibular information modulate alpha activity during spatial navigation: a mobile EEG study. (United States)

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


    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.

  8. Clofibric acid, a peroxisome proliferator-activated receptor alpha ligand, inhibits growth of human ovarian cancer. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Benedikt Valerian Ehinger


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

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

    Directory of Open Access Journals (Sweden)

    Marco Emanuele


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

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

    DEFF Research Database (Denmark)

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


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

  12. 'Localised creativity: a life span perspective'


    Worth, Piers J.


    This thesis is based around a biographic study of the lives of 40 individuals (24 men and 16 women) with a reputation for creative work in a localised context (such as an organisation). The study examines life span development patterns from birth to middle age (45 - 60 years of age) with data gained by biographic interview and thematic analysis. Participants selected for this study are creative in that they have a reputation for producing new, novel and useful or appropriate contributions in ...

  13. Metabolic adaptation to intermittent fasting is independent of peroxisome proliferator-activated receptor alpha. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Guolin Li


    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

  15. Alpha-Band Activity Reveals Spontaneous Representations of Spatial Position in Visual Working Memory. (United States)

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


    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.

  16. Salivary alpha amylase activity in human beings of different age groups subjected to psychological stress. (United States)

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


    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.

  17. 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.

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

    DEFF Research Database (Denmark)

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


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

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

    DEFF Research Database (Denmark)

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


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

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

    NARCIS (Netherlands)

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


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

  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.


    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.


    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. (United States)

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


    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


    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 (United States)

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


    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. 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


    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...

  7. 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

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

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


    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. 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.


    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

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


    low molecular weight recombinant human gelatin: development of a substitute for animal- derived gelatin with superior features, Protein Expr. 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

  11. Dopamine activates masculine sexual behavior independent of the estrogen receptor alpha. (United States)

    Wersinger, S R; Rissman, E F


    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.

  12. Structural basis for alpha fetoprotein-mediated inhibition of caspase-3 activity in hepatocellular carcinoma cells. (United States)

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


    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.

  13. 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: [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of)


    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.

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


    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.

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

    DEFF Research Database (Denmark)

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


    The mechanism of activation of the transient receptor potential vanilloid 4 (TRPV4) channel by 4alpha-phorbol esters was investigated by combining information from chemical modification of 4alpha-phorbol-didecanoate (4alpha-PDD, 2a), site-directed mutagenesis, Ca(2+) imaging, and 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...

  16. Effect of peroxisome proliferator-activated receptor alpha activators on tumor necrosis factor expression in mice during endotoxemia. (United States)

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


    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

  17. 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. (United States)

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


    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.

  18. 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


    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...

  19. CT-assisted localisation of intracranial processes

    Energy Technology Data Exchange (ETDEWEB)

    Luft, C.; Trenkler, J.; Hammer, B.; Valencak, E.


    With the software developed for the SOMATOM DRH computerized tomograph it is possible to mix a ROI into the digital radiogram (topogram) for projection of a lesion, such as a tumor, onto the topogram plane; the software also allows an image reconstruction taking the topogram as a reference image (topogram-initiated reconstruction). Combining these two relatively simple methods, and adding distance measurements in two planes, the neurosurgeon has at his disposal an objective CT-assisted means of precisely localising intracranial processes before surgery.

  20. CT-assisted localisation of intracranial processes

    International Nuclear Information System (INIS)

    Luft, C.; Trenkler, J.; Hammer, B.; Valencak, E.


    With the software developed for the SOMATOM DRH computerized tomograph it is possible to mix a ROI into the digital radiogram (topogram) for projection of a lesion, such as a tumor, onto the topogram plane; the software also allows an image reconstruction taking the topogram as a reference image (topogram-initiated reconstruction). Combining these two relatively simple methods, and adding distance measurements in two planes, the neurosurgeon has at his disposal an objective CT-assisted means of precisely localising intracranial processes before surgery. (orig.) [de

  1. Localisation in a Growth Model with Interaction (United States)

    Costa, M.; Menshikov, M.; Shcherbakov, V.; Vachkovskaia, M.


    This paper concerns the long term behaviour of a growth model describing a random sequential allocation of particles on a finite cycle graph. The model can be regarded as a reinforced urn model with graph-based interaction. It is motivated by cooperative sequential adsorption, where adsorption rates at a site depend on the configuration of existing particles in the neighbourhood of that site. Our main result is that, with probability one, the growth process will eventually localise either at a single site, or at a pair of neighbouring sites.

  2. The Anderson model for electron localisation

    International Nuclear Information System (INIS)

    Pruisken, A.M.M.; Schaefer, L.


    The Anderson model for localisation problems is treated with field theory employing the replica trick. We show that no valid perturbation theory results out of the usual (S2)2 formalism due to mishandling of symmetries. The problem is reformulated in terms of matrix fields. It is shown that the Anderson model asymptotically exhibits an exact local gauge symmetry. Elimination of massive longitudinal components leads to a non-compact sigma model, obtained earlier for the description of electronic disorder. We thus establish that the Anderson model is in the same universality class as Wegner's gauge invariant real matrix model. (orig.)

  3. Hypolipidaemic and antiplatelet activity of phenoxyacetic acid derivatives related to alpha-asarone. (United States)

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


    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.

  4. 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)


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Suarez, C


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

  6. To localise or to be localised with Wifi in the Hubei museum?

    NARCIS (Netherlands)

    Verbree, E.; Zlatanova, S.; Van Winden, K.; Van der Laan, E.B.; Makri, A.; Taizhou, L.; Haojun, A.


    Indoor localisation is in demand for a variety of applications within the built environment. An overall solution based on a single technology has not yet been determined. The aim of this paper is to gain insight on Signal Strength monitoring by a special kind of WiFi Monitors in comparison to the

  7. A machine-hearing system exploiting head movements for binaural sound localisation in reverberant conditions

    DEFF Research Database (Denmark)

    May, Tobias; Ma, Ning; Wierstorf, Hagen


    This paper is concerned with machine localisation of multiple active speech sources in reverberant environments using two (binaural) microphones. Such conditions typically present a problem for ‘classical’ binaural models. Inspired by the human ability to utilise head movements, the current study...

  8. Localisation of the neuropeptide PACAP and its receptors in the rat parathyroid and thyroid glands

    DEFF Research Database (Denmark)

    Fahrenkrug, Jan; Hannibal, Jens


    PACAP (pituitary adenylate cyclase activating polypeptide) is widely distributed neuropeptide acting via three subtypes of receptors, PAC(1), VPAC(1) and VPAC(2). Here we examined the localisation and nature of PACAP-immunoreactive nerves in the rat thyroid and parathyroid glands and defined the ...

  9. Passive RFID Localisation Framework in Smart Homes Healthcare Settings. (United States)

    Alsinglawi, Belal; Liu, Tony; Nguyen, Quang Vinh; Gunawardana, Upul; Maeder, Anthony; Simoff, Simeon


    In recent years, Smart Homes have become a solution to benefit impaired individuals and elderly in their daily life settings. In healthcare applications, pervasive technologies have enabled the practicality of personal monitoring using Indoor positioning technologies. Radio-Frequency Identification (RFID) is a promising technology, which is useful for non-invasive tracking of activities of daily living. Many implementations have focused on using battery-enabled tags like in RFID active tags, which require frequent maintenance and they are costly. Other systems can use wearable sensors requiring individuals to wear tags which may be inappropriate for elders. Successful implementations of a tracking system are dependent on multiple considerations beyond the physical performance of the solution, such as affordability and human acceptance. This paper presents a localisation framework using passive RFID sensors. It aims to provide a low cost solution for subject location in Smart Homes healthcare.

  10. Impact source localisation in aerospace composite structures (United States)

    De Simone, Mario Emanuele; Ciampa, Francesco; Boccardi, Salvatore; Meo, Michele


    The most commonly encountered type of damage in aircraft composite structures is caused by low-velocity impacts due to foreign objects such as hail stones, tool drops and bird strikes. Often these events can cause severe internal material damage that is difficult to detect and may lead to a significant reduction of the structure’s strength and fatigue life. For this reason there is an urgent need to develop structural health monitoring systems able to localise low-velocity impacts in both metallic and composite components as they occur. This article proposes a novel monitoring system for impact localisation in aluminium and composite structures, which is able to determine the impact location in real-time without a-priori knowledge of the mechanical properties of the material. This method relies on an optimal configuration of receiving sensors, which allows linearization of well-known nonlinear systems of equations for the estimation of the impact location. The proposed algorithm is based on the time of arrival identification of the elastic waves generated by the impact source using the Akaike Information Criterion. The proposed approach was demonstrated successfully on both isotropic and orthotropic materials by using a network of closely spaced surface-bonded piezoelectric transducers. The results obtained show the validity of the proposed algorithm, since the impact sources were detected with a high level of accuracy. The proposed impact detection system overcomes current limitations of other methods and can be retrofitted easily on existing aerospace structures allowing timely detection of an impact event.

  11. [Morphea or juvenile localised scleroderma: Case report]. (United States)

    Strickler, Alexis; Gallo, Silvanna; Jaramillo, Pedro; de Toro, Gonzalo


    Morphea or juvenile localised scleroderma (JLS) is an autoimmune, inflammatory, chronic, slowly progressive connective tissue disease of unknown cause that preferably affects skin and underlying tissues. To report a case of Juvenil Localised scleroderma in an 8-year old girl, contributing to an early diagnosis and treatment. The case is presented of an 8 year-old girl who presented with indurated hypopigmented plaques, of linear distribution in the right upper extremity of two years onset, together with papery texture hyperpigmented indurated plaques with whitish areas of thinned skin in right lower extremity, and leg and ankle swelling. The clinical features and diagnostic tests, including histology were compatible with linear and pansclerotic JLS. She started with immunosuppressive therapy, physiotherapy, and occupational therapy. We report a case of linear and pansclerotic ELJ type, in which there was a 2 year delay in diagnosis, however the response to treatment was positive as expected. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Hua Xing


    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.

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

    Directory of Open Access Journals (Sweden)

    Naoki Matsuo


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

  14. 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.


    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

  15. Effect of neohesperidin dihydrochalcone on the activity and stability of alpha-amylase: a comparative study on bacterial, fungal, and mammalian enzymes. (United States)

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


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  17. 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


    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)

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


    Strahler, Jana


    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...

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

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


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

  20. Strain localisation in mechanically layered rocks beneath detachment zones: insights from numerical modelling

    Directory of Open Access Journals (Sweden)

    L. Le Pourhiet


    Full Text Available We have designed a series of fully dynamic numerical simulations aimed at assessing how the orientation of mechanical layering in rocks controls the orientation of shear bands and the depth of penetration of strain in the footwall of detachment zones. Two parametric studies are presented. In the first one, the influence of stratification orientation on the occurrence and mode of strain localisation is tested by varying initial dip of inherited layering in the footwall with regard to the orientation of simple shear applied at the rigid boundary simulating a rigid hanging wall, all scaling and rheological parameter kept constant. It appears that when Mohr–Coulomb plasticity is being used, shear bands are found to localise only when the layering is being stretched. This corresponds to early deformational stages for inital layering dipping in the same direction as the shear is applied, and to later stages for intial layering dipping towards the opposite direction of shear. In all the cases, localisation of the strain after only γ=1 requires plastic yielding to be activated in the strong layer. The second parametric study shows that results are length-scale independent and that orientation of shear bands is not sensitive to the viscosity contrast or the strain rate. However, decreasing or increasing strain rate is shown to reduce the capacity of the shear zone to localise strain. In the later case, the strain pattern resembles a mylonitic band but the rheology is shown to be effectively linear. Based on the results, a conceptual model for strain localisation under detachment faults is presented. In the early stages, strain localisation occurs at slow rates by viscous shear instabilities but as the layered media is exhumed, the temperature drops and the strong layers start yielding plastically, forming shear bands and localising strain at the top of the shear zone. Once strain localisation has occured, the deformation in the shear band becomes

  1. 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


    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...

  2. 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.


    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

  3. 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)


    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.

  4. 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.


    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%)

  5. 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.


    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)

  6. Influence of thermodynamic parameter in Lanosterol 14alpha-demethylase inhibitory activity as antifungal agents: a QSAR approach. (United States)

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


    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.

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

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


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

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


    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

  10. Localisation of metastatic carcinoma by a radiolabelled monoclonal antibody

    Energy Technology Data Exchange (ETDEWEB)

    Smedley, H M; Ritson, A; Wraight, P; Sikora, K [Addenbrooke' s Hospital, Cambridge (UK); Hinchingbrooke Hospital, Huntingdon (UK)); Finan, P [St. James Hospital, Leeds (UK); Lennox, E S; Takei, F [Medical Research Council, Cambridge (UK)


    Rat monoclonal antibodies were prepared by immunising rats with human colorectal carcinoma cell membranes and fusing splenic lymphocytes with a rat myeloma. Hybridoma supernatants were screened by binding assays on membranes prepared from colorectal carcinoma tissue. One hybridoma supernatant, containing a monoclonal antibody with high binding activity on malignant compared to normal colon sections, was grown in large quantities in serum-free medium. After ammonium sulphate precipitation the antibody was purified by ion-exchange chromatography and labelled with /sup 131/I. Radiolabelled antibody was administered i.v. to 27 patients with colonic and other tumours. Scintigrams were obtained at 48 h. Computerised subtraction of the blood pool image revealed localised areas of uptake corresponding with areas of known disease in 13/16 patients with colorectal carcinoma and 3/4 patients with breast cancer.

  11. An innovative localisation algorithm for railway vehicles (United States)

    Allotta, B.; D'Adamio, P.; Malvezzi, M.; Pugi, L.; Ridolfi, A.; Rindi, A.; Vettori, G.


    In modern railway automatic train protection and automatic train control systems, odometry is a safety relevant on-board subsystem which estimates the instantaneous speed and the travelled distance of the train; a high reliability of the odometry estimate is fundamental, since an error on the train position may lead to a potentially dangerous overestimation of the distance available for braking. To improve the odometry estimate accuracy, data fusion of different inputs coming from a redundant sensor layout may be used. The aim of this work has been developing an innovative localisation algorithm for railway vehicles able to enhance the performances, in terms of speed and position estimation accuracy, of the classical odometry algorithms, such as the Italian Sistema Controllo Marcia Treno (SCMT). The proposed strategy consists of a sensor fusion between the information coming from a tachometer and an Inertial Measurements Unit (IMU). The sensor outputs have been simulated through a 3D multibody model of a railway vehicle. The work has provided the development of a custom IMU, designed by ECM S.p.a, in order to meet their industrial and business requirements. The industrial requirements have to be compliant with the European Train Control System (ETCS) standards: the European Rail Traffic Management System (ERTMS), a project developed by the European Union to improve the interoperability among different countries, in particular as regards the train control and command systems, fixes some standard values for the odometric (ODO) performance, in terms of speed and travelled distance estimation. The reliability of the ODO estimation has to be taken into account basing on the allowed speed profiles. The results of the currently used ODO algorithms can be improved, especially in case of degraded adhesion conditions; it has been verified in the simulation environment that the results of the proposed localisation algorithm are always compliant with the ERTMS requirements

  12. 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: [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)


    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.

  13. Enantioselective cellular localisation of europium(iii) coordination complexes. (United States)

    Frawley, Andrew T; Linford, Holly V; Starck, Matthieu; Pal, Robert; Parker, David


    The selective mitochondrial localisation of the Λ enantiomer of three different emissive europium(iii) complexes in NIH 3T3 and MCF7 cells contrasts with the behaviour of the Δ enantiomer, for which a predominant lysosomal localisation was observed by confocal microscopy. In each case, cell uptake occurs via macropinocytosis.

  14. Differences in finger localisation performance of patients with finger agnosia

    NARCIS (Netherlands)

    Anema, H.A.; Kessels, R.P.C.; de Haan, E.H.F.; Kappelle, L.J.; Leijten, F.S.; van Zandvoort, M.J.E.; Dijkerman, H.C.


    Several neuropsychological studies have suggested parallel processing of somatosensory input when localising a tactile stimulus on one's own by pointing towards it (body schema) and when localising this touched location by pointing to it on a map of a hand (body image). Usually these reports

  15. Differences in finger localisation performance of patients with finger agnosia

    NARCIS (Netherlands)

    Anema, H.A.; Kessels, R.P.C.; Haan, E.H.F. de; Kappelle, L.J.; Leijten, F.S.S.; Zandvoort, M.J.E. van; Dijkerman, H.C.


    Several neuropsychological studies have suggested parallel processing of somatosensory input when localising a tactile stimulus on ones own by pointing towards it (body schema) and when localising this touched location by pointing to it on a map of a hand (body image). Usually these reports describe

  16. Differences in finger localisation performance of patients with finger agnosia.

    NARCIS (Netherlands)

    Anema, H.A.; Kessels, R.P.C.; Haan, E.H.F. de; Kappelle, L.J.; Leijten, F.S.S.; Zandvoort, M.J. Van; Dijkerman, H.C.


    Several neuropsychological studies have suggested parallel processing of somatosensory input when localising a tactile stimulus on one's own by pointing towards it (body schema) and when localising this touched location by pointing to it on a map of a hand (body image). Usually these reports

  17. Localisation system in wireless sensor networks using ns-2

    CSIR Research Space (South Africa)

    Abu-Mahfouz, Adnan M


    Full Text Available -1 /************************************************************************** ********** * * File: readme.asn * * Author: Adnan Abu-Mahfouz * * Date: March 2012 * * Description: Localisation system in wireless sensor networks using ns-2... *************************************************************************** *********/ /************************************************************************** *************************************************************************** *****/ 1. Introduction: ns-2 contains several flexible features that encourage researchers to use ns-2 to investigate the characteristics of wireless sensor networks (WSNs). However, to implement and evaluate localisation algorithms, the current ns- 2...

  18. Amelogenesis imperfecta and localised aggressive periodontitis: A rare clinical entity

    Directory of Open Access Journals (Sweden)

    Gayatri Gundannavar


    Full Text Available This case report presents two female patients whose chief complaint was discoloration of teeth. On careful clinical examination it was found that the patients had features of amelogenesis imperfecta and localised aggressive periodontitis. This article will give an insight of clinical and radiographic features of amelogenesis imperfecta with localised aggressive periodontitis, which is a rare clinical entity.

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

  20. 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.


    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

  1. 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.


    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)

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

    NARCIS (Netherlands)


    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Crespo, M T; Acena, M L


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

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

    NARCIS (Netherlands)

    Bonnefond, M.; Jensen, O.


    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

  6. 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.


    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...

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

    DEFF Research Database (Denmark)

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


    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...

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

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

  9. 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


    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...

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

    Directory of Open Access Journals (Sweden)

    Elton Zeqiraj


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

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

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


    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.

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


    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

  14. 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.


    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.)

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


    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.

  16. 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


    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)

  17. Feasibility of magnetic marker localisation for non-palpable breast cancer

    NARCIS (Netherlands)

    Schermers, B.; van der Hage, Jos A.; Loo, C.E.; Vrancken Peeters, M.T.F.D.; Winter-Warnars, H. A.O.; Duijnhoven, F.H.; ten Haken, B.; Muller, S.H.; Ruers, T. J.M.


    Objectives Accurate tumour localisation is essential for breast-conserving surgery of non-palpable tumours. Current localisation technologies are associated with disadvantages such as logistical challenges and migration issues (wire guided localisation) or legislative complexities and high


    Energy Technology Data Exchange (ETDEWEB)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Li Jin-Lian


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

  20. 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.


    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.)

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  2. 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.


    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

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

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


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

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

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


    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.

  5. Localised states in organic semiconductors and their detection (United States)

    Imperia, Paolo


    oxadiazoles, studied because of their technological relevance, show complex thermograms, having several levels of localised states and depolarisation peaks. In particular well ordered films of an amphiphilic substituted 2-(p-nitrophenyl)-5-(p-undecylamidophenyl)-1,3,4-oxadiazole (NADPO) are characterised by rich TSL thermograms. A wide region of shallow traps, localised at Em = 4 meV, has been successfully fit by means of a first order kinetic equation having a Gaussian distribution of localised states. Two further peaks, having a different origin, have been characterised. The peaks at Tm = 221.5 K and Tm = 254.2 have activation energy of Em= 0.63 eV and Em = 0.66 eV, frequency factor s = 2.4x1012 s-1 and s = 1.85x1011 s-1, distribution width s = 0.045 eV and s = 0.088 eV respectively. Increasing the number of thermal cycle, a peak, probably connected with structural defects, appears at Tm = 197.7 K. The numerical analysis of this peak was performed by means of a first order equation containing a Gaussian distribution of traps. The activation energy of the trap level is centred at Em = 0.55 eV. The distribution is perfectly symmetric with a quite small width s = 0.028 eV. The frequency factor is s = 1.15 x 1012 s-1, resulting of the same order of magnitude of its neighbour peak at Tm = 221.5 K, having both, probably, the same origin. Furthermore the work demonstrates that the shape of the glow curves is strongly influenced by the excitation temperature and by the thermal cycles. For that reason Gaussian distributions of localised states can be confused with exponential distributions if the previous thermal history of the samples is not adequately considered. In den letzten Jahren ist eine Vielzahl neuer organischer Polymere und niedermolekularer Verbindungen synthetisiert worden, die sich als aktive Komponente für Elektrolumineszenz-Bauelemente und andere elektronische Anwendungen eignen. Trotz der großen technologischen Bedeutung und des erheblichen Fortschrittes, der bei

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

    Vinholes, Juliana; Vizzotto, Márcia


    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

  7. Synergisms in Alpha-glucosidase Inhibition and Antioxidant Activity of Camellia sinensis L. Kuntze and Eugenia uniflora L. Ethanolic Extracts. (United States)

    Vinholes, Juliana; Vizzotto, Márcia


    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

  8. 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


    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...

  9. 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.


    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)

  10. 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.


    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.

  11. 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


    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.

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

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


    Alpha-amylase is a kind of broadly used industrial enzymes, most of which have been exploited from terrestrial organism. Comparatively, alpha-amylase from marine environment was largely undeveloped. In this study, a novel alkalophilic alpha-amylase with high activity, Luteimonas abyssi alpha-amylase (LaaA), was cloned from deep-sea bacterium L. abyssi XH031(T) and expressed in Escherichia coli BL21. The gene has a length of 1428bp and encodes 475 amino acids with a 35-residue signal peptide. The specific activity of LaaA reached 8881U/mg at the optimum pH 9.0, which is obvious higher than other reported alpha-amylase. This enzyme can remain active at pH levels ranging from 6.0 to 11.0 and temperatures below 45°C, retaining high activity even at low temperatures (almost 38% residual activity at 10°C). In addition, 1mM Na(+), K(+), and Mn(2+) enhanced the activity of LaaA. To investigate the function of potential active sites, R227G, D229K, E256Q/H, H327V and D328V mutants were generated, and the results suggested that Arg227, Asp229, Glu256 and Asp328 were total conserved and essential for the activity of alpha-amylase LaaA. This study shows that the alpha-amylase LaaA is an alkali-tolerant and high-active amylase with strong potential for use in detergent industry. Copyright © 2016 Elsevier Inc. All rights reserved.

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


    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.

  14. Influence of polymer matrix and adsorption onto silica materials on the migration of alpha-tocopherol into 95% ethanol from active packaging. (United States)

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


    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.

  15. Blockade of alcohol's amnestic activity in humans by an alpha5 subtype benzodiazepine receptor inverse agonist. (United States)

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


    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.

  16. 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.


    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

  17. Generalised two target localisation using passive monopulse radar

    KAUST Repository

    Jardak, Seifallah


    The simultaneous lobing technique, also known as monopulse technique, has been widely used for fast target localisation and tracking purposes. Many works focused on accurately localising one or two targets lying within a narrow beam centred around the monopulse antenna boresight. In this study, a new approach is proposed, which uses the outputs of four antennas to rapidly localise two point targets present in the hemisphere. If both targets have the same elevation angle, the proposed scheme cannot detect them. To detect such targets, a second set of antennas is required. In this study, to detect two targets at generalised locations, the antenna array is divided into multiple overlapping sets each of four antennas. Two algorithms are proposed to combine the outputs from multiple sets and improve the detection performance. Simulation results show that the algorithm is able to localise both targets with <;2° mean square error in azimuth and elevation.

  18. Is the Pauli exclusion principle the origin of electron localisation? (United States)

    Rincón, Luis; Torres, F. Javier; Almeida, Rafael


    In this work, we inquire into the origins of the electron localisation as obtained from the information content of the same-spin pair density, γσ, σ(r2∣r1). To this end, we consider systems of non-interacting and interacting identical Fermions contained in two simple 1D potential models: (1) an infinite potential well and (2) the Kronig-Penney periodic potential. The interparticle interaction is considered through the Hartree-Fock approximation as well as the configuration interaction expansion. Morover, the electron localisation is described through the Kullback-Leibler divergence between γσ, σ(r2∣r1) and its associated marginal probability. The results show that, as long as the adopted method properly includes the Pauli principle, the electronic localisation depends only modestly on the interparticle interaction. In view of the latter, one may conclude that the Pauli principle is the main responsible for the electron localisation.


    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)


    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.

  20. Critical Factors in Transnational Oil Companies Localisation Decisions - Clusters and Portfolio Optimisation

    International Nuclear Information System (INIS)

    Kind, Hans Jarle; Osmundsen, Petter; Tverteraas, Ragnar


    Enhanced understanding of the factors determining trans national companies' localisation decisions is important for regulators and other stake holders concerned about maintaining current activity levels in a petroleum producing country. This article discusses localisation decisions in the context of theories of industrial clusters and real portfolio optimisation theory (materiality), which we argue are two fruitful lines of explanation for trans national companies' behaviour. The industrial cluster literature is concerned about the level of positive externalities associated with geographic clustering of related production activities. The concept of materiality, implying that investment projects in an oil province must be of a certain minimum size in order to be interesting for oil companies, is evaluated empirically and compared to predictions of mainstream economic theory. (author)

  1. Critical Factors in Transnational Oil Companies Localisation Decisions - Clusters and Portfolio Optimisation

    Energy Technology Data Exchange (ETDEWEB)

    Kind, Hans Jarle; Osmundsen, Petter; Tverteraas, Ragnar


    Enhanced understanding of the factors determining transnational companies' localisation decisions is important for regulators and other stakeholders concerned about maintaining current activity levels in a petroleum producing country. This article discusses localisation decisions in the context of theories of industrial clusters and real portfolio optimisation theory (materiality), which we argue are two fruitful lines of explanation for transnational companies' behaviour. The industrial cluster literature is concerned about the level of positive externalities associated with geographic clustering of related production activities. The concept of materiality, implying that investment projects in an oil province must be of a certain minimum size in order to be interesting for oil companies, is evaluated empirically and compared to predictions of mainstream economic theory. (author)

  2. Immunohistochemical localisation of d-β-aspartic acid in pingueculae


    Kaji, Y; Oshika, T; Okamoto, F; Fujii, N


    Background: D-β-Aspartic acid residues, which are biologically uncommon, have been reported to accumulate in various proteins of the living body with age. In the present study, D-β-aspartic acid-containing proteins were found to be localised in pingueculae, which represent one of the most prominent age-related ocular changes.Methods: Surgical specimens of conjunctivae with or without pingueculae were obtained from eight patients. Immunohistochemical localisation of D-β-aspartic acid-containin...

  3. Gross alpha and beta activity analyses in urine-a routine laboratory method for internal human radioactivity detection. (United States)

    Chen, Xiaowen; Zhao, Luqian; Qin, Hongran; Zhao, Meijia; Zhou, Yirui; Yang, Shuqiang; Su, Xu; Xu, Xiaohua


    The aim of this work was to develop a method to provide rapid results for humans with internal radioactive contamination. The authors hypothesized that valuable information could be obtained from gas proportional counter techniques by screening urine samples from potentially exposed individuals rapidly. Recommended gross alpha and beta activity screening methods generally employ gas proportional counting techniques. Based on International Standards Organization (ISO) methods, improvements were made in the evaporation process to develop a method to provide rapid results, adequate sensitivity, and minimum sample preparation and operator intervention for humans with internal radioactive contamination. The method described by an American National Standards Institute publication was used to calibrate the gas proportional counter, and urine samples from patients with or without radionuclide treatment were measured to validate the method. By improving the evaporation process, the time required to perform the assay was reduced dramatically. Compared with the reference data, the results of the validation samples were very satisfactory with respect to gross-alpha and gross-beta activities. The gas flow proportional counting method described here has the potential for radioactivity monitoring in the body. This method was easy, efficient, and fast, and its application is of great utility in determining whether a sample should be analyzed by a more complicated method, for example radiochemical and/or γ-spectroscopy. In the future, it may be used commonly in medical examination and nuclear emergency treatment.Health Phys. 106(5):000-000; 2014.

  4. Indoor Localisation Based on GSM Signals: Multistorey Building Study

    Directory of Open Access Journals (Sweden)

    Rafał Górak


    Full Text Available Among the accurate indoor localisation systems that are using WiFi, Bluetooth, or infrared technologies, the ones that are based on the GSM rely on a stable external infrastructure that can be used even in an emergency. This paper presents an accurate GSM indoor localisation system that achieves a median error of 4.39 metres in horizontal coordinates and up to 64 percent accuracy in floor prediction (for 84 percent of cases the floor prediction is mistaken by not more than a single floor. The test and reference measurements were made inside a six-floor academic building, with an irregular shape, whose dimensions are around 50 metres by 70 metres. The localisation algorithm uses GSM signal readings from the 7 strongest cells available in the GSM standard (or fewer, if fewer than 7 are available. We estimate the location by a three-step method. Firstly, we propose a point localisation solution (i.e., localisation based on only one measurement. Then, by applying the central tendency filters and the Multilayer Perceptron, we build a localisation system that uses a sequence of estimations of current and past locations. We also discuss major accuracy factors such as the number of observed signals or the types of spaces in the building.

  5. Localising welfare-to-work? Territorial flexibility and the New Deal for Young People


    Corinne Nativel; Peter Sunley; Ron Martin


    The move towards workfare and active labour-market policies is often alleged to be closely associated with the decentralisation and localisation of welfare delivery and agencies. In the United Kingdom, the New Deal for the young unemployed was designed to introduce local flexibility and discretion in delivery to mainstream labour-market policy. We use case studies of five local areas to examine the extent to which the programme has actually been decentralised and benefited from 'local flexibi...

  6. Hantaan Virus Nucleocapsid Protein Binds to Importin alpha Proteins and Inhibits Tumor Necrosis Factor Alpha-Induced Activation of Nuclear Factor Kappa B (United States)


    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. (United States)

    Valle, Marta; Maqueda, Ana Elda; Rabella, Mireia; Rodríguez-Pujadas, Aina; Antonijoan, Rosa Maria; Romero, Sergio; Alonso, Joan Francesc; Mañanas, Miquel Àngel; Barker, Steven; Friedlander, Pablo; Feilding, Amanda; Riba, Jordi


    Ayahuasca is an Amazonian psychotropic plant tea typically obtained from two plants, Banisteriopsis caapi and Psychotria viridis. It contains the psychedelic 5-HT2A and sigma-1 agonist N,N-dimethyltryptamine (DMT) plus β-carboline alkaloids with monoamine-oxidase (MAO)-inhibiting properties. Although the psychoactive effects of ayahuasca have commonly been attributed solely to agonism at the 5-HT2A receptor, the molecular target of classical psychedelics, this has not been tested experimentally. Here we wished to study the contribution of the 5-HT2A receptor to the neurophysiological and psychological effects of ayahuasca in humans. We measured drug-induced changes in spontaneous brain oscillations and subjective effects in a double-blind randomized placebo-controlled study involving the oral administration of ayahuasca (0.75mg DMT/kg body weight) and the 5-HT2A antagonist ketanserin (40mg). Twelve healthy, experienced psychedelic users (5 females) participated in four experimental sessions in which they received the following drug combinations: placebo+placebo, placebo+ayahuasca, ketanserin+placebo and ketanserin+ayahuasca. Ayahuasca induced EEG power decreases in the delta, theta and alpha frequency bands. Current density in alpha-band oscillations in parietal and occipital cortex was inversely correlated with the intensity of visual imagery induced by ayahuasca. Pretreatment with ketanserin inhibited neurophysiological modifications, reduced the correlation between alpha and visual effects, and attenuated the intensity of the subjective experience. These findings suggest that despite the chemical complexity of ayahuasca, 5-HT2A activation plays a key role in the neurophysiological and visual effects of ayahuasca in humans. 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: [Department of Biochemistry, College of Natural Sciences, Kangwon National University, 192-1 Hyoja-2-dong, Chuncheon 200-701 (Korea, Republic of)


    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. Antenna array geometry optimization for a passive coherent localisation system (United States)

    Knott, Peter; Kuschel, Heiner; O'Hagan, Daniel


    Passive Coherent Localisation (PCL), also known as Passive Radar, making use of RF sources of opportunity such as Radio or TV Broadcasting Stations, Cellular Phone Network Base Stations, etc. is an advancing technology for covert operation because no active radar transmitter is required. It is also an attractive addition to existing active radar stations because it has the potential to discover low-flying and low-observable targets. The CORA (Covert Radar) experimental passive radar system currently developed at Fraunhofer-FHR features a multi-channel digital radar receiver and a circular antenna array with separate elements for the VHF- and the UHF-range and is used to exploit alternatively Digital Audio (DAB) or Video Broadcasting (DVB-T) signals. For an extension of the system, a wideband antenna array is being designed for which a new discone antenna element has been developed covering the full DVB-T frequency range. The present paper describes the outline of the system and the numerical modelling and optimisation methods applied to solve the complex task of antenna array design: Electromagnetic full wave analysis is required for the parametric design of the antenna elements while combinatorial optimization methods are applied to find the best array positions and excitation coefficients for a regular omni-directional antenna performance. The different steps are combined in an iterative loop until the optimum array layout is found. Simulation and experimental results for the current system will be shown.

  10. Localised task-dependent motor-unit recruitment in the masseter. (United States)

    Schindler, H J; Hellmann, D; Giannakopoulos, N N; Eiglsperger, U; van Dijk, J P; Lapatki, B G


    Localised motor-unit (MU) recruitment in the masseter was analysed in this study. We investigated whether differential activation behaviour, which has already been reported for distant masseter regions, can also be detected in small muscle subvolumes at the level of single MUs. Two bipolar fine-wire electrodes and an intra-oral 3D bite-force transmitter were used to record intra-muscular electromyograms (EMG) resulting from controlled bite-forces of 10 healthy human subjects (mean age 24.1 ± 1.2 years). Two-hundred and seventeen decomposed MUs were organised into localised MU task groups with different (P < 0.001) force-direction-specific behaviour. Proportions of MUs involved in one, two, three or four examined tasks were 46%, 31%, 18% and 5%, respectively. This study provides evidence of the ability of the neuromuscular system to modify the mechanical output of small masseter subvolumes by differential control of adjacent MUs belonging to distinct task groups. Localised differential activation behaviour of the masseter may be the crucial factor enabling highly flexible and efficient adjustment of the muscle activity in response to complex local biomechanical needs, for example, continually varying bite-forces during the demanding masticatory process. © 2014 John Wiley & Sons Ltd.

  11. 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


    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.

  12. Voltage dependence of a stochastic model of activation of an alpha helical S4 sensor in a K channel membrane (United States)

    Vaccaro, S. R.


    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.

  13. 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


    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...

  14. 3-[2,4-Dimethoxybenzylidene]anabaseine (DMXB) selectively activates rat alpha7 receptors and improves memory-related behaviors in a mecamylamine-sensitive manner. (United States)

    Meyer, E M; Tay, E T; Papke, R L; Meyers, C; Huang, G L; de Fiebre, C M


    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.

  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. (United States)

    Fatmawati, Ni Nengah Dwi; Sakaguchi, Yoshihiko; Suzuki, Tomonori; Oda, Masataka; Shimizu, Kenta; Yamamoto, Yumiko; Sakurai, Jun; Matsushita, Osamu; Oguma, Keiji


    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. Antiulcerogenic activity of fractions and 3,15-dioxo-21alpha-hydroxy friedelane isolated from Maytenus robusta (Celastraceae). (United States)

    de Andrade, Sérgio Faloni; Comunello, Eros; Noldin, Vânia Floriani; Monache, Franco Delle; Cechinel Filho, Valdir; Niero, Rivaldo


    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.

  17. Alpha-PVP as an active component of herbal highs in Poland between 2013 and 2015. (United States)

    Byrska, Bogumiła; Stanaszek, Roman; Zuba, Dariusz


    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.

  18. Pharmacologic modulation of protein kinase C isozymes: the role of RACKs and subcellular localisation. (United States)

    Csukai, M; Mochly-Rosen, D


    Protein kinase C (PKC) isozymes are highly homologous kinases and several different isozymes can be present in a cell. Each isozyme is likely to mediate unique functions, but pharmacological tools to explore their isozyme-specific roles have not been available until recently. In this review, we describe the development and application of isozyme-selective inhibitors of PKC. The identification of these inhibitors stems from the observation that PKC isozymes are each localised to unique subcellular locations following activation. Inhibitors of this isozyme-unique localisation have been shown to act as selective inhibitors of the functions of individual isozymes. The identification of isozyme-specific inhibitors should allow the exploration of individual PKC isozyme function in a wide range of cell systems. Copyright 1999 The Italian Pharmacological Society.

  19. 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.


    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

  20. Localisation of Neuregulin 1-{beta}3 to different sub-nuclear structures alters gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ming; Trim, Carol M.; Gullick, William J., E-mail:


    Neuregulins are growth factors that signal via the ErbB3 and ErbB4 receptors. Here we show using immunohistochemistry that they are often expressed in the nucleus of a range of tumour types including soft tissue and breast. The Neuregulin 1 type I-{beta}3 (NRG1-{beta}3) isoform localises to two sub-nuclear compartments in animal cells, nucleoli and spliceosomes. We used NRG1-{beta}3 tagged with photoactivatable GFP and demonstrated that this re-localised from nucleoli to spliceosomes over 90 min. Tyrosine kinase activity was not required for retaining the NRG1-{beta}3 within the nucleus. Mutation of the lysines 14 and 16 or 15 and 16 together prevented nucleolar uptake while four positively charged residues were identified which were required for spliceosome uptake. Molecular modelling suggests that three of these may form a binding site. We showed using a kinome array that NRG1-{beta}3 and a mutant exclusively localising to spliceosomes increased phosphorylation and/or expression of the HER4 and HER2 receptors. Using a transcriptomic analysis the same two constructs induced expression of several messenger RNAs and we confirmed the increased expression at the protein level of the most highly induced, Heat Shock Protein 70B'. These results suggest that Neuregulin activates receptor signalling in spliceosomes leading to altered gene expression.

  1. Localisation of Neuregulin 1-β3 to different sub-nuclear structures alters gene expression

    International Nuclear Information System (INIS)

    Wang, Ming; Trim, Carol M.; Gullick, William J.


    Neuregulins are growth factors that signal via the ErbB3 and ErbB4 receptors. Here we show using immunohistochemistry that they are often expressed in the nucleus of a range of tumour types including soft tissue and breast. The Neuregulin 1 type I-β3 (NRG1-β3) isoform localises to two sub-nuclear compartments in animal cells, nucleoli and spliceosomes. We used NRG1-β3 tagged with photoactivatable GFP and demonstrated that this re-localised from nucleoli to spliceosomes over 90 min. Tyrosine kinase activity was not required for retaining the NRG1-β3 within the nucleus. Mutation of the lysines 14 and 16 or 15 and 16 together prevented nucleolar uptake while four positively charged residues were identified which were required for spliceosome uptake. Molecular modelling suggests that three of these may form a binding site. We showed using a kinome array that NRG1-β3 and a mutant exclusively localising to spliceosomes increased phosphorylation and/or expression of the HER4 and HER2 receptors. Using a transcriptomic analysis the same two constructs induced expression of several messenger RNAs and we confirmed the increased expression at the protein level of the most highly induced, Heat Shock Protein 70B'. These results suggest that Neuregulin activates receptor signalling in spliceosomes leading to altered gene expression.

  2. Interaction with extracellular matrix proteins influences Lsh/Ity/Bcg (candidate Nramp) gene regulation of macrophage priming/activation for tumour necrosis factor-alpha and nitrite release. (United States)

    Formica, S; Roach, T I; Blackwell, J M


    The murine resistance gene Lsh/Ity/Bcg regulates activation of macrophages for tumour necrosis factor-alpha (TNF-alpha)-dependent production of nitric oxide mediating antimicrobial activity against Leishmania, Salmonella and Mycobacterium. As Lsh is differentially expressed in macrophages from different tissue sites, experiments were performed to determine whether interaction with extracellular matrix (ECM) proteins would influence the macrophage TNF-alpha response. Plating of bone marrow-derived macrophages onto purified fibrinogen or fibronectin-rich L929 cell-derived matrices, but not onto mannan, was itself sufficient to stimulate TNF-alpha release, with significantly higher levels released from congenic B10.L-Lshr compared to C57BL/10ScSn (Lshs) macrophages. Only macrophages plated onto fibrinogen also released measurable levels of nitrites, again higher in Lshr compared to Lshs macrophages. Addition of interferon-gamma (IFN-gamma), but not bacterial lipopolysaccharide or mycobacterial lipoarabinomannan, as a second signal enhanced the TNF-alpha and nitrite responses of macrophages plated onto fibrinogen, particularly in the Lshr macrophages. Interaction with fibrinogen and fibronectin also primed macrophages for an enhanced TNF-alpha response to leishmanial parasites, but this was only translated into enhanced nitrite responses in the presence of IFN-gamma. In these experiments, Lshr macrophages remained superior in their TNF-alpha responses throughout, but to a degree which reflected the magnitude of the difference observed on ECM alone. Hence, the specificity for the enhanced TNF-alpha responses of Lshr macrophages lay in their interaction with fibrinogen and fibronectin ECM, while a differential nitrite response was only observed with fibrinogen and/or IFN-gamma. The results are discussed in relation to the possible function of the recently cloned candidate gene Nramp, which has structural identity to eukaryote transporters and an N-terminal cytoplasmic

  3. 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


    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

  4. The role and regulation of the peroxisome proliferator activated receptor alpha in human liver

    NARCIS (Netherlands)

    Kersten, Sander; Stienstra, Rinke


    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

  5. Quality of Life Outcomes after Primary Treatment for Clinically Localised Prostate Cancer: A Systematic Review. (United States)

    Lardas, Michael; Liew, Matthew; van den Bergh, Roderick C; De Santis, Maria; Bellmunt, Joaquim; Van den Broeck, Thomas; Cornford, Philip; Cumberbatch, Marcus G; Fossati, Nicola; Gross, Tobias; Henry, Ann M; Bolla, Michel; Briers, Erik; Joniau, Steven; Lam, Thomas B; Mason, Malcolm D; Mottet, Nicolas; van der Poel, Henk G; Rouvière, Olivier; Schoots, Ivo G; Wiegel, Thomas; Willemse, Peter-Paul M; Yuan, Cathy Yuhong; Bourke, Liam


    Current evidence-based management for clinically localised prostate cancer includes active surveillance, surgery, external beam radiotherapy (EBRT) and brachytherapy. The impact of these treatment modalities on quality of life (QoL) is uncertain. To systematically review comparative studies investigating disease-specific QoL outcomes as assessed by validated cancer-specific patient-reported outcome measures with at least 1 yr of follow-up after primary treatment for clinically localised prostate cancer. MEDLINE, EMBASE, AMED, PsycINFO, and Cochrane Library were searched to identify relevant studies. Studies were critically appraised for the risk of bias. A narrative synthesis was undertaken. Of 11486 articles identified, 18 studies were eligible for inclusion, including three randomised controlled trials (RCTs; follow-up range: 60-72 mo) and 15 nonrandomised comparative studies (follow-up range: 12-180 mo) recruiting a total of 13604 patients. Two RCTs recruited small cohorts and only one was judged to have a low risk of bias. The quality of evidence from observational studies was low to moderate. For a follow-up of up to 6 yr, active surveillance was found to have the lowest impact on cancer-specific QoL, surgery had a negative impact on urinary and sexual function when compared with active surveillance and EBRT, and EBRT had a negative impact on bowel function when compared with active surveillance and surgery. Data from one small RCT reported that brachytherapy has a negative impact on urinary function 1 yr post-treatment, but no significant urinary toxicity was reported at 5 yr. This is the first systematic review comparing the impact of different primary treatments on cancer-specific QoL for men with clinically localised prostate cancer, using validated cancer-specific patient-reported outcome measures only. There is robust evidence that choice of primary treatment for localised prostate cancer has distinct impacts on patients' QoL. This should be discussed in

  6. 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


    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...

  7. Whole blood assay for NK activity in splenectomized and non-splenectomized hairy cell leukemia patients during IFN-alpha-2b treatment

    DEFF Research Database (Denmark)

    Nielsen, B; Hokland, P; Ellegaard, J


    Natural killer cell (NK) activity in peripheral blood (PB) was followed longitudinally for up to 2 yr after initiation of low-dose IFN-alpha-2b therapy in nine hairy cell leukemia (HCL) patients. A whole blood NK (WB-NK) assay was employed in order to measure the NK activity per unit blood. The p...

  8. 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.


    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

  9. Effect of antitumour necrosis factor-alpha therapy on bone turnover in patients with active Crohn's disease: a prospective study. (United States)

    Ryan, B M; Russel, M G V M; Schurgers, L; Wichers, M; Sijbrandij, J; Stockbrugger, R W; Schoon, E


    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.

  10. Minimum detectable activity and false alarm rate relationships for alpha continuous air monitors

    International Nuclear Information System (INIS)

    Hoover, M.D.; Newton, G.J.


    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

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

    Directory of Open Access Journals (Sweden)

    Iuliia Vitko

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

  12. 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.

  13. 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...

  14. Alpha Blockers (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 ...

  15. Differences in genotoxic activity of alpha-Ni3S2 on human lymphocytes from nickel-hypersensitized and nickel-unsensitized donors. (United States)

    Arrouijal, F Z; Marzin, D; Hildebrand, H F; Pestel, J; Haguenoer, J M


    The genotoxic activity of alpha-Ni3S2 was assessed on human lymphocytes from nickel-hypersensitized (SSL) and nickel-unsensitized (USL) subjects. Three genotoxicity tests were performed: the sister chromatid exchange (SCE) test, the metaphase analysis test and the micronucleus test. (i) The SCE test (3-100 micrograms/ml) showed a weak but statistically significant increase in the number of SCE in both lymphocyte types with respect to controls, USL presenting a slightly higher SCE incidence but only at one concentration. (ii) The metaphase analysis test demonstrated a high dose-dependent clastogenic activity of alpha-Ni3S2 in both lymphocyte types. The frequency of chromosomal anomalies was significantly higher in USL than in SSL for all concentrations applied. (iii) The micronucleus test confirmed the dose-dependent clastogenic activity of alpha-Ni3S2 and the differences already observed between USL and SSL, i.e. the number of cells with micronuclei was statistically higher in USL. Finally, the incorporation study with alpha-63Ni3S2 showed a higher uptake of its solubilized fraction by USL. This allows an explanation of the different genotoxic action of nickel on the two cell types. In this study we demonstrated that hypersensitivity has an influence on the incorporation of alpha-Ni3S2 and subsequently on the different induction of chromosomal aberrations in human lymphocytes.

  16. Ratio of Circulating Estrogen Receptors Beta and Alpha (ERβ/ERα) Indicates Endoscopic Activity in Patients with Crohn's Disease. (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


    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.

  17. Relative left frontal activity in reappraisal and suppression of negative emotion: Evidence from frontal alpha asymmetry (FAA). (United States)

    Choi, Damee; Sekiya, Takahiro; Minote, Natsumi; Watanuki, Shigeki


    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.

  18. 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


    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

  19. Stabilization and activation of alpha-chymotrypsin in water-organic solvent systems by complex formation with oligoamines. (United States)

    Kudryashova, Elena V; Artemova, Tatiana M; Vinogradov, Alexei A; Gladilin, Alexander K; Mozhaev, Vadim V; Levashov, Andrey V


    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.

  20. 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.


    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

  1. 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.


    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

  2. Intracellular localisation of proteins to specific cellular areas by nanocapsule mediated delivery. (United States)

    Wang, Huabin; Chen, Ligang; Sun, Xianchao; Fu, Ailing


    Nanocapsules are promising carriers with great potential for intracellular protein transport. Although many studies have intended to improve cell uptake efficacy, there is an increasing interest in understanding of subcellular distribution of cargoes inside cells, which is essential for purposeful delivery of biomolecules into specific sites within cells. Herein, we interrogate the intracellular localisation of exogenous proteins, including fluorescein isothiocyanate (FITC)-labelled bovine serum albumin (BSA) and green fluorescent protein (GFP), mediated by specially designed nanocapsules. The results show that the designed nanocapsules can deliver the two types of fluorescent proteins into different cellular destinations (cytosol, nucleus or the whole cell), depending on the composition of nanocapsules. Meanwhile, several impact factors that influence the distribution of proteins in cells have also been investigated, and the results suggest that the localisation of capsule-mediated proteins in cells is strongly affected by the surface properties of nanocapsules, the types of stabilisers and proteins, and environmental temperatures. The rational control of intracellular localised delivery of exogenous proteins as we demonstrated in this study might open new avenues to obtain desired magnitude of drug effects for modulating cell activity.

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

    DEFF Research Database (Denmark)

    Jørgensen, Sebastian Beck; Wojtaszewski, Jørgen; Viollet, Benoit


    We tested the hypothesis that 5'AMP-activated protein kinase (AMPK) plays an important role in regulating the acute, exercise-induced activation of metabolic genes in skeletal muscle, which were dissected from whole-body a2- and a1-AMPK knockout (KO) and wild-type (WT) mice at rest, after treadmi...

  4. Dimerization inhibits the activity of receptor-like protein-tyrosine phosphatase-alpha

    DEFF Research Database (Denmark)

    Jiang, G; den Hertog, J; Su, J


    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...

  5. Effects of a dietary Aspergillus oryzae extract containing alpha-amylase activity on performance and carcass characteristics of finishing beef cattle. (United States)

    Tricarico, J M; Abney, M D; Galyean, M L; Rivera, J D; Hanson, K C; McLeod, K R; Harmon, D L


    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

  6. Localisation of beam offset jitter sources at ATF2

    CERN Document Server

    Pfingstner, J; Patecki, M; Schulte, D; Tomás, R


    For the commissioning and operation of modern particle accelerators, automated error detection and diagnostics methods are becoming increasingly important. In this paper, we present two such methods, which are capable of localising sources of beam offset jitter with a combination of correlation studies and so called degree of freedom plots. The methods were applied to the ATF2 beam line at KEK, where one of the major goals is the reduction of the beam offset jitter. Results of this localisation are shown in this paper. A big advantage of the presented method is its high robustness especially to varying optics parameters. Therefore, we believe that the developed beam offset jitter localisation methods can be easily applied to other accelerators.

  7. Differences in finger localisation performance of patients with finger agnosia. (United States)

    Anema, Helen A; Kessels, Roy P C; de Haan, Edward H F; Kappelle, L Jaap; Leijten, Frans S; van Zandvoort, Martine J E; Dijkerman, H Chris


    Several neuropsychological studies have suggested parallel processing of somatosensory input when localising a tactile stimulus on one's own by pointing towards it (body schema) and when localising this touched location by pointing to it on a map of a hand (body image). Usually these reports describe patients with impaired detection, but intact sensorimotor localisation. This study examined three patients with a lesion of the angular gyrus with intact somatosensory processing, but with selectively disturbed finger identification (finger agnosia). These patients performed normally when pointing towards the touched finger on their own hand but failed to indicate this finger on a drawing of a hand or to name it. Similar defects in the perception of other body parts were not observed. The findings provide converging evidence for the dissociation between body image and body schema and, more importantly, reveal for the first time that this distinction is also present in higher-order cognitive processes selectively for the fingers.

  8. An ultrastructural and irradiation study of diffuse and localised kinetochore

    International Nuclear Information System (INIS)

    Bokhari, F.S.


    An electron microscope study of plant types Luzula nivea and Cyperus eragrostis with diffuse kinetochores and Crepis neglecta with localised kinetochore showed that Luzula has a rather different kinetochore organisation from Cyperus, with features approaching the localised type of Crepis. These studies included an examination of the ultrastructure of the kinetochore at metaphase at low magnification in control and irradiated material of Luzula; the chromosomal ultrastructure at high magnification at interphase and all stages of mitosis in Luzula, Cyperus and Crepis; and the ultrastructure of the nucleolus in Luzula, Cyperus and Crepis. Light microscopic studies were also performed showing the effects of irradiation on first mitotic division in Cyperus, Luzula and Crepis, mitotic aberrations in Cyperus and Crepis and meiosis in Cyperus. Finally, the survival with the diffuse as opposed to the localised kinetochore in M 1 and M 2 generations following seed irradiation was studied. (U.K.)

  9. 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.


    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

  10. 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.

  11. Effect of the glass transition temperature on alpha-amylase activity in a starch matrix. (United States)

    Chaudhary, Vinita; Panyoyai, Naksit; Small, Darryl M; Shanks, Robert A; Kasapis, Stefan


    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.

  12. PPARgamma-PGC-1alpha activity is determinant of alcohol related breast cancer

    DEFF Research Database (Denmark)

    Koefoed Petersen, Rasmus; Benzon Larsen, Signe; Jensen, Ditte Marie


    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....

  13. Glucose decouples intracellular Ca2+ activity from glucagon secretion in mouse pancreatic islet alpha-cells.

    Directory of Open Access Journals (Sweden)

    Sylvain J Le Marchand

    Full Text Available The mechanisms of glucagon secretion and its suppression by glucose are presently unknown. This study investigates the relationship between intracellular calcium levels ([Ca(2+](i and hormone secretion under low and high glucose conditions. We examined the effects of modulating ion channel activities on [Ca(2+](i and hormone secretion from ex vivo mouse pancreatic islets. Glucagon-secreting α-cells were unambiguously identified by cell specific expression of fluorescent proteins. We found that activation of L-type voltage-gated calcium channels is critical for α-cell calcium oscillations and glucagon secretion at low glucose levels. Calcium channel activation depends on K(ATP channel activity but not on tetrodotoxin-sensitive Na(+ channels. The use of glucagon secretagogues reveals a positive correlation between α-cell [Ca(2+](i and secretion at low glucose levels. Glucose elevation suppresses glucagon secretion even after treatment with secretagogues. Importantly, this inhibition is not mediated by K(ATP channel activity or reduction in α-cell [Ca(2+](i. Our results demonstrate that glucose uncouples the positive relationship between [Ca(2+](i and secretory activity. We conclude that glucose suppression of glucagon secretion is not mediated by inactivation of calcium channels, but instead, it requires a calcium-independent inhibitory pathway.

  14. Real-time fMRI neurofeedback of the mediodorsal and anterior thalamus enhances correlation between thalamic BOLD activity and alpha EEG rhythm. (United States)

    Zotev, Vadim; Misaki, Masaya; Phillips, Raquel; Wong, Chung Ki; Bodurka, Jerzy


    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.

  15. Monitoring corrosion rates and localised corrosion in low conductivity water

    DEFF Research Database (Denmark)

    Hilbert, Lisbeth Rischel


    Monitoring of low corrosion rates and localised corrosion in a media with low conductivity is a challenge. In municipal district heating, quality control may be improved by implementing on-line corrosion monitoring if a suitable technique can be identified to measure both uniform and localised...... corrosion. Electrochemical techniques (LPR, EIS, crevice corrosion current) as well as direct measurement techniques (high-sensitive electrical resistance, weight loss) have been applied in operating plants. Changes in the corrosion processes are best monitored in non-aggressive, low conductivity media...

  16. Experimental investigation of edge localised modes in JET

    International Nuclear Information System (INIS)

    Lindholm Colton, A.


    Edge Localised Modes (ELMs) in the JET tokamak have been studied experimentally, using density profile and fluctuation data from a multichannel reflectometer and temperature profile data from an ECE heterodyne radiometer. The following topics have been investigated: The radial extent and localisation of the density and temperature profile perturbations caused by the ELMs. Fluctuations in the density and magnetic field in connection with the ELMs. The correlation between the repetition frequency of the L-H transition ELMs, and the plasma edge temperature and density. Trajectories in n-T space prior to ELMs later in the H-mode. (au) (39 refs.)

  17. 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.

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

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


    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.

  19. PDH-E1alpha dephosphorylation and activation in human skeletal muscle during exercise

    DEFF Research Database (Denmark)

    Pilegaard, Henriette; Birk, Jesper Bratz; Sacchetti, Massimo


    . 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...

  20. Predominant alpha2/beta2/gamma3 AMPK activation during exercise in human skeletal muscle

    DEFF Research Database (Denmark)

    Birk, Jesper Bratz; Wojtaszewski, Jørgen


    -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...

  1. 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.


    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)

  2. The Determination of Thorium Contents in Urine With Neutron Activation Analysis and Alpha Spectrometry

    International Nuclear Information System (INIS)



    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)

  3. 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


    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

  4. 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.


    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

  5. Transcriptome profiling reveals bisphenol A alternatives activate estrogen receptor alpha in human breast cancer cells (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...

  6. In-vitro alpha amylase inhibitory activity of the leaf extracts of Adenanthera pavonina. (United States)

    Wickramaratne, M Nirmali; Punchihewa, J C; Wickramaratne, D B M


    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

  7. Allogeneic transplantation for multiple myeloma: late relapse may occur as localised lytic lesion/plasmacytoma despite ongoing molecular remission. (United States)

    Byrne, J L; Fairbairn, J; Davy, B; Carter, I G; Bessell, E M; Russell, N H


    Allogeneic SCT for myeloma may be curative for young patients, but its role remains controversial because of a reported high TRM in some series. Since 1991, we have performed 25 allografts for myeloma using fully matched sibling donors. Of the 18 evaluable patients, 13 achieved CR at a median time of 2.5 months post-transplant. The five patients who were not in CR when assessed at 3 months received a short course of alpha-interferon and four subsequently achieved CR with this approach at a median of 82 days. One patient who failed to respond to IFN went on to achieve CR after four doses of DLI therapy, thus giving an overall CR rate of 72%. Seven patients have relapsed at a median of 4.7 years post-transplant (range 1.38-7.7 years) including two patients who had received IFN therapy. In five of these cases, relapse has been as a localised area of bone disease or isolated plasmacytoma with no evidence of marrow involvement by trephine biopsy or molecular analysis. All patients with localised relapse were treated with local radiotherapy +/-DLI and four are currently disease free despite two patients having had further treatment for a second localised lesion. Six patients died of TRM (24%) and the OS at 8 years is currently 69% with an EFS of 26%. These results suggest that allogeneic SCT for myeloma can be carried out with an acceptable TRM and a high CR rate. However, late relapses as localised disease may be a frequent finding and may represent foci of myeloma not eradicated by the conditioning. The use of pretransplant MRI scanning and top-up radiotherapy to involved areas may be useful in preventing this type of relapse.

  8. Pharmacologically relevant receptor binding characteristics and 5alpha-reductase inhibitory activity of free Fatty acids contained in saw palmetto extract. (United States)

    Abe, Masayuki; Ito, Yoshihiko; Oyunzul, Luvsandorj; Oki-Fujino, Tomomi; Yamada, Shizuo


    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

  9. Correlative and integrated light and electron microscopy of in-resin GFP fluorescence, used to localise diacylglycerol in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Peddie, Christopher J.; Blight, Ken; Wilson, Emma [Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY (United Kingdom); Melia, Charlotte [Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY (United Kingdom); Cell Biophysics Laboratory, London Research Institute, Cancer Research UK, London WC2A 3LY (United Kingdom); Department of Molecular Cell Biology, Leiden University Medical Centre, 2300 RC Leiden (Netherlands); Marrison, Jo [Department of Biology, The University of York, Heslington, York (United Kingdom); Carzaniga, Raffaella [Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY (United Kingdom); Domart, Marie-Charlotte [Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY (United Kingdom); Cell Biophysics Laboratory, London Research Institute, Cancer Research UK, London WC2A 3LY (United Kingdom); O' Toole, Peter [Department of Biology, The University of York, Heslington, York (United Kingdom); Larijani, Banafshe [Cell Biophysics Laboratory, London Research Institute, Cancer Research UK, London WC2A 3LY (United Kingdom); Cell Biophysics Laboratory, Unidad de Biofísica (CSIC-UPV/EHU),Sarriena s/n, 48940 Leioa (Spain); IKERBASQUE, Basque Foundation for Science, Bilbao (Spain); Collinson, Lucy M. [Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY (United Kingdom)


    Fluorescence microscopy of GFP-tagged proteins is a fundamental tool in cell biology, but without seeing the structure of the surrounding cellular space, functional information can be lost. Here we present a protocol that preserves GFP and mCherry fluorescence in mammalian cells embedded in resin with electron contrast to reveal cellular ultrastructure. Ultrathin in-resin fluorescence (IRF) sections were imaged simultaneously for fluorescence and electron signals in an integrated light and scanning electron microscope. We show, for the first time, that GFP is stable and active in resin sections in vacuo. We applied our protocol to study the subcellular localisation of diacylglycerol (DAG), a modulator of membrane morphology and membrane dynamics in nuclear envelope assembly. We show that DAG is localised to the nuclear envelope, nucleoplasmic reticulum and curved tips of the Golgi apparatus. With these developments, we demonstrate that integrated imaging is maturing into a powerful tool for accurate molecular localisation to structure. - Highlights: • GFP and mCherry fluorescence are preserved in heavy-metal stained mammalian cells embedded in resin • Fluorophores are stable and intensity is sufficient for detection in ultrathin sections • Overlay of separate LM and EM images from the same ultrathin section improves CLEM protein localisation precision • GFP is stable and active in the vacuum of an integrated light and scanning EM • Integrated light and electron microscopy shows new subcellular locations of the lipid diacylglycerol.

  10. Evaluation of estrogen receptor alpha activation by glyphosate-based herbicide constituents. (United States)

    Mesnage, Robin; Phedonos, Alexia; Biserni, Martina; Arno, Matthew; Balu, Sucharitha; Corton, J Christopher; Ugarte, Ricardo; Antoniou, Michael N


    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.

  11. Application of a Null-Beamformer to Source Localisation in MEG Data of Deep Brain Stimulation

    DEFF Research Database (Denmark)

    Mohseni, Hamid R.; Kringelbach, Morten L.; Smith, Penny Probert


    In this paper, we present an analysis of magnetoencephalography (MEG) signals from a patient with whole-body chronic pain in order to investigate changes in neural activity induced by DBS. The patient is one of the few cases treated using DBS of the anterior cingulate cortex (ACC). Using MEG...... the accuracy of our source localisation by correlating the predicted DBS electrode positions with their actual positions, previously identified using anatomical imaging. We also demonstrated increased activity in pain-related regions including the pre-supplementary motor area, brainstem periaqueductal gray...

  12. Characterisation of a novel proteolytic enzyme localised to goblet cells in rat and man

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier


    A proteolytic enzyme, ingobsin , purified from rat duodenal extracts is shown to be localised to intestinal goblet cells of both man and rat. Enzyme positive cells decrease in number from duodenum to colon. The enzyme is a 33 000 Mr protein with an isoelectric point of 5.1. The pH optimum...... for enzymatic activity is 7.4-8.0. Based on substrate specificity for arg-x, lys-x and to a lesser degree tyr-x, on the effect of diisopropylphosphorofluoride , Trasylol and phenylmethylsulfonylfluoride and on proteolytic activity towards intact proteins, ingobsin is classified as a serine proteinase...

  13. 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.


    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

  14. 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

  15. 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.


    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)

  16. Inhibitory Effect of Capparis spinosa Extract on Pancreatic Alpha-Amylase Activity

    Directory of Open Access Journals (Sweden)

    Mostafa Selfayan


    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.

  17. Increased renal alpha-epithelial sodium channel (ENAC) protein and increased ENAC activity in normal pregnancy. (United States)

    West, Crystal; Zhang, Zheng; Ecker, Geoffrey; Masilamani, Shyama M E


    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.

  18. Fibroblast Activation Protein-Alpha, a Serine Protease that Facilitates Metastasis by Modification of Diverse Microenvironments (United States)


    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

  19. Experimental system using an active method for the measurement of low alpha emitter grades

    International Nuclear Information System (INIS)

    Bernard, P.; Cance, M.


    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

  20. 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.


    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.)

  1. 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.


    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

  2. Rhodocytin (aggretin) activates platelets lacking alpha(2)beta(1) integrin, glycoprotein VI, and the ligand-binding domain of glycoprotein Ibalpha

    DEFF Research Database (Denmark)

    Bergmeier, W; Bouvard, D; Eble, J A


    Although alpha(2)beta(1) integrin (glycoprotein Ia/IIa) has been established as a platelet collagen receptor, its role in collagen-induced platelet activation has been controversial. Recently, it has been demonstrated that rhodocytin (also termed aggretin), a snake venom toxin purified from the v...

  3. 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.

  4. Nitric oxide mediates angiogenesis induced in vivo by platelet-activating factor and tumor necrosis factor-alpha. (United States)

    Montrucchio, G.; Lupia, E.; de Martino, A.; Battaglia, E.; Arese, M.; Tizzani, A.; Bussolino, F.; Camussi, G.


    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

  5. 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.


    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

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


    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.

  7. 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.


    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

  8. 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


    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

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

    CERN Document Server

    Singh, N L; Chintalapudi, S N


    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).

  10. 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)


    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.)

  11. Proposed development programme for a temporary containment system for alpha active decommissioning

    International Nuclear Information System (INIS)

    Pengelly, M.G.A.; Burnett, R.C.


    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)

  12. Parkinson's disease: acid-glucocerebrosidase activity and alpha-synuclein clearance. (United States)

    Blanz, Judith; Saftig, Paul


    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

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

    DEFF Research Database (Denmark)

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


    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....

  14. Time Localisation of Surface Defects on Optical Discs

    DEFF Research Database (Denmark)

    Odgaard, Peter Fogh; Wickerhauser, M.V.

    Many have experienced problems with their Compact Disc player when a disc with a scratch or a finger print is tried played. One way to improve the playability of discs with such a defect, is to locate the defect in time and then handle it in a special way. As a consequence this time localisation...

  15. Immunogold staining procedure for the localisation of regulatory peptides. (United States)

    Varndell, I M; Tapia, F J; Probert, L; Buchan, A M; Gu, J; De Mey, J; Bloom, S R; Polak, J M


    The use of protein A- and IgG-conjugated colloidal gold staining methods for the immuno-localisation of peptide hormones and neurotransmitters at light- and electron microscope level are described and discussed. Bright-field and dark-ground illumination modes have been used to visualise the gold-labelled antigenic sites at the light microscope level. Immunogold staining procedures at the ultrastructural level using region-specific antisera have been adopted to localise specific molecular forms of peptides including gastrin (G17 and G34), glucagon and pro-glucagon, insulin and pro-insulin, in normal tissue and in tumours of the gastroenteropancreatic system. Similar methods have been used to demonstrate the heterogeneity of p-type nerves in the enteric nervous system. Vasoactive intestinal polypeptide (VIP) has been localised to granular sites (mean +/- S.D. granule diameter = 98 +/- 19 nm) in nerve terminals of the enteric plexuses and in tumour cells of diarrhoeogenic VIP-producing neoplasias (mean +/- S.D. granule diameter = 126 +/- 37 nm) using immunogold procedures applied to ultraviolet-cured ultrathin sections. Co-localisation of amines and peptides in carotid body type I cells and in chromaffin cells of normal adrenal medulla and phaeochromocytomas has also been demonstrated. Advantages of the immunogold procedures over alternative immunocytochemical techniques are discussed.

  16. Human SLAM, indoor localisation of devices and users

    NARCIS (Netherlands)

    Bulten, W.; Rossum, A.C. van; Haselager, W.F.G.; Guerrero, J.E.


    The indoor localisation problem is more complex than just finding whereabouts of users. Finding positions of users relative to the devices of a smart space is even more important. Unfortunately, configuring such systems manually is a tedious process, requires expert knowledge, and is sensitive to

  17. Cutting Edge Localisation in an Edge Profile Milling Head

    NARCIS (Netherlands)

    Fernandez Robles, Laura; Azzopardi, George; Alegre, Enrique; Petkov, Nicolai


    Wear evaluation of cutting tools is a key issue for prolonging their lifetime and ensuring high quality of products. In this paper, we present a method for the effective localisation of cutting edges of inserts in digital images of an edge profile milling head. We introduce a new image data set of

  18. Application of the Localisation Platform Crowdin in Translator Education (United States)

    Kudla, Dominik


    This article is an attempt to briefly describe the potential of the online localisation platform Crowdin for the education of the future translators at universities and in private courses or workshops. This description is provided on the basis of the information gathered through the user experience of the author and uses the example of the Khan…

  19. Scanning Kelvin Probe applied to localised corrosion | Haque ...

    African Journals Online (AJOL)

    This paper focuses on specific applications of the SKP system. The instrument is calibrated, using different thickness of a model polymer Poly Vinyl Butyral (PVB) on mild steel and on galvanised steel. Artificial defects are used to show how the instrument is capable of detecting a localised corrosion cell and its ability to ...

  20. Role of tumor necrosis factor-alpha and platelet-activating factor in neoangiogenesis induced by synovial fluids of patients with rheumatoid arthritis. (United States)

    Lupia, E; Montrucchio, G; Battaglia, E; Modena, V; Camussi, G


    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.

  1. 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))


    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.

  2. 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


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

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  4. 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.


    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

  5. Approach to sensor node calibration for efficient localisation in wireless sensor networks in realistic scenarios

    CSIR Research Space (South Africa)

    Mwila, MK


    Full Text Available Localisation or position determination is one of the most important applications for the wireless sensor networks. Numerous current techniques for localisation of sensor nodes use the Received Signal Strength Indicator (RSSI) from sensor nodes...

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

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


    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. 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.


    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 out to determine the oxygen impurity at ≥ 100 ppm in Si matrix because this approach is not possible in Cu and stainless steel samples due to matrix activity. (author) 10 refs.; 1 fig.; 5 tabs

  8. Peroxisome proliferator activated receptor alpha regulates a male-specific cytochrome P450 in mouse liver. (United States)

    Jeffery, Brett; Choudhury, Agharul I; Horley, Neill; Bruce, Mary; Tomlinson, Simon R; Roberts, Ruth A; Gray, Tim J B; Barrett, David A; Shaw, P Nicholas; Kendall, David; Bell, David R


    We set out to find if the strain-specific, male-specific hepatic expression of Cyp4a protein in mouse was due to expression of Cyp4a12 and to understand the genetic basis for reported differences in expression. 12-Lauric acid hydroxylase (LAH) activity was found to show higher levels in male ddY, but not C57Bl/6, mouse liver microsomes. The expression of Cyp4a12 mRNA was studied using RNAase protection assays in male and female liver and kidney of nine mouse strains. Cyp4a12 was found to be highly expressed in male liver and kidney, but at much lower levels in female liver and kidney, in all strains studied. Western blotting with an antibody specific for Cyp4a12 confirmed that Cyp4a12 was expressed in a male specific fashion in C57Bl/6 mouse liver. RNAase protection analysis for Cyp4a10 and 14 in ddY mice revealed that neither of these genes showed male-specific expression. To further investigate genetic factors that control male-specific Cyp4a12 expression, PPARalpha+/+ and -/- mice were studied, showing that total P450 and 12-LAH activity was male-specific in +/+, but not -/- mice. RNAase protection assays were used to confirm that Cyp4a12 was lower in -/- mice. However, the male-specific Slp and MUP-1 genes retained hepatic male-specific levels of expression in +/+ and -/- mice, showing that the decrease in Cyp4a12 was not a general effect on male-specific expression. Thus, PPARalpha has a specific effect on constitutive expression of Cyp4a12.

  9. Nonlinear Recurrent Dynamics and Long-Term Nonstationarities in EEG Alpha Cortical Activity: Implications for Choosing Adequate Segment Length in Nonlinear EEG Analyses. (United States)

    Cerquera, Alexander; Vollebregt, Madelon A; Arns, Martijn


    Nonlinear analysis of EEG recordings allows detection of characteristics that would probably be neglected by linear methods. This study aimed to determine a suitable epoch length for nonlinear analysis of EEG data based on its recurrence rate in EEG alpha activity (electrodes Fz, Oz, and Pz) from 28 healthy and 64 major depressive disorder subjects. Two nonlinear metrics, Lempel-Ziv complexity and scaling index, were applied in sliding windows of 20 seconds shifted every 1 second and in nonoverlapping windows of 1 minute. In addition, linear spectral analysis was carried out for comparison with the nonlinear results. The analysis with sliding windows showed that the cortical dynamics underlying alpha activity had a recurrence period of around 40 seconds in both groups. In the analysis with nonoverlapping windows, long-term nonstationarities entailed changes over time in the nonlinear dynamics that became significantly different between epochs across time, which was not detected with the linear spectral analysis. Findings suggest that epoch lengths shorter than 40 seconds neglect information in EEG nonlinear studies. In turn, linear analysis did not detect characteristics from long-term nonstationarities in EEG alpha waves of control subjects and patients with major depressive disorder patients. We recommend that application of nonlinear metrics in EEG time series, particularly of alpha activity, should be carried out with epochs around 60 seconds. In addition, this study aimed to demonstrate that long-term nonlinearities are inherent to the cortical brain dynamics regardless of the presence or absence of a mental disorder.

  10. alpha-Adducin mutations increase Na/K pump activity in renal cells by affecting constitutive endocytosis: implications for tubular Na reabsorption. (United States)

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


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

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


    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.

  12. Metabolomics: An Essential Tool to Understand the Function of Peroxisome Proliferator–Activated Receptor Alpha (United States)

    Montanez, Jessica E.; Peters, Jeffrey M.; Correll, Jared B.; Gonzalez, Frank J.; Patterson, Andrew D.


    The peroxisome proliferator–activated receptor (PPAR) family of nuclear hormone transcription factors (PPARα, PPARβ/δ, and PPARγ) is regulated by a wide array of ligands including natural and synthetic chemicals. PPARs have important roles in control of energy metabolism and are known to influence inflammation, differentiation, carcinogenesis, and chemical toxicity. As such, PPARs have been targeted as therapy for common disorders such as cancer, metabolic syndrome, obesity, and diabetes. The recent application of metabolomics, or the global, unbiased measurement of small molecules found in biofluids, or extracts from cells, tissues, or organisms, has advanced our understanding of the varied and important roles that the PPARs have in normal physiology as well as in pathophysiological processes. Continued development and refinement of analytical platforms, and the application of new bioinformatics strategies, have accelerated the widespread use of metabolomics and have allowed further integration of small molecules into systems biology. Recent studies using metabolomics to understand PPARα function, as well as to identify PPARα biomarkers associated with drug efficacy/toxicity and drug-induced liver injury, will be discussed. PMID:23197196

  13. Peroxisome proliferator-activated receptor alpha, PPARα, directly regulates transcription of cytochrome P450 CYP2C8

    Directory of Open Access Journals (Sweden)

    Maria eThomas


    Full Text Available The cytochrome P450, CYP2C8, metabolises more than 60 clinically used drugs as well as endogenous substances including retinoic acid and arachidonic acid. However predictive factors for interindividual variability in the efficacy and toxicity of CYP2C8 drug substrates are essentially lacking. Recently we demonstrated that peroxisome proliferator-activated receptor alpha (PPARα, a nuclear receptor primarily involved in control of lipid and energy homeostasis directly regulates the transcription of CYP3A4. Here we investigated the potential regulation of CYP2C8 by PPARα. Two linked intronic SNPs in PPARα (rs4253728, rs4823613 previously associated with hepatic CYP3A4 status showed significant association with CYP2C8 protein level in human liver samples (N=150. Furthermore, siRNA-mediated knock-down of PPARα in HepaRG human hepatocyte cells resulted in up to ~60% and ~50% downregulation of CYP2C8 mRNA and activity, while treatment with the PPARα agonist WY14,643 lead to an induction by >150% and >100%, respectively. Using chromatin immunoprecipitation scanning assay we identified a specific upstream gene region that is occupied in vivo by PPARα. Electromobility shift assay demonstrated direct binding of PPARα to a DR-1 motif located at positions -2762/-2775bp upstream of the CYP2C8 transcription start site. We further validated the functional activity of this element using luciferase reporter gene assays in HuH7 cells. Moreover, based on our previous studies we demonstrated that WNT/β-catenin acts as a functional inhibitor of PPARα-mediated inducibility of CYP2C8 expression. In conclusion, our data suggest direct involvement of PPARα in both constitutive and inducible regulation of CYP2C8 expression in human liver, which is further modulated by WNT/ β-catenin pathway. PPARA gene polymorphism could have a modest influence on CYP2C8 phenotype.

  14. Spaceflight Activates Protein Kinase C Alpha Signaling and Modifies the Developmental Stage of Human Neonatal Cardiovascular Progenitor Cells. (United States)

    Baio, Jonathan; Martinez, Aida F; Bailey, Leonard; Hasaniya, Nahidh; Pecaut, Michael J; Kearns-Jonker, Mary


    Spaceflight impacts cardiovascular function in astronauts; however, its impact on cardiac development and the stem cells that form the basis for cardiac repair is unknown. Accordingly, further research is needed to uncover the potential relevance of such changes to human health. Using simulated microgravity (SMG) generated by two-dimensional clinorotation and culture aboard the International Space Station (ISS), we assessed the effects of mechanical unloading on human neonatal cardiovascular progenitor cell (CPC) developmental properties and signaling. Following 6-7 days of SMG and 12 days of ISS culture, we analyzed changes in gene expression. Both environments induced the expression of genes that are typically associated with an earlier state of cardiovascular development. To understand the mechanism by which such changes occurred, we assessed the expression of mechanosensitive small RhoGTPases in SMG-cultured CPCs and observed decreased levels of RHOA and CDC42. Given the effect of these molecules on intracellular calcium levels, we evaluated changes in noncanonical Wnt/calcium signaling. After 6-7 days under SMG, CPCs exhibited elevated levels of WNT5A and PRKCA. Similarly, ISS-cultured CPCs exhibited elevated levels of calcium handling and signaling genes, which corresponded to protein kinase C alpha (PKCα), a calcium-dependent protein kinase, activation after 30 days. Akt was activated, whereas phosphorylated extracellular signal-regulated kinase levels were unchanged. To explore the effect of calcium induction in neonatal CPCs, we activated PKCα using hWnt5a treatment on Earth. Subsequently, early cardiovascular developmental marker levels were elevated. Transcripts induced by SMG and hWnt5a-treatment are expressed within the sinoatrial node, which may represent embryonic myocardium maintained in its primitive state. Calcium signaling is sensitive to mechanical unloading and directs CPC developmental properties. Further research both in space and on Earth

  15. Germ plasm localisation of the HELICc of Vasa in Drosophila: analysis of domain sufficiency and amino acids critical for localisation (United States)

    Wang, Szu-Chieh; Hsu, Hao-Jen; Lin, Gee-Way; Wang, Ting-Fang; Chang, Chun-Che; Lin, Ming-Der


    Formation of the germ plasm drives germline specification in Drosophila and some other insects such as aphids. Identification of the DEAD-box protein Vasa (Vas) as a conserved germline marker in flies and aphids suggests that they share common components for assembling the germ plasm. However, to which extent the assembly order is conserved and the correlation between functions and sequences of Vas remain unclear. Ectopic expression of the pea aphid Vas (ApVas1) in Drosophila did not drive its localisation to the germ plasm, but ApVas1 with a replaced C-terminal domain (HELICc) of Drosophila Vas (DmVas) became germ-plasm restricted. We found that HELICc itself, through the interaction with Oskar (Osk), was sufficient for germ-plasm localisation. Similarly, HELICc of the grasshopper Vas could be recruited to the germ plasm in Drosophila. Nonetheless, germ-plasm localisation was not seen in the Drosophila oocytes expressing HELICcs of Vas orthologues from aphids, crickets, and mice. We further identified that glutamine (Gln) 527 within HELICc of DmVas was critical for localisation, and its corresponding residue could also be detected in grasshopper Vas yet missing in the other three species. This suggests that Gln527 is a direct target of Osk or critical to the maintenance of HELICc conformation.

  16. sup. alpha. N-acetyl derivatives of. beta. -endorphin-(1-31) and -(1-27) regulate the supraspinal antinociceptive activity of different opioids in mice

    Energy Technology Data Exchange (ETDEWEB)

    Garzon, J.; Sanchez-Blazquez, P. (Cajal Institute, Madrid (Spain))


    {sup {alpha}}N-acetyl human {beta}-endorphin(1-31) injected icv to mice antagonized the analgesic activity of {beta}-endorphin-(1-31) and morphine whereas the analgesia evoked by DADLE and DAGO was enhanced by this treatment. The modulatory activity of {sup {alpha}}N-acetyl {beta}-endorphin-(1-31) was exhibited at remarkable low doses (fmols) reaching a maximum that persisted even though the dose was increased 100,000 times. The regulatory effect of a single dose of the acetylated neuropeptide lasted for 24h. The activity of {sup {alpha}}N-acetyl human {beta}-endorphin(1-31) was partially retained by the shorter peptide {sup {alpha}}N-acetyl human {beta}-endorphin-(1-27) and to a lesser extent by {beta}-endorphin-(1-27), {beta}-endorphin-(1-31) lacked this regulatory activity on opioid analgesia. Acetylated {beta}-endorphin-(1-31) displayed a biphasic curve when competing with 5 pM ({sup 125}I)-Tyr{sup 27} human {beta}-endorphin-(1-31) specific binding, the first step was abolished with an apparent IC{sub 50} of 0.35 nM, and the rest with an IC{sub 50} of 200 nM. It is suggested that {sup {alpha}}N-acetyl {beta}-endorphin-(1-31) changed the efficiency of the opioid analgesics by acting upon a specific substrate that is functionally coupled to the opioid receptor, presumably the guanine nucleotide binding regulatory proteins G{sub i}/G{sub 0}.

  17. Longitudinal and immediate effect of Kundalini Yoga on salivary levels of cortisol and activity of alpha-amylase and its effect on perceived stress

    Directory of Open Access Journals (Sweden)

    Jocelyn N García-Sesnich


    Full Text Available Context: Stress is defined as an alteration of an organism's balance in response to a demand perceived from the environment. Diverse methods exist to evaluate physiological response. A noninvasive method is salivary measurement of cortisol and alpha-amylase. A growing body of evidence suggests that the regular practice of Yoga would be an effective treatment for stress. Aims: To determine the Kundalini Yoga (KY effect, immediate and after 3 months of regular practice, on the perception of psychological stress and the salivary levels of cortisol and alpha-amylase activity. Settings and Design: To determine the psychological perceived stress, levels of cortisol and alpha-amylase activity in saliva, and compare between the participants to KY classes performed for 3 months and a group that does not practice any type of yoga. Subjects and Methods: The total sample consisted of 26 people between 18 and 45-year-old; 13 taking part in KY classes given at the Faculty of Dentistry, University of Chile and 13 controls. Salivary samples were collected, enzyme-linked immunosorbent assay was performed to quantify cortisol and kinetic reaction test was made to determine alpha-amylase activity. Perceived Stress Scale was applied at the beginning and at the end of the intervention. Statistical Analysis Used: Statistical analysis was applied using Stata v11.1 software. Shapiro–Wilk test was used to determine data distribution. The paired analysis was fulfilled by t-test or Wilcoxon signed-rank test. T-test or Mann–Whitney's test was applied to compare longitudinal data. A statistical significance was considered when P< 0.05. Results: KY practice had an immediate effect on salivary cortisol. The activity of alpha-amylase did not show significant changes. A significant decrease of perceived stress in the study group was found. Conclusions: KY practice shows an immediate effect on salivary cortisol levels and on perceived stress after 3 months of practice.

  18. Longitudinal and Immediate Effect of Kundalini Yoga on Salivary Levels of Cortisol and Activity of Alpha-Amylase and Its Effect on Perceived Stress. (United States)

    García-Sesnich, Jocelyn N; Flores, Mauricio Garrido; Ríos, Marcela Hernández; Aravena, Jorge Gamonal


    Stress is defined as an alteration of an organism's balance in response to a demand perceived from the environment. Diverse methods exist to evaluate physiological response. A noninvasive method is salivary measurement of cortisol and alpha-amylase. A growing body of evidence suggests that the regular practice of Yoga would be an effective treatment for stress. To determine the Kundalini Yoga (KY) effect, immediate and after 3 months of regular practice, on the perception of psychological stress and the salivary levels of cortisol and alpha-amylase activity. To determine the psychological perceived stress, levels of cortisol and alpha-amylase activity in saliva, and compare between the participants to KY classes performed for 3 months and a group that does not practice any type of yoga. The total sample consisted of 26 people between 18 and 45-year-old; 13 taking part in KY classes given at the Faculty of Dentistry, University of Chile and 13 controls. Salivary samples were collected, enzyme-linked immunosorbent assay was performed to quantify cortisol and kinetic reaction test was made to determine alpha-amylase activity. Perceived Stress Scale was applied at the beginning and at the end of the intervention. Statistical analysis was applied using Stata v11.1 software. Shapiro-Wilk test was used to determine data distribution. The paired analysis was fulfilled by t -test or Wilcoxon signed-rank test. T -test or Mann-Whitney's test was applied to compare longitudinal data. A statistical significance was considered when P < 0.05. KY practice had an immediate effect on salivary cortisol. The activity of alpha-amylase did not show significant changes. A significant decrease of perceived stress in the study group was found. KY practice shows an immediate effect on salivary cortisol levels and on perceived stress after 3 months of practice.

  19. Neuroimmune Interactions in Schizophrenia: Focus on Vagus Nerve Stimulation and Activation of the Alpha-7 Nicotinic Acetylcholine Receptor

    Directory of Open Access Journals (Sweden)

    Fabiana Maria das Graças Corsi-Zuelli


    Full Text Available Schizophrenia is one of the most debilitating mental disorders and is aggravated by the lack of efficacious treatment. Although its etiology is unclear, epidemiological studies indicate that infection and inflammation during development induces behavioral, morphological, neurochemical, and cognitive impairments, increasing the risk of developing schizophrenia. The inflammatory hypothesis of schizophrenia is also supported by clinical studies demonstrating systemic inflammation and microglia activation in schizophrenic patients. Although elucidating the mechanism that induces this inflammatory profile remains a challenge, mounting evidence suggests that neuroimmune interactions may provide therapeutic advantages to control inflammation and hence schizophrenia. Recent studies have indicated that vagus nerve stimulation controls both peripheral and central inflammation via alpha-7 nicotinic acetylcholine receptor (α7nAChR. Other findings have indicated that vagal stimulation and α7nAChR-agonists can provide therapeutic advantages for neuropsychiatric disorders, such as depression and epilepsy. This review analyzes the latest results regarding: (I the immune-to-brain pathogenesis of schizophrenia; (II the regulation of inflammation by the autonomic nervous system in psychiatric disorders; and (III the role of the vagus nerve and α7nAChR in schizophrenia.

  20. Neuroimmune Interactions in Schizophrenia: Focus on Vagus Nerve Stimulation and Activation of the Alpha-7 Nicotinic Acetylcholine Receptor (United States)

    Corsi-Zuelli, Fabiana Maria das Graças; Brognara, Fernanda; Quirino, Gustavo Fernando da Silva; Hiroki, Carlos Hiroji; Fais, Rafael Sobrano; Del-Ben, Cristina Marta; Ulloa, Luis; Salgado, Helio Cesar; Kanashiro, Alexandre; Loureiro, Camila Marcelino


    Schizophrenia is one of the most debilitating mental disorders and is aggravated by the lack of efficacious treatment. Although its etiology is unclear, epidemiological studies indicate that infection and inflammation during development induces behavioral, morphological, neurochemical, and cognitive impairments, increasing the risk of developing schizophrenia. The inflammatory hypothesis of schizophrenia is also supported by clinical studies demonstrating systemic inflammation and microglia activation in schizophrenic patients. Although elucidating the mechanism that induces this inflammatory profile remains a challenge, mounting evidence suggests that neuroimmune interactions may provide therapeutic advantages to control inflammation and hence schizophrenia. Recent studies have indicated that vagus nerve stimulation controls both peripheral and central inflammation via alpha-7 nicotinic acetylcholine receptor (α7nAChR). Other findings have indicated that vagal stimulation and α7nAChR-agonists can provide therapeutic advantages for neuropsychiatric disorders, such as depression and epilepsy. This review analyzes the latest results regarding: (I) the immune-to-brain pathogenesis of schizophrenia; (II) the regulation of inflammation by the autonomic nervous system in psychiatric disorders; and (III) the role of the vagus nerve and α7nAChR in schizophrenia. PMID:28620379

  1. Relationship between peroxisome proliferator-activated receptor alpha activity and cellular concentration of 14 perfluoroalkyl substances in HepG2 cells. (United States)

    Rosenmai, Anna Kjerstine; Ahrens, Lutz; le Godec, Théo; Lundqvist, Johan; Oskarsson, Agneta


    Peroxisome proliferator-activated receptor alpha (PPARα) is a molecular target for perfluoroalkyl substances (PFASs). Little is known about the cellular uptake of PFASs and how it affects the PPARα activity. We investigated the relationship between PPARα activity and cellular concentration in HepG2 cells of 14 PFASs, including perfluoroalkyl carboxylates (PFCAs), perfluoroalkyl sulfonates and perfluorooctane sulfonamide (FOSA). Cellular concentrations were determined by high-performance liquid chromatography-tandem mass spectrometry and PPARα activity was determined in transiently transfected cells by reporter gene assay. Cellular uptake of the PFASs was low (0.04-4.1%) with absolute cellular concentrations in the range 4-2500 ng mg -1 protein. Cellular concentration of PFCAs increased with perfluorocarbon chain length up to perfluorododecanoate. PPARα activity of PFCAs increased with chain length up to perfluorooctanoate. The maximum induction of PPARα activity was similar for short-chain (perfluorobutanoate and perfluoropentanoate) and long-chain PFCAs (perfluorododecanoate and perfluorotetradecanoate) (approximately twofold). However, PPARα activities were induced at lower cellular concentrations for the short-chain homologs compared to the long-chain homologs. Perfluorohexanoate, perfluoroheptanoate, perfluorooctanoate, perfluorononanoate (PFNA) and perfluorodecanoate induced PPARα activities >2.5-fold compared to controls. The concentration-response relationships were positive for all the tested compounds, except perfluorooctane sulfonate PFOS and FOSA, and were compound-specific, as demonstrated by differences in the estimated slopes. The relationships were steeper for PFCAs with chain lengths up to and including PFNA than for the other studied PFASs. To our knowledge, this is the first report establishing relationships between PPARα activity and cellular concentration of a broad range of PFASs. Copyright © 2017 John Wiley & Sons, Ltd.

  2. How AI localisation in plant tissues determines the targeted pest spectrum of different chemistries

    DEFF Research Database (Denmark)

    Buchholz, Anke; Trapp, Stefan

    penetration as first crucial step can be modified by formulation whereas the active ingredient (AI) distribution within cells is usually solely determined by physicochemical properties. This passive AI distribution was calculated with the Fick-Nernst-Planck equation implemented in a cell model....... The predictions were compared to the measured biological effects against three different arthropods. Test compounds differed in log P (-0.1 to 4.3) and pKa (4.1 to 10.7). Efficacies in different bioassays are discussed with the postulated cellular AI localisation and the individual feeding behaviour...

  3. Endothelial-monocyte activating polypeptide II alters fibronectin based endothelial cell adhesion and matrix assembly via alpha5 beta1 integrin

    International Nuclear Information System (INIS)

    Schwarz, Margaret A.; Zheng, Hiahua; Liu, Jie; Corbett, Siobhan; Schwarz, Roderich E.


    Mature Endothelial-Monocyte Activating Polypeptide (mEMAP) II functions as a potent antiangiogenic peptide. Although the anti-tumor effect of mEMAP II has been described, little is known regarding its mechanism of action. Observations that mEMAP II induced apoptosis only in a subset of migrating and proliferating endothelial cells (EC) suggests a targeted effect on cells engaged in angiogenic activities which are known to rely upon cell adhesion and migration. Indeed, we demonstrate that mEMAP II inhibited fibronectin (FN) dependent microvascular EC (MEC) adhesion and spreading and we show that this depends upon the alpha5 beta1 integrin. Immunofluorescence analysis demonstrated that mEMAP II-dependent blockade of FN-alpha5 beta1 interactions was associated with disassembly of both actin stress fiber networks and FN matrix. These findings suggest that mEMAP II blocks MEC adhesion and spreading on fibronectin, via a direct interaction with the integrin alpha5 beta1, thus implicating that alpha5 integrin may be a mediator of mEMAP II's antiangiogenic function

  4. The Effect of Nigella Sativa Extract on Alpha-ketoglutarate Activity and Histopathologic Changes on Rat Liver Induced by Monosodium Glutamate

    Directory of Open Access Journals (Sweden)

    Ala Sh Emhemed Eshami


    Full Text Available Monosodium glutamate (MSG is a commonly used food additive and found in most soups, fish, and processed meat. The use of MSG in food is growing. However, the fear of consuming MSG has increased in the last few years due to the adverse reactions and toxicity in the liver. Nigella sativa (NS is used as traditional medicine for the treatment of many diseases. It has been extensively investigated in recent years due to its notable pharmacological properties such as inhibit oxidative stress. The present study was undertaken to investigate the effect of different doses of Nigella Sativa on alpha KGDH activity and liver histology of MSG-induced rats. The animals (n=30 were grouped into A (control, B (treated with MSG 1g/ , C (treated with MSG 1g/ and NS 0.1 g/, D (treated with MSG 1g/ and NS 0.2 g/, E (treated with MSG 1g/ and NS 0.4 g/ and F (given a daily NS extract 0.2 g/ Alpha KGDH activity was investigated using ELISA method and liver histopathology by light microscope. The MSG treatment increased Alpha KGDH activity and disturbed liver architecture, hemorrhage in the central veins, areas of necrosis, vacuolation and increased inflammatory cells infiltration. The condition was normalized by treatment NS on dose 0.2 and 0.4 g/ The findings showed that the administration of MSG increases alpha KGDH and induces damage in liver tissue. Nigella sativa extract can reduce alpha KGDH and prevent liver damage caused by MSG.

  5. Free fatty acids induce ER stress and block antiviral activity of interferon alpha against hepatitis C virus in cell culture

    Directory of Open Access Journals (Sweden)

    Gunduz Feyza


    Full Text Available Abstract Background Hepatic steatosis is recognized as a major risk factor for liver disease progression and impaired response to interferon based therapy in chronic hepatitis C (CHC patients. The mechanism of response to interferon-alpha (IFN-α therapy under the condition of hepatic steatosis is unexplored. We investigated the effect of hepatocellular steatosis on hepatitis C virus (HCV replication and IFN-α antiviral response in a cell culture model. Methods Sub-genomic replicon (S3-GFP and HCV infected Huh-7.5 cells were cultured with a mixture of saturated (palmitate and unsaturated (oleate long-chain free fatty acids (FFA. Intracytoplasmic fat accumulation in these cells was visualized by Nile red staining and electron microscopy then quantified by microfluorometry. The effect of FFA treatment on HCV replication and IFN-α antiviral response was measured by flow cytometric analysis, Renilla luciferase activity, and real-time RT-PCR. Results FFA treatment induced dose dependent hepatocellular steatosis and lipid droplet accumulation in the HCV replicon cells was confirmed by Nile red staining, microfluorometry, and by electron microscopy. Intracellular fat accumulation supports replication more in the persistently HCV infected culture than in the sub-genomic replicon (S3-GFP cell line. FFA treatment also partially blocked IFN-α response and viral clearance by reducing the phosphorylation of Stat1 and Stat2 dependent IFN-β promoter activation. We show that FFA treatment induces endoplasmic reticulum (ER stress response and down regulates the IFNAR1 chain of the type I IFN receptor leading to defective Jak-Stat signaling and impaired antiviral response. Conclusion These results suggest that intracellular fat accumulation in HCV cell culture induces ER stress, defective Jak-Stat signaling, and attenuates the antiviral response, thus providing an explanation to the clinical observation regarding how hepatocellular steatosis influences IFN

  6. Gastroprotective effect of alpha-pinene and its correlation with antiulcerogenic activity of essential oils obtained from Hyptis species (United States)

    Pinheiro, Marcelo de Almeida; Magalhães, Rafael Matos; Torres, Danielle Mesquita; Cavalcante, Rodrigo Cardoso; Mota, Francisca Sheila Xavier; Oliveira Coelho, Emanuela Maria Araújo; Moreira, Henrique Pires; Lima, Glauber Cruz; Araújo, Pamella Cristina da Costa; Cardoso, José Henrique Leal; de Souza, Andrelina Noronha Coelho; Diniz, Lúcio Ricardo Leite


    Background: Alpha-pinene (α-pinene) is a monoterpene commonly found in essential oils with gastroprotective activity obtained from diverse medicinal plants, including Hyptis species. The genus Hyptis (lamiaceae) consists of almost 400 species widespread in tropical and temperate regions of America. In the north and northeastern Brazil, some Hyptis species are used in traditional medicine to treat gastrointestinal disturbances. Objective: The present study has investigated the gastoprotective effect of purified α-pinene in experimental gastric ulcer induced by ethanol and indomethacin in mice. Materials and Methods: Gastric ulcers were induced in male Swiss mice (20-30 g) by oral administration of absolute ethanol or indomethacin 45 min after oral pretreatment with vehicle, standard control drugs or α-pinene (10, 30, and 100 mg/kg). One hour after the ulcerative challenges, the stomach were removed, and gastric lesions areas measured. The effects of α-pinene on the gastric juice acidity were determined by pylorus ligation model. The gastrointestinal motility and mucus depletion were determined by measuring the gastric levels of phenol red and alcian blue, respectively. Hematoxylin and eosin stained sections of gastric mucosa of the experimental groups were used for histology analysis. Results: α-pinene pretreatment inhibited ethanol-induced gastric lesions, reduced volume and acidity of the gastric juice and increased gastric wall mucus (P < 0.05). Furthermore, we showed an interesting correlation between concentration of α-pinene and gastroprotective effect of Hyptis species (P Pearson = 0.98). Conclusion: Our data showed that the α-pinene exhibited significant antiulcerogenic activity and a great correlation between concentration of α-pinene and gastroprotective effect of Hyptis species was also observed. PMID:25709221

  7. Changes in autonomic nervous system activity after treatment with alpha-blocker in men with lower urinary tract symptoms

    Directory of Open Access Journals (Sweden)

    Kang Hee Shim


    Full Text Available Purpose: To determine changes in autonomic nervous system activity after treatment in men with lower urinary tract symptoms (LUTS, we evaluated changes in patients' symptoms, uroflowmetry, and heart rate variability (HRV after treatment with alpha-blockers for 12 weeks. Materials and Methods: Ninety-five men who had LUTS (International Prostate Symptom Score [IPSS] ≥8 were included in this study. We divided them into two groups on the basis of a low frequency/high frequency (LF/HF ratio of 1.6. After treatment with Xatral XL (Handok Inc., Korea 10 mg for 3 months, we rechecked their IPSS, uroflowmetry, HRV and compared these with the baseline measurements. Results: Fifty-four men were assigned to the low LF/HF group (group A: LF/HF ≤1.6 and 41 men to the high LF/HF group (group B: LF/HF >1.6. At baseline and 12 weeks, none of the parameters differed significantly between the groups except for HF, which is one of the parameters of HRV. IPSS, the IPSS-voiding subscore, and the IPSS-storage subscore decreased and maximal uroflow increased significantly after 12 weeks of treatment. Whereas the baseline LF/HF ratio increased from 0.89±0.407 to 1.80±1.804 after treatment in group A, it decreased from 3.93±5.471 to 1.79±1.153 in group B. Conclusions: The efficacies of Xatral XL were clear in both groups. We found that the LF/HF ratio in the two groups merged to a value of approximately 1.79 after treatment. We suggest that this could be a clue to the importance of balance in autonomic nervous system activity in men with LUTS.

  8. 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. (United States)

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


    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.

  9. Activity, splice variants, conserved peptide motifs, and phylogeny of two new alpha1,3-fucosyltransferase families (FUT10 and FUT11). (United States)

    Mollicone, Rosella; Moore, Stuart E H; Bovin, Nicolai; Garcia-Rosasco, Marcela; Candelier, Jean-Jacques; Martinez-Duncker, Iván; Oriol, Rafael


    We report the cloning of three splice variants of the FUT10 gene, encoding for active alpha-l-fucosyltransferase-isoforms of 391, 419, and 479 amino acids, and two splice variants of the FUT11 gene, encoding for two related alpha-l-fucosyltransferases of 476 and 492 amino acids. The FUT10 and FUT11 appeared 830 million years ago, whereas the other alpha1,3-fucosyltransferases emerged 450 million years ago. FUT10-391 and FUT10-419 were expressed in human embryos, whereas FUT10-479 was cloned from adult brain and was not found in embryos. Recombinant FUT10-419 and FUT10-479 have a type II trans-membrane topology and are retained in the endoplasmic reticulum (ER) by a membrane retention signal at their NH(2) termini. The FUT10-479 has, in addition, a COOH-ER membrane retention signal. The FUT10-391 is a soluble protein without a trans-membrane domain or ER retention signal that transiently localizes to the Golgi and then is routed to the lysosome. After transfection in COS7 cells, the three FUT10s and at least one FUT11, link alpha-l-fucose onto conalbumin glycopeptides and biantennary N-glycan acceptors but not onto short lactosaminyl acceptor substrates as do classical monoexonic alpha1,3-fucosyltransferases. Modifications of the innermost core GlcNAc of the N-glycan, by substitution with ManNAc or with an opened GlcNAc ring or by the addition of an alpha1,6-fucose, suggest that the FUT10 transfer is performed on the innermost GlcNAc of the core chitobiose. We can exclude alpha1,3-fucosylation of the two peripheral GlcNAcs linked to the trimannosyl core of the acceptor, because the FUT10 fucosylated biantennary N-glycan product loses both terminal GlcNAc residues after digestion with human placenta alpha-N-acetylglucosaminidase.

  10. Water Leak Localisation and Recovery in Tore Supra

    International Nuclear Information System (INIS)

    Martinez, A.; Samaille, F.; Chantant, M.; Hatchressian, J.-C.


    For almost 20 years, Tore Supra (TS) Tokamak uses water as a coolant for its plasma facing and in-vessels components. It can be considered as ITER relevant on this particular aspect. During plasma operation in TS, the water inlet temperature and outlet pressure are 120 o C and 2.4 MPa respectively, while baking is performed at 200 o C and 2 Mpa. It happened, that unexpected localized power deposits damaged in-vessels components leading to more or less large water leaks. In order to protect the vacuum vessel from over-pressurisation in case of large water leaks and to avoid the release of eventual activated materials, a pressure suppression system, composed of two rupture disks and a relief pipe header, has been designed. In the event of smaller leaks, the issue for Tore Supra operations is to apply methods capable of detecting and localising leaking water cooling circuits inside the vacuum vessel within an acceptable time. For this purpose, drainage and drying systems have been designed and manufactured to evacuate completely the water in the components and vacuum vessel, facilitating, in that way, leak testing procedure of the components. A new system allows the localization of the leaky circuit remotely by using the cooling loops monitoring system. The sub-circuits can be selected, isolated and de pressurized by the operator. Simultaneously the vacuum is monitored in the vessel and analyzed with a mass spectrometer. The water resulting from the steam condensation in the cold parts of the vacuum vessel is pumped by a new specific vacuum system in the lower parts of the machine and stored in tanks to avoid dissipation of activated products in the environment. Filters are implemented on the outlets lines of the pumps. The in-vessels components fed by the upper part of the cooling loop are connected in parallel and the water inlets and outlets are located on top of the machine, so some difficulties were encountered to drain-off completely this components. Presently

  11. Staphylococcal superantigen-like 5 activates platelets and supports platelet adhesion under flow conditions, which involves glycoprotein Ib alpha and alpha(IIb)beta(3)

    NARCIS (Netherlands)

    De Haas, C. J. C.; Weeterings, C.; Vughs, M. M.; De Groot, P. G.; Van Strijp, J. A.; Lisman, T.


    Objectives: Staphylococcal superantigen-like 5 (SSL5) is an exoprotein secreted by Staphylococcus aureus that has been shown to inhibit neutrophil rolling over activated endothelial cells via a direct interaction with P-selectin glycoprotein ligand 1 (PSGL-1). Methods and Results: When purified

  12. Removal of an endocrine disrupting chemical (17 alpha-ethinyloestradiol) from wastewater effluent by activated carbon adsorption: Effects of activated carbon type and competitive adsorption

    Energy Technology Data Exchange (ETDEWEB)

    Ifelebuegu, A.O.; Lester, J.N.; Churchley, J.; Cartmell, E. [Cranfield University, Cranfield (United Kingdom). School of Water Science


    Granular activated carbon has been extensively used for the adsorption of organic micropollutants for potable water production. In this study the removal of an endocrine disrupting chemical from wastewater final effluent by three types of granular activated carbon (wood, coconut and coal based) has been investigated in batch adsorption experiments and correlated with the removal of chemical oxygen demand (COD), total organic carbon (TOC) and ultraviolet absorbance (UV). The results obtained demonstrated 17 alpha-ethinyloestradiol (EE2) removals of 98.6%, 99.3%, and 96.4% were achieved by the coal based (ACo), coconut based (ACn) and wood based (AWd) carbons respectively at the lowest dose of carbon (0.1 gl{sup -1}). The other adsorbates investigated all exhibited good removal. At an equilibrium concentration of 7 mgl{sup -1} the COD adsorption capacities were 3.16 mg g{sup -1}, 4.8 mg g{sup -1} and 7.1 mg g{sup -1} for the wood, coconut and coal based carbons respectively. Overall, the order of removal efficiency of EE2 and the other adsorbates for the three activated carbons was ACn {gt} ACo {gt} AWd. The adsorption capacities of the carbons were found to be reduced by the effects of other competing adsorbates in the wastewater effluent.

  13. Capsule-odometer: a concept to improve accurate lesion localisation. (United States)

    Karargyris, Alexandros; Koulaouzidis, Anastasios


    In order to improve lesion localisation in small-bowel capsule endoscopy, a modified capsule design has been proposed incorporating localisation and - in theory - stabilization capabilities. The proposed design consists of a capsule fitted with protruding wheels attached to a spring-mechanism. This would act as a miniature odometer, leading to more accurate lesion localization information in relation to the onset of the investigation (spring expansion e.g., pyloric opening). Furthermore, this capsule could allow stabilization of the recorded video as any erratic, non-forward movement through the gut is minimised. Three-dimensional (3-D) printing technology was used to build a capsule prototype. Thereafter, miniature wheels were also 3-D printed and mounted on a spring which was attached to conventional capsule endoscopes for the purpose of this proof-of-concept experiment. In vitro and ex vivo experiments with porcine small-bowel are presented herein. Further experiments have been scheduled.

  14. Primary hepatocellular carcinoma localised by a radiolabelled monoclonal antibody

    Energy Technology Data Exchange (ETDEWEB)

    Markham, N; Ritson, A; James, O; Curtin, N; Bassendine, M; Sikora, K


    A rat monoclonal antibody, YPC2/38.8, was selected from a panel of antibodies derived by immunising rats with fresh human colorectal carcinoma. It was found to bind to a 30,000 dalton protein present on the cell surface of normal colon and liver. This protein was increased 10-fold on primary hepatocellular carcinoma (PHC) cells. After labelling with /sup 131/I, YPC2/38.8 was shown to localise human PHCs grown as xenografts in immunosuppressed mice. The authors conclude that YPC2/38.8 may have potential for diagnostic localisation and possibly thence for the selective targeting of drugs or toxins in patients with PHC arising in a liver unaffected by significant parenchymal disease. 16 refs.; 4 figs.; 1 table.

  15. Spinal activation of alpha7-nicotinic acetylcholine receptor attenuates posttraumatic stress disorder-related chronic pain via suppression of glial activation. (United States)

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


    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.

  16. Regional Patterns of Elevated Alpha and High-Frequency Electroencephalographic Activity during Nonrapid Eye Movement Sleep in Chronic Insomnia: A Pilot Study (United States)

    Riedner, Brady A.; Goldstein, Michael R.; Plante, David T.; Rumble, Meredith E.; Ferrarelli, Fabio; Tononi, Giulio; Benca, Ruth M.


    Study Objectives: To examine nonrapid eye movement (NREM) sleep in insomnia using high-density electroencephalography (EEG). Methods: All-night sleep recordings with 256 channel high-density EEG were analyzed for 8 insomnia subjects (5 females) and 8 sex and age-matched controls without sleep complaints. Spectral analyses were conducted using unpaired t-tests and topographical differences between groups were assessed using statistical non-parametric mapping. Five minute segments of deep NREM sleep were further analyzed using sLORETA cortical source imaging. Results: The initial topographic analysis of all-night NREM sleep EEG revealed that insomnia subjects had more high-frequency EEG activity (> 16 Hz) compared to good sleeping controls and that the difference between groups was widespread across the scalp. In addition, the analysis also showed that there was a more circumscribed difference in theta (4–8 Hz) and alpha (8–12 Hz) power bands between groups. When deep NREM sleep (N3) was examined separately, the high-frequency difference between groups diminished, whereas the higher regional alpha activity in insomnia subjects persisted. Source imaging analysis demonstrated that sensory and sensorimotor cortical areas consistently exhibited elevated levels of alpha activity during deep NREM sleep in insomnia subjects relative to good sleeping controls. Conclusions: These results suggest that even during the deepest stage of sleep, sensory and sensorimotor areas in insomnia subjects may still be relatively active compared to control subjects and to the rest of the sleeping brain. Citation: Riedner BA, Goldstein MR, Plante DT, Rumble ME, Ferrarelli F, Tononi G, Benca RM. Regional patterns of elevated alpha and high-frequency electroencephalographic activity during nonrapid eye movement sleep in chronic insomnia: a pilot study. SLEEP 2016;39(4):801–812. PMID:26943465

  17. Alpha-Hydroxylation of lignoceric and nervonic acids in the brain. Effects of altered thyroid function on postnatal development of the hydroxylase activity. (United States)

    Murad, S; Strycharz, G D; Kishimoto, Y


    Rat brain postnuclear preparations catalyzed the alpha-hydroxylation of nervonic acid with an apparent Km of 3 muM. Evidence has been presented which suggests that nervonic acid in the brain is hydroxylated by the same enzyme system which hydroxylates lignoceric acid. The hydroxylase activity in brains of normal (euthyroid) rats increased rapidly from a low in the period immediately following birth to a maximum at the 23rd day and then declined to a low level characteristic of the mature brain. Neonatal hypothyroidism retarded the development of the activity and shifted its peak to the 39th day after birth. Conversely, neonatal hyperthyroidism accelerated the entire developmental pattern and shifted the peak to the 16th day after birth. The hydroxylase activity in mouse brain was also increased by thyroid hormone administration from the 13th through the 18th day after birth. Unlike normal mice, the low activity in jimpy mice was not affected by this treatment. It is concluded that thyroid hormones play an important role in the control of brain fatty acid alpha-hydroxylation. The stimulation of alpha-hydroxy fatty acid synthesis in response to hyperthyroidism during the early postnatal period may be one of the major effects of thyroid hormones in accelerating myelination of the central nervous system.

  18. Regional Patterns of Elevated Alpha and High-Frequency Electroencephalographic Activity during Nonrapid Eye Movement Sleep in Chronic Insomnia: A Pilot Study. (United States)

    Riedner, Brady A; Goldstein, Michael R; Plante, David T; Rumble, Meredith E; Ferrarelli, Fabio; Tononi, Giulio; Benca, Ruth M


    To examine nonrapid eye movement (NREM) sleep in insomnia using high-density electroencephalography (EEG). All-night sleep recordings with 256 channel high-density EEG were analyzed for 8 insomnia subjects (5 females) and 8 sex and age-matched controls without sleep complaints. Spectral analyses were conducted using unpaired t-tests and topographical differences between groups were assessed using statistical non-parametric mapping. Five minute segments of deep NREM sleep were further analyzed using sLORETA cortical source imaging. The initial topographic analysis of all-night NREM sleep EEG revealed that insomnia subjects had more high-frequency EEG activity (> 16 Hz) compared to good sleeping controls and that the difference between groups was widespread across the scalp. In addition, the analysis also showed that there was a more circumscribed difference in theta (4-8 Hz) and alpha (8-12 Hz) power bands between groups. When deep NREM sleep (N3) was examined separately, the high-frequency difference between groups diminished, whereas the higher regional alpha activity in insomnia subjects persisted. Source imaging analysis demonstrated that sensory and sensorimotor cortical areas consistently exhibited elevated levels of alpha activity during deep NREM sleep in insomnia subjects relative to good sleeping controls. These results suggest that even during the deepest stage of sleep, sensory and sensorimotor areas in insomnia subjects may still be relatively active compared to control subjects and to the rest of the sleeping brain. © 2016 Associated Professional Sleep Societies, LLC.

  19. ALPHA/AMPU, Radionuclide Radioactivity from Alpha Spectrometer Measurements

    International Nuclear Information System (INIS)

    Sill, D.S.


    1 - Description of program or function: The two computer programs, ALPHA and AMPU, take raw data obtained from alpha spectrometry and from these calculate activities and uncertainties of the radionuclides present in the sample. ALPHA determines activities of any alpha emitter in a sample that has been directly precipitated with NdF 3 . AMPU determines the Pu-239, Pu-238,and Am-241 activities using Pu-236 and Am-243 tracers. 2 - Method of solution: These programs propagate all random and systematic uncertainties, found anywhere in the experimental process, to the final result. The result is rounded and is in decimal agreement with the uncertainty. 3 - Restrictions on the complexity of the problem: In ALPHA, a chemical yield of 98% is assumed

  20. La Carte de Localisation Probable des Avalanches (CPLA

    Directory of Open Access Journals (Sweden)

    Gilles BORREL


    Full Text Available La Carte de Localisation Probable des Avalanches (CPLA indique l’enveloppe des limites extrêmes connues atteintes par les avalanches, ainsi que les travaux de protection associés. Il s’agit d’un document informatif et non d’une carte de risque. Depuis 1990, les données thématiques sont numérisées.

  1. Regulation of hepatic peroxisome proliferator-activated receptor alpha expression but not adiponectin by dietary protein in finishing pigs. (United States)

    Weber, T E; Kerr, B J; Spurlock, M E


    Soy protein regulates adiponectin and peroxisome proliferator-activated receptor alpha (PPARalpha) in some species, but the effect of dietary soy protein on adiponectin and PPARalpha in the pig has not been studied. Therefore, the objective of this study was to determine whether soya bean meal reduction or replacement influences serum adiponectin, adiponectin mRNA, serum metabolites and the expression of PPARalpha and other genes involved in lipid deposition. Thirty-three pigs (11 pigs per treatment) were subjected to one of three dietary treatments: (i) reduced crude protein (CP) diet containing soya bean meal (RCP-Soy), (ii) high CP diet containing soya bean meal (HCP-Soy) or (iii) high CP diet with corn gluten meal replacing soya bean meal (HCP-CGM) for 35 days. Dietary treatment had no effect on overall growth performance, feed intake or measures of body composition. There was no effect of dietary treatment on serum adiponectin or leptin. Dietary treatment did not affect the abundance of the mRNAs for adiponectin, PPARalpha, PPARgamma2, lipoprotein lipase or fatty acid synthase in adipose tissue. The mRNA expression of PPARalpha, PPARgamma2, lipoprotein lipase or fatty acid synthetase in loin muscle was not affected by dietary treatment. In liver tissue, the relative abundance of PPARalpha mRNA was greater (p Soy diets when compared to pigs fed RCP-Soy or HCP-CGM diets. Hepatic mRNA expression of acyl-CoA oxidase or fatty acid synthase was not affected by dietary treatment. Western blot analysis indicated that hepatic PPARalpha protein levels were decreased (p Soy diets when compared to pigs fed the HCP-Soy diets. These data suggest that increasing the soy protein content of swine diets increases hepatic expression of PPARalpha without associated changes in body composition.

  2. Alpha-Adrenoceptor Antagonists Improve Memory by Activating -methyl-D-Aspartate-Induced Ion Currents in the Rat Hippocampus

    Directory of Open Access Journals (Sweden)

    Chang Hee Kim


    Full Text Available Purpose: Alpha1 (α1-adrenoceptor antagonists are widely used to treat lower urinary tract symptoms. These drugs not only act on peripheral tissues, but also cross the blood-brain barrier and affect the central nervous system. Therefore, α1-adrenoceptor antagonists may enhance brain functions. In the present study, we investigated the effects of tamsulosin, an α1-adrenoceptor antagonist, on short-term memory, as well as spatial learning and memory, in rats. Methods: The step-down avoidance test was used to evaluate short-term memory, and an eight-arm radial maze test was used to evaluate spatial learning and memory. TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining was performed in order to evaluate the effect of tamsulosin on apoptosis in the hippocampal dentate gyrus. Patch clamp recordings were used to evaluate the effect of tamsulosin on ionotropic glutamate receptors, such as N-methyl-D-aspartate (NMDA, amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA, and kainate receptors, in hippocampal CA1 neurons. Results: Tamsulosin treatment improved short-term memory, as well as spatial learning and memory, without altering apoptosis. The amplitudes of NMDA-induced ion currents were dose-dependently increased by tamsulosin. However, the amplitudes of AMPA- and kainate-induced ion currents were not affected by tamsulosin. Conclusions: Tamsulosin enhanced memory function by activating NMDA receptor-mediated ion currents in the hippocampus without initiating apoptosis. The present study suggests the possibility of using tamsulosin to enhance memory under normal conditions, in addition to its use in treating overactive bladder.

  3. Kyste hydatique à localisation costo vertébrale (United States)

    Marouf, Rachid


    L'hydatidose est une affection parasitaire due à la contamination de l'homme par la forme larvaire de ténia échinococcus granulosus, la forme costo vertébrale est une localisation très rare qui représente 0,18 à 1,21% de l'ensemble des localisations hydatiques. Nous rapportons le cas d'une femme de 32 ans qui présente un kyste hydatique multi vésiculaire à localisation costovertébrale, traité par chirurgie radicale associée à un traitement médical anti parasitaire pour une durée de 6 mois, avec bonne évolution. L'atteinte costo-vertébrale par la maladie hydatique est rare et l’évolution est insidieuse. Malgré un traitement chirurgical radical, la fréquence des récidives rend le pronostic sombre. PMID:25922632

  4. Diagnostic approach to localised organising pneumonia--A case report. (United States)

    Djurić, Mirna; Považan, Djordje; Djurić, Dejan; Eri, Živka; Trudić, Anika


    Localised organising pneumonia, radiologically presented with oval or round shadows mimicing lung cancer or metastases, is a major issue in differential diagnosis. A female patient was hospitalized to clarified the etiology of multiple nodular lung lesions. The chest X-ray and the chest computed tomography (CT) revealed bilateral patchy and nodular shadows, and round lung lesions, respectively. Neither sputum analyses, nor histology of bronchoscopy samples clarified the etiology of these lung lesions. As secondary deposits in the lungs were suspected, video-assisted thoracoscopy and anterolateral right minithoracotomy with atypical upper and lower lobe resection were performed. The frozen-section analysis suggested the benign nature of the lesion, and the definite histopathological finding of localised organising pneumonia was established. Due to bilateral lung lesions, corticosteroids were applied. Seven weeks later, the chest CT finding revealed a total regression of the lesions. A surgical resection was necessary to diagnose the localised organising pneumonia which mimiced secondary malignant lesions, thus establishing the definite etiology of lung lesions. Bronchoscopic cryobiopsy, recently introduced in order to obtain peripheral lung biopsy samples, has provided new possibilities in the diagnosis and treatment of neoplastic and non-neoplastic lung diseases.

  5. Hydroxysteroid dehydrogenase HSD1L is localised to the pituitary–gonadal axis of primates

    Directory of Open Access Journals (Sweden)

    A Daniel Bird


    Full Text Available Steroid hormones play clinically important and specific regulatory roles in the development, growth, metabolism, reproduction and brain function in human. The type 1 and 2 11-beta hydroxysteroid dehydrogenase enzymes (11β-HSD1 and 2 have key roles in the pre-receptor modification of glucocorticoids allowing aldosterone regulation of blood pressure, control of systemic fluid and electrolyte homeostasis and modulation of integrated metabolism and brain function. Although the activity and function of 11β-HSDs is thought to be understood, there exists an open reading frame for a distinct 11βHSD-like gene; HSD11B1L, which is present in human, non-human primate, sheep, pig and many other higher organisms, whereas an orthologue is absent in the genomes of mouse, rat and rabbit. We have now characterised this novel HSD11B1L gene as encoded by 9 exons and analysis of EST library transcripts indicated the use of two alternate ATG start sites in exons 2 and 3, and alternate splicing in exon 9. Relatively strong HSD11B1L gene expression was detected in human, non-human primate and sheep tissue samples from the brain, ovary and testis. Analysis in non-human primates and sheep by immunohistochemistry localised HSD11B1L protein to the cytoplasm of ovarian granulosa cells, testis Leydig cells, and gonadatroph cells in the anterior pituitary. Intracellular localisation analysis in transfected human HEK293 cells showed HSD1L protein within the endoplasmic reticulum and sequence analysis suggests that similar to 11βHSD1 it is membrane bound. The endogenous substrate of this third HSD enzyme remains elusive with localisation and expression data suggesting a reproductive hormone as a likely substrate.

  6. Design and synthesis of novel sulfonamide-containing bradykinin hB2 receptor antagonists. 2. Synthesis and structure-activity relationships of alpha,alpha-cycloalkylglycine sulfonamides. (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


    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.

  7. Calibration of sources for alpha spectroscopy systems

    International Nuclear Information System (INIS)

    Freitas, I.S.M.; Goncalez, O.L.


    This paper describes the calibration methodology for measuring the total alpha activity of plane and thin sources with the Alpha Spectrometer for Silicon Detector in the Nuclear Measures and Dosimetry laboratory at IEAv/CTA. (author)

  8. Comparative analysis of dose rates in bricks determined by neutron activation analysis, alpha counting and X-ray fluorescence analysis for the thermoluminescence fine grain dating method

    Czech Academy of Sciences Publication Activity Database

    Bártová, H.; Kučera, Jan; Musílek, L.; Trojek, T.


    Roč. 104, NOV (2014), s. 393-397 ISSN 0969-806X. [1st International Conference on Dosimetry and its Applications (ICDA). Prague, 23.6.2013-28.6.2013] R&D Projects: GA MŠk(XE) LM2011019 Institutional support: RVO:61389005 Keywords : Alpha coutning * neutron activation analysis * X-ray fluorescence * thermoluminescence dating * dose rate Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 1.380, year: 2014

  9. Treatment of alpha bearing wastes

    International Nuclear Information System (INIS)


    This report deals with the current state of the art of alpha waste treatment, which is an integral part of the overall nuclear waste management system. The International Atomic Energy Agency (IAEA) defines alpha bearing waste as 'waste containing one or more alpha emitting radionuclides, usually actinides, in quantities above acceptable limits'. The limits are established by national regulatory bodies. The limits above which wastes are considered as alpha contaminated refer to the concentrations of alpha emitters that need special consideration for occupational exposures and/or potential safety, health, or environmental impact during one or more steps from generation through disposal. Owing to the widespread use of waste segregation by source - that is, based upon the 'suspect origin' of the material - significant volumes of waste are being handled as alpha contaminated which, in fact, do not require such consideration by reason of risk or environmental concern. The quantification of de minimis concepts by national regulatory bodies could largely contribute to the safe reduction of waste volumes and associated costs. Other factors which could significantly contribute to the reduction of alpha waste arisings are an increased application of assaying and sorting, instrumentation and the use of feedback mechanisms to control or modify the processes which generate these wastes. Alpha bearing wastes are generated during fabrication and reprocessing of nuclear fuels, decommissioning of alpha contaminated facilities, and other activities. Most alpha wastes are contact handled, but a small portion may require shielding or remote handling because of high levels of neutron (n), beta (β), or gamma (γ) emissions associated with the waste material. This report describes the sources and characteristics of alpha wastes and strategies for alpha waste management. General descriptions of treatment processes for solid and liquid alpha wastes are included. 71 refs, 14 figs, 9 tabs

  10. Mps1 kinase-dependent Sgo2 centromere localisation mediates cohesin protection in mouse oocyte meiosis I. (United States)

    El Yakoubi, Warif; Buffin, Eulalie; Cladière, Damien; Gryaznova, Yulia; Berenguer, Inés; Touati, Sandra A; Gómez, Rocío; Suja, José A; van Deursen, Jan M; Wassmann, Katja


    A key feature of meiosis is the step-wise removal of cohesin, the protein complex holding sister chromatids together, first from arms in meiosis I and then from the centromere region in meiosis II. Centromeric cohesin is protected by Sgo2 from Separase-mediated cleavage, in order to maintain sister chromatids together until their separation in meiosis II. Failures in step-wise cohesin removal result in aneuploid gametes, preventing the generation of healthy embryos. Here, we report that kinase activities of Bub1 and Mps1 are required for Sgo2 localisation to the centromere region. Mps1 inhibitor-treated oocytes are defective in centromeric cohesin protection, whereas oocytes devoid of Bub1 kinase activity, which cannot phosphorylate H2A at T121, are not perturbed in cohesin protection as long as Mps1 is functional. Mps1 and Bub1 kinase activities localise Sgo2 in meiosis I preferentially to the centromere and pericentromere respectively, indicating that Sgo2 at the centromere is required for protection.In meiosis I centromeric cohesin is protected by Sgo2 from Separase-mediated cleavage ensuring that sister chromatids are kept together until their separation in meiosis II. Here the authors demonstrate that Bub1 and Mps1 kinase activities are required for Sgo2 localisation to the centromere region.

  11. PDGFR alpha signaling in the primary cilium regulates NHE1-dependent fibroblast migration via coordinated differential activity of MEK1/2-ERK1/2-p90(RSK) and AKT signaling pathways

    DEFF Research Database (Denmark)

    Clement, Ditte L.; Mally, Sabine; Stock, Christian


    In fibroblasts, platelet-derived growth factor receptor alpha (PDGFR alpha) is upregulated during growth arrest and compartmentalized to the primary cilium. PDGF-AA mediated activation of the dimerized ciliary receptor produces a phosphorylation cascade through the PI3K-AKT and MEK1/2-ERK1/2 path...

  12. Differential in vitro inhibitory activity against HIV-1 of alpha-(1-3- and alpha-(1-6-D-mannose specific plant lectins : Implication for microbicide development

    Directory of Open Access Journals (Sweden)

    Balzarini Jan


    Full Text Available Abstract Background Plant lectins such as Galanthus nivalis agglutinin (GNA and Hippeastrum hybrid agglutinin (HHA are natural proteins able to link mannose residues, and therefore inhibit HIV-target cell interactions. Plant lectins are candidate for microbicide development. Objective To evaluate the activity against HIV of the mannose-specific plant lectins HHA and GNA at the cellular membrane level of epithelial cells and monocyte-derived dendritic cells (MDDC, two potential target cells of HIV at the genital mucosal level. Methods The inhibitory effects of HHA and GNA were evaluated on HIV adsorption to genital epithelial HEC-1A cell line, on HIV transcytosis throughout a monolayer of polarized epithelial HEC-1A cells, on HIV adsorption to MDDC and on transfer of HIV from MDDC to autologous T lymphocytes. Results HHA faintly inhibited attachment to HEC-1A cells of the R5-tropic HIV-1Ba-L strain, in a dose-dependent manner, whereas GNA moderately inhibited HIV adsorption in the same context, but only at high drug doses. Only HHA, but not GNA, inhibited HIV-1JR-CSF transcytosis in a dose-dependent manner. By confocal microscopy, HHA, but not GNA, was adsorbed at the epithelial cell surface, suggesting that HHA interacts specifically with receptors mediating HIV-1 transcytosis. Both plant lectins partially inhibited HIV attachment to MDDC. HHA inhibited more efficiently the transfer of HIV from MDDC to T cell, than GNA. Both HHA and GNA lacked toxicity below 200 μg/ml irrespective the cellular system used and do not disturb the monolayer integrity of epithelial cells. Conclusion These observations demonstrate higher inhibitory activities of the lectin plant HHA by comparison to GNA, on HIV adsorption to HEC-1A cell line, HIV transcytosis through HEC-1A cell line monolayer, HIV adsorption to MDDC and HIV transfer from MDDC to T cells, highlighting the potential interest of HHA as effective microbicide against HIV.

  13. Proteinaceous alpha-araylase inhibitors

    DEFF Research Database (Denmark)

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


    -amylase inhibitors belong to seven different protein structural families, most of which also contain evolutionary related proteins without inhibitory activity. Two families include bifunctional inhibitors acting both on alpha-amylases and proteases. High-resolution structures are available of target alpha...

  14. The Contribution of Peroxisome Proliferator-Activated Receptor Alpha to the Relationship Between Toxicokinetics and Toxicodynamics of Trichloroethylene. (United States)

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


    Exposure to the ubiquitous environmental contaminant trichloroethylene (TCE) is associated with cancer and non-cancer toxicity in both humans and rodents. Peroxisome proliferator-activated receptor-alpha (PPARα) is thought to be playing a role in liver toxicity in rodents through activation of the receptor by the TCE metabolite trichloroacetic acid (TCA). However, most studies using genetically altered mice have not assessed the potential for PPARα to alter TCE toxicokinetics, which may lead to differences in TCA internal doses and hence confound inferences as to the role of PPARα in TCE toxicity. To address this gap, male and female wild type (129S1/SvImJ), Pparα-null, and humanized PPARα (hPPARα) mice were exposed intragastrically to 400 mg/kg TCE in single-dose (2, 5 and 12 h) and repeat-dose (5 days/week, 4 weeks) studies. Interestingly, following either a single- or repeat-dose exposure to TCE, levels of TCA in liver and kidney were lower in Pparα-null and hPPARα mice as compared with those in wild type mice. Levels of trichloroethanol (TCOH) were similar in all strains. TCE-exposed male mice consistently had higher levels of TCA and TCOH in all tissues compared with females. Additionally, in both single- and repeat-dose studies, a similar degree of induction of PPARα-responsive genes was observed in liver and kidney of hPPARα and wild type mice, despite the difference in hepatic and renal TCA levels. Additional sex- and strain-dependent effects were observed in the liver, including hepatocyte proliferation and oxidative stress, which were not dependent on TCA or TCOH levels. These data demonstrate that PPARα status affects the levels of the putative PPARα agonist TCA following TCE exposure. Therefore, interpretations of studies using Pparα-null and hPPARα mice need to consider the potential contribution of genotype-dependent toxicokinetics to observed differences in toxicity, rather than attributing such differences only to receptor

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

    Directory of Open Access Journals (Sweden)

    Diana Henz


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

  16. DOSEmanPRO - active electronic online personal air sampler for detection of radon progeny long lived alpha nuclides

    International Nuclear Information System (INIS)

    Streil, T.; Oeser, V.


    Full text: Using the micro system - technology we developed a online personal air sampler not bigger than a mobile phone, to open a new dimension in personal dosimetry of inhaled radioactive aerosols. The DOSEman PRO containing an internal pump with a continuous air flow of 0.15 I/min sample the radon progeny or other nuclides on a millipore filter with excellent spectroscopic resolution. A 1.5 cm 2 light protected ion-implanted silicon detector analyses the alpha radiation at the filter. This small detector head contains also the pre amplification and pulse processing. The alpha radiation of the radon progeny and the long lived alpha nuclides is analyzed by a 60 channel spectrometer. The energy resolution of the online analyzed filter spectra is in the order of 150 keV. Mechanical and electronic design enables one to distinguish the long lived alpha nuclides from the radon and thoron progeny very easily. Using a special algorithm we correct the influence of the tailing of the radon progeny to the long lived alpha nuclides and take into consideration possible interference in determining the long lived alpha nuclides. Because of the air sampling volume of nearly 10 I/h, the system has a high efficiency. The detection limit by 2 hours sampling time is 0.05 Bq/m 3 alpha nuclide concentration. In a modified device for air sampling especially of long-lived alpha nuclides like uranium, radium or plutonium, the flow rate is increased to 0,3 1/min e.g. during a 10 h sampling period we can detect 0.005 Bq/m 3 in a low radon atmosphere. Assuming increased radon progeny concentration, the statistical error for the long lived alpha nuclides will be higher, but in most of the cases for use in nuclear facilities low radon concentrations are ambient conditions. This concept of an electronic personal air sampler with an alpha spectroscopy offers some outstanding advantages compared to passive dosimeters or off-line alpha air filters: The dose value and the nuclide concentration is

  17. In vitro anti-diabetic activity of flavonoids and pheophytins from Allophylus cominia Sw . on PTP1B, DPPIV, alpha-glucosidase and alpha-amylase enzymes. (United States)

    Semaan, D G; Igoli, J O; Young, L; Marrero, E; Gray, A I; Rowan, E G


    Ethno-botanical information from diabetic patients in Cuba led to the identification of Allophylus cominia as a possible source of new drugs for the treatment of type 2 diabetes mellitus (T2-DM). Chemical characterization of the extracts from A. cominia was carried out using chromatographic and spectroscopic methods. The extracts were tested for their activity on PTP1B, DPPIV, α-glucosidase enzymes and α-amylase. The flavonoid rich fractions from A. cominia inhibited DPPIV enzyme (75.3±2.33%) at 30µg/ml and produced a concentration-dependent inhibition against DPPIV with a Ki value of 2.6µg/ml. At 30µg/ml, flavonoids and pheophytins extracts significantly inhibited PTP1B enzyme (100±2.6% and 68±1% respectively). The flavonoids, pheophytin A and pheophytin B fractions showed significant concentration-dependent inhibition against PTP1B with Ki values of 3µg/ml, 0.64µg/ml and 0.88µg/ml respectively. At 30µg/ml, the flavonoid fraction significantly inhibited α-glucosidase enzyme (86±0.3%) in a concentration-dependent pattern with a Ki value of 2µg/ml. None of the fractions showed significant effects on α-amylase. Fatty acids, tannins, pheophytins A and B, and a mixture of flavonoids were detected in the methanolic extract from A. cominia. The identified flavonoids were mearnsitrin, quercitrin, quercetin-3-alloside, and naringenin-7-glucoside. The pharmacological effects of the extracts from A. cominia earlier observed in experimental diabetic models was confirmed in this study. Thus a new drug or formulation for the treatment of T2-DM could be developed from A. cominia. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  18. Contribution for new genetic markers of rheumatoid arthritis activity and severity: sequencing of the tumor necrosis factor-alpha gene promoter. (United States)

    Fonseca, João Eurico; Cavaleiro, João; Teles, José; Sousa, Elsa; Andreozzi, Valeska L; Antunes, Marília; Amaral-Turkman, Maria A; Canhão, Helena; Mourão, Ana F; Lopes, Joana; Caetano-Lopes, Joana; Weinmann, Pamela; Sobral, Marta; Nero, Patrícia; Saavedra, Maria J; Malcata, Armando; Cruz, Margarida; Melo, Rui; Braña, Araceli; Miranda, Luis; Patto, José V; Barcelos, Anabela; da Silva, José Canas; Santos, Luís M; Figueiredo, Guilherme; Rodrigues, Mário; Jesus, Herberto; Quintal, Alberto; Carvalho, Teresa; da Silva, José A Pereira; Branco, Jaime; Queiroz, Mário Viana


    The objective of this study was to assess whether clinical measures of rheumatoid arthritis activity and severity were influenced by tumor necrosis factor-alpha (TNF-alpha) promoter genotype/haplotype markers. Each patient's disease activity was assessed by the disease activity score using 28 joint counts (DAS28) and functional capacity by the Health Assessment Questionnaire (HAQ) score. Systemic manifestations, radiological damage evaluated by the Sharp/van der Heijde (SvdH) score, disease-modifying anti-rheumatic drug use, joint surgeries, and work disability were also assessed. The promoter region of the TNF-alpha gene, between nucleotides -1,318 and +49, was sequenced using an automated platform. Five hundred fifty-four patients were evaluated and genotyped for 10 single-nucleotide polymorphism (SNP) markers, but 5 of these markers were excluded due to failure to fall within Hardy-Weinberg equilibrium or to monomorphism. Patients with more than 10 years of disease duration (DD) presented significant associations between the -857 SNP and systemic manifestations, as well as joint surgeries. Associations were also found between the -308 SNP and work disability in patients with more than 2 years of DD and radiological damage in patients with less than 10 years of DD. A borderline effect was found between the -238 SNP and HAQ score and radiological damage in patients with 2 to 10 years of DD. An association was also found between haplotypes and the SvdH score for those with more than 10 years of DD. An association was found between some TNF-alpha promoter SNPs and systemic manifestations, radiological progression, HAQ score, work disability, and joint surgeries, particularly in some classes of DD and between haplotypes and radiological progression for those with more than 10 years of DD.

  19. Inhibition of 5-alpha-reductase activity induces stromal remodeling and smooth muscle de-differentiation in adult gerbil ventral prostate. (United States)

    Corradi, Lara S; Góes, Rejane M; Carvalho, Hernandes F; Taboga, Sebastião R


    Prostatic differentiation during embryogenesis and its further homeostatic state maintenance during adult life depend on androgens. Dihydrotestosterone, which is synthesized from testosterone by 5 alpha-reductase (5 alpha-r), is the active molecule triggering androgen action within the prostate. In the present work, we examined the effects of 5 alpha-reductase inhibition by finasteride in the ventral prostate (VP) of the adult gerbil, employing histochemical and electron microscopy techniques to demonstrate the morphological and organizational changes of the organ. After 10 days of finasteride treatment at a dose of 100 mg/kg/day, the prostatic complex (VP and dorsolateral prostate) absolute weight was reduced to about 18%. The epithelial cells became short and cuboidal, with less secretory blebs and reduced acid phosphatase activity. The luminal sectional area diminished, suggestive of decreased secretory activity. The stromal/epithelial ratio increased, the stroma becoming thicker but less cellular. There was a striking accumulation of collagen fibrils, which was accompanied by an increase in deposits of amorphous granular material adjacent to the basal lamina and in the clefts between smooth muscle cells (SMC). Additionally, the periacinar smooth muscle became loosely packed. Some SMC were atrophic and showed a denser array of the cytoskeleton, whereas other SMC had a highly irregular outline with numerous spine-like projections. The present data indicate that 5 alpha-r inhibition causes epithelial and stromal changes by affecting intra-prostatic hormone levels. These alterations are probably the result of an imbalance of the homeostatic interaction between the epithelium and the underlying stroma.

  20. Enhanced Noradrenergic Activity Potentiates Fear Memory Consolidation and Reconsolidation by Differentially Recruiting alpha1- and beta-Adrenergic Receptors (United States)

    Gazarini, Lucas; Stern, Cristina A. Jark; Carobrez, Antonio P.; Bertoglio, Leandro J.


    Consolidation and reconsolidation are phases of memory stabilization that diverge slightly. Noradrenaline is known to influence both processes, but the relative contribution of alpha1- and beta-adrenoceptors is unclear. The present study sought to investigate this matter by comparing their recruitment to consolidate and/or reconsolidate a…