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Sample records for adenosine monophosphate camp

  1. "cAMP sponge": a buffer for cyclic adenosine 3', 5'-monophosphate.

    Directory of Open Access Journals (Sweden)

    Konstantinos Lefkimmiatis

    Full Text Available BACKGROUND: While intracellular buffers are widely used to study calcium signaling, no such tool exists for the other major second messenger, cyclic AMP (cAMP. METHODS/PRINCIPAL FINDINGS: Here we describe a genetically encoded buffer for cAMP based on the high-affinity cAMP-binding carboxy-terminus of the regulatory subunit RIbeta of protein kinase A (PKA. Addition of targeting sequences permitted localization of this fragment to the extra-nuclear compartment, while tagging with mCherry allowed quantification of its expression at the single cell level. This construct (named "cAMP sponge" was shown to selectively bind cAMP in vitro. Its expression significantly suppressed agonist-induced cAMP signals and the downstream activation of PKA within the cytosol as measured by FRET-based sensors in single living cells. Point mutations in the cAMP-binding domains of the construct rendered the chimera unable to bind cAMP in vitro or in situ. Cyclic AMP sponge was fruitfully applied to examine feedback regulation of gap junction-mediated transfer of cAMP in epithelial cell couplets. CONCLUSIONS: This newest member of the cAMP toolbox has the potential to reveal unique biological functions of cAMP, including insight into the functional significance of compartmentalized signaling events.

  2. Cyclic adenosine monophosphate signal pathway in targeted therapy of lymphoma

    Institute of Scientific and Technical Information of China (English)

    DOU Ai-xia; WANG Xin

    2010-01-01

    Objective To review the role of cyclic adenosine monophosphate (cAMP) signal pathway in the pathogenesis oflymphoma and explore a potential lymphoma therapy targeted on this signaling pathway.Data sources The data cited in this review were mainly obtained from the articles listed in Medline and PubMed,published from January 1995 to June 2009. The search terms were "cAMP" and "lymphoma".Study selection Articles regarding the role of the cAMP pathway in apoptosis of lymphoma and associated cells and itspotential role in targeted therapy of lymphoma.Results In the transformation of lymphocytic malignancies, several signal pathways are involved. Among of them, thecAMP pathway has attracted increasing attention because of its apoptosis-inducing role in several lymphoma cells. cAMPpathway impairment is found to influence the prognosis of lymphoma. Targeted therapy to the cAMP pathway seems tobe a new direction for lymphoma treatment, aiming at restoring the cAMP function.Conclusions cAMP signal pathway has different effects on various lymphoma cells. cAMP analogues andphosphodiesterase 4B (PDE4B) inhibitors have potential clinical significance. However, many challenges remain inunderstanding the various roles of such agents.

  3. Plasma concentrations of the cyclic nucleotides, adenosine 3',5'-monophosphate and guanosine 3'.5'-monophosphate, in healthy adults treated with theophylline

    DEFF Research Database (Denmark)

    Fenger, M; Eriksen, P B; Andersen, O;

    1982-01-01

    Plasma concentrations of cyclic adenosine monophosphate and cyclic guanosine monophosphate were measured in 10 health adults before, during and after periods of theophylline administration. Cyclic adenosine monophosphate concentrations did not change significantly, but cyclic guanosine monophosph...

  4. Effects of plant extract neferine on cyclic adenosine monophosphate and cyclic guanosine monophosphate levels in rabbit corpus cavernosum in vitro

    Institute of Scientific and Technical Information of China (English)

    Jun Chen; Ji-Hong Liu; Tao Wang; Heng-Jun Xiao; Chun-Ping Yin; Jun Yang

    2008-01-01

    Aim: To further investigate the relaxation mechanism of neferine (Nef), a bis-benzylisoquinoline alkaloid extracted (isolated) from the green seed embryo of Nelumbo nucifera Gaertn in China, on rabbit corpus cavernosum tissue in vitro. Methods: The effects of Nef on the concentrations of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in isolated and incubated rabbit corpus cavernosum tissue were re-corded using125Ⅰ radioimmunoassay. Results: The basal concentration of cAMP in corpus cavernosum tissue was 5.67±0.97 pmol/mg. Nef increased the cAMP concentration in a dose-dependent manner (P 0.05). The accumulation of cAMP induced by prostaglandin E1(PGE1, a stimulator of cAMP production) was also augmented by Nef in a dose-dependent manner (P 0.05). Also,sodium nitroprusside (SNP, a stimulator of cGMP production)-induced cGMP production was not enhanced by Nef (P > 0.05). Conclusion: Nef, with its relaxation mechanism, can enhance the concentration of cAMP in rabbit corpus cavernosum tissue, probably by inhibiting phosphodiesterase activity.

  5. The role of bicarbonate ions and of adenosine 3',5'-monophosphate (cAMP) in chloride transport by epithelial cells of bullfrog small intestine.

    Science.gov (United States)

    Armstrong, W M; Youmans, S J

    1980-01-01

    In an HCO3-free medium, isolated segments of bullfrog small intestine, stripped of their external muscle layers, displayed a small, serosal positive PD that did not, on the average, differ significantly from zero. Similarly, in this medium, the mean values of Isc and of net Na+ and Cl- absorption under short-circuit conditions did not differ significantly from zero. External HCO3- (25 mM) induced a highly significant serosal negative PD and Isc and a large net absorption of Cl-. Net Cl- absorption exceeded Isc, i.e., there was a significant net flux, JR, which was consistent with a net secretion of HCO3-. The ratio of the internal Cl-activity of the absorptive cells (alpha Cli) to its equilibrium value was larger in the presence than in the absence of HCO3-. In the presence of HCO3-, cAMP, added to the serosal medium, reversed the serosal negative PD and Isc, and inhibited, though it did not completely abolish, net Cl- absorption. JR was unchanged; tissue Cl- and alpha Cli were reduced, and tissue Na+ decreased and tissue K+ increased. When HCO3- and Cl- were removed from the bathing medium, the electrical response of the tissue to cAMP, though greatly attenuated, was not completely abolished. Under these conditions, cAMP induced a significant net Na+ absorption. A model for ion transport in the absorptive cells of the small intestine is proposed that is consistent with these findings. PMID:6249145

  6. Cyclic adenosine 3',5'-monophosphate and germination of sporangiospores from the fungus Mucor.

    Science.gov (United States)

    Orlowski, M

    1980-06-01

    Cyclic adenosine 3',5'-monophosphate (cAMP) metabolism was examined in germinating sporangiospores of Mucor genevensis and Mucor mucedo. Exogenous cAMP prevented normal hyphal development from sporangiospores. Internal pools of cAMP fluctuated profoundly during development. Spherical growth of the spores was characterized by large pools of cAMP whereas germ tube emergence and hyphal elongation were characterized by small pools of cAMP. These observations suggest a possible role for cAMP in sporangiospore germination. Adenylate cyclase activities fluctuated significantly during germination with maximum values attained during spherical growth. In contrast, cAMP phosphodiesterase activities remained constant throughout germination. Internal cAMP levels may therefore be regulated by adjustment of adenylate cyclase activities. The binding of cAMP by soluble cell proteins was measured. cAMP-binding activity changed greatly during germination. Dormant and spherically growing spores possessed the highest activities. Developing hyphae contained the lowest activities. Use of the photoaffinity label, 8-azido-[32P]cAMP, in conjunction with sodium dodecyl sulfate-polyacrylamide-gel electrophoresis allowed the identification of a small population of morphogenetic-stage-specific proteins which bind cAMP and may be of regulatory significance to development.

  7. Plasma concentrations of the cyclic nucleotides, adenosine 3',5'-monophosphate and guanosine 3'.5'-monophosphate, in healthy adults treated with theophylline

    DEFF Research Database (Denmark)

    Fenger, M; Eriksen, P B; Andersen, O;

    1982-01-01

    Plasma concentrations of cyclic adenosine monophosphate and cyclic guanosine monophosphate were measured in 10 health adults before, during and after periods of theophylline administration. Cyclic adenosine monophosphate concentrations did not change significantly, but cyclic guanosine monophosph......Plasma concentrations of cyclic adenosine monophosphate and cyclic guanosine monophosphate were measured in 10 health adults before, during and after periods of theophylline administration. Cyclic adenosine monophosphate concentrations did not change significantly, but cyclic guanosine...... monophosphate concentrations decreased by 29% on average when theophylline was administered. The change in cyclic guanosine monophosphate was not correlated to the plasma concentration of theophylline in the range studied....

  8. Measuring the dynamics of cyclic adenosine monophosphate level in living cells induced by low-level laser irradiation using bioluminescence resonance energy transfer

    Science.gov (United States)

    Huang, Yimei; Zheng, Liqin; Yang, Hongqin; Chen, Jiangxu; Wang, Yuhua; Li, Hui; Xie, Shusen; Zeng, Haishan

    2015-05-01

    Several studies demonstrated that the cyclic adenosine monophosphate (cAMP), an important second messenger, is involved in the mechanism of low-level laser irradiation (LLLI) treatment. However, most of these studies obtained the cAMP level in cell culture extracts or supernatant. In this study, the cAMP level in living cells was measured with bioluminescence resonance energy transfer (BRET). The effect of LLLI on cAMP level in living cells with adenosine receptors blocked was explored to identify the role of adenosine receptors in LLLI. The results showed that LLLI increased the cAMP level. Moreover, the rise of cAMP level was light dose dependent but wavelength independent for 658-, 785-, and 830-nm laser light. The results also exhibited that the adenosine receptors, a class of G protein-coupled receptor (GPCR), modulated the increase of cAMP level induced by LLLI. The cAMP level increased more significantly when the A3 adenosine receptors (A3R) were blocked by A3R antagonist compared with A1 adenosine receptor or A2a adenosine receptor blocked in HEK293T cells after LLLI, which was in good agreement with the adenosine receptors' expressions. All these results suggested that measuring the cAMP level with BRET could be a useful technique to study the role of GPCRs in living cells under LLLI.

  9. Complex Formation of Adenosine 3',5'-Cyclic Monophosphate with β-Cyclodextrin: Kinetics and Mechanism by Ultrasonic Relaxation

    International Nuclear Information System (INIS)

    Adenosine 3',5'-cyclic monophosphate (cAMP) is a second messenger responsible for a multitude of cellular responses. In this study, we utilized β-cyclodextrin (β-CD) as an artificial receptor with a hydrophobic cavity to elucidate the inclusion kinetics of cAMP in a hydrophobic environment using the ultrasonic relaxation method. The results revealed that the interaction of cAMP with β-CD followed a single relaxation curve as a result of host-guest interactions. The inclusion of cAMP into the β-CD cavity was found to be a diffusion-controlled reaction. The dissociation of cAMP from the β-CD cavity was slower than that of adenosine 5'-monophosphate (AMP). The syn and anti glycosyl conformations of adenine nucleotides are considered to play an important role in formation of the inclusion complex. Taken together, our findings indicate that hydrophobic interactions are involved in the inclusion complex formation of cAMP with β-CD and provide insight into the interactions of cAMP with cAMP-binding proteins

  10. The clinical correlation of regulatory T cells and cyclic adenosine monophosphate in enterovirus 71 infection.

    Directory of Open Access Journals (Sweden)

    Shih-Min Wang

    Full Text Available Brainstem encephalitis (BE and pulmonary edema (PE are notable complications of enterovirus 71 (EV71 infection.This study investigated the immunoregulatory characterizations of EV71 neurological complications by disease severity and milrinone treatment.Patients <18 years with virologically confirmed EV71 infections were enrolled and divided into 2 groups: the hand, foot, and mouth disease (HFMD or BE group, and the autonomic nervous system (ANS dysregulation or PE group. Cytokine and cyclic adenosine monophosphate (cAMP levels, and the regulatory T cell (Tregs profiles of the patients were determined.Patients with ANS dysregulation or PE exhibited significantly low frequency of CD4(+CD25(+Foxp3+ and CD4(+Foxp3(+ T cells compared with patients with HFMD or BE. The expression frequency of CD4-CD8- was also significantly decreased in patients with ANS dysregulation or PE. Among patients with ANS dysregulation or PE, the expression frequency of CD4+Foxp3+ increased markedly after milrinone treatment, and was associated with reduction of plasma levels IL-6, IL-8 and IL-10. Plasma concentrations of cAMP were significantly decreased in patients with ANS dysregulation or PE compared with patients with HFMD or BE; however, cAMP levels increased after milrinone treatment.These findings suggested decreased different regulatory T populations and cAMP expression correlate with increased EV71 disease severity. Improved outcome after milrinone treatment may associate with increased regulatory T populations, cAMP expression and modulation of cytokines levels.

  11. Evidence against mediation of adenosine-3',5'-cyclic monophosphate in the bud-inducing effect of cytokinins in moss protonemata

    Directory of Open Access Journals (Sweden)

    J. Scheneider

    2015-05-01

    Full Text Available Effects Oif adenosdne-3',5'-cyclic monophosphate (cAMP, N6,O2-dibuityryl adenosine-3',5'-cyclic monophosphate (DBcAMP, caffeine and theophylline on the bud-inducing activity of cytokinin in the protonema of two moss species, Ceratodon purpureus and Funaria hygrometrica were examined. The sub-stances have been found ineffective as gametophore bud inducers. Some synergism between cytokinin and cAMP or DBcAMP was observed with relation to the buds' growth, but this effect is nonspecific since it can be obtained with 5'-AMP or 5'-GMiP as well, The results seem to exclude the possibility of an involvement of cAMP as a second messenger in the mechanism of cytokinin action on morphogenetic processes in moss protonemata.

  12. Investigation on the occurrence and significance of cyclic adenosine 3':5'-monophosphate in phytoplankton and natural aquatic communities

    Energy Technology Data Exchange (ETDEWEB)

    Francko, D.A.

    1980-01-01

    This study demonstrates, on the basis of several analyanalytical criteria, that the production and extracellular release of cyclic adenosine 3':5'-monophosphate (cAMP) is widespread among phytoplankton species. The production and release of CAMP varied markedly among different species grown under similar environmental conditions, and intraspecifically during the life cycle of a given algal species. This investigation marks the first time cAMP has been investigated in natural aquatic systems. An examination of epilimnetic lakewater samples from Lawrence Lake, a hardwater oligotrophic lake, and Wintergreen Lake, a hardwater hypereutrophic lake, both in southwestern Michigan, demonstrated that cAMP existed in both particulate-associated and dissolved forms in these systems.

  13. Cilostazol Improves Developmental Competence of Pig Oocytes by Increasing Intraoocyte Cyclic Adenosine Monophosphate Level and Delaying Meiotic Resumption.

    Science.gov (United States)

    Elahi, F; Lee, H; Lee, Y; Park, B; Lee, J; Hyun, S-H; Lee, E

    2016-04-01

    Cilostazol (CLZ) is a cyclic adenosine monophosphate (cAMP) modulator that influences the steady state of the meiotic stage. This study was conducted to determine the effects of CLZ treatment during in vitro maturation (IVM) on developmental competence of pig oocytes. Immature oocytes were exposed to 0 (control), 0.5, 2 and 4 μm CLZ during the first 22 h of IVM. Nuclear maturation, intraoocyte glutathione content and embryo cleavage after parthenogenesis (PA) and somatic cell nuclear transfer (SCNT) were not influenced by CLZ at any concentrations. However, 4 μm CLZ significantly (p formation after PA (52.1% vs 38.7-46.0%) and SCNT relative to other concentrations (40.8% vs 25.0-30.7%). The mean cell numbers of SCNT blastocysts were significantly increased by 4 μm CLZ compared to the control (42.6 cells vs 35.3 cells/blastocyst). CLZ treatment significantly increased the intraoocyte cAMP level and effectively arrested oocytes at the germinal vesicle (GV) and GV break down stages compared to the control (74.5% vs 45.4%). Our results demonstrated that improved developmental competence of PA and SCNT pig embryos occurred via better synchronization of nuclear and cytoplasmic maturation induced by increased cAMP and delayed meiotic resumption after CLZ treatment. PMID:26834044

  14. [Concentration of prostaglandins and cyclic adenosine-3',5'-monophosphate in the tissues of rats].

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    Komissarenko, V P; Slavnov, V N; Epsheĭn, E V; Malinkovich, V D

    1977-04-01

    The content of prostaglandines (PG) and cyclic 3',5'-adenosine monphosphate (cAMP) was investigated in rat tissues by the radioisotopic method of competitive binding. Maximum quantities of both PG and cAMP were revealed in the same most actively functioning organs: the brain, incretory glands, small intestine. Fatty tissue showed minimum quantities of these substances. Results indicate a close functional relationship between the PG synthesis and adenylatecyclase activity in the body tissues.

  15. Protective effects of inhibition of adenosine monophosphate activated protein kinase activity against cerebral ischemia-reperfusion injury in mice

    Institute of Scientific and Technical Information of China (English)

    补娟

    2013-01-01

    Objective To observe the effect of inhibition of adenosine monophosphate activated protein kinase (AMPK) on shape,function and inflammatory factor of microglia for mice after cerebral ischemia-reperfusion

  16. Investigation on the occurrence and significance of cyclic adenosine 3':5'-monophosphate in phytoplankton and natural aquatic communities

    Energy Technology Data Exchange (ETDEWEB)

    Francko, D.A.

    1980-01-01

    This study is an investigation into the occurrence and potential functions of cyclic adenosine 3':5'-monophosphate (cAMP), a potent and ubiquitous metabolic regulatory molecule in heterotrophic organisms, in phytoplankton and in natural aquatic communities. Laboratory-cultured phytoplankton were grown under both optimal and suboptimal nutrient regimes under constant temperature and illumination regimes. Cellular and extracellular cAMP production, characterized by a number of biochemical techniques, was correlated with growth rate dynamics, chlorophyll a synthesis, /sup 14/C-bicarbonate uptake, alkaline phosphatase activity, and heterocyst formation. The blue-green alga Anabaena flos-aquae was used as a model system in the examination of these metabolic variables. Additionally, this alga was used to test the effects of perturbation of cAMP levels on the aforementioned metabolic variables. Investigations on the occurrence and seasonal dynamics of cAMP in aquatic systems were conducted on Lawrence Lake, a hardwater oligotrophic lake, and on Wintergreen Lake, a hardwater hypereutrophic lake, both in southwestern Michigan. Putative cAMP from both systems was characterized by several biochemical techniques. Weekly sampling of particulate and dissolved cAMP in the epilimnia of both lakes was correlated with data on the rates of primary productivity, alkaline phosphatase activity, chlorophyll a synthesis and changes in phytoplankton community structure.

  17. Medium optimization for the production of cyclic adenosine 3',5'-monophosphate by Microbacterium sp. no. 205 using response surface methodology.

    Science.gov (United States)

    Chen, Xiao-Chun; Bai, Jian-Xin; Cao, Jia-Ming; Li, Zhen-Jiang; Xiong, Jian; Zhang, Lei; Hong, Yuan; Ying, Han-Jie

    2009-01-01

    Response surface methodology was employed to optimize medium composition for the production of cyclic adenosine 3',5'-monophosphate (cAMP) with Microbacterium sp. no. 205. A fractional factorial design (2(11-7)) was applied to evaluate the effects of different components in the medium. K(2)HPO(4), MgSO(4) and NaF were found to significantly influence on the cAMP production. The steepest ascent method was used to access the optimal region of the medium composition. The concentrations of the three factors were optimized subsequently using central composite design and response surface methodology. The optimal medium composition to achieve the optimal cAMP production was determined (g/L): K(2)HPO(4), 12.78; MgSO(4), 3.53 and NaF, 0.18. The corresponding cAMP concentration was 8.50 g/L, which was about 1.8-fold increase compared with that using the original medium. Validation experiments were also carried out to prove the adequacy and the accuracy of the model obtained. The cAMP fermentation in 5L fermenter reached 9.87 g/L. PMID:18778935

  18. Icariin upregulates phosphorylated cyclic adenosine monophosphate response element binding protein levels in the hippocampus of the senescence- accelerated mouse

    Institute of Scientific and Technical Information of China (English)

    Zhanwei Zhang; Ting Zhang; Keli Dong

    2012-01-01

    At 8 weeks after intragastric administration of icariin to senescence-accelerated mice (P8 strain), Morris water maze results showed that escape latency was shortened, and the number of platform crossings was increased. Immunohistochemical staining and western blot assay detected signifi-cantly increased levels of cyclic adenosine monophosphate response element binding protein. These results suggest that icariin upregulates phosphorylated cyclic adenosine monophosphate response element binding protein levels and improves learning and memory functions in hippo-campus of the senescence-accelerated mouse.

  19. Low-power laser irradiation promotes the proliferation and osteogenic differentiation of human periodontal ligament cells via cyclic adenosine monophosphate

    Institute of Scientific and Technical Information of China (English)

    Jyun-Yi Wu; Chia-Hsin Chen; Li-Yin Yeh; Ming-Long Yeh; Chun-Chan Ting; Yan-Hsiung Wang

    2013-01-01

    Retaining or improving periodontal ligament (PDL) function is crucial for restoring periodontal defects. The aim of this study was to evaluate the physiological effects of low-power laser irradiation (LPLI) on the proliferation and osteogenic differentiation of human PDL (hPDL) cells. Cultured hPDL cells were irradiated (660 nm) daily with doses of 0, 1, 2 or 4 J?cm22. Cell proliferation was evaluated by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, and the effect of LPLI on osteogenic differentiation was assessed by Alizarin Red S staining and alkaline phosphatase (ALP) activity. Additionally, osteogenic marker gene expression was confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR). Our data showed that LPLI at a dose of 2 J?cm22 significantly promoted hPDL cell proliferation at days 3 and 5. In addition, LPLI at energy doses of 2 and 4 J?cm22 showed potential osteogenic capacity, as it stimulated ALP activity, calcium deposition, and osteogenic gene expression. We also showed that cyclic adenosine monophosphate (cAMP) is a critical regulator of the LPLI-mediated effects on hPDL cells. This study shows that LPLI can promote the proliferation and osteogenic differentiation of hPDL cells. These results suggest the potential use of LPLI in clinical applications for periodontal tissue regeneration.

  20. Triiodothyronine causes rapid reversal of alpha 1/cyclic adenosine monophosphate synergism on brown adipocyte respiration and type II deiodinase activity.

    Science.gov (United States)

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

    1991-12-01

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

  1. Bronchial responsiveness to adenosine 5 '-monophosphate (AMP) and methacholine differ in their relationship with airway allergy and baseline FEV

    NARCIS (Netherlands)

    De Meer, G; Heederik, D; Postma, DS

    2002-01-01

    Bronchial hyperresponsiveness (BHR) and inflammation are central hallmarks of asthma. Studies in patients with asthma suggest that BHR to adenosine 5'-monophosphate (AMP) is a better marker of bronchial inflammation than BHR to methacholine. The association between markers of airway inflammation and

  2. Influences of dibutyryl cyclic adenosine monophosphate and forskolin on human sperm motility in vitro

    Institute of Scientific and Technical Information of China (English)

    Ji-HongLIU; YangLI; Zheng-GuoCAO; Zhang-QunYE

    2003-01-01

    Aim: To study the influences of dibutyryl cyclic adenosine monophosphate (dbcAMP) and forskolin on human sperm motility in vitro. Methods: Semen samples, aseptically obtained by masturbation and prepared by swim-up technique from 20 fertile men, were incubated with different concenlrations of dbcAMP and forskolin at 37℃. Measurements were carried out after l0 min, 20 min, 30 min and 60 min incubation. Motility parameters were estimated by using an automatic analyzing system. Results: Treatment with dbcAMP or forskolin resulted in a significant increase in sperm motility and progressive motility. The larger the concenlrations of dbcAMP or forskolin,the greater the effect appeared. The straight linear velocity and curvilinear velocity were not affected by both agents.Conclusion: dbcAMP and forskolin increase the motility and progressive motility of human sperm in vitro. ( Asian J Androl 2003 Jun; 5: 113-115)

  3. Adsorption of nucleotides on biomimetic apatite: The case of adenosine 5‧ monophosphate (AMP)

    Science.gov (United States)

    Hammami, K.; Feki, H. El; Marsan, O.; Drouet, C.

    2015-10-01

    This work investigates the interaction between the nucleotide adenosine 5‧ monophosphate molecule (AMP) and a biomimetic nanocrystalline carbonated apatite as a model for bone mineral. The analogy of the apatite phase used in this work with biological apatite was first pointed out by complementary techniques. AMP adsorption isotherms were then investigated. Obtained data were fitted to a Sips isotherm with an exponent greater than one suggesting positive cooperativity among adsorbed molecules. The data were compared to a previous study relative to the adsorption of another nucleotide, cytidine monophosphate (CMP) onto a similar substrate, evidencing some effect of the chemical nature of the nucleic base. An enhanced adsorption was observed under acidic (pH 6) conditions as opposed to pH 7.4, which parallels the case of DNA adsorption on biomimetic apatite. An estimated standard Gibbs free energy associated to the adsorption process (ΔG°ads ≅ -22 kJ/mol) intermediate between "physisorption" and "chemisorption" was found. The analysis of the solids after adsorption pointed to the preservation of the main characteristics of the apatite substrate but shifts or enhancements of Raman bands attributed to AMP showed the existence of chemical interactions involving both the phosphate and adenine parts of AMP. This contribution adds to the works conducted in view of better understanding the interaction of DNA/RNA and their constitutive nucleotides and the surface of biomimetic apatites. It could prove helpful in disciplines such as bone diagenesis (DNA/apatite interface in aged bones) or nanomedicine (setup of DNA- or RNA-loaded apatite systems). Also, the adsorption of nucleic acids on minerals like apatites could have played a role in the preservation of such biomolecules in the varying conditions known to exist at the origin of life on Earth, underlining the importance of dedicated adsorption studies.

  4. Dielectric spectra broadening as a signature for dipole-matrix interaction. III. Water in adenosine monophosphate/adenosine-5'-triphosphate solutions.

    Science.gov (United States)

    Puzenko, Alexander; Levy, Evgeniya; Shendrik, Andrey; Talary, Mark S; Caduff, Andreas; Feldman, Yuri

    2012-11-21

    In this, the third part of our series on the dielectric spectrum symmetrical broadening of water, we consider the nucleotide aqueous solutions. Where in Parts I [E. Levy et al., J. Chem. Phys. 136, 114502 (2012)] and II [E. Levy et al., J. Chem. Phys. 136, 114503 (2012)], the dipole-dipole or ion-dipole interaction had a dominant feature, now the interplay between these two types of dipole-matrix interactions will be considered. We present the results of high frequency dielectric measurements of different concentrations of adenosine monophosphate/adenosine-5'-triphosphate aqueous solutions. We observed the Cole-Cole broadening of the main relaxation peak of the solvent in the solutions. Moreover, depending on the nucleotide concentration, we observed both types of dipole-matrix interaction. The 3D trajectory approach (described in detail in Part I) is applied in order to highlight the differences between the two types of interaction.

  5. Dielectric spectra broadening as a signature for dipole-matrix interaction. III. Water in adenosine monophosphate/adenosine-5'-triphosphate solutions.

    Science.gov (United States)

    Puzenko, Alexander; Levy, Evgeniya; Shendrik, Andrey; Talary, Mark S; Caduff, Andreas; Feldman, Yuri

    2012-11-21

    In this, the third part of our series on the dielectric spectrum symmetrical broadening of water, we consider the nucleotide aqueous solutions. Where in Parts I [E. Levy et al., J. Chem. Phys. 136, 114502 (2012)] and II [E. Levy et al., J. Chem. Phys. 136, 114503 (2012)], the dipole-dipole or ion-dipole interaction had a dominant feature, now the interplay between these two types of dipole-matrix interactions will be considered. We present the results of high frequency dielectric measurements of different concentrations of adenosine monophosphate/adenosine-5'-triphosphate aqueous solutions. We observed the Cole-Cole broadening of the main relaxation peak of the solvent in the solutions. Moreover, depending on the nucleotide concentration, we observed both types of dipole-matrix interaction. The 3D trajectory approach (described in detail in Part I) is applied in order to highlight the differences between the two types of interaction. PMID:23181321

  6. Regulation of insulin-like growth factor I transcription by cyclic adenosine 3',5'-monophosphate (cAMP) in fetal rat bone cells through an element within exon 1: protein kinase A-dependent control without a consensus AMP response element

    Science.gov (United States)

    McCarthy, T. L.; Thomas, M. J.; Centrella, M.; Rotwein, P.

    1995-01-01

    Insulin-like growth factor I (IGF-I) is a locally synthesized anabolic growth factor for bone. IGF-I synthesis by primary fetal rat osteoblasts (Ob) is stimulated by agents that increase the intracellular cAMP concentration, including prostaglandin E2 (PGE2). Previous studies with Ob cultures demonstrated that PGE2 enhanced IGF-I transcription through selective use of IGF-I promoter 1, with little effect on IGF-I messenger RNA half-life. Transient transfection of Ob cultures with an array of promoter 1-luciferase reporter fusion constructs has now allowed localization of a potential cis-acting promoter element(s) responsible for cAMP-stimulated gene expression to the 5'-untranslated region (5'-UTR) of IGF-I exon 1, within a segment lacking a consensus cAMP response element. Our evidence derives from three principal observations: 1) a transfection construct containing only 122 nucleotides (nt) of promoter 1 and 328 nt of the 5'-UTR retained full PGE2-stimulated reporter expression; 2) maximal PGE2-driven reporter expression required the presence of nt 196 to 328 of exon 1 when tested within the context of IGF-I promoter 1; 3) cotransfection of IGF-I promoter-luciferase-reporter constructs with a plasmid encoding the alpha-isoform of the catalytic subunit of murine cAMP-dependent protein kinase (PKA) produced results comparable to those seen with PGE2 treatment, whereas cotransfection with a plasmid encoding a mutant regulatory subunit of PKA that cannot bind cAMP blocked PGE2-induced reporter expression. Deoxyribonuclease I footprinting of the 5'-UTR of exon 1 demonstrated protected sequences at HS3A, HS3B, and HS3D, three of six DNA-protein binding sites previously characterized with rat liver nuclear extracts. Of these three regions, only the HS3D binding site is located within the functionally identified hormonally responsive segment of IGF-I exon 1. These results directly implicate PKA in the control of IGF-I gene transcription by PGE2 and identify a segment of

  7. Antagonists of chemoattractants reveal separate receptors for cAMP, folic acid and pterin in Dictyostelium

    NARCIS (Netherlands)

    Haastert, Peter J.M. van; Wit, René J.W. de; Konijn, Theo M.

    1982-01-01

    Adenosine 3’,5’-monophosphate (cAMP), folic acid and pterin are chemoattractants in the cellular slime molds. The cAMP analog, 3’-amino-cAMP, inhibits a chemotactic reaction to cAMP at a concentration at which the analog is chemotactically inactive. The antagonistic effect of 3’-amino-cAMP on the ch

  8. Hepatitis C virus core protein induces energy metabolism disorders of hepatocytes by down-regulation of silent mating type information regulation 2 homolog-1 and adenosine monophosphate-acti vated protein kinase signaling pathway

    Institute of Scientific and Technical Information of China (English)

    于建武

    2013-01-01

    Objective To study the role of silent mating type information regulation2homotog-1(SIRT1)-adenosine monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway in hepatitis C virus core protein(HCV-core)induced energy metabolism disorders

  9. Selective Phosphonylation of 5'-Adenosine Monophosphate (5'-AMP) via Pyrophosphite [PPi(III)

    Science.gov (United States)

    Kaye, Karl; Bryant, David E.; Marriott, Katie E. R.; Ohara, Shohei; Fishwick, Colin W. G.; Kee, Terence P.

    2016-05-01

    We describe here experiments which demonstrate the selective phospho-transfer from a plausibly prebiotic condensed phosphorus (P) salt, pyrophosphite [H2P2O5 2-; PPi(III)], to the phosphate group of 5'-adenosine mono phosphate (5'-AMP). We show further that this P-transfer process is accelerated both by divalent metal ions (M2+) and by organic co-factors such as acetate (AcO-). In this specific case of P-transfer from PPi(III) to 5'-AMP, we show a synergistic enhancement of transfer in the combined presence of M2+ & AcO-. Isotopic labelling studies demonstrate that hydrolysis of the phosphonylated 5'-AMP, [P(III)P(V)-5'-AMP], proceeds via nuceophilic attack of water at the Pi(III) terminus.

  10. The expression of cyclic adenosine monophosphate responsive element modulator in rat sertoli cells following seminal extract administration

    Science.gov (United States)

    Akmal, Muslim; Siregar, Tongku Nizwan; Wahyuni, Sri; Hamny; Nasution, Mustafa Kamal; Indriati, Wiwik; Panjaitan, Budianto; Aliza, Dwinna

    2016-01-01

    Aim: This study aims to determine the effect of seminal vesicle extract on cyclic adenosine monophosphate responsive element modulator (CREM) expression in rat Sertoli cells. Materials and Methods: This study examined the expression of CREM on 20 male rats (Rattus norvegicus) at 4 months of age, weighing 250-300 g. The rats were divided into four groups: K0, KP1, KP2, and KP3. K0 group was injected with 0.2 ml normal saline; KP1 was injected with 25 mg cloprostenol (Prostavet C, Virbac S. A); KP2 and KP3 were injected with 0.2 and 0.4 ml seminal vesicle extract, respectively. The treatments were conducted 5 times within 12-day interval. At the end of the study, the rats were euthanized by cervical dislocation; then, the testicles were necropsied and processed for histology observation using immunohistochemistry staining. Results: CREM expression in rat Sertoli cells was not altered by the administration of either 0.2 or 0.4 ml seminal vesicle extract. Conclusion: The administration of seminal vesicle extract is unable to increase CREM expression in rat Sertoli cells. PMID:27733803

  11. The expression of cyclic adenosine monophosphate responsive element modulator in rat sertoli cells following seminal extract administration

    Directory of Open Access Journals (Sweden)

    Muslim Akmal

    2016-09-01

    Full Text Available Aim: This study aims to determine the effect of seminal vesicle extract on cyclic adenosine monophosphate responsive element modulator (CREM expression in rat Sertoli cells. Materials and Methods: This study examined the expression of CREM on 20 male rats (Rattus norvegicus at 4 months of age, weighing 250-300 g. The rats were divided into four groups: K0, KP1, KP2, and KP3. K0 group was injected with 0.2 ml normal saline; KP1 was injected with 25 mg cloprostenol (Prostavet C, Virbac S. A; KP2 and KP3 were injected with 0.2 and 0.4 ml seminal vesicle extract, respectively. The treatments were conducted 5 times within 12-day interval. At the end of the study, the rats were euthanized by cervical dislocation; then, the testicles were necropsied and processed for histology observation using immunohistochemistry staining. Results: CREM expression in rat Sertoli cells was not altered by the administration of either 0.2 or 0.4 ml seminal vesicle extract. Conclusion: The administration of seminal vesicle extract is unable to increase CREM expression in rat Sertoli cells.

  12. Beneficial effects of metformin on primary cardiomyocytes via activation of adenosine monophosphate-activated protein kinase

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-fang; ZHANG Jin-ying; LI Ling; ZHAO Xiao-yan

    2011-01-01

    Background Metformin has become a cornerstone in the treatment of patients with type-2 diabetes. Accumulated evidence suggests that metformin supports direct cardiovascular effects. The present study aimed to investigate if metformin has beneficial effects on primary cardiomyocytes damaged by H2O2, and reveal the potential mechanism of action of metformin.Methods Cardiomyocytes were incubated in the presence of 100 umol/L. H2O2 for 12 hours. Cardiomyocytes were pretreated with metformin at different concentrations and time and with aminoimidazole carboxamide ribonucleotide (AICAR) (500 umol/L), an adenosine monophophate (AMP)-activated protein kinase (AMPK) agonist for 60 minutes before the addition of H2O2. Other cells were preincubated with compound C (an AMPK antagonist, 20 umol/L) for 4 hours. The viability and apoptosis of cells were analyzed. AMPK, endothelial nitric oxide synthase (eNOS), and transforming growth factor (TGF)-β1 were analyzed using immunblotting.Results Metformin had antagonistic effects on the influences of H2O2 on cell viability and attenuated oxidative stress-induced apoptosis. Metformin also increased phosphorylation of AMPK and eNOS, and reduced the expression of TGF-β1, basic fibroblast growth factor (bFGF), and tumor necrosis factor (TNF)-α.Conclusions Metformin has beneficial effects on cardiomyocytes, and this effect involves activation of the AMPK-eNOS pathway. Metformin may be potentially beneficial for the treatment of heart disease.

  13. Application of graphene-ionic liquid-chitosan composite-modified carbon molecular wire electrode for the sensitive determination of adenosine-5′-monophosphate

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Fan [Key Laboratory of Tropical Medicinal Plant Chemistry of Ministry of Education, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou 571158 (China); Gong, Shixing; Xu, Li; Zhu, Huanhuan [College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042 (China); Sun, Zhenfan [Key Laboratory of Tropical Medicinal Plant Chemistry of Ministry of Education, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou 571158 (China); Sun, Wei, E-mail: swyy26@hotmail.com [Key Laboratory of Tropical Medicinal Plant Chemistry of Ministry of Education, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou 571158 (China)

    2013-12-01

    In this paper, a graphene (GR) ionic liquid (IL) 1-octyl-3-methylimidazolium hexafluorophosphate and chitosan composite-modified carbon molecular wire electrode (CMWE) was fabricated by a drop-casting method and further applied to the sensitive electrochemical detection of adenosine-5′-monophosphate (AMP). CMWE was prepared with diphenylacetylene (DPA) as the modifier and the binder. The properties of modified electrode were examined by scanning electron microscopy, cyclic voltammetry and electrochemical impedance spectroscopy. Electrochemical behaviors of AMP was carefully investigated with enhanced responses appeared, which was due to the presence of GR-IL composite on the electrode surface with excellent electrocatalytic ability. A well-defined oxidation peak of AMP appeared at 1.314 V and the electrochemical parameters were calculated by electrochemical methods. Under the selected conditions, the oxidation peak current of AMP was proportional to its concentration in the range from 0.01 μM to 80.0 μM with the detection limit as 3.42 nM (3σ) by differential pulse voltammetry. The proposed method exhibited good selectivity and was applied to the detection of vidarabine monophosphate injection samples with satisfactory results. - Highlights: • A graphene, ionic liquid 1-octyl-3-methylimidazolium hexafluorophosphate and chitosan composite were prepared. • Composite-modified carbon molecular wire electrode was fabricated and characterized. • A sensitive electrochemical method for the detection of adenosine-5′-monophosphate was established.

  14. Application of graphene-ionic liquid-chitosan composite-modified carbon molecular wire electrode for the sensitive determination of adenosine-5′-monophosphate

    International Nuclear Information System (INIS)

    In this paper, a graphene (GR) ionic liquid (IL) 1-octyl-3-methylimidazolium hexafluorophosphate and chitosan composite-modified carbon molecular wire electrode (CMWE) was fabricated by a drop-casting method and further applied to the sensitive electrochemical detection of adenosine-5′-monophosphate (AMP). CMWE was prepared with diphenylacetylene (DPA) as the modifier and the binder. The properties of modified electrode were examined by scanning electron microscopy, cyclic voltammetry and electrochemical impedance spectroscopy. Electrochemical behaviors of AMP was carefully investigated with enhanced responses appeared, which was due to the presence of GR-IL composite on the electrode surface with excellent electrocatalytic ability. A well-defined oxidation peak of AMP appeared at 1.314 V and the electrochemical parameters were calculated by electrochemical methods. Under the selected conditions, the oxidation peak current of AMP was proportional to its concentration in the range from 0.01 μM to 80.0 μM with the detection limit as 3.42 nM (3σ) by differential pulse voltammetry. The proposed method exhibited good selectivity and was applied to the detection of vidarabine monophosphate injection samples with satisfactory results. - Highlights: • A graphene, ionic liquid 1-octyl-3-methylimidazolium hexafluorophosphate and chitosan composite were prepared. • Composite-modified carbon molecular wire electrode was fabricated and characterized. • A sensitive electrochemical method for the detection of adenosine-5′-monophosphate was established

  15. Cardiac cAMP: production, hydrolysis, modulation and detection

    OpenAIRE

    Cédric eBOULARAN; Céline eGALES

    2015-01-01

    Cyclic adenosine 3’,5’-monophosphate (cAMP) modulates a broad range of biological processes including the regulation of cardiac myocyte contractile function where it constitutes the main second messenger for β-adrenergic receptors’ signaling to fulfill positive chronotropic, inotropic and lusitropic effects. A growing number of studies pinpoint the role of spatial organization of the cAMP signaling as an essential mechanism to regulate cAMP outcomes in cardiac physiology. Here, we will briefl...

  16. Cardiac cAMP: production, hydrolysis, modulation and detection

    OpenAIRE

    Boularan, Cédric; Gales, Céline

    2015-01-01

    Cyclic adenosine 3′,5′-monophosphate (cAMP) modulates a broad range of biological processes including the regulation of cardiac myocyte contractile function where it constitutes the main second messenger for β-adrenergic receptors' signaling to fulfill positive chronotropic, inotropic and lusitropic effects. A growing number of studies pinpoint the role of spatial organization of the cAMP signaling as an essential mechanism to regulate cAMP outcomes in cardiac physiology. Here, we will briefl...

  17. Investigating real-time activation of adenosine receptors by bioluminescence resonance energy transfer technique

    Science.gov (United States)

    Huang, Yimei; Yang, Hongqin; Zheng, Liqin; Chen, Jiangxu; Wang, Yuhua; Li, Hui; Xie, Shusen

    2013-02-01

    Adenosine receptors play important roles in many physiological and pathological processes, for example regulating myocardial oxygen consumption and the release of neurotransmitters. The activations of adenosine receptors have been studied by some kinds of techniques, such as western blot, immunohistochemistry, etc. However, these techniques cannot reveal the dynamical response of adenosine receptors under stimulation. In this paper, bioluminescence resonance energy transfer technique was introduced to study the real-time activation of adenosine receptors by monitoring the dynamics of cyclic adenosine monophosphate (cAMP) level. The results showed that there were significant differences between adenosine receptors on real-time responses under stimulation. Moreover, the dynamics of cAMP level demonstrated that competition between adenosine receptors existed. Taken together, our study indicates that monitoring the dynamics of cAMP level using bioluminescence resonance energy transfer technique could be one potential approach to investigate the mechanism of competitions between adenosine receptors.

  18. cAMP biosensors applied in molecular pharmacological studies of G protein-coupled receptors

    DEFF Research Database (Denmark)

    Mathiesen, Jesper Mosolff; Vedel, Line; Bräuner-Osborne, Hans

    2013-01-01

    Cyclic adenosine monophosphate (cAMP) is a common second messenger that mediates numerous biological responses. Intracellular cAMP levels are increased by activation of G(s)-coupled G protein-coupled receptors (GPCRs) and decreased by activation of G(i)-coupled GPCRs via the adenylyl cyclase. Man...

  19. A Temporal-Specific and Transient cAMP Increase Characterizes Odorant Classical Conditioning

    Science.gov (United States)

    Cui, Wen; Smith, Andrew; Darby-King, Andrea; Harley, Carolyn W.; McLean, John H.

    2007-01-01

    Increases in cyclic adenosine monophosphate (cAMP) are proposed to initiate learning in a wide variety of species. Here, we measure changes in cAMP in the olfactory bulb prior to, during, and following a classically conditioned odor preference trial in rat pups. Measurements were taken up to the point of maximal CREB phosphorylation in olfactory…

  20. Sevoflurane effects on cyclic adenosine monophosphate response element binding protein, phosphorylated cyclic adenosine monophosphate response element binding protein, and Livin expression in the cortex and hippocampus of a vascular cognitive impairment rat model

    Institute of Scientific and Technical Information of China (English)

    Bin Wu; Ling Dan; Xianlin Zhu

    2009-01-01

    BACKGROUND: Neuronal necrosis and apoptosis play important roles in the pathophysiology of cerebral ischemia and resulting cognitive impairment. However, inhibition of neuronal necrosis and apoptosis has been shown to attenuate cognitive impairment following cerebral ischemia.OBJECTIVE: To investigate the effects of sevoflurane on cyclic adenosine monophosphate response element binding protein (CREB), phosphorylated CREB (pCREB), and Livin expression in the cortex and hippocampus of a rat model of vascular cognitive impairment.DESIGN, TIME AND SETTING: A randomized, controlled experiment was performed in the Chongqing Key Laboratory of Neurology between June 2007 and July 2008.MATERIALS: Sevoflurane was provided by Abbott Laboratory, UK; Morris water maze was provided by Chinese Academy of Medical Sciences, China; goat anti-rat CREB, goat anti-rat pCREB and goat anti-rat Livin antibodies were provided by Biosource International, USA.METHODS: A total of 42 female, Wistar rats were randomly assigned to the following groups: sham operation, vascular cognitive impairment, and sevoflurane treatment. The vascular cognitive impairment rat model was established by permanent bilateral occlusion of both common carotid arteries, and 1.0 MAC sevoflurane was immediately administered by inhalation for 2 hours.MAIN OUTCOME MEASURES: CREB, pCREB, and Livin expression was measured in the cortex and hippocampus by Western blot and reverse transcription-polymerase chain reaction. Behavior was evaluated with Morris water maze.RESULTS: CREB, pCREB, and Livin expression in the sevoflurane treatment group was significantly greater than the vascular cognitive impairment group (P<0.01). However, expression of CREB and pCREB was significantly less in the sevoflurane treatment and vascular cognitive impairment groups, compared with the sham operation group (P<0.01). Livin expression in the sevoflurane treatment and vascular cognitive impairment groups was significantly greater than the sham

  1. [The secretion of adenosin 3',5'-monophosphate after hydrokinetic and ecbolic stimulation in the canine pancreas (author's transl)].

    Science.gov (United States)

    Teufel, H; Boeckmann, U

    1981-05-01

    The secretion of cAMP is studied in vivo and in the isolated perfused canine pancreas after administration of secretin and CCK or caerulein in comparison with hydrokinetic or ecbolic secretory events as well as with the magnitude and time course of changes in tissue cAMP. 1) The total output of cAMP and pancreatic juice shows a significant and positive correlation after stimulation with secretin. The linear correspondence between cAMP concentration and secretory rates of pancreatic juice beyond 3 ml/5 min and their non-linear, reciprocal correlation at lower rates of fluid secretion point to an active as well as to a passive secretory mechanism for cAMP. 2) CCK and caerulein increase secretion of cAMP too. The output of cAMP however neither corresponds to the time course of protein secretion nor correlates quantitatively with the latter. 3) The behaviour of cAMP secretion and concentration in the pancreatic juice after administration of secretin and CCK or caerulein as well as differs from the changes in tissue cAMP levels. The respective maximum of cAMP output after addition of secretin or ecbolic secretagogues during the greatest decrease in cellular cAMP levels yields on the average about 1% of the estimated reduction in total tissue cAMP content. The results indicate a functional coherence in secretion of pancreatic juice and cAMP but oppose the assumption, that essential amounts of cAMP are released during exocytosis of zymogen granules. The secretion of cAMP may be possibly influenced by cytoplasmatic cAMP levels, but neither reflects the present changes in cellular cAMP nor seems to be of a regulatory importance for the latter. PMID:6265337

  2. Elevated leukocyte phosphodiesterase as a basis for depressed cyclic adenosine monophosphate responses in the Basenji greyhound dog model of asthma

    International Nuclear Information System (INIS)

    The BG dog manifests various characteristics of human asthma, including airway hyperreactivity to low concentrations of methacholine. Studies have suggested that airway hyperreactivity in asthma is related to inadequate intracellular cAMP responses. The authors studied cAMP characteristics in MNL from 19 BG and 14 mongrel dogs. beta-Adrenergic receptors were assessed by 125I CYP in the presence and absence of propranolol. The responses of cAMP to ISO were measured by radioimmunoassay. Adenylate cyclase activity was determined in homogenized MNL preparations by cAMP generation. PDE activity was quantitated by radioenzyme assay. Mongrel dog leukocyte ISO-stimulated cAMP levels doubled, whereas there were negligible increases in MNL from BG dogs. Basal PDE levels were higher in BG dogs than in mongrel dogs. The PDE inhibitor Ro 20-1724 restored ISO-stimulated cAMP responses in MNL of BG dogs. Adenylate cyclase activity was not lower in MNL homogenates from BG dogs than in mongrel dogs. Cells from both BG and mongrel dogs demonstrated similar receptor numbers and affinities of saturable, specific beta-adrenergic binding over a 10 pM to 400 pM range. The results suggest that depressed cAMP responses in BG dogs are due to high PDE activity rather than to a defect in the beta-adrenergic receptor adenylate cyclase system

  3. Assay of adenosine 3',5' cyclic monophosphate by stimulation of protein kinase: a method not involving radioactivity

    Energy Technology Data Exchange (ETDEWEB)

    Handa, A.K.; Bressan, R.A.

    1980-03-01

    In order to meet a need for a cAMP assay which is not subject to interference by compounds in plant extracts, and which is suitable for use on occasions separated by many /sup 32/P half-lives, an assay based on cAMP-dependent protein kinase has been developed which does not require the use of (..gamma..-/sup 32/P)ATP. Instead of measuring the cAMP-stimulated increase in the rate of transfer of (..gamma..-/sup 32/P) phosphate from (..gamma..-/sup 32/P)ATP to protein, the rate of loss of ATP from the reaction mixture is determined. The ATP remaining after the protein kinase reaction is assayed by ATP-dependent chemiluminescence of the firefly luciferin-luciferase system. Under conditions of the protein kinase reaction in which a readily measurable decrease in ATP concentration occurs, the logarithm of the concentration of ATP decreases in proportion to the cAMP concentration, i.e., the reaction can be described by the equation: (ATP) = (ATP)/sub 0/ e/sup -(cAMP)kt/. The assay based on this relationship can detect less than 1 pmol of cAMP. The levels of cAMP found with this assay after partial purification of the cAMP from rat tissue, algal cells, and the media in which the cells were grown agreed with measurements made by the cAMP binding-competition assay of Gilman, and the potein kinase stimulation assay based on transfer of (/sup 32/P) phosphate from (..gamma..-/sup 32/P)ATP to protein. All of the enzymes and chemicals required for the assay of cAMP by protein kinase catalyzed loss of ATP can be stored frozen for months, making the assay suitable for occasional use.

  4. Cardiac cAMP: production, hydrolysis, modulation and detection.

    Science.gov (United States)

    Boularan, Cédric; Gales, Céline

    2015-01-01

    Cyclic adenosine 3',5'-monophosphate (cAMP) modulates a broad range of biological processes including the regulation of cardiac myocyte contractile function where it constitutes the main second messenger for β-adrenergic receptors' signaling to fulfill positive chronotropic, inotropic and lusitropic effects. A growing number of studies pinpoint the role of spatial organization of the cAMP signaling as an essential mechanism to regulate cAMP outcomes in cardiac physiology. Here, we will briefly discuss the complexity of cAMP synthesis and degradation in the cardiac context, describe the way to detect it and review the main pharmacological arsenal to modulate its availability. PMID:26483685

  5. Characterization of cell surface adenosine 3',5'-monophosphate-binding proteins in Y-1 mouse adrenal tumor cells

    International Nuclear Information System (INIS)

    Adrenal cortical cells are known to export cAMP and have binding proteins and cAMP-dependent protein kinase activity associated with their plasma membranes. Because these properties suggest a function for extracellular cAMP, we have undertaken a search for specific cell surface receptors for this cyclic nucleotide. Y-1 mouse adrenal tumor cells actively export cAMP by an energy-dependent process. Analysis of Scatchard plots of the equilibrium binding of [3H]cAMP to these cells indicate the existence of two classes of cAMP binders: one with high affinity (K/sub a/ . 2.9 X 10(9) M-1) and another with low affinity (K/sub a/ . 7.0 X 10(7) M-1). The cell surface localization of these binders was established by the sensitivity of both the [3H]cAMP-binding proteins and the [32P]8-N3-cAMP photoaffinity labeled proteins of intact cells to mild trypsin digestion and by the surface distribution of a BSA-O2-monosuccinyl cAMP-gold complex revealed by electron microscopy. Analysis of radioautograms of cell surface cAMP-binding proteins from confluent monolayer tumor cells, photoaffinity labeled with [32P]8-N3-cAMP and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed two major 32P-labeled protein bands which were indistinguishable from the 49,000 and 55,000 mol wt regulatory subunits of the cytosolic protein kinase isoenzymes of this cell. These observations along with the demonstration of cell surface, cAMP-dependent protein kinase activity in the mouse adrenal tumor cell strongly suggest that these cAMP-binding proteins function as regulatory proteins for cell surface protein kinases

  6. Identification, characterization, and hormonal regulation of 3', 5'-cyclic adenosine monophosphate-dependent protein kinases in rat Sertoli cells.

    Science.gov (United States)

    Landmark, B F; Fauske, B; Eskild, W; Skålhegg, B; Lohmann, S M; Hansson, V; Jahnsen, T; Beebe, S J

    1991-11-01

    Recent studies have disclosed multiple isoforms of regulatory (R) and catalytic (C) subunits of cAMP-dependent protein kinase (PKA) at the protein and messenger RNA (mRNA) levels. The purpose of the present study was to identify, characterize, and quantify individual R subunits in rat Sertoli cells both at the mRNA and protein levels. Unstimulated Sertoli cells contain high levels of R (approximately 9.2 +/- 0.8 pmol/mg protein) and C (approximately 7.3 +/- 0.7 pmol/mg protein). Stimulation with (Bt)2cAMP (0.1 mM) for 24 and 48 h revealed a time-dependent increase in [3H]cAMP-binding activity. During the same time period the catalytic activity remained relatively constant, resulting in an increase in the R/C ratio from approximately 1.3 to 3.0. Using diethylaminoethyl cellulose chromatography, 8-N3-[32P]cAMP photoaffinity labeling, autophosphorylation by gamma-[32P]ATP, and specific antibodies, we show that unstimulated Sertoli cells contain approximately 75% RI alpha, 25% RII alpha, and very low levels of RII beta. Stimulation of Sertoli cells with (Bt)2cAMP (0.1 mM, 48 h) was associated with a 2.1-fold increase in RI alpha (6.6-14 pmol/mg) and a 10- to 20-fold increase in RII beta (less than 0.1-1.1 pmol/mg), with little or no change in RII alpha (1.9-2.3 pmol/mg). Treatment with cAMP was associated with a slight increase in RI/RII ratio (3.3-4.1). mRNA levels for RII beta increased 30- to 50-fold after (Bt)2cAMP stimulation, whereas only minor changes in mRNA levels for RI alpha, RII alpha, and C alpha were observed (1.5- to 2.0-fold). mRNA levels for RI beta, C beta, and C gamma were not detected in either unstimulated or in cAMP-stimulated Sertoli cells. It is concluded that chronic treatment with cAMP changes the relative proportion of R subunits of PKA in a manner reflecting the changing levels in respective mRNAs. Furthermore, such treatment is associated with the appearance of a new PKA R subunit (RII beta), which is absent in untreated Sertoli cells. PMID

  7. Leptin interferes with 3',5'-Cyclic Adenosine Monophosphate (cAMP signaling to inhibit steroidogenesis in human granulosa cells

    Directory of Open Access Journals (Sweden)

    HoYuen Basil

    2009-10-01

    Full Text Available Abstract Background Obesity has been linked to an increased risk of female infertility. Leptin, an adipocytokine which is elevated during obesity, may influence gonadal function through modulating steroidogenesis in granulosa cells. Methods The effect of leptin on progesterone production in simian virus 40 immortalized granulosa (SVOG cells was examined by Enzyme linked immunosorbent assay (ELISA. The effect of leptin on the expression of the steroidogenic enzymes (StAR, P450scc, 3betaHSD in SVOG cells was examined by real-time PCR and Western blotting. The mRNA expression of leptin receptor isoforms in SVOG cells were examined by using PCR. SVOG cells were co-treated with leptin and specific pharmacological inhibitors to identify the signaling pathways involved in leptin-reduced progesterone production. Silencing RNA against leptin receptor was used to determine that the inhibition of leptin on cAMP-induced steroidogenesis acts in a leptin receptor-dependent manner. Results and Conclusion In the present study, we investigated the cellular mechanisms underlying leptin-regulated steroidogenesis in human granulosa cells. We show that leptin inhibits 8-bromo cAMP-stimulated progesterone production in a concentration-dependent manner. Furthermore, we show that leptin inhibits expression of the cAMP-stimulated steroidogenic acute regulatory (StAR protein, the rate limiting de novo protein in progesterone synthesis. Leptin induces the activation of ERK1/2, p38 and JNK but only the ERK1/2 (PD98059 and p38 (SB203580 inhibitors attenuate the leptin-induced inhibition of cAMP-stimulated StAR protein expression and progesterone production. These data suggest that the leptin-induced MAPK signal transduction pathway interferes with cAMP/PKA-stimulated steroidogenesis in human granulosa cells. Moreover, siRNA mediated knock-down of the endogenous leptin receptor attenuates the effect of leptin on cAMP-induced StAR protein expression and progesterone production, suggesting that the effect of leptin on steroidogenesis in granulosa cells is receptor dependent. In summary, leptin acts through the MAPK pathway to downregulate cAMP-induced StAR protein expression and progesterone production in immortalized human granulosa cells. These results suggest a possible mechanism by which gonadal steroidogenesis could be suppressed in obese women.

  8. The role of nitric oxide in the phosphorylation of cyclic adenosine monophosphate-responsive element-binding protein in the spinal cord after intradermal injection of capsaicin.

    Science.gov (United States)

    Wu, Jing; Fang, Li; Lin, Qing; Willis, William D

    2002-06-01

    We investigated the involvement of nitric oxide (NO) in the phosphorylation of cyclic adenosine monophosphate-responsive element-binding protein (CREB) in the spinal cord of rats during central sensitization after intradermal capsaicin injection. CREB and phosphorylated CREB (p-CREB) were measured by immunoblotting. The level of p-CREB increased by 20 minutes, peaked between 20 and 60 minutes after capsaicin injection, and started to decrease after 150 minutes. CREB itself did not show an obvious change after capsaicin injection. The p-CREB expression on the ipsilateral side of the spinal dorsal horn, but not on the contralateral side, increased significantly after capsaicin injection. The increase in p-CREB induced by capsaicin injection was partially blocked by pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor, administered through a microdialysis fiber placed across the spinal cord. D-NAME, an inactive form of L-NAME, had no effect. CREB phosphorylation, not the level of CREB, was induced within 20 minutes by microdialysis administration of SIN-1, an NO donor. These results indicate that CREB phosphorylation in the spinal cord results from both endogenous and exogenous NO release and that p-CREB may play a role in central sensitization or in longer-term changes in gene expression induced by strong peripheral noxious stimulation. PMID:14622772

  9. Imaging alterations of cardiomyocyte cAMP microdomains in disease

    Directory of Open Access Journals (Sweden)

    Alexander eFroese

    2015-08-01

    Full Text Available 3’,5’-cyclic adenosine monophosphate (cAMP is an important second messenger which regulates heart function by acting in distinct subcellular microdomains. Recent years have provided deeper mechanistic insights into compartmentalized cAMP signaling and its link to cardiac disease. In this mini review, we summarize newest developments in this field achieved by cutting-edge biochemical and biophysical techniques. We further compile the data from different studies into a bigger picture of so far uncovered alterations in cardiomyocyte cAMP microdomains which occur in compensated cardiac hypertrophy and chronic heart failure. Finally, future research directions and translational perspectives are briefly discussed.

  10. Role of 3'-5'-cyclic adenosine monophosphate on the epidermal growth factor dependent survival in mammary epithelial cells.

    Science.gov (United States)

    Grinman, Diego Y; Romorini, Leonardo; Presman, Diego M; Rocha-Viegas, Luciana; Coso, Omar A; Davio, Carlos; Pecci, Adali

    2016-01-01

    Epidermal growth factor (EGF) has been suggested to play a key role in the maintenance of epithelial cell survival during lactation. Previously, we demonstrated that EGF dependent activation of PI3K pathway prevents apoptosis in confluent murine HC11 cells cultured under low nutrient conditions. The EGF protective effect is associated with increased levels of the antiapoptotic protein Bcl-XL. Here, we identify the EGF-dependent mechanism involved in cell survival that converges in the regulation of bcl-X expression by activated CREB. EGF induces Bcl-XL expression through activation of a unique bcl-X promoter, the P1; being not only the PI3K/AKT signaling pathway but also the increase in cAMP levels and the concomitant PKA/CREB activation necessary for both bcl-XL upregulation and apoptosis avoidance. Results presented in this work suggest the existence of a novel connection between the EGF receptor and the adenylate cyclase that would have an impact in preventing apoptosis under low nutrient conditions.

  11. Adenosine monophosphate-activated protein kinase activation enhances embryonic neural stem cell apoptosis in a mouse model of amyotrophic lateral sclerosis

    Institute of Scientific and Technical Information of China (English)

    Yanling Sui; Zichun Zhao; Rong Liu; Bin Cai; Dongsheng Fan

    2014-01-01

    Alterations in embryonic neural stem cells play crucial roles in the pathogenesis of amyotrophic lateral sclerosis. We hypothesized that embryonic neural stem cells from SOD1G93A individuals might be more susceptible to oxidative injury, resulting in a propensity for neurodegeneration at later stages. In this study, embryonic neural stem cells obtained from human superoxide dis-mutase 1 mutant (SOD1G93A) and wild-type (SOD1WT) mouse models were exposed to H2O2. We assayed cell viability with mitochondrial succinic dehydrogenase colorimetric reagent, and measured cell apoptosis by lfow cytometry. Moreover, we evaluated the expression of the adenos-ine monophosphate-activated protein kinase (AMPK)α-subunit, paired box 3 (Pax3) protein, and p53 in western blot analyses. Compared with SOD1WT cells, SOD1G93A embryonic neural stem cells were more likely to undergo H2O2-induced apoptosis. Phosphorylation of AMPKαin SOD1G93A cells was higher than that in SOD1WT cells. Pax3 expression was inversely correlated with the phosphorylation levels of AMPKα. p53 protein levels were also correlated with AMPKαphosphorylation levels. Compound C, an inhibitor of AMPKα, attenuated the effects of H2O2. These results suggest that embryonic neural stem cells from SOD1G93A mice are more susceptible to apoptosis in the presence of oxidative stress compared with those from wild-type controls, and the effects are mainly mediated by Pax3 and p53 in the AMPKα pathway.

  12. Effect of the growth stage and cultivar on policosanol profiles of barley sprouts and their adenosine 5'-monophosphate-activated protein kinase activation.

    Science.gov (United States)

    Seo, Woo Duck; Yuk, Heung Joo; Curtis-Long, Marcus J; Jang, Ki Chang; Lee, Jin Hwan; Han, Sang-Ik; Kang, Hang Won; Nam, Min Hee; Lee, Sung-Joon; Lee, Ji Hae; Park, Ki Hun

    2013-02-01

    Adenosine 5'-monophosphate-activated protein kinase (AMPK) is an intracellular sensor that can regulate glucose levels within the cell. For this reason, it is well-known to be a target for drugs against diabetes and obesity. AMPK was activated significantly by the hexane extract of barley sprouts. This AMPK activation emerges across the growth stages of the sprout, becoming most significant (3 times above the initial stages) 10 days after sprouting. After this time, the activation decreased between 13 and 20 days post-sprouting. Analysis of the hexane extracts by gas chromatography-mass spectrometry showed that the amounts of policosanols (PCs, which are linear, primary aliphatic alcohols with 20-30 carbons) in the plant dramatically increased between 5 days (109.7 mg/100 g) and 10 days (343.7 mg/100 g) post-sprouting and then levels fell back down, reaching 76.4 mg/100 g at 20 days post-sprouting. This trend is consistent with PCs being the active ingredient in the barley plants. We validate this by showing that hexacosanol is an activator of AMPK. The richest cultivar for PCs was found to be the Daejin cultivar. Cultivars had a significant effect on the total PC content (113.2-183.5 mg/100 g) within the plant up to 5 days post-sprouting. However this dependence upon the cultivar was not so apparent at peak stages of PC production (10 days post-sprouting). The most abundant PC in barley sprout, hexacosanol, contributed 62-80% of the total PC content at every stage. These results are valuable to determine the optimal times of harvest to obtain the highest yield of PCs. PMID:23301834

  13. A high isoflavone diet decreases 5' adenosine monophosphate-activated protein kinase activation and does not correct selenium-induced elevations in fasting blood glucose in mice.

    Science.gov (United States)

    Stallings, Michael T; Cardon, Brandon R; Hardman, Jeremy M; Bliss, Tyler A; Brunson, Scott E; Hart, Chris M; Swiss, Maria D; Hepworth, Squire D; Christensen, Merrill J; Hancock, Chad R

    2014-04-01

    Selenium (Se) has been implicated as a micronutrient that decreases adenosine monophosphate-activated protein kinase (AMPK) signaling and may increase diabetes risk by reducing insulin sensitivity. Soy isoflavones (IF) are estrogen-like compounds that have been shown to attenuate insulin resistance, hyperglycemia, adiposity, and increased AMPK activation. We hypothesized that a high IF (HIF) diet would prevent the poor metabolic profile associated with high Se intake. The purpose of this study was to examine changes in basal glucose metabolism and AMPK signaling in response to an HIF diet and/or supplemental Se in a mouse model. Male FVB mice were divided into groups receiving either a control diet with minimal IF (low IF) or an HIF diet. Each dietary group was further subdivided into groups receiving either water or Se at a dose of 3 mg Se/kg body weight daily, as Se-methylselenocysteine (SMSC). After 5 months, mice receiving SMSC had elevated fasting glucose (P < .05) and a tendency for glucose intolerance (P = .08). The increase in dietary IF did not result in improved fasting blood glucose. Interestingly, after 6 months, HIF-fed mice had decreased basal AMPK activation in liver and skeletal muscle tissue (P < .05). Basal glucose metabolism was changed by SMSC supplementation as evidenced by increased fasting blood glucose and glucose intolerance. High dietary IF levels did not protect against aberrant blood glucose. In FVB mice, decreased basal AMPK activation is not the mechanism through which Se exerts its effect. These results suggest that more research must be done to elucidate the role of Se and IF in glucose metabolism.

  14. Dietary effects of adenosine monophosphate to enhance growth, digestibility, innate immune responses and stress resistance of juvenile red sea bream, Pagrus major.

    Science.gov (United States)

    Hossain, Md Sakhawat; Koshio, Shunsuke; Ishikawa, Manabu; Yokoyama, Saichiro; Sony, Nadia Mahjabin

    2016-09-01

    Our study explored the dietary effects of adenosine monophosphate (AMP) to enhance growth, digestibility, innate immune responses and stress resistance of juvenile red sea bream. A semi-purified basal diet supplemented with 0% (Control), 0.1% (AMP-0.1), 0.2% (AMP-0.2), 0.4% (AMP-0.4) and 0.8% (AMP-0.8) purified AMP to formulate five experimental diets. Each diet was randomly allocated to triplicate groups of fish (mean initial weight 3.4 g) for 56 days. The results indicated that dietary AMP supplements tended to improve growth performances. One of the best ones was found in diet group AMP-0.2, followed by diet groups AMP-0.1, AMP-0.4 and AMP-0.8. The Apparent digestibility coefficients (dry matter, protein and lipid) also improved by AMP supplementation and the significantly highest dry matter digestibility was observed in diet group AMP-0.2. Fish fed diet groups AMP-0.2 and AMP-0.4 had significantly higher peroxidase and bactericidal activities than fish fed the control diet. Nitro-blue-tetrazolium (NBT) activity was found to be significantly (P  0.05) by dietary supplementation. In contrast, catalase activity decreased with AMP supplementation. Moreover, the fish fed AMP supplemented diets had better improvement (P stress resistances. Interestingly, the fish fed diet groups AMP-0.2 and AMP-0.4 showed the least oxidative stress condition. Finally it is concluded that, dietary AMP supplementation enhanced the growth, digestibility, immune response and stress resistance of red sea bream. The regression analysis revealed that a dietary AMP supplementation between 0.2 and 0.4% supported weight gain and lysozyme activity as a marker of immune functions for red sea bream, which is also inline with the most of the growth and health performance parameters of fish under present experimental conditions. PMID:27514786

  15. Ablation of adenosine monophosphate-activated protein kinaseα1 in vascular smooth muscle cells promotes diet-induced atherosclerotic calcification in vivo

    Institute of Scientific and Technical Information of China (English)

    CAI Zhe-jun; DING Ye; ZHANG Miao; LU Qiu-lun; WU Sheng-nan; ZHU Huai-ping; SONG Ping; ZOU Ming-hui

    2016-01-01

    AIM:Atherosclerotic calcification is highly linked with plaque instability and cardiovascular events .Adenosine monophosphate-activated protein kinase ( AMPK) has been involved in the pathogenesis of various cardiovascular disease .The contributions of AMPKαsubunits to the development of atherosclerotic calcification in vivo remained unknown .We hypothesized that AMPKαsubunits may play a role in the development of atherosclerotic calcification .METHODS: Atherosclerotic calcification was generated by 24-week fed of western diet in ApoE-/-background mice .Calcification was evaluated in aortic roots and innominate arteries of ApoE-/-mice or in mice with dual deficiencies of ApoE and AMPKαsubunits globally ( AMPKα1 and AMPKα2 ) , or vascular smooth muscle cell ( VSMC)-specific or macrophage-specific knockout of AMPKα1 with atherosclerotic calcification pone diet . The mechanism of AMPKα1 in regulating Runx2 was further explored in human aortic VSMC .RESULTS: Ablation of AMPKα1 but not AMPKα2 in ApoE-/-background promoted atherosclerotic calcification with increased Runt -related transcription factor ( Runx2 ) expression in VSMC compared with ApoE-/-mice.Conversely, chronic administration of metformin, which activated AMPK, markedly reduced ath-erosclerotic calcification and Runx2 expression in ApoE-/-mice but had less effects in ApoE-/-/AMPKα1 -/-mice.Furthermore, VSMC-but not macrophage-specific deficiency of AMPKα1 in ApoE-/-background promoted atherosclerotic calcification in vivo com-pared with the controls .AMPKα1 silencing in human aortic VSMC prevented Runx 2 from proteasome degradation to trigger osteoblastic differentiation of VSMC .Conversely , activation of AMPK led to Runx 2 instability by inducing its small ubiquitin-like modifier modifi-cation (SUMOylation).Protein inhibitor of activated STAT-1 (PIAS1), the SUMO E3-ligase of Runx2, was directly phosphorylated by AMPKα1 at serine 510, to enhance its SUMO E3-ligase activity.Ablation of PIAS1

  16. Conservation and divergence of the cyclic adenosine monophosphate-protein kinase A (cAMP–PKA) pathway in two plant-pathogenic fungi: Fusarium graminearum and F. verticillioides

    Science.gov (United States)

    The cyclic AMP (cAMP)-PKA pathway is a central signaling cascade that transmits extracellular stimuli and governs cell responses through the second messenger cAMP. The importance of cAMP signaling in fungal biology has been well documented. Two key conserved components, adenylate cyclase (AC) and ca...

  17. Cardiac cAMP: production, hydrolysis, modulation and detection

    Directory of Open Access Journals (Sweden)

    Cédric eBOULARAN

    2015-10-01

    Full Text Available Cyclic adenosine 3’,5’-monophosphate (cAMP modulates a broad range of biological processes including the regulation of cardiac myocyte contractile function where it constitutes the main second messenger for β-adrenergic receptors’ signaling to fulfill positive chronotropic, inotropic and lusitropic effects. A growing number of studies pinpoint the role of spatial organization of the cAMP signaling as an essential mechanism to regulate cAMP outcomes in cardiac physiology. Here, we will briefly discuss the complexity of cAMP synthesis and degradation in the cardiac context, describe the way to detect it and review the main pharmacological arsenal to modulate its availability.

  18. The importance of dietary modulation of cAMP and insulin signaling in adipose tissue and the development of obesity

    DEFF Research Database (Denmark)

    Madsen, Lise; Kristiansen, Karsten

    2010-01-01

    Adipose tissue plays a pivotal role in whole body energy homeostasis. In this review, we summarize knowledge of the seemingly paradoxical roles of insulin and cyclic adenosine monophosphate (cAMP) signaling in adipocyte differentiation and function, emphasizing the interplay between the two...... branches of cAMP signaling, the canonical protein kinase A-dependent pathways and the novel exchange protein activated by cAMP (Epac)-dependent pathways, and insulin signaling. We discuss how macronutrients via changes in the balance between insulin- and cAMP-dependent signaling can affect the development...

  19. Cyclic 3'-5'-adenosine monophosphate binds to annexin I and regulates calcium-dependent membrane aggregation and ion channel activity.

    Science.gov (United States)

    Cohen, B E; Lee, G; Arispe, N; Pollard, H B

    1995-12-27

    The annexin (Anx) gene family comprises a set of calcium-dependent membrane binding proteins, which have been implicated in a wide variety of cellular processes including membrane fusion and calcium channel activity. We report here that cAMP activates Ca(2+)-dependent aggregation of both phosphatidylserine (PS) liposomes and bovine chromaffin granules driven by [des 1-12]annexin I (lipocortin I, Anx1). The mechanism of cAMP action involves an increase in AnxI-dependent cooperativity on the rate of such a reaction without affecting the corresponding k1/2 values. Cyclic AMP causes the values of the Hill coefficient (nH) for AnxI to change from 3 to 6 in both PS liposomes and chromaffin granules. By contrast, ATP inhibits the rate of aggregation activity without affecting the cooperativity or the extent of aggregation process. We were also able to photolabel Anx1 specifically with an 8-azido analogue of cAMP by a calcium-independent process. Such a process is saturable, yielding a Kd = 0.8 microM by Scatchard analysis. Specific displacement occurs in the presence of cAMP and ATP. Finally, we found that cAMP alters the conductance of calcium channels formed by AnxI in planar lipid bilayers. We interpret these data to indicate that AnxI binds both calcium and cAMP independently, and that both actions have functional consequences. This is the first report of a nucleotide binding function for a member of the annexin gene family.

  20. Ontogeny of catecholamine and adenosine receptor-mediated cAMP signaling of embryonic red blood cells: role of cGMP-inhibited phosphodiesterase 3 and hemoglobin.

    Science.gov (United States)

    Baumann, R; Blass, C; Götz, R; Dragon, S

    1999-12-15

    We have previously shown that the cAMP signaling pathway controls major aspects of embryonic red blood cell (RBC) function in avian embryos (Glombitza et al, Am J Physiol 271:R973, 1996; and Dragon et al, Am J Physiol 271:R982, 1996) that are important for adaptation of the RBC gas transport properties to the progressive hypercapnia and hypoxia of later stages of avian embryonic development. Data about the ontogeny of receptor-mediated cAMP signaling are lacking. We have analyzed the response of primitive and definitive chick embryo RBC harvested from day 3 to 18 of development towards forskolin, beta-adrenergic, and A2 receptor agonists. The results show a strong response of immature definitive and primitive RBC to adenosine A2 and beta-adrenergic receptor agonists, which is drastically reduced in the last stage of development, coincident with the appearance of mature, transcriptionally inactive RBC. Modulation of cGMP-inhibited phosphodiesterase 3 (PDE3) has a controlling influence on cAMP accumulation in definitive RBC. Under physiological conditions, PDE3 is inhibited due to activation of soluble guanylyl cyclase (sGC). Inhibition of sGC with the specific inhibitor ODQ decreases receptor-mediated stimulation of cAMP production; this effect is reversed by the PDE3 inhibitor milrinone. sGC is acitivated by nitric oxide (NO), but we found no evidence for production of NO by erythrocyte NO-synthase. However, embryonic hemoglobin releases NO in an oxygen-linked manner that may activate guanylyl cyclase.

  1. A comparison of the effects of divalent and trivalent cations on parathyroid hormone release, 3',5'-cyclic-adenosine monophosphate accumulation, and the levels of inositol phosphates in bovine parathyroid cells.

    Science.gov (United States)

    Brown, E M; Fuleihan G el-H; Chen, C J; Kifor, O

    1990-09-01

    We compared the effects of a series of di- and trivalent cations on various aspects of parathyroid function to investigate whether these polyvalent cations act on the parathyroid cell through a similar mechanism. Like high extracellular concentrations of Ca2+, high levels of barium (Ba2+), strontium (Sr2+), gadolinium (Gd3+), europium (Eu3+), terbium (Tb3+), and ytterbium (Yb3+) [corrected] each inhibited low calcium-stimulated PTH release and showed IC50 values (the concentration producing half of the maximal inhibitory effect) of 1.12 mM, 1.18 mM, 2.2 microM, 2.5 microM, 0.89 microM, and 15 microM, respectively. The inhibitory effects of both divalent (Ca2+ and Ba2+) and trivalent (Gd3+) cations were reversible by 76-100% after removal of the cation, suggesting that the polyvalent cation-mediated reduction in PTH release was not due to nonspecific toxicity. The same di- and trivalent cations produced an 80-90% decrease in agonist-stimulated cAMP accumulation with a similar order of potency as for their effects on PTH release. Preincubation overnight with pertussis toxin totally prevented the inhibitory effects of the trivalent cations on cAMP accumulation. The same di- and trivalent cations also increased the accumulation of inositol monophosphate, inositol bisphosphate, and inositol trisphosphate. Their effects on this parameter differed from those on PTH release and cAMP accumulation in several respects. First, Ba2+ and Sr2+, rather than being equipotent with Ca2+, were about 2-fold less potent in increasing the levels of inositol phosphates. Second, the trivalent cations were 5-50-fold less potent in raising inositol phosphates than in modulating PTH release and cAMP accumulation, and all were nearly equipotent. These results show that trivalent cations of the lanthanide series mimic the actions of divalent cations on several aspects of parathyroid function, and likely do so by interacting with the cell surface "Ca2(+)-receptor-like mechanism" through which

  2. Arginine vasopressin increases cellular free calcium concentration and adenosine 3',5'-monophosphate production in rat renal papillary collecting tubule cells in culture

    Energy Technology Data Exchange (ETDEWEB)

    Ishikawa, S.; Okada, K.; Saito, T.

    1988-09-01

    The role of calcium (Ca) in the cellular action of arginine vasopressin (AVP) was examined in rat renal papillary collecting tubule cells in culture. AVP increased both the cellular free Ca concentration ((Ca2+)i) using fura-2, and cAMP production in a dose-dependent manner. AVP-induced cellular Ca mobilization was totally blocked by the antagonist to the antidiuretic action of AVP, and somewhat weakened by the antagonist to the vascular action of AVP. 1-Deamino-8-D-AVP (dDAVP). an antidiuretic analog of AVP, also increased (Ca2+) significantly. Cellular Ca mobilization was not obtained with cAMP, forskolin (a diterpene activator of adenylate cyclase), or phorbol-12-myristate-13-acetate. The early phase of (Ca2+)i depended on the intracellular Ca pool, since an AVP-induced rise in (Ca2+)i was obtained in cells pretreated with Ca-free medium containing 1 mM EGTA, verapamil, or cobalt, which blocked cellular Ca uptake. Also, AVP increased /sup 45/Ca2+ influx during the initial 10 min, which initiated the sustained phase of cellular Ca mobilization. However, cellular cAMP production induced by AVP during the 10-min observation period was diminished in the cells pretreated with Ca-free medium, verapamil, or cobalt, but was still significantly higher than the basal level. This was also diminished by a high Ca concentration in medium. These results indicate that 1) AVP concomitantly regulates cellular free Ca as well as its second messenger cAMP production; 2) AVP-induced elevation of cellular free Ca is dependent on both the cellular Ca pool and extracellular Ca; and 3) there is an optimal level of extracellular Ca to modulate the AVP action in renal papillary collecting tubule cells.

  3. Diabetic complications within the context of aging: Nicotinamide adenine dinucleotide redox, insulin C-peptide, sirtuin 1-liver kinase B1-adenosine monophosphate-activated protein kinase positive feedback and forkhead box O3.

    Science.gov (United States)

    Ido, Yasuo

    2016-07-01

    Recent research in nutritional control of aging suggests that cytosolic increases in the reduced form of nicotinamide adenine dinucleotide and decreasing nicotinamide adenine dinucleotide metabolism plays a central role in controlling the longevity gene products sirtuin 1 (SIRT1), adenosine monophosphate-activated protein kinase (AMPK) and forkhead box O3 (FOXO3). High nutrition conditions, such as the diabetic milieu, increase the ratio of reduced to oxidized forms of cytosolic nicotinamide adenine dinucleotide through cascades including the polyol pathway. This redox change is associated with insulin resistance and the development of diabetic complications, and might be counteracted by insulin C-peptide. My research and others' suggest that the SIRT1-liver kinase B1-AMPK cascade creates positive feedback through nicotinamide adenine dinucleotide synthesis to help cells cope with metabolic stress. SIRT1 and AMPK can upregulate liver kinase B1 and FOXO3, key factors that help residential stem cells cope with oxidative stress. FOXO3 directly changes epigenetics around transcription start sites, maintaining the health of stem cells. 'Diabetic memory' is likely a result of epigenetic changes caused by high nutritional conditions, which disturb the quiescent state of residential stem cells and impair tissue repair. This could be prevented by restoring SIRT1-AMPK positive feedback through activating FOXO3. PMID:27181414

  4. Plasma levels of cAMP, cGMP and CGRP in sildenafil-induced headache

    DEFF Research Database (Denmark)

    Kruuse, Christina Rostrup; Frandsen, E; Schifter, S;

    2004-01-01

    Sildenafil, a selective inhibitor of the cyclic guanosine monophosphate (cGMP) degrading phosphodiestrase 5 (PDE5), induced migraine without aura in 10 of 12 migraine patients and in healthy subjects it induced significantly more headache than placebo. The aim of the present study was to determine...... whether the pain-inducing effects of sildenafil would be reflected in plasma levels of important signalling molecules in migraine: cGMP, cyclic adenosine monophosphate (cAMP) and calcitonin gene-related peptide (CGRP). Ten healthy subjects (four women, six men) and 12 patients (12 women) suffering from...... migraine without aura were included in two separate double-blind, placebo-controlled, cross-over studies in which placebo or sildenafil 100 mg was administered orally. Plasma levels of CGRP, cAMP and cGMP were determined in blood from the antecubital vein. Despite the ability of sildenafil to induce...

  5. Early glycogen synthase kinase-3β and protein phosphatase 2A independent tau dephosphorylation during global brain ischaemia and reperfusion following cardiac arrest and the role of the adenosine monophosphate kinase pathway.

    Science.gov (United States)

    Majd, Shohreh; Power, John H T; Koblar, Simon A; Grantham, Hugh J M

    2016-08-01

    Abnormal tau phosphorylation (p-tau) has been shown after hypoxic damage to the brain associated with traumatic brain injury and stroke. As the level of p-tau is controlled by Glycogen Synthase Kinase (GSK)-3β, Protein Phosphatase 2A (PP2A) and Adenosine Monophosphate Kinase (AMPK), different activity levels of these enzymes could be involved in tau phosphorylation following ischaemia. This study assessed the effects of global brain ischaemia/reperfusion on the immediate status of p-tau in a rat model of cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR). We reported an early dephosphorylation of tau at its AMPK sensitive residues, Ser(396) and Ser(262) after 2 min of ischaemia, which did not recover during the first two hours of reperfusion, while the tau phosphorylation at GSK-3β sensitive but AMPK insensitive residues, Ser(202) /Thr(205) (AT8), as well as the total amount of tau remained unchanged. Our data showed no alteration in the activities of GSK-3β and PP2A during similar episodes of ischaemia of up to 8 min and reperfusion of up to 2 h, and 4 weeks recovery. Dephosphorylation of AMPK followed the same pattern as tau dephosphorylation during ischaemia/reperfusion. Catalase, another AMPK downstream substrate also showed a similar pattern of decline to p-AMPK, in ischaemic/reperfusion groups. This suggests the involvement of AMPK in changing the p-tau levels, indicating that tau dephosphorylation following ischaemia is not dependent on GSK-3β or PP2A activity, but is associated with AMPK dephosphorylation. We propose that a reduction in AMPK activity is a possible early mechanism responsible for tau dephosphorylation. PMID:27177932

  6. 二甲双胍通过激活腺苷酸活化蛋白激酶(AMPK)的抗肿瘤机制%Antitumor Mechanism of Metformin via Adenosine Monophosphate-activated Protein Kinase (AMPK) Activation

    Institute of Scientific and Technical Information of China (English)

    陈兆煜; 王连唐; 陈雁扬

    2013-01-01

    Metformin, as a traditional oral hypoglycemic agent, is commonly used in the clinical treatment for type 2 diabetes. Recently, a large number of epidemiological researches have shown that metformin could reduce the tumor morbidity of type 2 diabetes, moreover, it has also been indicated that metformin could inhibit the growth, proliferation and transformation of cancer cells in metabolic pathways, cell cycle, oxidative stress and cancer/tumor stem cells transformation via AMPK pathway activation. But the antitumor effect of metformin via AMPK activation still exists arguments, and the deifnite mechanism remains to be further investigated and conifrmed by extensive clinical trials.%二甲双胍是一种传统的口服降糖药,临床上普遍用于2型糖尿病的治疗。近年来大量流行病学研究报道二甲双胍能够降低2型糖尿病患者的肿瘤发病率,亦有研究发现二甲双胍能在代谢途径、细胞周期、氧化应激、肿瘤干细胞转化等方面通过激活腺苷酸活化蛋白激酶(adenosine monophosphate-activated protein kinase, AMPK)信号通路,从而抑制肿瘤细胞的生长、增殖以及转化。但二甲双胍通过激活AMPK的抗肿瘤机制仍存在着争议,其确切的作用机制有待进一步深入的研究,同时亟需大规模的临床试验来证实。

  7. Twitching motility and cAMP levels: signal transduction through a single methyl-accepting chemotaxis protein.

    Science.gov (United States)

    Jansari, Vibhuti H; Potharla, Vishwakanth Y; Riddell, Geoff T; Bardy, Sonia L

    2016-06-01

    The Pseudomonas aeruginosa Chp chemosensory system regulates twitching motility, intracellular adenosine 3('') 5(')-cyclic monophosphate (cAMP) levels and is postulated to be involved in directional twitching towards phosphatidylethanolamine (PE). Because PilJ is the only methyl-accepting chemotaxis protein (MCP) identified in the Chp system, we determined the role of PilJ in mediating signal transduction for the distinct outputs of this system. Mutants that lack the periplasmic domain of PilJ (pilJΔ74-273) showed lower levels of cAMP but retained directional twitching towards PE. While initial studies revealed reduced twitching motility by PilJΔ74-273, this was due to decreased cAMP levels. Our data illustrate the importance of the periplasmic domain of PilJ in regulating cAMP. This is the first time a defined domain within PilJ has been identified as having a distinct role in signal transduction. PMID:27190147

  8. Targeting brain tumor cAMP: the case for sex-specific therapeutics

    Directory of Open Access Journals (Sweden)

    Nicole M Warrington

    2015-07-01

    Full Text Available A relationship between cyclic adenosine 3’, 5’-monophosphate (cAMP levels and brain tumor biology has been evident for nearly as long as cAMP and its synthetase, adenylate cyclase (ADCY have been known. The importance of the pathway in brain tumorigenesis has been demonstrated in vitro and in multiple animal models. Recently, we provided human validation for a cooperating oncogenic role for cAMP in brain tumorigenesis when we found that SNPs in ADCY8 were correlated with glioma (brain tumor risk in individuals with Neurofibromatosis type 1 (NF1. Together, these studies provide a strong rationale for targeting cAMP in brain tumor therapy. However, the cAMP pathway is well known to be sexually dimorphic, and SNPs in ADCY8 affected glioma risk in a sex-specific fashion, elevating the risk for females while protecting males. The cAMP pathway can be targeted at multiple levels in the regulation of its synthesis and degradation. Sex differences in response to drugs that target cAMP regulators indicate that successful targeting of the cAMP pathway for brain tumor patients is likely to require matching specific mechanisms of drug action with patient sex.

  9. Discovery and Preclinical Characterization of 6-Chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1H-indole-3-carboxylic Acid (PF-06409577), a Direct Activator of Adenosine Monophosphate-activated Protein Kinase (AMPK), for the Potential Treatment of Diabetic Nephropathy.

    Science.gov (United States)

    Cameron, Kimberly O; Kung, Daniel W; Kalgutkar, Amit S; Kurumbail, Ravi G; Miller, Russell; Salatto, Christopher T; Ward, Jessica; Withka, Jane M; Bhattacharya, Samit K; Boehm, Markus; Borzilleri, Kris A; Brown, Janice A; Calabrese, Matthew; Caspers, Nicole L; Cokorinos, Emily; Conn, Edward L; Dowling, Matthew S; Edmonds, David J; Eng, Heather; Fernando, Dilinie P; Frisbie, Richard; Hepworth, David; Landro, James; Mao, Yuxia; Rajamohan, Francis; Reyes, Allan R; Rose, Colin R; Ryder, Tim; Shavnya, Andre; Smith, Aaron C; Tu, Meihua; Wolford, Angela C; Xiao, Jun

    2016-09-01

    Adenosine monophosphate-activated protein kinase (AMPK) is a protein kinase involved in maintaining energy homeostasis within cells. On the basis of human genetic association data, AMPK activators were pursued for the treatment of diabetic nephropathy. Identification of an indazole amide high throughput screening (HTS) hit followed by truncation to its minimal pharmacophore provided an indazole acid lead compound. Optimization of the core and aryl appendage improved oral absorption and culminated in the identification of indole acid, PF-06409577 (7). Compound 7 was advanced to first-in-human trials for the treatment of diabetic nephropathy.

  10. Post-meal responses of elongation factor 2 (eEF2) and adenosine monophosphate-activated protein kinase (AMPK) to leucine and carbohydrate supplements for regulating protein synthesis duration and energy homeostasis in rat skeletal muscle.

    Science.gov (United States)

    Wilson, Gabriel J; Moulton, Christopher J; Garlick, Peter J; Anthony, Tracy G; Layman, Donald K

    2012-11-13

    Previous research demonstrates that the anabolic response of muscle protein synthesis (MPS) to a meal is regulated at the level of translation initiation with signals derived from leucine (Leu) and insulin to activate mTORC1 signaling. Recent evidence suggests that the duration of the meal response is limited by energy status of the cell and inhibition of translation elongation factor 2 (eEF2). This study evaluates the potential to extend the anabolic meal response with post-meal supplements of Leu or carbohydrates. Adult (~256 g) male Sprague-Dawley rats were food deprived for 12 h, then either euthanized before a standard meal (time 0) or at 90 or 180 min post-meal. At 135 min post-meal, rats received one of five oral supplements: 270 mg leucine (Leu270), 80:40:40 mg leucine, isoleucine, and valine (Leu80), 2.63 g carbohydrates (CHO2.6), 1 g carbohydrates (CHO1.0), or water (Sham control). Following the standard meal, MPS increased at 90 min then declined to pre-meal baseline at 180 min. Rats administered Leu270, Leu80, CHO2.6, or CHO1.0 maintained elevated rates of MPS at 180 min, while Sham controls declined from peak values. Leu80 and CHO1.0 treatments maintained MPS, but with values intermediate between Sham controls and Leu270 and CHO2.6 supplements. Consistent with MPS findings, the supplements maintained elongation activity and cellular energy status by preventing increases in AMP/ATP and phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), acetyl-CoA carboxylase ACC and eEF2. The impact of the supplements on MPS and cellular energy status was in proportion to the energy content within the individual treatments (i.e., Leu270 > Leu80; CHO2.6 > CHO1.0), but the Leu supplements produced a disproportionate anabolic stimulation of MPS, eEF2 and energy status with significantly lower energy content. In summary, the incongruity between MPS and translation initiation at 180 min reflects a block in translation elongation due to reduced

  11. Genistein suppresses tumor necrosis factor α-induced inflammation via modulating reactive oxygen species/Akt/nuclear factor ΚB and adenosine monophosphate-activated protein kinase signal pathways in human synoviocyte MH7A cells

    Directory of Open Access Journals (Sweden)

    Li J

    2014-03-01

    inhibit IL-1β, IL-6, and IL-8 production induced by TNF-α. In addition, we also found that pretreatment with the adenosine monophosphate-activated protein kinase (AMPK agonist 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside obviously inhibited TNF-α-induced proinflammatory cytokine production. These observations suggest that the inhibitory effect of genistein on TNF-α-induced proinflammatory cytokine production is dependent on AMPK activation. Conclusion: These findings indicate that genistein suppressed TNF-α-induced inflammation by inhibiting the ROS/Akt/NF-ΚB pathway and promoting AMPK activation in MH7A cells. Keywords: genistein, rheumatoid arthritis, cytokine, signal transduction, inflammation

  12. Overexpression of human selenoprotein H in neuronal cells enhances mitochondrial biogenesis and function through activation of protein kinase A, protein kinase B, and cyclic adenosine monophosphate response element-binding protein pathway.

    Science.gov (United States)

    Mehta, Suresh L; Mendelev, Natalia; Kumari, Santosh; Andy Li, P

    2013-03-01

    Mitochondrial biogenesis is activated by nuclear encoded transcription co-activator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), which is regulated by several upstream factors including protein kinase A and Akt/protein kinase B. We have previously shown that selenoprotein H enhances the levels of nuclear regulators for mitochondrial biogenesis, increases mitochondrial mass and improves mitochondrial respiratory rate, under physiological condition. Furthermore, overexpression of selenoprotein H protects neuronal HT22 cells from ultraviolet B irradiation-induced cell damage by lowering reactive oxygen species production, and inhibiting activation of caspase-3 and -9, as well as p53. The objective of this study is to identify the cell signaling pathways by which selenoprotein H initiates mitochondrial biogenesis. We first confirmed our previous observation that selenoprotein H transfected HT22 cells increased the protein levels of nuclear-encoded mitochondrial biogenesis factors, peroxisome proliferator-activated receptor γ coactivator-1α, nuclear respiratory factor 1 and mitochondrial transcription factor A. We then observed that total and phosphorylation of protein kinase A, Akt/protein kinase B and cyclic adenosine monophosphate response element-binding protein (CREB) were significantly increased in selenoprotein H transfected cells compared to vector transfected HT22 cells. To verify whether the observed stimulating effects on mitochondrial biogenesis pathways are caused by selenoprotein H and mediated through CREB, we knocked down selenoprotein H mRNA level using siRNA and inhibited CREB with napthol AS-E phosphate in selenoprotein H transfected cells and repeated the measurements of the aforementioned biomarkers. Our results revealed that silencing of selenoprotein H not only decreased the protein levels of PGC-1α, nuclear respiratory factor 1 and mitochondrial transcription factor A, but also decreased the total and

  13. Post-Meal Responses of Elongation Factor 2 (eEF2 and Adenosine Monophosphate-Activated Protein Kinase (AMPK to Leucine and Carbohydrate Supplements for Regulating Protein Synthesis Duration and Energy Homeostasis in Rat Skeletal Muscle

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    Donald K. Layman

    2012-11-01

    Full Text Available Previous research demonstrates that the anabolic response of muscle protein synthesis (MPS to a meal is regulated at the level of translation initiation with signals derived from leucine (Leu and insulin to activate mTORC1 signaling. Recent evidence suggests that the duration of the meal response is limited by energy status of the cell and inhibition of translation elongation factor 2 (eEF2. This study evaluates the potential to extend the anabolic meal response with post-meal supplements of Leu or carbohydrates. Adult (~256 g male Sprague-Dawley rats were food deprived for 12 h, then either euthanized before a standard meal (time 0 or at 90 or 180 min post-meal. At 135 min post-meal, rats received one of five oral supplements: 270 mg leucine (Leu270, 80:40:40 mg leucine, isoleucine, and valine (Leu80, 2.63 g carbohydrates (CHO2.6, 1 g carbohydrates (CHO1.0, or water (Sham control. Following the standard meal, MPS increased at 90 min then declined to pre-meal baseline at 180 min. Rats administered Leu270, Leu80, CHO2.6, or CHO1.0 maintained elevated rates of MPS at 180 min, while Sham controls declined from peak values. Leu80 and CHO1.0 treatments maintained MPS, but with values intermediate between Sham controls and Leu270 and CHO2.6 supplements. Consistent with MPS findings, the supplements maintained elongation activity and cellular energy status by preventing increases in AMP/ATP and phosphorylation of adenosine monophosphate-activated protein kinase (AMPK, acetyl-CoA carboxylase ACC and eEF2. The impact of the supplements on MPS and cellular energy status was in proportion to the energy content within the individual treatments (i.e., Leu270 > Leu80; CHO2.6 > CHO1.0, but the Leu supplements produced a disproportionate anabolic stimulation of MPS, eEF2 and energy status with significantly lower energy content. In summary, the incongruity between MPS and translation initiation at 180 min reflects a block in translation elongation due to

  14. Metformin inhibits nuclear factor-κB activation and inflammatory cytokines expression induced by high glucose via adenosine monophosphate-activated protein kinase activation in rat glomerular mesangial cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Gu Junfei; Ye Shandong; Wang Shan; Sun Wenjia; Hu Yuanyuan

    2014-01-01

    Background The renoprotective mechanisms of adenosine monophosphate (AMP)-activated protein kinase (AMPK) agonist-metformin have not been stated clearly.We hypothesized that metformin may ameliorate inflammation via AMPK interaction with critical inflammatory cytokines The aim of this study was to observe the effects of metformin on expression of nuclear factor-κB (NF-κB),monocyte chemoattractant protein-1 (MCP-1),intercellular adhesion molecule-1 (ICAM-1) and transforming growth factor-beta 1 (TGF-β1) induced by high glucose (HG) in cultured rat glomerular mesangial cells (MCs).Methods MCs were cultured in the medium with normal concentration glucose (group NG,5.6 mmol/L),high concentration glucose (group HG,25 mmol/L) and different concentrations of metformin (group M1,M2,M3).After 48-hour exposure,the supernatants and MCs were collected.The expression of NF-κB,MCP-1,ICAM-1,and TGF-β1 mRNA was analyzed by real time polymerase chain reaction.Westem blotting was used to detect the expression of AMPK,phospho-Thr-172 AMPK (p-AMPK),NF-κB p65,MCP-1,ICAM-1,and TGF-β1 protein.Results After stimulated by HG,the expression of NF-κB,MCP-1,ICAM-1,TGF-β1 mRNA and protein of MCs in group HG increased significantly compared with group NG (P <0.05).Both genes and protein expression of NF-κB,MCP-1,ICAM-1,TGF-β1 of MCs induced by high glucose were markedly reduced after metformin treatment in a dose-dependent manner (P <0.05).The expression of p-AMPK increased with the rising of metformin concentration,presenting the opposite trend,while the level of total-AMPK protein was unchanged with exposure to HG or metformin.Conlusion Metformin can suppress the expression of NF-κB,MCP-1,ICAM-1 and TGF-β1 of glomerular MCs induced by high glucose via AMPK activation,which may partlv contribute to its reno-protection.

  15. The Combined Inhibitory Effect of the Adenosine A1 and Cannabinoid CB1 Receptors on cAMP Accumulation in the Hippocampus Is Additive and Independent of A1 Receptor Desensitization

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    André Serpa

    2015-01-01

    Full Text Available Adenosine A1 and cannabinoid CB1 receptors are highly expressed in hippocampus where they trigger similar transduction pathways. We investigated how the combined acute activation of A1 and CB1 receptors modulates cAMP accumulation in rat hippocampal slices. The CB1 agonist WIN55212-2 (0.3–30 μM decreased forskolin-stimulated cAMP accumulation with an EC50 of 6.6 ± 2.7 μM and an Emax⁡ of 31% ± 2%, whereas for the A1 agonist, N6-cyclopentyladenosine (CPA, 10–150 nM, an EC50 of 35 ± 19 nM, and an Emax⁡ of 29% ± 5 were obtained. The combined inhibitory effect of WIN55212-2 (30 μM and CPA (100 nM on cAMP accumulation was 41% ± 6% (n=4, which did not differ (P>0.7 from the sum of the individual effects of each agonist (43% ± 8% but was different (P<0.05 from the effects of CPA or WIN55212-2 alone. Preincubation with CPA (100 nM for 95 min caused desensitization of adenosine A1 activity, which did not modify the effect of WIN55212-2 (30 μM on cAMP accumulation. In conclusion, the combined effect of CB1 and A1 receptors on cAMP formation is additive and CB1 receptor activity is not affected by short-term A1 receptor desensitization.

  16. Involvement of the second messenger cAMP in gravity-signal transduction in physarum

    Science.gov (United States)

    Block, I.; Rabien, H.; Ivanova, K.

    The aim of the investigation was to clarify, whether cellular signal processing following graviperception involves second messenger pathways. The test object was a most gravisensitive free-living ameboid cell, the myxomycete (acellular slime mold) Physarum polycephalum. It was demonstrated that the motor response is related to acceleration-dependent changes in the levels of the cellular second messenger cyclic adenosine monophosphate (cAMP). Rotating Physarum plasmodia in the gravity field of the Earth about a horizontal axis increased their cAMP concentration. Depriving the cells for a few days of the acceleration stimulus (near weightlessness in a space experiment on STS-69) slightly lowered plasmodial cAMP levels. Thus, the results provide first indications that the acceleration-stimulus signal transduction chain of Physarum uses an ubiquitous second messenger pathway.

  17. Genetics Home Reference: adenosine monophosphate deaminase deficiency

    Science.gov (United States)

    ... links) CLIMB: Children Living with Inherited Metabolic Diseases Muscular Dystrophy Association: Myoadenylate Deaminase Deficiency Genetic Testing Registry (1 link) Muscle AMP deaminase deficiency ...

  18. The Popeye Domain Containing Genes and cAMP Signaling

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    Thomas Brand

    2014-05-01

    Full Text Available 3'-5'-cyclic adenosine monophosphate (cAMP is a second messenger, which plays an important role in the heart. It is generated in response to activation of G-protein-coupled receptors (GPCRs. Initially, it was thought that protein kinase A (PKA exclusively mediates cAMP-induced cellular responses such as an increase in cardiac contractility, relaxation, and heart rate. With the identification of the exchange factor directly activated by cAMP (EPAC and hyperpolarizing cyclic nucleotide-gated (HCN channels as cAMP effector proteins it became clear that a protein network is involved in cAMP signaling. The Popeye domain containing (Popdc genes encode yet another family of cAMP-binding proteins, which are prominently expressed in the heart. Loss-of-function mutations in mice are associated with cardiac arrhythmia and impaired skeletal muscle regeneration. Interestingly, the cardiac phenotype, which is present in both, Popdc1 and Popdc2 null mutants, is characterized by a stress-induced sinus bradycardia, suggesting that Popdc proteins participate in cAMP signaling in the sinuatrial node. The identification of the two-pore channel TREK-1 and Caveolin 3 as Popdc-interacting proteins represents a first step into understanding the mechanisms of heart rate modulation triggered by Popdc proteins.

  19. Identification of a specific assembly of the G protein Golf as a critical and regulated module of dopamine and adenosine-activated cAMP pathways in the striatum

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    Denis eHervé

    2011-08-01

    Full Text Available In the principal neurons of striatum (medium spiny neurons, MSNs, cAMP pathway is primarily activated through the stimulation of dopamine D1 and adenosine A2A receptors, these receptors being mainly expressed in striatonigral and striatopallidal MSNs, respectively. Since cAMP signaling pathway could be altered in various physiological and pathological situations, including drug addiction and Parkinson’s disease, it is of crucial importance to identify the molecular components involved in the activation of this pathway. In MSNs, cAMP pathway activation is not dependent on the classical Gs GTP-binding protein but requires a specific G protein subunit heterotrimer containing Galpha-olf/beta2/gamma7 in particular association with adenylate cyclase type 5. This assembly forms an authentic functional signaling unit since loss of one of its members leads to defects of cAMP pathway activation in response to D1 or A2A receptor stimulation, inducing dramatic impairments of behavioral responses dependent on these receptors. Interestingly, D1 receptor-dependent cAMP signaling is modulated by the neuronal levels of Galpha-olf, indicating that Galpha-olf represents the rate-limiting step in this signaling cascade and could constitute a critical element for regulation of D1 receptor responses. In both Parkinsonian patients and several animal models of Parkinson’s disease, the lesion of dopamine neurons produces a prolonged elevation of Galpha-olf levels. This observation gives an explanation for the cAMP pathway hypersensitivity to D1 stimulation, occurring despite an unaltered D1 receptor density. In conclusion, alterations in the highly specialized assembly of Galpha-olf/beta2/gamma7 subunits can happen in pathological conditions, such as Parkinson’s disease, and it could have important functional consequences in relation to changes in D1 receptor signaling in the striatum.

  20. The combined inhibitory effect of the adenosine A1 and cannabinoid CB1 receptors on cAMP accumulation in the hippocampus is additive and independent of A1 receptor desensitization.

    Science.gov (United States)

    Serpa, André; Correia, Sara; Ribeiro, Joaquim A; Sebastião, Ana M; Cascalheira, José F

    2015-01-01

    Adenosine A1 and cannabinoid CB1 receptors are highly expressed in hippocampus where they trigger similar transduction pathways. We investigated how the combined acute activation of A1 and CB1 receptors modulates cAMP accumulation in rat hippocampal slices. The CB1 agonist WIN55212-2 (0.3-30 μM) decreased forskolin-stimulated cAMP accumulation with an EC50 of 6.6±2.7 μM and an Emax of 31%±2%, whereas for the A1 agonist, N6-cyclopentyladenosine (CPA, 10-150 nM), an EC50 of 35±19 nM, and an Emax of 29%±5 were obtained. The combined inhibitory effect of WIN55212-2 (30 μM) and CPA (100 nM) on cAMP accumulation was 41%±6% (n=4), which did not differ (P>0.7) from the sum of the individual effects of each agonist (43%±8%) but was different (PCB1 and A1 receptors on cAMP formation is additive and CB1 receptor activity is not affected by short-term A1 receptor desensitization.

  1. Genetically-encoded tools for cAMP probing and modulation in living systems.

    Directory of Open Access Journals (Sweden)

    Valeriy M Paramonov

    2015-09-01

    Full Text Available Intracellular 3'-5'-cyclic adenosine monophosphate (cAMP is one of the principal second messengers downstream of a manifold of signal transduction pathways, including the ones triggered by G protein-coupled receptors. Not surprisingly, biochemical assays for cAMP have been instrumental for basic research and drug discovery for decades, providing insights into cellular physiology and guiding pharmaceutical industry. However, despite impressive track record, the majority of conventional biochemical tools for cAMP probing share the same fundamental shortcoming - all the measurements require sample disruption for cAMP liberation. This common bottleneck, together with inherently low spatial resolution of measurements (as cAMP is typically analyzed in lysates of thousands of cells, underpin the ensuing limitations of the conventional cAMP assays: 1 genuine kinetic measurements of cAMP levels over time in a single given sample are unfeasible; 2 inability to obtain precise information on cAMP spatial distribution and transfer at subcellular levels, let alone the attempts to pinpoint dynamic interactions of cAMP and its effectors. At the same time, tremendous progress in synthetic biology over the recent years culminated in drastic refinement of our toolbox, allowing us not only to bypass the limitations of conventional assays, but to put intracellular cAMP life-span under tight control – something, that seemed scarcely attainable before. In this review article we discuss the main classes of modern genetically-encoded tools tailored for cAMP probing and modulation in living systems. We examine the capabilities and weaknesses of these different tools in the context of their operational characteristics and applicability to various experimental set-ups involving living cells, providing the guidance for rational selection of the best tools for particular needs.

  2. Eosinophil viability is increased by acidic pH in a cAMP- and GPR65-dependent manner.

    Science.gov (United States)

    Kottyan, Leah C; Collier, Ann R; Cao, Khanh H; Niese, Kathryn A; Hedgebeth, Megan; Radu, Caius G; Witte, Owen N; Khurana Hershey, Gurjit K; Rothenberg, Marc E; Zimmermann, Nives

    2009-09-24

    The microenvironment of the lung in asthma is acidic, yet the effect of acidity on inflammatory cells has not been well established. We now demonstrate that acidity inhibits eosinophil apoptosis and increases cellular viability in a dose-dependent manner between pH 7.5 and 6.0. Notably, acidity induced eosinophil cyclic adenosine 5'-monophosphate (cAMP) production and enhanced cellular viability in an adenylate cyclase-dependent manner. Furthermore, we identify G protein-coupled receptor 65 (GPR65) as the chief acid-sensing receptor expressed by eosinophils, as GPR65-deficient eosinophils were resistant to acid-induced eosinophil cAMP production and enhanced viability. Notably, GPR65(-/-) mice had attenuated airway eosinophilia and increased apoptosis in 2 distinct models of allergic airway disease. We conclude that eosinophil viability is increased in acidic microenvironments in a cAMP- and GPR65-dependent manner. PMID:19641187

  3. Eosinophil viability is increased by acidic pH in a cAMP- and GPR65-dependent manner

    OpenAIRE

    Kottyan, Leah C.; Collier, Ann R.; Cao, Khanh H.; Niese, Kathryn A; Hedgebeth, Megan; Radu, Caius G.; Owen N Witte; Gurjit K Khurana Hershey; Rothenberg, Marc E.; Zimmermann, Nives

    2009-01-01

    The microenvironment of the lung in asthma is acidic, yet the effect of acidity on inflammatory cells has not been well established. We now demonstrate that acidity inhibits eosinophil apoptosis and increases cellular viability in a dose-dependent manner between pH 7.5 and 6.0. Notably, acidity induced eosinophil cyclic adenosine 5′-monophosphate (cAMP) production and enhanced cellular viability in an adenylate cyclase–dependent manner. Furthermore, we identify G protein-coupled receptor 65 (...

  4. Regulative effect of corticotropin-releasing hormone on the concentration of cytoplasmic cyclic adenosine monophosphate and Ca2+in hypothalamic neuron%促肾上腺皮质激素释放激素对下丘脑神经元胞浆内环磷酸腺苷和Ca2+浓度的调节作用

    Institute of Scientific and Technical Information of China (English)

    张云东; 顾小红; 朱佩芳; 王正国; 赵继宗; 周继红; 许民辉; 邹咏文

    2006-01-01

    BACKGROUND: The activation of hypothalamus-pituitary-adrenal cortex axis may play key role in the increasing expression of hypothalamic corticotropin-re-leasing hormone (CRH) during stress reaction. However by what way to induce the CRH expression in hypothalamic neuron, and whether CRH can activate hypothalamic neurons are still not very clear.OBJECTIVE: To observe the changes of intracellular cyclic adenosine monophosphate (cAMP) and cytoplasmic Ca2+ concentration in the hypothalamic neurons cultured in vitro due to exogenous CRH stimulation.DESIGN: Comparative observation experiment.SETTING: Research Institute of Surgery, Daping Hospital, Third Military Medical University of Chinese PLA; Department of Neurosurgery , Tiantan Hospital, Capital University of Medical Sciences MATERIALS: This experiment was carried out in the Research Institute of Surgery, Daping Hospital, Third Military Medical University of Chinese PLA between December 1999 and March 2002. Hypothalamus was obtained from fetus rat at pregnancy of 17 days for the in vitro culture of hypothalamic neurons.METHODS: Hypothalamic neurons were co-cultured with exogenous CRH,with or without pretreatment with specific CRH 1 receptor antagonist -CP-154526. hypothalamic neurons were randomized into: ① CRH (10-12,10-10, 10-8, 10-6 mol/L) stimulation group. ② CP-154526(500 μmol/L)pretreatment aud CRH ( 10-12, 10-10, 10-8,10-6 mol/L) stimulation group. ③Hypothalamic neurons in corresponding normal control group were exposed to the isotonic saline stimulation. PTI fluorescence image system was used to determine and analyze the change of cytoplasmic free Ca2+ concentration in hypothalamic neurons due to exogenous CRH stimulation and RIA was used to detect the neuronal cAMP content.MAIN OUTCOME MEASURES: ①Cytoplasmic free Ca2+ concentration in hypothalamic neurons. ②cAMP content in hypothalamic neurons.RESULTS: The cytoplasmic free Ca2+ concentration and cAMP content were relatively lower in the

  5. Effect of cholera toxin on cAMP levels and Na/sup +/ influx in isolated intestinal epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Hyun, C.S.; Kimmich, G.A.

    1982-09-01

    Freshly isolated chicken intestinal cells contain approximately 20 pmol adenosine 3',5'-cyclic monophosphate (cAMP)/mg cellular protein. Incubation with 3 ..mu..g/ml cholera toxin (CT) at 37/sup 0/C induces an elevation of cellular cAMP beginning 10-15 min after initial exposure. The response is linear with time for 40-50 min and causes a six- to eightfold increase over control levels at steady state. Dibutyryl cAMP and agents that increase cAMP production inhibit Na/sup +/ influx into the isolated enterocytes. Chlorpromazine completely abolishes the toxin-induced elevation of cAMP in the isolated cells and also reverses the effect on Na/sup +/ entry. The data provide evidence for a cAMP-mediated control of intestinal cell Na/sup +/ uptake, which may represent the mechanistic basis for the antiabsorptive effect of CT on Na/sup +/ during induction of intestinal secretory activity. Studies on the time-dependent effects of chlorpromazine on both intracellular cAMP concentration and Na/sup +/ influx suggest that the reactivation of the Na/sup +/ transport system after cAMP-induced inhibition is slow relative to the disappearance of cAMP.

  6. Studies on the Correlation between Germination and cAMP Content of Different Color Chlamydospores in Ustiloginoidea virens

    Institute of Scientific and Technical Information of China (English)

    Xiaojuan LI; Erming LIU; Yuan LI; Zuohua REN; Lang YANG; Juanfang CHEN; Dandan HONG; Shuangqing LIU; Xinyu ZHOU; Minjie LIU

    2016-01-01

    Ustilaginoidea virens is the causal agent of a serious disease of rice. To reveal the relationship between germination and the 3'-5'-cyclic adenosine monophosphate (cAMP) content from the dormant (black or green-black) and non-dormant(yel ow) chlamydospore in Ustiloginoidea virens,this study adopts ultrasonic-bath method and high-performance liquid chromatography (HPLC) method, for extraction cAMP content of the different color chlamydospore. The results demonstrated that, as for the freshly chlamydospores col ected from the false smut bal s during their germination, cAMP content of yel ow chlamydospore ap-peared a slight growth during 0-12 h, and showed a rapid declining as the germination time extended (12-48 h) . Above al , in yel ow chlamydospores, the germination rate and the content of cAMP presented a very notably negative correlation (|r|=0.861 9>r0.01=0.834), but the correlation between germination rate and content of cAMP was not obvious in black chlamydospores. The germination rate and the content of cAMP presented a notably positive correlation under different storage period (0, 2, 4, 6, 8, 10 months) of the two color chlamydospores (the yel ow of chlamydospore: |r| = 0.785 1 > r0.05 = 0.707; the black of chlamy-dospore: |r| = 0.957 9 > r0.05 = 0.707).

  7. Hydrogen sulfide inhibits A2A adenosine receptor agonist induced β-amyloid production in SH-SY5Y neuroblastoma cells via a cAMP dependent pathway.

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    Bhushan Vijay Nagpure

    Full Text Available Alzheimer's disease (AD is the leading cause of senile dementia in today's society. Its debilitating symptoms are manifested by disturbances in many important brain functions, which are influenced by adenosine. Hence, adenosinergic system is considered as a potential therapeutic target in AD treatment. In the present study, we found that sodium hydrosulfide (NaHS, an H2S donor, 100 µM attenuated HENECA (a selective A2A receptor agonist, 10-200 nM induced β-amyloid (1-42 (Aβ42 production in SH-SY5Y cells. NaHS also interfered with HENECA-stimulated production and post-translational modification of amyloid precursor protein (APP by inhibiting its maturation. Measurement of the C-terminal APP fragments generated from its enzymatic cleavage by β-site amyloid precursor protein cleaving enzyme 1 (BACE1 showed that NaHS did not have any significant effect on β-secretase activity. However, the direct measurements of HENECA-elevated γ-secretase activity and mRNA expressions of presenilins suggested that the suppression of Aβ42 production in NaHS pretreated cells was mediated by inhibiting γ-secretase. NaHS induced reductions were accompanied by similar decreases in intracellular cAMP levels and phosphorylation of cAMP responsive element binding protein (CREB. NaHS significantly reduced the elevated cAMP and Aβ42 production caused by forskolin (an adenylyl cyclase, AC agonist alone or forskolin in combination with IBMX (a phosphodiesterase inhibitor, but had no effect on those caused by IBMX alone. Moreover, pretreatment with NaHS significantly attenuated HENECA-elevated AC activity and mRNA expressions of various AC isoforms. These data suggest that NaHS may preferentially suppress AC activity when it was stimulated. In conclusion, H2S attenuated HENECA induced Aβ42 production in SH-SY5Y neuroblastoma cells through inhibiting γ-secretase via a cAMP dependent pathway.

  8. Effects of papaverine and vasointestinal polypeptide on penile and vascular cAMP and cGMP in control and diabetic animals: an in vitro study.

    Science.gov (United States)

    Miller, M A; Morgan, R J; Thompson, C S; Mikhailidis, D P; Jeremy, J Y

    1995-06-01

    Adenosine 3'5'-cyclic monophosphate (cAMP) and guanosine 3'5'-cyclic monophosphate (cGMP) mediate penile erection. We have previously established that adenylate and guanylate cyclase activity is elevated in the diabetic rat penis and aorta. This study investigates the action of papaverine and vasoactive intestinal polypeptide (VIP) on these cyclases. The aortae and penes of Sprague Dawley rats (n = 7) were stimulated with VIP and papaverine. Diabetes mellitus (DM) was induced in Sprague Dawley rats (n = 7) with streptozotocin and the penile and aortic tissues were treated with VIP. The penes, aortae and carotid arteries of New Zealand White rabbits were similarly processed. cAMP and cGMP generation was measured by radioimmunoassay. In all tissues: VIP stimulated cAMP synthesis; VIP did not increase cGMP levels; papaverine was without effect on either cAMP or cGMP synthesis. VIP-stimulated cAMP was significantly enhanced in the diabetic rat penis and aorta; there was also a significant elevation in the basal levels of cGMP in these tissues. These data: (1) consolidate that cAMP is a mediator of penile erection, (2) indicate that papaverine and VIP elicit erection by different mechanisms, (3) suggest that an enhanced penile capacity to generate cAMP in DM may constitute an adaptive response to counteract the previously reported reduction in VIP content and VIP receptors, and (4) indicate that the penile and vascular tissues of the rabbit respond in a similar manner to VIP and papaverine. PMID:7496446

  9. CSF concentrations of cAMP and cGMP are lower in patients with Creutzfeldt-Jakob disease but not Parkinson's disease and amyotrophic lateral sclerosis.

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    Patrick Oeckl

    Full Text Available BACKGROUND: The cyclic nucleotides cyclic adenosine-3',5'-monophosphate (cAMP and cyclic guanosine-3',5'-monophosphate (cGMP are important second messengers and are potential biomarkers for Parkinson's disease (PD, amyotrophic lateral sclerosis (ALS and Creutzfeldt-Jakob disease (CJD. METHODOLOGY/PRINCIPAL FINDINGS: Here, we investigated by liquid chromatography/tandem mass spectrometry (LC-MS/MS the cerebrospinal fluid (CSF concentrations of cAMP and cGMP of 82 patients and evaluated their diagnostic potency as biomarkers. For comparison with a well-accepted biomarker, we measured tau concentrations in CSF of CJD and control patients. CJD patients (n = 15 had lower cAMP (-70% and cGMP (-55% concentrations in CSF compared with controls (n = 11. There was no difference in PD, PD dementia (PDD and ALS cases. Receiver operating characteristic (ROC curve analyses confirmed cAMP and cGMP as valuable diagnostic markers for CJD indicated by the area under the curve (AUC of 0.86 (cAMP and 0.85 (cGMP. We calculated a sensitivity of 100% and specificity of 64% for cAMP and a sensitivity of 67% and specificity of 100% for cGMP. The combination of both nucleotides increased the sensitivity to 80% and specificity to 91% for the term cAMPxcGMP (AUC 0.92 and to 93% and 100% for the ratio tau/cAMP (AUC 0.99. CONCLUSIONS/SIGNIFICANCE: We conclude that the CSF determination of cAMP and cGMP may easily be included in the diagnosis of CJD and could be helpful in monitoring disease progression as well as in therapy control.

  10. A Cistanches Herba Fraction/β-Sitosterol Causes a Redox-Sensitive Induction of Mitochondrial Uncoupling and Activation of Adenosine Monophosphate-Dependent Protein Kinase/Peroxisome Proliferator-Activated Receptor γ Coactivator-1 in C2C12 Myotubes: A Possible Mechanism Underlying the Weight Reduction Effect

    Directory of Open Access Journals (Sweden)

    Hoi Shan Wong

    2015-01-01

    Full Text Available Previous studies have demonstrated that HCF1, a semipurified fraction of Cistanches Herba, causes weight reduction in normal diet- and high fat diet-fed mice. The weight reduction was associated with the induction of mitochondrial uncoupling and changes in metabolic enzyme activities in mouse skeletal muscle. To further investigate the biochemical mechanism underlying the HCF1-induced weight reduction, the effect of HCF1 and its active component, β-sitosterol (BSS, on C2C12 myotubes was examined. Incubation with HCF1/BSS caused a transient increase in mitochondrial membrane potential (MMP, possibly by fluidizing the mitochondrial inner membrane. The increase in MMP was paralleled to an increase in mitochondrial reactive oxygen species (ROS production. Mitochondrial ROS, in turn, triggered a redox-sensitive induction of mitochondrial uncoupling by uncoupling protein 3 (UCP3. Biochemical analysis indicated that HCF1 was capable of activating an adenosine monophosphate-dependent protein kinase/peroxisome proliferator-activated receptor γ coactivator-1 pathway and thereby increased the expression of cytochrome c oxidase and UCP3. Animal studies using mitochondrial recoupler also confirmed the role of mitochondrial uncoupling in the HCF1-induced weight reduction. In conclusion, a HCF1/BSS causes the redox-sensitive induction of mitochondrial uncoupling and activation of AMPK/PGC-1 in C2C12 myotubes, with resultant reductions in body weight and adiposity by increased energy consumption.

  11. Proteomic signatures implicate cAMP in light and temperature responses in Arabidopsis thaliana

    KAUST Repository

    Thomas, Ludivine

    2013-05-01

    The second messenger 3\\'-5\\'-cyclic adenosine monophosphate (cAMP) and adenylyl cyclases (ACs), enzymes that catalyse the formation of cAMP from ATP, are increasingly recognized as important signaling molecules in a number of physiological responses in higher plants. Here we used proteomics to identify cAMP-dependent protein signatures in Arabidopsis thaliana and identify a number of differentially expressed proteins with a role in light- and temperature-dependent responses, notably photosystem II subunit P-1, plasma membrane associated cation-binding protein and chaperonin 60 β. Based on these proteomics results we conclude that, much like in cyanobacteria, algae and fungi, cAMP may have a role in light signaling and the regulation of photosynthesis as well as responses to temperature and we speculate that ACs could act as light and/or temperature sensors in higher plants. Biological significance: This current study is significant since it presents the first proteomic response to cAMP, a novel and key second messenger in plants. It will be relevant to researchers in plant physiology and in particular those with an interest in second messengers and their role in biotic and abiotic stress responses. © 2013 Elsevier B.V.

  12. Adenyl cyclases and cAMP in plant signaling - Past and present

    KAUST Repository

    Gehring, Christoph A

    2010-06-25

    In lower eukaryotes and animals 3\\'-5\\'-cyclic adenosine monophosphate (cAMP) and adenyl cyclases (ACs), enzymes that catalyse the formation of cAMP from ATP, have long been established as key components and second messengers in many signaling pathways. In contrast, in plants, both the presence and biological role of cAMP have been a matter of ongoing debate and some controversy. Here we shall focus firstly on the discovery of cellular cAMP in plants and evidence for a role of this second messenger in plant signal transduction. Secondly, we shall review current evidence of plant ACs, analyse aspects of their domain organisations and the biological roles of candidate molecules. In addition, we shall assess different approaches based on search motifs consisting of functionally assigned amino acids in the catalytic centre of annotated and/or experimentally tested nucleotide cyclases that can contribute to the identification of novel candidate molecules with AC activity such as F-box and TIR proteins. 2010 Gehring; licensee BioMed Central Ltd.

  13. Active site coupling in PDE:PKA complexes promotes resetting of mammalian cAMP signaling.

    Science.gov (United States)

    Krishnamurthy, Srinath; Moorthy, Balakrishnan Shenbaga; Xin Xiang, Lim; Xin Shan, Lim; Bharatham, Kavitha; Tulsian, Nikhil Kumar; Mihalek, Ivana; Anand, Ganesh S

    2014-09-16

    Cyclic 3'5' adenosine monophosphate (cAMP)-dependent-protein kinase (PKA) signaling is a fundamental regulatory pathway for mediating cellular responses to hormonal stimuli. The pathway is activated by high-affinity association of cAMP with the regulatory subunit of PKA and signal termination is achieved upon cAMP dissociation from PKA. Although steps in the activation phase are well understood, little is known on how signal termination/resetting occurs. Due to the high affinity of cAMP to PKA (KD ∼ low nM), bound cAMP does not readily dissociate from PKA, thus begging the question of how tightly bound cAMP is released from PKA to reset its signaling state to respond to subsequent stimuli. It has been recently shown that phosphodiesterases (PDEs) can catalyze dissociation of bound cAMP and thereby play an active role in cAMP signal desensitization/termination. This is achieved through direct interactions with the regulatory subunit of PKA, thereby facilitating cAMP dissociation and hydrolysis. In this study, we have mapped direct interactions between a specific cyclic nucleotide phosphodiesterase (PDE8A) and a PKA regulatory subunit (RIα isoform) in mammalian cAMP signaling, by a combination of amide hydrogen/deuterium exchange mass spectrometry, peptide array, and computational docking. The interaction interface of the PDE8A:RIα complex, probed by peptide array and hydrogen/deuterium exchange mass spectrometry, brings together regions spanning the phosphodiesterase active site and cAMP-binding sites of RIα. Computational docking combined with amide hydrogen/deuterium exchange mass spectrometry provided a model for parallel dissociation of bound cAMP from the two tandem cAMP-binding domains of RIα. Active site coupling suggests a role for substrate channeling in the PDE-dependent dissociation and hydrolysis of cAMP bound to PKA. This is the first instance, to our knowledge, of PDEs directly interacting with a cAMP-receptor protein in a mammalian system, and

  14. Changes in the Arabidopsis thaliana Proteome Implicate cAMP in Biotic and Abiotic Stress Responses and Changes in Energy Metabolism

    KAUST Repository

    Alqurashi, May

    2016-06-01

    The second messenger 3′,5′-cyclic adenosine monophosphate (cAMP) is increasingly recognized as having many different roles in plant responses to environmental stimuli. To gain further insights into these roles, Arabidopsis thaliana cell suspension culture was treated with 100 nM of cell permeant 8-bromo-cAMP for 5 or 10 min. Here, applying mass spectrometry and comparative proteomics, 20 proteins were identified as differentially expressed and we noted a specific bias in proteins with a role in abiotic stress, particularly cold and salinity, biotic stress as well as proteins with a role in glycolysis. These findings suggest that cAMP is sufficient to elicit specific stress responses that may in turn induce complex changes to cellular energy homeostasis.

  15. Selective induction of gene expression and second-messenger accumulation in Dictyostelium discoideum by the partial chemotactic antagonist 8-p-chlorophenylthioadenosine 3',5'-cyclic monophosphate

    NARCIS (Netherlands)

    Peters, Dorien J.M.; Bominaar, Anthony A.; Snaar-Jagalska, B. Ewa; Brandt, Raymond; Haastert, Peter J.M. van; Ceccarelli, Adriano; Williams, Jeffrey G.; Schaap, Pauline

    1991-01-01

    During development of the cellular slime mold Dictyostelium discoideum, cAMP induces chemotaxis and expression of different classes of genes by means of interaction with surface cAMP receptors. We describe a cAMP derivative, 8-p-chlorophenylthioadenosine 3',5'-cyclic monophosphate (8-CPT-cAMP), whic

  16. Biochemical characterization and cellular imaging of a novel, membrane permeable fluorescent cAMP analog

    Directory of Open Access Journals (Sweden)

    Zaccolo Manuela

    2008-06-01

    Full Text Available Abstract Background A novel fluorescent cAMP analog (8-[Pharos-575]- adenosine-3', 5'-cyclic monophosphate was characterized with respect to its spectral properties, its ability to bind to and activate three main isoenzymes of the cAMP-dependent protein kinase (PKA-Iα, PKA-IIα, PKA-IIβ in vitro, its stability towards phosphodiesterase and its ability to permeate into cultured eukaryotic cells using resonance energy transfer based indicators, and conventional fluorescence imaging. Results The Pharos fluorophore is characterized by a Stokes shift of 42 nm with an absorption maximum at 575 nm and the emission peaking at 617 nm. The quantum yield is 30%. Incubation of the compound to RIIα and RIIβ subunits increases the amplitude of excitation and absorption maxima significantly; no major change was observed with RIα. In vitro binding of the compound to RIα subunit and activation of the PKA-Iα holoenzyme was essentially equivalent to cAMP; RII subunits bound the fluorescent analog up to ten times less efficiently, resulting in about two times reduced apparent activation constants of the holoenzymes compared to cAMP. The cellular uptake of the fluorescent analog was investigated by cAMP indicators. It was estimated that about 7 μM of the fluorescent cAMP analog is available to the indicator after one hour of incubation and that about 600 μM of the compound had to be added to intact cells to half-maximally dissociate a PKA type IIα sensor. Conclusion The novel analog combines good membrane permeability- comparable to 8-Br-cAMP – with superior spectral properties of a modern, red-shifted fluorophore. GFP-tagged regulatory subunits of PKA and the analog co-localized. Furthermore, it is a potent, PDE-resistant activator of PKA-I and -II, suitable for in vitro applications and spatial distribution evaluations in living cells.

  17. Interaction between cAMP and intracellular Ca(2+)-signaling pathways during odor-perception and adaptation in Drosophila.

    Science.gov (United States)

    Murmu, Meena Sriti; Martin, Jean-René

    2016-09-01

    Binding of an odorant to olfactory receptors triggers cascades of second messenger systems in olfactory receptor neurons (ORNs). Biochemical studies indicate that the transduction mechanism at ORNs is mediated by cyclic adenosine monophosphate (cAMP) and/or inositol,1,4,5-triphosphate (InsP3)-signaling pathways in an odorant-dependent manner. However, the interaction between these two second messenger systems during olfactory perception or adaptation processes is much less understood. Here, we used interfering-RNAi to disrupt the level of cAMP alone or in combination with the InsP3-signaling pathway cellular targets, InsP3 receptor (InsP3R) or ryanodine receptor (RyR) in ORNs, and quantify at ORN axon terminals in the antennal lobe, the odor-induced Ca(2+)-response. In-vivo functional bioluminescence Ca(2+)-imaging indicates that a single 5s application of an odor increased Ca(2+)-transients at ORN axon terminals. However, compared to wild-type controls, the magnitude and duration of ORN Ca(2+)-response was significantly diminished in cAMP-defective flies. In a behavioral assay, perception of odorants was defective in flies with a disrupted cAMP level suggesting that the ability of flies to correctly detect an odor depends on cAMP. Simultaneous disruption of cAMP level and InsP3R or RyR further diminished the magnitude and duration of ORN response to odorants and affected the flies' ability to detect an odor. In conclusion, this study provides functional evidence that cAMP and InsP3-signaling pathways act in synergy to mediate odor processing within the ORN axon terminals, which is encoded in the magnitude and duration of ORN response. PMID:27212269

  18. [C-AMP concentration in various organs of female rats and in human ovaries with aging (author's transl)].

    Science.gov (United States)

    Arima, M

    1982-02-01

    The change in 3',5'-cyclic adenosine monophosphate (c-AMP) concentration was observed in various organs of rats in gonadal cycle in adult group and with aging (30, 70, 100, 120 weeks), and in human ovaries with aging. 1) The average c-AMP concentration of ovaries of rats showed a significant change with estrus cycle and was higher in the following sequence: proestrus, diestrus II, diestrus I and estrus phase. This tendency was also seen in hypothalamus and pituitary, but was not statistically significant, 2) The average c-AMP concentration in tissues began to decline significantly from 70 weeks in cerebral cortex and hypothalamus, and from 80 weeks in ovaries. However, on the other hand the concentrations in pituitary, liver and adrenal declined markedly from 100 weeks. 3) The c-AMP in ovaries of 80 weeks rats by pregnant mare serum (PMS) road increased by 0.5-fold in concentration, and by 0.6-fold in whole tissue relative to that of 30 weeks rats. 4) A significant difference in serum LH and FSH level between ovarian artery and vein was not found in cycling mature group, non-cycling climacteric group and post-menopausal group of women. 5) Both average concentrations and total values of c-AMP in ovaries of non-cycling climacteric and post-menopausal women were lower than those of mature cycling women. This fact may imply a different response by ovarian tissues such as corpus luteum, follicle and other tissues to gonadotropin. From these results of c-AMP in tissues, it is concluded that the decline of ovarian function with aging of rats was relatively earlier than pituitary, although being delayed compared with hypothalamus, and were the ovarian function in humans declined in the premenopausal period.

  19. [Isolation of inosine-5'-monophosphate from fish muscles].

    Science.gov (United States)

    Tugaĭ, V A; Akulin, V N; Epshteĭn, L M

    1987-01-01

    Conditions for transformation of tissue adenosine-5'-monophosphate (AMP) into inosine-5'-monophosphate (IMP) with the aid of endogenic AMP-aminohydrolase are developed resting on the studied properties of AMP-aminohydrolase (EC 3.5.4.6) from saltwater fish muscles (one of the enzymes participating in the nucleotide metabolism). Sorption of the nucleotide is performed on the activated charcoals A gamma-3 A gamma-5 which eluate IMP from acid solutions. It reduces the process of isolation, permits application of the acid wash solutions to remove salts; the alkaline ethyl alcohol-aid elution at the subsequent stages accelerates the process of nucleotide concentration by means of vacuum evaporation. The suggested approaches allow developing a simple method of IMP production from fish tissues which diminishes the cost of preparation.

  20. FimL regulates cAMP synthesis in Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Yuki F Inclan

    Full Text Available Pseudomonas aeruginosa, a ubiquitous bacteria found in diverse ecological niches, is an important cause of acute infections in immunocompromised individuals and chronic infections in patients with Cystic Fibrosis. One signaling molecule required for the coordinate regulation of virulence factors associated with acute infections is 3', 5'-cyclic adenosine monophosphate, (cAMP, which binds to and activates a catabolite repressor homolog, Vfr. Vfr controls the transcription of many virulence factors, including those associated with Type IV pili (TFP, the Type III secretion system (T3SS, the Type II secretion system, flagellar-mediated motility, and quorum sensing systems. We previously identified FimL, a protein with histidine phosphotransfer-like domains, as a regulator of Vfr-dependent processes, including TFP-dependent motility and T3SS function. In this study, we carried out genetic and physiologic studies to further define the mechanism of action of FimL. Through a genetic screen designed to identify suppressors of FimL, we found a putative cAMP-specific phosphodiesterase (CpdA, suggesting that FimL regulates cAMP levels. Inactivation of CpdA increases cAMP levels and restores TFP-dependent motility and T3SS function to fimL mutants, consistent with in vivo phosphodiesterase activity. By constructing combinations of double and triple mutants in the two adenylate cyclase genes (cyaA and cyaB, fimL, and cpdA, we show that ΔfimL mutants resemble ΔcyaB mutants in TM defects, decreased T3SS transcription, and decreased cAMP levels. Similar to some of the virulence factors that they regulate, we demonstrate that CyaB and FimL are polarly localized. These results reveal new complexities in the regulation of diverse virulence pathways associated with acute P. aeruginosa infections.

  1. 牙龈卟啉单胞菌合成环二腺苷酸的高效液相色谱-串联质谱法定性分析%Qualitative analysis of bis-(3’-5’)-cyclic dimeric adenosine monophosphate ofPorphyromonas gingivalis by high per-formance liquid chromatography coupled with mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    谭咏梅; 杨小军; 杜娟; 赵望泓; 陈晓丹; 侯晋

    2016-01-01

    目的:定性检测牙龈卟啉单胞菌(P. gingivalis)是否能产生细菌信号分子环二腺苷酸(c-di-AMP),为探索其在P. gingivalis生命代谢以及牙周炎免疫中的作用奠定基础。方法以P. gingivalis标准菌株ATCC33277为实验菌株,抽提细菌内核酸物质作为样品,配置c-di-AMP标准品,通过高效液相色谱-串联质谱法(HPLC-MS/MS)和高效液相色谱法(HPLC)对样品进行验证。结果 HPLC-MS/MS检出限按照信噪比(S/N)3∶1计算,c-di-AMP标准品出峰的保留时间为7.49 min,P. gingivalis提取物样品在保留时间为8.82 min时有目标峰出现(大于3 S/N)。HPLC检测结果表明,P. gingivalis核酸提取物样品及c-di-AMP标准品均在15.7 min处出现目标峰,且二者的紫外吸收光谱相同。结论牙龈卟啉单胞菌核酸提取物中含有c-di-AMP,牙龈卟啉单胞菌可以合成产生c-di-AMP。%Objective To test whether Porphyromonas gingivalis (P. gingivalis) could produce bacterial signal molecule, bis-(3’-5’)-cyclic dimeric adenosine monophosphate (c-di-AMP) and lay the foundation for explorations of its roles in life metabolism and periodontitis immunity of P. gingivalis. Methods P. gingivalis standard strain ATCC33277 was used as the experimental strain to extract nucleic acids from the bacteria. Then, c-di-AMP was detected using high performance liquid chromatography coupled with mass spectrometry (HPLC-MS/MS). Subsequently, HPLC was used to validate the sample further. Results Based on the signal/noise (S/N) for 3∶1, the limit of determination of HPLC-MS/MS for peak time of c-di-AMP standard substances was 7.49 min and nucleic acid extractions from P. gingivalis was 8.82 min (S/N>3). Further confirmation of HPLC showed that nucleic acid extractions from both P. gingivalis and c-di-AMP standard substances presented goal absorbent peaks at 15.7 min, with the same ultraviolet absorbent spectrum. Conclusion The nucleic

  2. Changes in ganglioside contents, plasma sialic acid and cAMP levels in experimental hepatoma in mice

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Abstract The present sutdy was designed to assess whether changes in glycolipids and cyclic AMP contents might serve as markers for the diagnosis of malignancy in the liver. The experimental model was a transplantable murine hepatoma. Experimental mice were divided into three groups:(1) a therapeutic group. which had been transplanted with hepatoma and treated with the antimetabolism drug 5-flurouracil(0.2mg/day i.p).(2) a control group, which had been transplanted with hepatoma and treated with 0.2ml 0.9% NaCl day and (3) a normal group of mice . The ganglioside and cAMP contents in the hepatoma tissue, plasma cAMP, total and lipid-bound sialic acid levels and red blood cell memebrane sialic acid levels were determined. Results showed that the ganglioside content, total and lipid-bound sialic acid levels in the control group were significantly higher than those in the livers of normal mice(P<0.01) while these respective values in the therapeutic group were significantly lower than those in the control group(P<0.01).The cAMP levels of tumor tissues and plasma in the control group were lower than those in normal mice. No significant difference in red blood cell membrane sialic acid content was observed between the therapeutic and control groups though levels for both were higher than those in normal mice. These results indicate that ganglioside ocntent and sialic acid levels in hepatoma tissues were significantly elevated, and cAMP levels in hepatoma tissues were significantly decreased during proliferation and abnormal differentiation. Key words transplantable hepatoma, gangliosides , sialic acid, cyclic adenosine mono-phosphate, 5-flurouracil 摘自Molecular and cellular biochemistry, 2000; Vol 207,29~33 该杂志摘要被美国科学引证索引(SCI)收录

  3. Role of dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein in neuronal signal transmission and integration%多巴胺和环磷酸腺苷调节的磷酸蛋白在神经元信号传递及整合中的地位

    Institute of Scientific and Technical Information of China (English)

    刘凤莲

    2005-01-01

    目的:阐明多巴胺和环磷酸腺苷调节的磷酸蛋白在神经元信号传递及整合中的中心作用,为神经系统疾病的治疗和功能恢复提供基础研究的假说理论.资料来源:应用计算机检索Medline数据库1980-01/2004-12的相关文献,检索词为"DARPP-32"和"role',限定文章语言种类为英文.同时计算机检索中国期刊全文数据库和万方数据库1980-01/2004-12的相关文献,检索词为"磷酸蛋白,作用",限定文章种类为中文.资料选择:对所选择的98篇资料进行初审,选取与目的有直接关系的文章,纳入标准:①随机对照试验.②专著中的章节.排除重复性研究和Meta分析.资料提炼:共收集到29篇关于多巴胺和环磷酸腺苷调节的磷酸蛋白的研究原著、综述和书籍文献.根据其相应的结果和讨论进行资料概括、综合和提炼.资料综合:①ARPP-32蛋白是脑内新纹状体等重要核团的神经元内存在的一种具有多方面信息调节与整合作用的蛋白质.②多巴胺、谷氨酸等神经递质与相应受体结合后,使多巴胺和环磷酸腺苷调节的磷酸蛋白的34-苏氨酸等磷酸化状态发生改变,继之影响磷酸酯酶Ⅰ、磷酸酯酶2B等重要磷酸酯酶的活性,从而使神经元内从各种途径获取的信息得以整合,神经元的生理功能及其控制的行为发生改变.③多巴胺和环磷酸腺苷调节的磷酸蛋白的功能与多种神经递质及其受体密切相关.④多巴胺和环磷酸腺苷调节的磷酸蛋白的功能可用基因敲除技术进行探究.结论:多巴胺和环磷酸腺苷调节的磷酸蛋白在复杂的神经元信号传递和整合过程中居于中心位置.对多巴胺和环磷酸腺苷调节的磷酸蛋白的研究也将为神经系统疾病如帕金森症、亨廷顿症、精神分裂症及吸毒成瘾等治疗和康复提供有效的依据和手段.%OBJECTIVE: To elucidate the central role of dopamine-and cyclic adenosine 3 ',5

  4. Dysregulation of hepatic cAMP levels via altered Pde4b expression plays a critical role in alcohol-induced steatosis.

    Science.gov (United States)

    Avila, Diana V; Barker, David F; Zhang, JingWen; McClain, Craig J; Barve, Shirish; Gobejishvili, Leila

    2016-09-01

    Alcohol-induced hepatic steatosis is a significant risk factor for progressive liver disease. Cyclic adenosine monophosphate (cAMP) signalling has been shown to significantly regulate lipid metabolism; however, the role of altered cAMP homeostasis in alcohol-mediated hepatic steatosis has never been studied. Our previous work demonstrated that increased expression of hepatic phosphodiesterase 4 (Pde4), which specifically hydrolyses and decreases cAMP levels, plays a pathogenic role in the development of liver inflammation/injury. The aim of this study was to examine the role of PDE4 in alcohol-induced hepatic steatosis. C57BL/6 wild-type and Pde4b knockout (Pde4b(-/-) ) mice were pair-fed control or ethanol liquid diets. One group of wild-type mice received rolipram, a PDE4-specific inhibitor, during alcohol feeding. We demonstrate for the first time that an early increase in PDE4 enzyme expression and a resultant decrease in hepatic cAMP levels are associated with the significant reduction in carnitine palmitoyltransferase 1A (Cpt1a) expression. Notably, alcohol-fed (AF) Pde4b(-/-) mice and AF wild-type mice treated with rolipram had significantly lower hepatic free fatty acid content compared with AF wild-type mice. Importantly, PDE4 inhibition in alcohol-fed mice prevented the decrease in hepatic Cpt1a expression via the Pparα/Sirt1/Pgc1α pathway. These results demonstrate that the alcohol- induced increase in hepatic Pde4, specifically Pde4b expression, and compromised cAMP signalling predispose the liver to impaired fatty acid oxidation and the development of steatosis. Moreover, these data also suggest that hepatic PDE4 may be a clinically relevant therapeutic target for the treatment of alcohol-induced hepatic steatosis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:27287961

  5. EXPERIMENTAL STUDY ON THE EFFECT OF ACUPUNCTURE ON TROPISM-DISTRIBUTION OF TETRAMETHYLPYRAZINE AND THE CONTENT OF cAMP IN ARTHRITIS RATS

    Institute of Scientific and Technical Information of China (English)

    GU Yu; CHEN Yi-guo

    2005-01-01

    Objective: To verify two hypotheses: 1) Acupuncture can increase the re-distribution of tetramethylpyrazine (ligustrazine) hydrochloride (TMPH) to the target organs in adjuvant arthritic rats. 2) Cyclic Adenosine-3', 5'-monophosphate (cAMP) is one of the guidance cues involved in this event. Methods: A total of 40 Wistar rats were randomized into blank control (BC), model (MO), medication (ME), Acupuncture (Acu) and Acu+ME groups, with 8 cases in each group. Arthritis model was established by subcutaneous injection of complete Freund's adjuvant (0.1 mL) into the rat's foot pad. Electroacupuncture (15 Hz, 0.2-0.3V) was applied to bilateral "Daling"(大陵PC 7), "Taichong" (太冲LR 3) and "Xiguan" (膝关LR 7) for 20 min, and the contents of TMPH in the heart, liver, kidney and the foot (affected focus) tissues and the contents of cAMP in the heart and liver tissues were determined with high performance liquid chromatography and radioimmunoassay techniques respectively. Results: Compared with medication group, the TMPH contents in the heart, liver, kidney and the affected foot tissues in Acu-ME group was obviously higher (P<0.05, P<0.01). In comparison with ME and Acu groups, the cAMP contents in the heart and liver in Acu+ME group was also significantly higher (P<0.05, P<0.01). No significant differences were found between ME and Acu+ME groups in TMPH content of kidney and between Acu+ME and BC groups in cAMP contents in both liver and heart tissues. Conclusion: Acupuncture may promote the target-tropism distribution of ligustrazine, and cAMP may play an important role in it.

  6. 2型糖尿病患者骨骼肌脂肪酸含量及腺苷酸活化蛋白激酶α表达和活性的变化%Expression and activity of adenosine monophosphate-activated protein kinase α and its effects on fatty acid metabolism in skeletal muscle in patients with type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    胡淑国; 苏冠明; 杨洋; 刘琼; 王丽慧; 高丽娟

    2015-01-01

    Objective To observe the expression and activity of adenosine monophosphate-activated protein kinaseα(AMPK⁃α) in skeletal muscle in type 2 diabetes mellitus(T2DM ), and investigate its role in lipid accumulation in skeletal muscle and insulin resistance. Methods A total of 20 cases with or without T2DM who received selective surgery in the Second Hospital of Shijiazhuang City between June 2013 and June 2014 were enrolled from department of orthopedics. These patients were divided into two groups:diabetic group(DM group, n=10) and non⁃diabetic group(NC group, n=10), 6 and 7 males and 4 and 3 females respectively, the mean age was (62±10) years and (63±9) years. Blood pressure was calculated and blood samples were drawn from an antecubial vein for measurement of plasma glucose, insulin, lipid and free fat acid(FFA). Insulin sensitivity index (ISI) was calculated. Skeletal muscle tissue was collected and analyzed en bloc for triglyceride, long⁃chain acyl⁃CoA esters(LCACoAs), AMPK⁃α1 and AMPK⁃α2 mRNA expression, as well as protein expression of AMPK⁃α1, AMPK⁃α2 and phosphorylated AMPK⁃α(p⁃AMPK⁃α). The data of the two groups were compared with t⁃test. Results The levels of blood glycated hemoglobin A1c, fasting plasma glucose(FPG), fasting insulin(FINS), triglyceride(TG), FFA were all significantly higher in DM group than those in NC group (t=4.96, 4.50, 2.28, 2.12, 2.15, all P DM group than that in NC group (-4.9±0.6 vs-3.7±0.5, t=-6.71, P<0.05). The triglyceride and LCACoAs in skeletal muscle were both higher in DM group than those in NC group((6.0±1.6)μmol/g vs (4.5±1.6)μmol/g, (3.1 ± 1.1 )μmol/g vs (2.1 ± 1.0)μmol/g, t=2.13, 2.11, both P<0.05). Compared with those in NC group, the expression of AMPK-α2 mRNA and protein levels of AMPK-α2 and P-AMPK-α in skeletal muscle decreased in DM group((0.89±0.21)×105 vs (1.23±0.19)×105, 0.69±0.09 vs 0.77±0.08, 0.48±0.09 vs 0.57± 0.10, t=-3.87,-2.29,-2.15, all P<0

  7. Effect of cAMP on short-circuit current in isolated human ciliary body

    Institute of Scientific and Technical Information of China (English)

    WU Ren-yi; MA Ning; HU Qian-qian

    2013-01-01

    Background Cyclic adenosine monophosphate (cAMP) could activate chloride channels in bovine ciliary body and trigger an increase in the ionic current (short-circuit current,Isc) across the ciliary processes in pigs.The purpose of this study was to investigate how cAMP modulates Isc in isolated human ciliary processes and the possible involvement of chloride transport across the tissue in cAMP-induced Isc change.Methods In an Ussing-type chamber system,the Isc changes induced by the cAMP analogue 8-bromo-cAMP and an adenylyl cyclase activator forskolin in isolated human ciliary processes were assessed.The involvement of Cl-component in the bath solution was investigated.The effect of Cl-channel (10 μmol/L niflumic acid and 1 mmol/L 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS)),K+ channel (10 mmol/L tetraethylammonium chloride (TEA)),or Na+ channel blockers (1 mmol/L amiloride) on 8-bromo-cAMP-induced Isc change was also studied.Results Dose-dependently,8-bromo-cAMP (10 nmol/L-30 μmol/L) or forskolin (10 nmol/L-3 μmol/L) increased Isc across the ciliary processes with an increase in negative potential difference on the non-pigmented epithelium (NPE) side of the tissue.Isc increase induced by 8-bromo-cAMP was more pronounced when the drug was applied on the NPE side than on the pigmented epithelium side.When the tissue was bathed in low Cl-solutions,the Isc increase was significantly inhibited.Finally,niflumic acid and DIDS,but not TEA or amiloride,significantly prevented the Isc increase induced by 8-bromo-cAMP.Conclusions cAMP stimulates stroma-to-aqueous anionic transport in isolated human ciliary processes.Chloride is likely to be among the ions,the transportation of which across the tissue is triggered by cAMP,suggesting the potential role of cAMP in the process of aqueous humor formation in human eyes.

  8. Reduced rate of adenosine triphosphate synthesis by in vivo 31P nuclear magnetic resonance spectroscopy and downregulation of PGC-1beta in distal skeletal muscle following burn.

    Science.gov (United States)

    Tzika, A Aria; Mintzopoulos, Dionyssios; Padfield, Katie; Wilhelmy, Julie; Mindrinos, Michael N; Yu, Hongue; Cao, Haihui; Zhang, Qunhao; Astrakas, Loukas G; Zhang, Jiangwen; Yu, Yong-Ming; Rahme, Laurence G; Tompkins, Ronald G

    2008-02-01

    Using a mouse model of burn trauma, we tested the hypothesis that severe burn trauma corresponding to 30% of total body surface area (TBSA) causes reduction in adenosine triphosphate (ATP) synthesis in distal skeletal muscle. We employed in vivo 31P nuclear magnetic resonance (NMR) in intact mice to assess the rate of ATP synthesis, and characterized the concomitant gene expression patterns in skeletal muscle in burned (30% TBSA) versus control mice. Our NMR results showed a significantly reduced rate of ATP synthesis and were complemented by genomic results showing downregulation of the ATP synthase mitochondrial F1 F0 complex and PGC-1beta gene expression. Our findings suggest that inflammation and muscle atrophy in burns are due to a reduced ATP synthesis rate that may be regulated upstream by PGC-1beta. These findings implicate mitochondrial dysfunction in distal skeletal muscle following burn injury. That PGC-1beta is a highly inducible factor in most tissues and responds to common calcium and cyclic adenosine monophosphate (cAMP) signaling pathways strongly suggests that it may be possible to develop drugs that can induce PGC-1beta.

  9. Adenosine and adenosine receptors: Newer therapeutic perspective

    Directory of Open Access Journals (Sweden)

    Manjunath S

    2009-01-01

    Full Text Available Adenosine, a purine nucleoside has been described as a ′retaliatory metabolite′ by virtue of its ability to function in an autocrine manner and to modify the activity of a range of cell types, following its extracellular accumulation during cell stress or injury. These effects are largely protective and are triggered by binding of adenosine to any of the four adenosine receptor subtypes namely A1, A2a, A2b, A3, which have been cloned in humans, and are expressed in most of the organs. Each is encoded by a separate gene and has different functions, although overlapping. For instance, both A1 and A2a receptors play a role in regulating myocardial oxygen consumption and coronary blood flow. It is a proven fact that adenosine plays pivotal role in different physiological functions, such as induction of sleep, neuroprotection and protection against oxidative stress. Until now adenosine was used for certain conditions like paroxysmal supraventricular tachycardia (PSVT and Wolff Parkinson White (WPW syndrome. Now there is a growing evidence that adenosine receptors could be promising therapeutic targets in a wide range of conditions including cardiac, pulmonary, immunological and inflammatory disorders. After more than three decades of research in medicinal chemistry, a number of selective agonists and antagonists of adenosine receptors have been discovered and some have been clinically evaluated, although none has yet received regulatory approval. So this review focuses mainly on the newer potential role of adenosine and its receptors in different clinical conditions.

  10. Lesbian camp: An unearthing.

    Science.gov (United States)

    Nielsen, Elly-Jean

    2016-01-01

    Camp-a sensibility, a style, and a form of artistic self-expression-is an elusive concept said to be in the eye of the beholder. To refute Susan Sontag's ( 1966 ) claims that camp is apolitical and not especially homosexual, a number of recent scholarly works have been geared toward revealing camp's fundamental gayness. With the odd footnote aside, lesbian camp has been collapsed into the category of gay male camp, if not eclipsed entirely. Despite the negligible efforts made to legitimize lesbian camp, there are numerous salient cultural examples one might draw on to illustrate, typify, and substantiate a lesbian camp sensibility. I lay the ground work for this scholarly exercise by outlining various definitions and critiques of camp, and by discussing its history and application to queer theory. Then, to unveil lesbian camp, three non-mutually exclusive categories are discussed: classic, erotic, and radical. By gathering various strands of inquiry, and various textual examples (e.g., photography, artistic performances, and literary tropes), this article attempts to reach a more inclusive and nuanced understanding of lesbian camp. PMID:26701773

  11. Suppression of adenosine-activated chloride transport by ethanol in airway epithelia.

    Directory of Open Access Journals (Sweden)

    Sammeta V Raju

    Full Text Available Alcohol abuse is associated with increased lung infections. Molecular understanding of the underlying mechanisms is not complete. Airway epithelial ion transport regulates the homeostasis of airway surface liquid, essential for airway mucosal immunity and lung host defense. Here, air-liquid interface cultures of Calu-3 epithelial cells were basolaterally exposed to physiologically relevant concentrations of ethanol (0, 25, 50 and 100 mM for 24 hours and adenosine-stimulated ion transport was measured by Ussing chamber. The ethanol exposure reduced the epithelial short-circuit currents (I(SC in a dose-dependent manner. The ion currents activated by adenosine were chloride conductance mediated by cystic fibrosis transmembrane conductance regulator (CFTR, a cAMP-activated chloride channel. Alloxazine, a specific inhibitor for A(2B adenosine receptor (A(2BAR, largely abolished the adenosine-stimulated chloride transport, suggesting that A(2BAR is a major receptor responsible for regulating the chloride transport of the cells. Ethanol significantly reduced intracellular cAMP production upon adenosine stimulation. Moreover, ethanol-suppression of the chloride secretion was able to be restored by cAMP analogs or by inhibitors to block cAMP degradation. These results imply that ethanol exposure dysregulates CFTR-mediated chloride transport in airways by suppression of adenosine-A(2BAR-cAMP signaling pathway, which might contribute to alcohol-associated lung infections.

  12. Adenosine Receptors and Asthma

    OpenAIRE

    Wilson, Constance N; Nadeem, Ahmed; Spina, Domenico; Brown, Rachel; Page, Clive P.; Jamal Mustafa, S.

    2009-01-01

    The pathophysiological processes underlying respiratory diseases like asthma are complex, resulting in an overwhelming choice of potential targets for the novel treatment of this disease. Despite this complexity, asthmatic subjects are uniquely sensitive to a range of substances like adenosine, thought to act indirectly to evoke changes in respiratory mechanics and in the underlying pathology, and thereby to offer novel insights into the pathophysiology of this disease. Adenosine is of partic...

  13. Recreation Summer Camps 2016

    Data.gov (United States)

    Montgomery County of Maryland — List of all Camps (Register here:https://apm.activecommunities.com/montgomerycounty/Home) to include Aquatics, Basketball, Soccer, Special Interest, General Sports,...

  14. Registration Summer Camp 2016

    CERN Multimedia

    2016-01-01

    Reminder: registration for the CERN Staff Association Summer Camp is now open for children from 4 to 6 years old.   More information on the website: http://nurseryschool.web.cern.ch/. The summer camp is open to all children. The proposed cost is 480.-CHF/week, lunch included. The camp will be open weeks 27, 28, 29 and 30, from 8:30 a.m. to 5:30 p.m. For further questions, you are welcome to contact us by email at Summer.Camp@cern.ch. CERN Staff Association

  15. Dibutyryl c-AMP as an inducer of sporidia formation: Biochemical and antigenic changes during morphological differentiation of Karnal bunt (Tilletia indica) pathogen in axenic culture

    Indian Academy of Sciences (India)

    Anil Kumar; Kaushlendra Tripathi; Manish Rana; Shalini Purwar; G K Garg

    2004-03-01

    Effect of dibutyryl adenosine 3′,5′-cyclic monophosphate (dbc-AMP), an analogue of c-AMP, was investigated on growth and morphological differentiation of Tilletia indica. Exponential growth was observed up to 21 days in both presence and absence of dbc-AMP; however, increasing concentration of dbc-AMP was deleterious to mycelial growth in liquid culture. A slow increase of mycelial biomass up to 21 days and decline at 30 days in the presence of 2.5 mM dbc-AMP was observed, therefore, this concentration was chosen in subsequent investigations. The inhibitory influence of dbc-AMP was further substantiated by decrease in soluble protein. The fungus on exposure to dbc-AMP experienced morphological differentiation from vegetative mycelial phase to sporogenous mycelial phase, and was induced to produce filiform sporidia. Use of quantitative ELISA further suggested that sporidia formation took more than 21 days in the presence of dbc-AMP. Variations of proteins during different stages of T. indica grown in the presence and absence of dbc-AMP suggested the expression of stage-specific proteins or differential expression of proteins induced by dbc-AMP. The changes in expression of cell surface antigens as evidenced from decrease and increase binding of anti-mycelial and anti-sporidial anti-bodies in dbc-AMP treated culture by ELISA was further interpreted on the basis of morphological differentiation from mycelial to sporidial phase.

  16. Adenosine stimulates DNA fragmentation in human thymocytes by Ca(2+)-mediated mechanisms.

    Science.gov (United States)

    Szondy, Z

    1994-12-15

    Incubation of human thymocytes with an optimum concentration of adenosine and its receptor site agonist, 2-chloroadenosine, induced increases in intracellular cyclic AMP (cAMP) (from a resting 0.6 +/- 0.1 to 4.1 +/- 0.2 pmol/10(7) cells within 5 min) and Ca2+ (from the resting 85 +/- 7 nM to a peak of 210 +/- 25 nM) levels and resulted in internucleosomal DNA fragmentation and cell death (apoptosis). Other adenosine analogues were also effective at inducing DNA fragmentation, the order of potency being 2-p-(carboxyethylphenylethylamino)-5'-carboxyamidoadenosine 13399-13402], at 60 ng/ml concentration also prevented adenosine-induced DNA fragmentation when added prior to adenosine. This suggested a complex cross-talk between the adenosine-triggered signal transduction cascade and the activation state of protein kinase C in regulating apoptosis of human thymocytes. PMID:7818494

  17. Camp's "Disneyland" Effect.

    Science.gov (United States)

    Renville, Gary

    1999-01-01

    Describes the positive mental, physical, and social growth impacts that the camping experience had on the author, and urges camp program evaluation to plan and implement such changes. Sidebar lists steps of effective evaluation: program goals and objectives, goals of evaluation, implementation of evaluation, data analysis, and findings and…

  18. VisionCamp

    DEFF Research Database (Denmark)

    Lassen, Astrid Heidemann; Løwe Nielsen, Suna

    2009-01-01

    . Baseret på forløbet VisionCamp 2008, der satte eksplicit fokus på at kombinere fagfeltet "supply chain management" og kreativitet, illustrerer artiklen camp-metodens relevans og peger på centrale del-elementer i entreprenante kompetencer (kreative kompetencer, teknisk/faglige kompetencer og relationelle...

  19. Overexpression, purification and crystallographic analysis of a unique adenosine kinase from Mycobacterium tuberculosis

    International Nuclear Information System (INIS)

    Adenosine kinase from M. tuberculosis has been overexpressed, purified and crystallized in the presence of adenosine. Structure determination using molecular replacement with diffraction data collected at 2.2 Å reveals a dimeric structure. Adenosine kinase from Mycobacterium tuberculosis is the only prokaryotic adenosine kinase that has been isolated and characterized. The enzyme catalyzes the phosphorylation of adenosine to adenosine monophosphate and is involved in the activation of 2-methyladenosine, a compound that has demonstrated selective activity against M. tuberculosis. The mechanism of action of 2-methyladenosine is likely to be different from those of current tuberculosis treatments and this compound (or other adenosine analogs) may prove to be a novel therapeutic intervention for this disease. The M. tuberculosis adenosine kinase was overexpressed in Escherichia coli and the enzyme was purified with activity comparable to that reported previously. The protein was crystallized in the presence of adenosine using the vapour-diffusion method. The crystals diffracted X-rays to high resolution and a complete data set was collected to 2.2 Å using synchrotron radiation. The crystal belonged to space group P3121, with unit-cell parameters a = 70.2, c = 111.6 Å, and contained a single protein molecule in the asymmetric unit. An initial structural model of the protein was obtained by the molecular-replacement method, which revealed a dimeric structure. The monomers of the dimer were related by twofold crystallographic symmetry. An understanding of how the M. tuberculosis adenosine kinase differs from the human homolog should aid in the design of more potent and selective antimycobacterial agents that are selectively activated by this enzyme

  20. Adenosine and sleep

    International Nuclear Information System (INIS)

    Behavioral and biochemical approaches have been used to determine the relative contribution of endogenous adenosine and adenosine receptors to the sleep-wake cycle in the rat. Adenosine concentrations in specific areas of the rat brain were not affected by 24 hours of total sleep deprivation, or by 24 or 48 hours of REM sleep deprivation. In order to assess the effect of REM sleep deprivation on adenosine A1 receptors, 3H-L-PIA binding was measured. The Bmax values for 3H-L-PIA binding to membrane preparations of the cortices and corpus striata from 48 hour REM sleep-deprived animals were increased 14.8% and 23%, respectively. These increases were not maintained following the cessation of sleep deprivation and recovered within 2 hours. The results of a 96 hour REM deprivation experiment were similar to those of the 48 hour REM sleep deprivation experiment. However, these increases were not evident in similar structures taken from stress control animals, and conclusively demonstrated that the changes in 3H-L-PIA binding resulted from REM sleep deprivation and not from stress

  1. Adenosine and sleep

    Energy Technology Data Exchange (ETDEWEB)

    Yanik, G.M. Jr.

    1987-01-01

    Behavioral and biochemical approaches have been used to determine the relative contribution of endogenous adenosine and adenosine receptors to the sleep-wake cycle in the rat. Adenosine concentrations in specific areas of the rat brain were not affected by 24 hours of total sleep deprivation, or by 24 or 48 hours of REM sleep deprivation. In order to assess the effect of REM sleep deprivation on adenosine A/sub 1/ receptors, /sup 3/H-L-PIA binding was measured. The Bmax values for /sup 3/H-L-PIA binding to membrane preparations of the cortices and corpus striata from 48 hour REM sleep-deprived animals were increased 14.8% and 23%, respectively. These increases were not maintained following the cessation of sleep deprivation and recovered within 2 hours. The results of a 96 hour REM deprivation experiment were similar to those of the 48 hour REM sleep deprivation experiment. However, these increases were not evident in similar structures taken from stress control animals, and conclusively demonstrated that the changes in /sup 3/H-L-PIA binding resulted from REM sleep deprivation and not from stress.

  2. Defective insulin response of cyclic adenosine monophosphate-dependent protein kinase in insulin-resistant humans.

    OpenAIRE

    Kida, Y; Nyomba, B L; Bogardus, C; Mott, D M

    1991-01-01

    Insulin-stimulated glycogen synthase activity in human muscle correlates with insulin-mediated glucose disposal and is reduced in insulin-resistant subjects. Inhibition of the cyclic AMP-dependent protein kinase (A-kinase) is considered as a possible mechanism of insulin action for glycogen synthase activation. In this study, we investigated the time course of insulin action on human muscle A-kinase activity during a 2-h insulin infusion in 13 insulin-sensitive (group S) and 7 insulin-resista...

  3. Hitler's Death Camps.

    Science.gov (United States)

    Wieser, Paul

    1995-01-01

    Presents a high school lesson on Hitler's death camps and the widespread policy of brutality and oppression against European Jews. Includes student objectives, instructional procedures, and a chart listing the value of used clothing taken from the Jews. (CFR)

  4. CDC Disease Detective Camp

    Centers for Disease Control (CDC) Podcasts

    2010-08-02

    The CDC Disease Detective Camp gives rising high school juniors and seniors exposure to key aspects of the CDC, including basic epidemiology, infectious and chronic disease tracking, public health law, and outbreak investigations. The camp also helps students explore careers in public health.  Created: 8/2/2010 by Centers for Disease Control and Prevention (CDC).   Date Released: 8/2/2010.

  5. Hypoxanthine-guanine phosphoribosyltransferase and inosine 5’-monophosphate dehydrogenase activities in three mammalian species: aquatic (Mirounga angustirostris, semiaquatic (Lontra longicaudis annectens and terrestrial (Sus scrofa

    Directory of Open Access Journals (Sweden)

    Myrna eBarjau Perez-Milicua

    2015-07-01

    Full Text Available Aquatic and semiaquatic mammals have the capacity of breath hold (apnea diving. Northern elephant seals (Mirounga angustirostris have the ability to perform deep and long duration dives; during a routine dive, adults can hold their breath for 25 min. Neotropical river otters (Lontra longicaudis annectens can hold their breath for about 30 sec. Such periods of apnea may result in reduced oxygen concentration (hypoxia and reduced blood supply (ischemia to tissues. Production of adenosine 5’-triphosphate (ATP requires oxygen, and most mammalian species, like the domestic pig (Sus scrofa, are not adapted to tolerate hypoxia and ischemia, conditions that result in ATP degradation. The objective of this study was to explore the differences in purine synthesis and recycling in erythrocytes and plasma of three mammalian species adapted to different environments: aquatic (northern elephant seal (n=11, semiaquatic (neotropical river otter (n=4 and terrestrial (domestic pig (n=11. Enzymatic activity of hypoxanthine-guanine phosphoribosyltransferase (HGPRT was determined by spectrophotometry, and activity of inosine 5’-monophosphate dehydrogenase (IMPDH and the concentration of hypoxanthine (HX, inosine 5’-monophosphate (IMP, adenosine 5’-monophosphate (AMP, adenosine 5’-diphosphate (ADP, ATP, guanosine 5’-diphosphate (GDP, guanosine 5’-triphosphate (GTP, and xanthosine 5’-monophosphate (XMP were determined by high-performance liquid chromatography (HPLC. The activities of HGPRT and IMPDH and the concentration of HX, IMP, AMP, ADP, ATP, GTP and XMP in erythrocytes of domestic pigs were higher than in erythrocytes of northern elephant seals and river otters. These results suggest that under basal conditions (no diving, sleep apnea or exercise, aquatic and semiaquatic mammals have less purine mobilization than their terrestrial counterparts.

  6. Involvement of adenosine A2a receptor in intraocular pressure decrease induced by 2-(1-octyn-1-yl)adenosine or 2-(6-cyano-1-hexyn-1-yl)adenosine.

    Science.gov (United States)

    Konno, Takashi; Murakami, Akira; Uchibori, Takehiro; Nagai, Akihiko; Kogi, Kentaro; Nakahata, Norimichi

    2005-04-01

    The aim of the present study is to clarify the mechanism for the decrease in intraocular pressure by 2-alkynyladenosine derivatives in rabbits. The receptor binding analysis revealed that 2-(1-octyn-1-yl)adenosine (2-O-Ado) and 2-(6-cyano-1-hexyn-1-yl)adenosine (2-CN-Ado) selectively bound to the A(2a) receptor with a high affinity. Ocular hypotensive responses to 2-O-Ado and 2-CN-Ado were inhibited by the adenosine A(2a)-receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (CSC), but not by the adenosine A(1)-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) or the adenosine A(2b)-receptor antagonist alloxazine. In addition, 2-O-Ado and 2-CN-Ado caused an increase in outflow facility, which was inhibited by CSC, but not by DPCPX or alloxazine. Moreover, 2-O-Ado and 2-CN-Ado increased cAMP in the aqueous humor, and the 2-O-Ado-induced an increase in cAMP was inhibited by CSC. These results suggest that 2-O-Ado and 2-CN-Ado reduced intraocular pressure via an increase in outflow facility. The ocular hypotension may be mainly mediated through the activation of adenosine A(2a) receptor, although a possible involvement of adenosine A(1) receptor cannot be completely ruled out. 2-O-Ado and 2-CN-Ado are useful lead compounds for the treatment of glaucoma.

  7. Involvement of adenosine A2a receptor in intraocular pressure decrease induced by 2-(1-octyn-1-yl)adenosine or 2-(6-cyano-1-hexyn-1-yl)adenosine.

    Science.gov (United States)

    Konno, Takashi; Murakami, Akira; Uchibori, Takehiro; Nagai, Akihiko; Kogi, Kentaro; Nakahata, Norimichi

    2005-04-01

    The aim of the present study is to clarify the mechanism for the decrease in intraocular pressure by 2-alkynyladenosine derivatives in rabbits. The receptor binding analysis revealed that 2-(1-octyn-1-yl)adenosine (2-O-Ado) and 2-(6-cyano-1-hexyn-1-yl)adenosine (2-CN-Ado) selectively bound to the A(2a) receptor with a high affinity. Ocular hypotensive responses to 2-O-Ado and 2-CN-Ado were inhibited by the adenosine A(2a)-receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (CSC), but not by the adenosine A(1)-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) or the adenosine A(2b)-receptor antagonist alloxazine. In addition, 2-O-Ado and 2-CN-Ado caused an increase in outflow facility, which was inhibited by CSC, but not by DPCPX or alloxazine. Moreover, 2-O-Ado and 2-CN-Ado increased cAMP in the aqueous humor, and the 2-O-Ado-induced an increase in cAMP was inhibited by CSC. These results suggest that 2-O-Ado and 2-CN-Ado reduced intraocular pressure via an increase in outflow facility. The ocular hypotension may be mainly mediated through the activation of adenosine A(2a) receptor, although a possible involvement of adenosine A(1) receptor cannot be completely ruled out. 2-O-Ado and 2-CN-Ado are useful lead compounds for the treatment of glaucoma. PMID:15821340

  8. Adenosine and Sleep

    OpenAIRE

    Bjorness, Theresa E.; Greene, Robert W.

    2009-01-01

    Over the last several decades the idea that adenosine (Ado) plays a role in sleep control was postulated due in large part to pharmacological studies that showed the ability of Ado agonists to induce sleep and Ado antagonists to decrease sleep. A second wave of research involving in vitro cellular analytic approaches and subsequently, the use of neurochemical tools such as microdialysis, identified a population of cells within the brainstem and basal forebrain arousal centers, with activity t...

  9. The adenosine metabolite inosine is a functional agonist of the adenosine A2A receptor with a unique signaling bias.

    Science.gov (United States)

    Welihinda, Ajith A; Kaur, Manmeet; Greene, Kelly; Zhai, Yongjiao; Amento, Edward P

    2016-06-01

    Inosine is an endogenous purine nucleoside that is produced by catabolism of adenosine. Adenosine has a short half-life (approximately 10s) and is rapidly deaminated to inosine, a stable metabolite with a half-life of approximately 15h. Resembling adenosine, inosine acting through adenosine receptors (ARs) exerts a wide range of anti-inflammatory and immunomodulatory effects in vivo. The immunomodulatory effects of inosine in vivo, at least in part, are mediated via the adenosine A2A receptor (A2AR), an observation that cannot be explained fully by in vitro pharmacological characterization of inosine at the A2AR. It is unclear whether the in vivo effects of inosine are due to inosine or a metabolite of inosine engaging the A2AR. Here, utilizing a combination of label-free, cell-based, and membrane-based functional assays in conjunction with an equilibrium agonist-binding assay we provide evidence for inosine engagement at the A2AR and subsequent activation of downstream signaling events. Inosine-mediated A2AR activation leads to cAMP production with an EC50 of 300.7μM and to extracellular signal-regulated kinase-1 and -2 (ERK1/2) phosphorylation with an EC50 of 89.38μM. Our data demonstrate that inosine produces ERK1/2-biased signaling whereas adenosine produces cAMP-biased signaling at the A2AR, highlighting pharmacological differences between these two agonists. Given the in vivo stability of inosine, our data suggest an additional, previously unrecognized, mechanism that utilizes inosine to functionally amplify and prolong A2AR activation in vivo. PMID:26903141

  10. Rehabilitating camp cities : community driven planning for urbanised refugee camps

    OpenAIRE

    Misselwitz, Philipp

    2009-01-01

    Focussing on Palestine refugee camps in the Near East, this dissertation aims to shed light on the potential relevance of urban planning to refugee camp environments worldwide. In particular, there is a focus on the role architects and urban planners can play in facilitating participatory planning processes as well as providing guidance and expertise in the development of a spatial vision for Camp Cities. Part I - The Urbanisation of Refugee Camps as a Global Challenge The first part o...

  11. The camp model for entrepreneurship teaching

    DEFF Research Database (Denmark)

    Bager, Torben

    2011-01-01

    Artiklen omhandler brugen af camps i entrepreneurship undervising - illustreret med danske camp eksempler Udgivelsesdato: online 31.03.2010......Artiklen omhandler brugen af camps i entrepreneurship undervising - illustreret med danske camp eksempler Udgivelsesdato: online 31.03.2010...

  12. Effect of activating γ-aminobutyric acid B receptors on the expression of phosphorylated cyclic adenosine monophosphate response element binding protein and N-methyl-D-aspartate receptor subunit 2B in the spinal dorsal horn in rats with diabetic neuropathic pain%激活γ-氨基丁酸B型受体对糖尿病神经痛大鼠脊髓背角磷酸化环磷酸腺苷反应元件结合蛋白和N-甲基-D-天冬氨酸受体2B亚基表达的影响

    Institute of Scientific and Technical Information of China (English)

    刘朋; 郭闻亚; 赵晓南; 吕艳霞; 魏淑明; 王秀丽

    2013-01-01

    目的 利用γ-氨基丁酸B型受体(GABAR)受体激动剂(巴氯芬)和拮抗剂(CGP55845),探讨激活GABAB受体对糖尿病神经痛大鼠脊髓背角磷酸化环磷酸腺苷反应元件结合蛋白(p-CREB)和N-甲基-D-天冬氨酸受体2B亚基(NMDA-2B、NR2B)表达的影响.方法 62只SD雄性大鼠随机分为两组:正常对照组(C组)和糖尿病神经痛模型组(D组),腹腔分别注射生理盐水或链脲佐菌素(STZ,60 mg/kg).50只大鼠腹腔注射STZ,4周后36只大鼠成功制备成糖尿病神经痛(DNP)模型并鞘内置管,根据鞘内给药(共20μ1)随机分为3组(n=12):DNP对照组(D1组):生理盐水10 μl+生理盐水10μ;巴氯芬组(D2组):生理盐水10 μ1+巴氯芬0.5μg;CGP55845+巴氯芬组(D3组):CGP55845 10 μg+巴氯芬0.5 μg;12只同周龄正常大鼠腹腔注射生理盐水并鞘内置管作为C组,鞘内注射生理盐水10μl+生理盐水10μl.4组大鼠两次鞘内注射间隔15 min,连续4d,每天鞘内注射前、后30 min测定大鼠50%机械缩足阈值(PWT),各时点分别为:T1、T2、T3、T4,最后1次测完后取大鼠脊髓背角,采用分子生物学方法测定p-CREB、环磷酸腺苷反应元件结合蛋白(CREB)和NR2B受体表达变化.结果 与C组比较,D1、D3两组大鼠T1-T4各时点PWT明显降低(P<0.05),p-CREB和NR2B蛋白表达及NR2B mRNA表达明显增多(P<0.05);与D1组比较,D2组大鼠各时点PWT显著升高(P<0.05);与D1组p-CREB(0.76 ±0.13)、NR2B(1.28 ±0.14)蛋白表达、NR2B mRNA表达(0.83±0.10)比较,D2组p-CREB (0.45±0.08)和NR2B(0.88 0.13)蛋白表达及NR2B mRNA表达(0.53±0.08)显著降低(P<0.05).4组间比较,CREB蛋白表达差异无统计学意义(P>0.05).结论 激活GABAB受体可使糖尿病神经痛大鼠脊髓背角p-CREB、NR2B蛋白表达下调,抑制糖尿病神经痛.%Objective To investigate the effect of activating γ-aminobutyric acid(GABAB) receptors on the expression of phosphorylated cyclic adenosine monophosphate response element

  13. CCI: A Worldwide Camping Community.

    Science.gov (United States)

    Fawver, Gary Keith

    1992-01-01

    Describes the efforts of Christian Camping International (CCI), an alliance of Christian camping associations from Australia, Canada, the Far East, Latin America, New Zealand, United States, South Africa, Japan, and Brazil. The purpose of CCI is to help develop effective Christian camps, conferences, and retreat ministries. (LP)

  14. Adenosine and the adenosine A2A receptor agonist, CGS21680, upregulate CD39 and CD73 expression through E2F-1 and CREB in regulatory T cells isolated from septic mice.

    Science.gov (United States)

    Bao, Rui; Shui, Xianqi; Hou, Jiong; Li, Jinbao; Deng, Xiaoming; Zhu, Xiaoyan; Yang, Tao

    2016-09-01

    The number of regulatory T cells (Treg cells) and the expression of ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1; also known as CD39) and 5'-ectonucleotidase (NT5E; also known as CD73) on the Treg cell surface are increased during sepsis. In this study, to determine the factors leading to the high expression of CD39 and CD73, and the regulation of the CD39/CD73/adenosine pathway in Treg cells under septic conditions, we constructed a mouse model of sepsis and separated the Treg cells using a flow cytometer. The Treg cells isolated from the peritoneal lavage and splenocytes of the mice were treated with adenosine or the specific adenosine A2A receptor agonist, CGS21680, and were transfected with specific siRNA targeting E2F transcription factor 1 (E2F-1) or cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), which are predicted transcription regulatory factors of CD39 or CD73. The regulatory relationships among these factors were then determined by western blot analysis and dual-luciferase reporter assay. In addition, changes in adenosine metabolism were measured in the treated cells. The results revealed that adenosine and CGS21680 significantly upregulated CD39 and CD73 expression (PTreg cell surface during sepsis. Adenosine and its A2A receptor agonist served as the signal transducer factors of the CD39/CD73/adenosine pathway, accelerating adenosine generation. Our study may benefit further research on adenosine metabolism for the treatment of sepsis. PMID:27430240

  15. Imaging Adenosine Triphosphate (ATP).

    Science.gov (United States)

    Rajendran, Megha; Dane, Eric; Conley, Jason; Tantama, Mathew

    2016-08-01

    Adenosine triphosphate (ATP) is a universal mediator of metabolism and signaling across unicellular and multicellular species. There is a fundamental interdependence between the dynamics of ATP and the physiology that occurs inside and outside the cell. Characterizing and understanding ATP dynamics provide valuable mechanistic insight into processes that range from neurotransmission to the chemotaxis of immune cells. Therefore, we require the methodology to interrogate both temporal and spatial components of ATP dynamics from the subcellular to the organismal levels in live specimens. Over the last several decades, a number of molecular probes that are specific to ATP have been developed. These probes have been combined with imaging approaches, particularly optical microscopy, to enable qualitative and quantitative detection of this critical molecule. In this review, we survey current examples of technologies available for visualizing ATP in living cells, and identify areas where new tools and approaches are needed to expand our capabilities.

  16. Running Boot Camp

    CERN Document Server

    Toporek, Chuck

    2008-01-01

    When Steve Jobs jumped on stage at Macworld San Francisco 2006 and announced the new Intel-based Macs, the question wasn't if, but when someone would figure out a hack to get Windows XP running on these new "Mactels." Enter Boot Camp, a new system utility that helps you partition and install Windows XP on your Intel Mac. Boot Camp does all the heavy lifting for you. You won't need to open the Terminal and hack on system files or wave a chicken bone over your iMac to get XP running. This free program makes it easy for anyone to turn their Mac into a dual-boot Windows/OS X machine. Running Bo

  17. A Summer Camp

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    正This summer,I had some special days.I joined Dongzhou International Educational Exchange Summer Camp. First,I will tell you about our foreign teachers,they are Shrina and Rebecca. They are friendly and beautiful.They are students at Oxford University. We talked about many things:famous people,subjects in England,different jobs, our deal days,western star signs,what can we say in a restaurant and so on.

  18. Interprofessional Flight Camp.

    Science.gov (United States)

    Alfes, Celeste M; Rowe, Amanda S

    2016-01-01

    The Dorothy Ebersbach Academic Center for Flight Nursing in Cleveland, OH, holds an annual flight camp designed for master's degree nursing students in the acute care nurse practitioner program, subspecializing in flight nursing at the Frances Payne Bolton School of Nursing at Case Western Reserve University. The weeklong interprofessional training is also open to any health care provider working in an acute care setting and focuses on critical care updates, trauma, and emergency care within the critical care transport environment. This year, 29 graduate nursing students enrolled in a master's degree program from Puerto Rico attended. Although the emergency department in Puerto Rico sees and cares for trauma patients, there is no formal trauma training program. Furthermore, the country only has 1 rotor wing air medical transport service located at the Puerto Rico Medical Center in San Juan. Flight faculty and graduate teaching assistants spent approximately 9 months planning for their participation in our 13th annual flight camp. Students from Puerto Rico were extremely pleased with the learning experiences at camp and expressed particular interest in having more training time within the helicopter flight simulator.

  19. Clinical Implication of the Changes of cAMP, TXA2 and PGI2 in CSF of Asphyxiated Newborns

    Institute of Scientific and Technical Information of China (English)

    刘汉楚; 常立文; 陈晔; 夏世文; 张晓慧

    2003-01-01

    Summary: To evaluate the changes of 3', 5'-cyclic adenosine monophosphate (cAMP), thrombox-ane A2(TXA2) and prostacyclin (PGI2) in cerebrospinal fluid (CSF) in the asphyxiated newborn andexplore their roles in hypoxic-ischamic brain damage (HIBD). Thirty-six full term newborns were di-vided into 3 groups, including 12 with moderate-severe hypoxic-ischaemic encephalopathy (HIE), 13with mild HIE, 11 without HIE (control group). The levels of cAMP, TXB2 (TXA2 metabolite) and6-keto-PGF1α(PGI2 metabolite) in CSF and plasma were measured 36-72 h after birth by RIA, andthe concentrations were expressed as nM/L (cAMP), ng/L(TXB2 and 6-keto-PGF1α). The infantswere followed-up at 6 and 12 month of age and Mental Development Index (MD1) and PsychomotorDevelopment Index (PDI) were measured using Bayley Scales of Infant Development (BSID). TheCSF cAMP level in moderate-severe HIE group was 8.60±2.40, significantly lower than that of themild HIE group (14.83±2.84) and the control group (24. 43±2.39) (for both P<0. 01). The lev-els of TXB2 and 6-keto-PGF1α in CFS in the moderate-severe HIE group (206.06±29.74, 168.47±23.02, respectively) were significantly higher than in the mild HIE group (83. 37±28.57, 131.42±16.57, respectively, P<0. 01) and the control group (41. 77± 21.58, 86. 23±13.05, respectively,P<0. 01). The level changes of cAMP,TXB2 and 6-keto-PGF1α in plasma in all groups were similarto those in CSF, but no significant difference was found between mild HIE group and the controlgroup (P>0. 05). The follow-up results showed that MDI and PDI of the moderate-severe HIEgroup were the lowest (84. 79±13.34, 83. 50±13.28, respectively), followed by mild HIE group(102, 19±7. 02, 99. 94±9.08, respectively) , with the control group being the highest (116. 63±12.08, 116. 69±10. 87, respectively). Univariate analysis showed some significant difference (themoderate-severe HIE group vs. the mild HIE group or the control group, P<0. 01; the mild HIEgroup

  20. Activation of adenosine receptors and inhibition of cyclooxygenases: two recent pharmacological approaches to modulation of radiation suppressed hematopoiesis

    International Nuclear Information System (INIS)

    Searching for drugs conforming to requirements for protection and/or treatment of radiation-induced damage belongs to the most important tasks of current radiobiology. In the Laboratory of Experimental Hematology, Institute of Biophysics, v.v.i., Academy of Sciences of the Czech Republic, Brno, Czech Republic, two original approaches for stimulation of radiation-suppressed hematopoiesis have been tested in recent years, namely activation of adenosine receptors and inhibition of cyclooxygenases. Non-selective activation of adenosine receptors, induced by combined administration of dipyridamole, a drug preventing adenosine uptake and supporting thus its extracellular receptor-mediated action, and adenosine monophosphate, an adenosine prodrug, has been found to stimulate hematopoiesis when the drugs were given either pre- or post-irradiation. When synthetic adenosine receptor agonists selective for individual adenosine receptor subtypes were tested, stimulatory effects in myelosuppressed mice have been found after administration of IB-MECA, a selective adenosine A3 receptor agonist. Non-selective cyclooxygenase inhibitors, inhibiting both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), indomethacin, diclofenac, or flurbiprofen, have been observed to act positively on radiation-perturbed hematopoiesis in sublethally irradiated mice. However, their undesirable gastrointestinal side effects have been found to negatively influence survival of lethally irradiated animals. Recently tested selective COX-2 inhibitor meloxicam, preserving protective action of COX-1-synthesized prostaglandins in the gastrointestinal tissues, has been observed to retain the hematopoiesis-stimulating effects of non-selective cyclooxygenase inhibitors and to improve the survival of animals exposed to lethal radiation doses. These findings bear evidence for the possibility to use selective adenosine A3 receptor agonists and selective COX-2 inhibitors in human practice for treatment of

  1. A Camp in the Desert

    OpenAIRE

    Heise, Aaron Kent

    2006-01-01

    A house is pulled apart into its separate rooms and joined in the out-of-doors. This collection of rooms is recognized as a camp. This move is in agreement with the site of the house, which is the foothills of the Rincon Mountains, twenty miles east of Tucson, Arizona, and bordering along Saguaro National Monument. The collection of structures that make up the buildings of the camp are joined by a path that encircles the camp, and also describes the active life of the camp. The design o...

  2. Registration Day-Camp 2016

    CERN Multimedia

    Nursery School

    2016-01-01

    Reminder Registration for the CERN Staff Association Day-camp are open for children from 4 to 6 years old More information on the website: http://nurseryschool.web.cern.ch/. The day-camp is open to all children. An inscription per week is proposed, cost 480.-CHF/week, lunch included The camp will be open weeks 27, 28, 29 and 30, from 8:30 am to 5:30 pm. For further questions, thanks you for contacting us by email at Summer.Camp@cern.ch.

  3. Summer Camp, July 2016

    CERN Multimedia

    Staff Association

    2016-01-01

    During the month of July, the Staff Association’s Children’s Day-Care Centre and School EVEE held a summer camp for 4- to 6-year-olds. 24 children altogether joined in on the adventures. On the summer camp, the children got to “travel” to a different continent of the world every week. Day after day, they would pass through make-believe Customs upon arrival and get their passports stamped by a “customs officer”. For the first week, we went on a trip to Africa. In the spirit of the theme, the children got to do plenty of crafts and coloring, make their own little bindles and play various games. They even had the chance to visit the Museum of Ethnography in Geneva (MEG), learn to play the balafon and make musical instruments with Sterrenlab. For the second week, we set off to discover the Americas, exploring both the South and the North. Alongside different workshops (singing, dancing, storytelling, crafts), the children could enjoy several special ac...

  4. Kids Camping Takes the Challenge.

    Science.gov (United States)

    James, Vickie L.; Hohnbaum, Claudia

    2002-01-01

    A Wisconsin Girl Scout camp integrated The Healthy Kids Challenge into its program. The camp evaluated policies related to meals, snacks, physical activities, team building, and self-esteem. Staff inservice training resulted in healthier meals on the same budget and developed ownership of the program. Campers and families had opportunities to…

  5. Regulation of aggregate size and pattern by adenosine and caffeine in cellular slime molds

    Directory of Open Access Journals (Sweden)

    Jaiswal Pundrik

    2012-01-01

    Full Text Available Abstract Background Multicellularity in cellular slime molds is achieved by aggregation of several hundreds to thousands of cells. In the model slime mold Dictyostelium discoideum, adenosine is known to increase the aggregate size and its antagonist caffeine reduces the aggregate size. However, it is not clear if the actions of adenosine and caffeine are evolutionarily conserved among other slime molds known to use structurally unrelated chemoattractants. We have examined how the known factors affecting aggregate size are modulated by adenosine and caffeine. Result Adenosine and caffeine induced the formation of large and small aggregates respectively, in evolutionarily distinct slime molds known to use diverse chemoattractants for their aggregation. Due to its genetic tractability, we chose D. discoideum to further investigate the factors affecting aggregate size. The changes in aggregate size are caused by the effect of the compounds on several parameters such as cell number and size, cell-cell adhesion, cAMP signal relay and cell counting mechanisms. While some of the effects of these two compounds are opposite to each other, interestingly, both compounds increase the intracellular glucose level and strengthen cell-cell adhesion. These compounds also inhibit the synthesis of cAMP phosphodiesterase (PdsA, weakening the relay of extracellular cAMP signal. Adenosine as well as caffeine rescue mutants impaired in stream formation (pde4- and pdiA- and colony size (smlA- and ctnA- and restore their parental aggregate size. Conclusion Adenosine increased the cell division timings thereby making large number of cells available for aggregation and also it marginally increased the cell size contributing to large aggregate size. Reduced cell division rates and decreased cell size in the presence of caffeine makes the aggregates smaller than controls. Both the compounds altered the speed of the chemotactic amoebae causing a variation in aggregate size

  6. The arylpiperazine derivatives N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide and N-benzyl-4-(2-diphenyl)-1-piperazinehexanamide exert a long-lasting inhibition of human serotonin 5-HT7 receptor binding and cAMP signaling.

    Science.gov (United States)

    Atanes, Patricio; Lacivita, Enza; Rodríguez, Javier; Brea, José; Burgueño, Javier; Vela, José Miguel; Cadavid, María Isabel; Loza, María Isabel; Leopoldo, Marcello; Castro, Marián

    2013-12-01

    We performed a detailed in vitro pharmacological characterization of two arylpiperazine derivatives, compound N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide (LP-211) previously identified as a high-affinity brain penetrant ligand for 5-hydroxytryptamine (serotonin) type 7 (5-HT7) receptors, and its analog N-benzyl-4-(2-diphenyl)-1-piperazinehexanamide (MEL-9). Both ligands exhibited competitive displacement of [(3)H]-(2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine ([(3)H]-SB-269970) radioligand binding and insurmountable antagonism of 5-carboxamidotryptamine (5-CT)-stimulated cyclic adenosine monophosphate (cAMP) signaling in human embryonic kidney (HEK293) cells stably expressing human 5-HT7 receptors. They also inhibited forskolin-stimulated adenylate cyclase activity in 5-HT7-expressing HEK293 cells but not in the parental cell line. The compounds elicited long-lasting (at least 24 h) concentration-dependent inhibition of radioligand binding at 5-HT7-binding sites in whole-cell radioligand binding assays, after pretreatment of the cells with the compounds and subsequent compound removal. In cAMP assays, pretreatment of cells with the compounds rendered 5-HT7 receptors unresponsive to 5-CT and also rendered 5-HT7-expressing HEK293 cells unresponsive to forskolin. Compound 1-(2-biphenyl)piperazine (RA-7), a known active metabolite of LP-211 present in vivo, was able to partially inhibit 5-HT7 radioligand binding in a long-lasting irreversible manner. Hence, LP-211 and MEL-9 were identified as high-affinity long-acting inhibitors of human 5-HT7 receptor binding and function in cell lines. The detailed in vitro characterization of these two pharmacological tools targeting 5-HT7 receptors may benefit the study of 5-HT7 receptor function and it may lead to the development of novel selective pharmacological tools with defined functional properties at 5-HT7 receptors. PMID:25505568

  7. Fluoroquinolones as potential photochemotherapeutic agents: covalent addition to guanosine monophosphate.

    Science.gov (United States)

    Fasani, Elisa; Manet, Ilse; Capobianco, Massimo L; Monti, Sandra; Pretali, Luca; Albini, Angelo

    2010-08-21

    The triplet aryl cation photochemically generated from fluoroquinolones bearing a fluoro atom at position 8 attacks guanosine monophosphate (k(r) > 10(9) M(-1)s(-1)) and forms covalent adducts. The reaction is a model for the implementation of oxygen-independent photochemotherapy. PMID:20571620

  8. Comparison of work motivation in camp supervisors and camp counselors in Greek private camps

    Directory of Open Access Journals (Sweden)

    George Costa

    2008-06-01

    Full Text Available The purpose of this study was twofold. First, the study sought to better understand the work motivators that led camp supervisors and counselors to accept their job. Second, the study sought to better understand the ranking and rating of 20 work motivators from supervisors and camp counselors. Responders to the research questionnaire (n=121 were camp supervisory staff and counselors, age 15-55, working in seven private camps in Greece. Two instruments were used to collect data. The first instrument collected demographic data while the second instrument focused on ranking and rating 20 work motivators. The study suggested that Herzberg's theory (Motivator / Hygiene does not apply on a full scale. The results suggested that supervisory staff indicated good working conditions, meeting other people and carrying out personal growth are important. In addition, they don't like travel and don't consider working in a camp, as a stable job. The camp counselors want to have fun in their job and the opportunity to work with youth. They also don't consider working in a camp, as a stable job and they don't accept the responsibility in proportion to their position.

  9. Slave Labor Camps of the Third Reich.

    Science.gov (United States)

    Stone, Adolf

    1983-01-01

    Describes the ground rules used by Nazi architects in choosing the sites for slave labor camps. While some, like Auschwitz, became extermination camps, others also produced armaments. One camp, Theresienstadt, became a "model" camp to show to reporters and Red Cross representatives. (CS)

  10. cAMP-independent dilation of coronary arterioles to adenosine : role of nitric oxide, G proteins, and K(ATP) channels.

    Science.gov (United States)

    Hein, T W; Kuo, L

    1999-10-01

    Adenosine is known to play an important role in the regulation of coronary blood flow during metabolic stress. However, there is sparse information on the mechanism of adenosine-induced dilation at the microcirculatory levels. In the present study, we examined the role of endothelial nitric oxide (NO), G proteins, cyclic nucleotides, and potassium channels in coronary arteriolar dilation to adenosine. Pig subepicardial coronary arterioles (50 to 100 microm in diameter) were isolated, cannulated, and pressurized to 60 cm H(2)O without flow for in vitro study. The arterioles developed basal tone and dilated dose dependently to adenosine. Disruption of endothelium, blocking of endothelial ATP-sensitive potassium (K(ATP)) channels by glibenclamide, and inhibition of NO synthase by N(G)-nitro-L-arginine methyl ester and of soluble guanylyl cyclase by 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one produced identical attenuation of vasodilation to adenosine. Combined administration of these inhibitors did not further attenuate the vasodilatory response. Production of NO from coronary arterioles was significantly increased by adenosine. Pertussis toxin, but not cholera toxin, significantly inhibited vasodilation to adenosine, and this inhibitory effect was only evident in vessels with an intact endothelium. Tetraethylammonium, glibenclamide, and a high concentration of extraluminal KCl abolished vasodilation of denuded vessels to adenosine; however, inhibition of calcium-activated potassium channels by iberiotoxin had no effect on this dilation. Rp-8-Br-cAMPS, a cAMP antagonist, inhibited vasodilation to cAMP analog 8-Br-cAMP but failed to block adenosine-induced dilation. Furthermore, vasodilations to 8-Br-cAMP and sodium nitroprusside were not inhibited by glibenclamide, indicating that cAMP- and cGMP-induced dilations are not mediated by the activation of K(ATP) channels. These results suggest that adenosine activates both endothelial and smooth muscle pathways to exert

  11. Registration Day-Camp 2016

    CERN Multimedia

    Nursery School

    2016-01-01

    Registration for the CERN SA Day-camp are open for children from 4 to 6 years old From March 14 to 25 for children already enrolled in CERN SA EVE and School From April 4 to 15 for the children of CERN members of the personnel (MP) From April 18 for other children More information on the website: http://nurseryschool.web.cern.ch/. The day-camp is open to all children. An inscription per week is proposed, cost 480.-CHF/week, lunch included The camp will be open weeks 27, 28, 29 and 30, from 8:30 am to 5:30 pm. For further questions, thanks you for contacting us by email at Summer.Camp@cern.ch.

  12. Regulation of adenosine levels during cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Stephanie CHU; Wei XIONG; Dali ZHANG; Hanifi SOYLU; Chao SUN; Benedict C ALBENSI; Fiona E PARKINSON

    2013-01-01

    Adenosine is a neuromodulator with its level increasing up to 100-fold during ischemic events,and attenuates the excitotoxic neuronal injury.Adenosine is produced both intracellularly and extracellularly,and nucleoside transport proteins transfer adenosine across plasma membranes.Adenosine levels and receptor-mediated effects of adenosine are regulated by intracellular ATP consumption,cellular release of ATP,metabolism of extracellular ATP (and other adenine nucleotides),adenosine influx,adenosine efflux and adenosine metabolism.Recent studies have used genetically modified mice to investigate the relative contributions of intra-and extracellular pathways for adenosine formation.The importance of cortical or hippocampal neurons as a source or a sink of adenosine under basal and hypoxic/ischemic conditions was addressed through the use of transgenic mice expressing human equilibrative nucleoside transporter 1 (hENT1) under the control of a promoter for neuron-specific enolase.From these studies,we conclude that ATP consumption within neurons is the primary source of adenosine in neuronal cultures,but not in hippocampal slices or in vivo mice exposed to ischemic conditions.

  13. cAMP response element binding protein1 is essential for activation of steroyl co-enzyme a desaturase 1 (Scd1 in mouse lung type II epithelial cells.

    Directory of Open Access Journals (Sweden)

    Nisha Antony

    Full Text Available Cyclic AMP Response Element-Binding Protein 1 (Creb1 is a transcription factor that mediates cyclic adenosine 3', 5'-monophosphate (cAMP signalling in many tissues. Creb1(-/- mice die at birth due to respiratory failure and previous genome-wide microarray analysis of E17.5 Creb1(-/- fetal mouse lung identified important Creb1-regulated gene targets during lung development. The lipogenic enzymes stearoyl-CoA desaturase 1 (Scd1 and fatty acid synthase (Fasn showed highly reduced gene expression in Creb1(-/- lungs. We therefore hypothesized that Creb1 plays a crucial role in the transcriptional regulation of genes involved in pulmonary lipid biosynthetic pathways during lung development. In this study we confirmed that Scd1 and Fasn mRNA levels were down regulated in the E17.5 Creb1(-/- mouse lung while the lipogenic-associated transcription factors SrebpF1, C/ebpα and Pparγ were increased. In vivo studies using germline (Creb1(-/- and lung epithelial-specific (Creb1(EpiΔ/Δ Creb1 knockout mice showed strongly reduced Scd1, but not Fasn gene expression and protein levels in lung epithelial cells. In vitro studies using mouse MLE-15 epithelial cells showed that forskolin-mediated activation of Creb1 increased both Scd1 gene expression and protein synthesis. Additionally, MLE15 cells transfected with a dominant-negative ACreb vector blocked forskolin-mediated stimulation of Scd1 gene expression. Lipid profiling in MLE15 cells showed that dominant-negative ACreb suppressed forskolin-induced desaturation of ether linked lipids to produce plasmalogens, as well as levels of phosphatidylethanolamine, ceramide and lysophosphatidylcholine. Taken together these results demonstrate that Creb1 is essential for the induction and maintenance of Scd1 in developing fetal mouse lung epithelial cells.

  14. Voltammetric and impedance studies of inosine-5'-monophosphate and hypoxanthine

    OpenAIRE

    Oliveira-Brett, Ana Maria; Silva, Luís A.; Farace, Giosi; Vadgama, Pankaj; Christopher M. A. Brett

    2003-01-01

    The oxidation mechanism and adsorption of inosine 5'-monophosphate and hypoxanthine were investigated in solutions of different pH using voltammetric and impedance methods at glassy carbon electrodes. For both compounds, the pH dependence from differential pulse voltammetry showed that the same number of electrons and protons are involved in the rate-determining step of the electrochemical reaction. In the case of hypoxanthine, it was also possible to study the effect of different concentrati...

  15. RECIPIENT PRETRANSPLANT INOSINE MONOPHOSPHATE DEHYDROGENASE ACTIVITY IN NONMYELOABLATIVE HCT

    Science.gov (United States)

    Bemer, Meagan J.; Risler, Linda J.; Phillips, Brian R.; Wang, Joanne; Storer, Barry E.; Sandmaier, Brenda M.; Duan, Haichuan; Raccor, Brianne S.; Boeckh, Michael J.; McCune, Jeannine S.

    2014-01-01

    Mycophenolic acid, the active metabolite of mycophenolate mofetil (MMF), inhibits inosine monophosphate dehydrogenase (IMPDH) activity. IMPDH is the rate-limiting enzyme involved in de novo synthesis of guanosine nucleotides and catalyzes the oxidation of inosine 5’- monophosphate (IMP) to xanthosine 5’-monophosphate (XMP). We developed a highly sensitive liquid chromatography–mass spectrometry method to quantitate XMP concentrations in peripheral blood mononuclear cells (PMNC) isolated from the recipient pretransplant and used this method to determine IMPDH activity in 86 nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) patients. The incubation procedure and analytical method yielded acceptable within-sample and within-individual variability. Considerable between-individual variability was observed (12.2-fold). Low recipient pretransplant IMPDH activity was associated with increased day +28 donor T-cell chimerism, more acute graft-versus-host disease (GVHD), lower neutrophil nadirs, and more cytomegalovirus reactivation, but not with chronic GVHD, relapse, non-relapse mortality, or overall mortality. We conclude that quantitation of the recipient’s pretransplant IMPDH activity in PMNC lysate could provide a useful biomarker to evaluate a recipient’s sensitivity to MMF, but confirmatory studies are needed. Further trials should be conducted to confirm our findings and to optimize postgrafting immunosuppression in nonmyeloablative HCT recipients. PMID:24923537

  16. Camp for Youth With Type 1 Diabetes.

    Science.gov (United States)

    Fegan-Bohm, Kelly; Weissberg-Benchell, Jill; DeSalvo, Daniel; Gunn, Sheila; Hilliard, Marisa

    2016-08-01

    Camps for youth with type 1 diabetes (T1D) have grown in size and scope since they first emerged in the 1920s. Anecdotal evidence suggests that attending camp with other youth with T1D is beneficial, largely attributed to sharing fun, active experiences and removing the isolation of living with diabetes. However, few studies have evaluated the psychosocial and medical impacts of T1D camp attendance during and after camp sessions. In addition, T1D camps have been a setting for numerous studies on a variety of T1D-related research questions not related to camp itself, such as testing novel diabetes management technologies in an active, non-laboratory setting. This paper reviews the evidence of psychosocial and medical outcomes associated with T1D camp attendance across the globe, provides an overview of other research conducted at camp, and offers recommendations for future research conducted at T1D camp. PMID:27292106

  17. Role of adenosine 5'-monophosphate-activated protein kinase subunits in skeletal muscle mammalian target of rapamycin signaling

    DEFF Research Database (Denmark)

    Deshmukh, Atul S.; Treebak, Jonas Thue; Long, Yun Chau;

    2008-01-01

    AMP-activated protein kinase (AMPK) is an important energy-sensing protein in skeletal muscle. Mammalian target of rapamycin (mTOR) mediates translation initiation and protein synthesis through ribosomal S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). AMPK...... activation reduces muscle protein synthesis by down-regulating mTOR signaling, whereas insulin mediates mTOR signaling via Akt activation. We hypothesized that AMPK-mediated inhibitory effects on mTOR signaling depend on catalytic alpha2 and regulatory gamma3 subunits. Extensor digitorum longus muscle from...... AMPK alpha2 knockout (KO), AMPK gamma3 KO, and respective wild-type (WT) littermates (C57BL/6) were incubated in the presence of 5-aminoimidazole-4-carboxamide-1-beta-d-ribonucleoside (AICAR), insulin, or AICAR plus insulin. Phosphorylation of AMPK, Akt, and mTOR-associated signaling proteins were...

  18. Role of the Peroxisome Proliferator-Activated Receptors, Adenosine Monophosphate-Activated Kinase, and Adiponectin in the Ovary

    Directory of Open Access Journals (Sweden)

    Joëlle Dupont

    2008-01-01

    Full Text Available The mechanisms controlling the interaction between energy balance and reproduction are the subject of intensive investigations. The integrated control of these systems is probably a multifaceted phenomenon involving an array of signals governing energy homeostasis, metabolism, and fertility. Two fuel sensors, PPARs, a superfamily of nuclear receptors and the kinase AMPK, integrate energy control and lipid and glucose homeostasis. Adiponectin, one of the adipocyte-derived factors mediate its actions through the AMPK or PPARs pathway. These three molecules are expressed in the ovary, raising questions about the biological actions of fuel sensors in fertility and the use of these molecules to treat fertility problems. This review will highlight the expression and putative role of PPARs, AMPK, and adiponectin in the ovary, particularly during folliculogenesis, steroidogenesis, and oocyte maturation.

  19. Role of adenosine 5'-monophosphate-activated protein kinase in interleukin-6 release from isolated mouse skeletal muscle

    DEFF Research Database (Denmark)

    Glund, Stephan; Treebak, Jonas Thue; Long, Yun Chau;

    2009-01-01

    IL-6 is released from skeletal muscle during exercise and has consequently been implicated to mediate beneficial effects on whole-body metabolism. Using 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), a pharmacological activator of 5'-AMP-activated protein kinase (AMPK), we tested...... the hypothesis that AMPK modulates IL-6 release from isolated muscle. Skeletal muscle from AMPKalpha2 kinase-dead transgenic, AMPKalpha1 knockout (KO) and AMPKgamma3 KO mice and respective wild-type littermates was incubated in vitro, in the absence or presence of 2 mmol/liter AICAR. Skeletal muscle...... from wild-type mice was also incubated with the AMPK activator A-769662. Incubation of mouse glycolytic extensor digitorum longus and oxidative soleus muscle for 2 h was associated with profound IL-6 mRNA production and protein release, which was suppressed by AICAR (P < 0.001). Basal IL-6 release from...

  20. Dissociation of beta-adrenoceptor-induced effects on amylase secretion and cyclic adenosine 3', 5' monophosphate accumulation.

    OpenAIRE

    Carlsöö, B.; Danielsson, A; Henriksson, R.; Idahl, L A

    1982-01-01

    By using a multi-channel microperifusion system the effects of noradrenaline, the beta1-adrenoceptor agonist prenalterol, and the beta2-selective agonist terbutaline were studied on amylase pig submandibular glands. 2 Noradrenaline caused significant amylase discharge and cyclic AMP accumulation. 3 Prenalterol was as effective as noradrenaline in causing amylase release but did not significantly affect the cyclic AMP content. 4 Terbutaline stimulated cyclic AMP accumulation, but had little ef...

  1. Nucleic acid molecules encoding isopentenyl monophosphate kinase, and methods of use

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, Rodney B. (Pullman, WA); Lange, Bernd M. (Pullman, WA)

    2001-01-01

    A cDNA encoding isopentenyl monophosphate kinase (IPK) from peppermint (Mentha x piperita) has been isolated and sequenced, and the corresponding amino acid sequence has been determined. Accordingly, an isolated DNA sequence (SEQ ID NO:1) is provided which codes for the expression of isopentenyl monophosphate kinase (SEQ ID NO:2), from peppermint (Mentha x piperita). In other aspects, replicable recombinant cloning vehicles are provided which code for isopentenyl monophosphate kinase, or for a base sequence sufficiently complementary to at least a portion of isopentenyl monophosphate kinase DNA or RNA to enable hybridization therewith. In yet other aspects, modified host cells are provided that have been transformed, transfected, infected and/or injected with a recombinant cloning vehicle and/or DNA sequence encoding isopentenyl monophosphate kinase. Thus, systems and methods are provided for the recombinant expression of the aforementioned recombinant isopentenyl monophosphate kinase that may be used to facilitate its production, isolation and purification in significant amounts. Recombinant isopentenyl monophosphate kinase may be used to obtain expression or enhanced expression of isopentenyl monophosphate kinase in plants in order to enhance the production of isopentenyl monophosphate kinase, or isoprenoids derived therefrom, or may be otherwise employed for the regulation or expression of isopentenyl monophosphate kinase, or the production of its products.

  2. Characterization of inosine monophosphate dehydrogenase from Staphylococcus aureus ATCC12600 and its involvement in biofilm formation

    Directory of Open Access Journals (Sweden)

    S. Yeswanth

    2013-10-01

    Full Text Available Background: In Staphylococcus aureus purine metabolism plays a crucial role in the formation of biofilm which is a key pathogenic factor. The present study is aimed in the characterization of inosine monophosphate dehydrogenase (IMPDH from Staphylococcus aureus ATCC 12600. Methods: IMPDH gene was amplified using primers designed from IMPDH gene sequence of S. aureus reported in the database. Then polymerase chain reaction (PCR product was cloned in the Sma I site of M13mp18 and expressed in Escherichia coli JM109. The recombinant IMPDH (rIMPDH was overexpressed with 1 mM isopropyl beta-D-1- thiogalactopyranoside (IPTG; Michaelis constant (Km, maximum enzyme velocity (Vmax and catalytic constant (Kcat of expressed IMPDH were determined. Results: The enzyme kinetics of IMPDH grown under aerobic conditions showed a Km of 43.71±1.56 µM, Vmax of 0.247±0.84/µM/mg/min and Kcat of 2.74±0.015/min while in anaerobic conditions the kinetics showed Km of 42.81±3.154/ µM, Vmax of 0.378±0.036 µM/mg/min and Kcat of 4.78±0.021 /min, indicating elevated levels of IMPDH activity under anaerobic conditions. Three-folds increased activity in the presence of 1 mM adenosine triphosphate (ATP correlated with biofilm formation. The kinetics of pure rIMPDH were close to the native IMPDH of S. aureus ATCC12600 and the enzyme showed single band in sodium dodecyl sulphate polyacrylamide gel electrophoresis with a molecular weight of 53 KDa. Conclusions: Elevated activity of IMPDH was observed in S. aureus grown under anaerobic conditions and this was correlated with the biofilm formation indicating the linkage between purine metabolism and pathogenesis.

  3. Optimization of benzoxazole-based inhibitors of Cryptosporidium parvum inosine 5'-monophosphate dehydrogenase.

    Science.gov (United States)

    Gorla, Suresh Kumar; Kavitha, Mandapati; Zhang, Minjia; Chin, James En Wai; Liu, Xiaoping; Striepen, Boris; Makowska-Grzyska, Magdalena; Kim, Youngchang; Joachimiak, Andrzej; Hedstrom, Lizbeth; Cuny, Gregory D

    2013-05-23

    Cryptosporidium parvum is an enteric protozoan parasite that has emerged as a major cause of diarrhea, malnutrition, and gastroenteritis and poses a potential bioterrorism threat. C. parvum synthesizes guanine nucleotides from host adenosine in a streamlined pathway that relies on inosine 5'-monophosphate dehydrogenase (IMPDH). We have previously identified several parasite-selective C. parvum IMPDH (CpIMPDH) inhibitors by high-throughput screening. In this paper, we report the structure-activity relationship (SAR) for a series of benzoxazole derivatives with many compounds demonstrating CpIMPDH IC50 values in the nanomolar range and >500-fold selectivity over human IMPDH (hIMPDH). Unlike previously reported CpIMPDH inhibitors, these compounds are competitive inhibitors versus NAD(+). The SAR study reveals that pyridine and other small heteroaromatic substituents are required at the 2-position of the benzoxazole for potent inhibitory activity. In addition, several other SAR conclusions are highlighted with regard to the benzoxazole and the amide portion of the inhibitor, including preferred stereochemistry. An X-ray crystal structure of a representative E·IMP·inhibitor complex is also presented. Overall, the secondary amine derivative 15a demonstrated excellent CpIMPDH inhibitory activity (IC50 = 0.5 ± 0.1 nM) and moderate stability (t1/2 = 44 min) in mouse liver microsomes. Compound 73, the racemic version of 15a, also displayed superb antiparasitic activity in a Toxoplasma gondii strain that relies on CpIMPDH (EC50 = 20 ± 20 nM), and selectivity versus a wild-type T. gondii strain (200-fold). No toxicity was observed (LD50 > 50 μM) against a panel of four mammalian cells lines.

  4. Elevation of extracellular adenosine enhances haemopoiesis-stimulating effects of G-CSF in normal and gamma-irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Hofer, M.; Pospisil, M.; Netikiva, J.; Hola, J. [Institute of Biophysics, Academy of Sciences of the Czech Republic (Czech Republic)

    1997-03-01

    Effects of combined treatment with drugs elevating extracellular adenosine (dipyridamole /DP/, inhibiting the extracellular uptake of adenosine, and adenosine monophosphate /AMP/, an adenosine pro-drug), and G-CSF (granulocyte colony-stimulating factor) on haemopoiesis of normal and gamma-irradiated mice were ascertained. The agents were administered alone or in combination in a 4-day regimen. In normal, unirradiated animals, the haematological endpoints were determined 24 hours after the completion of the treatment. It was shown that the effects of G-CSF, i.e., increases in peripheral blood neutrophils, granulocyte-macrophage progenitor cells (GM-CFC) and morphologically recognizable granulocyte cells in femoral marrow and a decrease in the marrow erythroid cells, can be enhanced by the combination of DP plus AMP administrated 30 minutes before G-CSF. Furthermore, it was found that the stimulatory action of DP plus AMP was expressed particularly at lower doses of G-CSF (1.5, 3, and 4.5 {mu}g/d). In experiments with irradiated mice, when the 4-day therapeutic regimen was applied on days 3 to 6 following irradiation with the dose of 4 Gy, analogical stimulation of granulopoiesis was observed in the recovery phase on days 14 and 18 after irradiation. As example, see Fig. 1 for counts of granulocyte cells in femoral bone marrow. (authors)

  5. Elevation of extracellular adenosine enhances haemopoiesis-stimulating effects of G-CSF in normal and gamma-irradiated mice

    International Nuclear Information System (INIS)

    Effects of combined treatment with drugs elevating extracellular adenosine (dipyridamole /DP/, inhibiting the extracellular uptake of adenosine, and adenosine monophosphate /AMP/, an adenosine pro-drug), and G-CSF (granulocyte colony-stimulating factor) on haemopoiesis of normal and gamma-irradiated mice were ascertained. The agents were administered alone or in combination in a 4-day regimen. In normal, unirradiated animals, the haematological endpoints were determined 24 hours after the completion of the treatment. It was shown that the effects of G-CSF, i.e., increases in peripheral blood neutrophils, granulocyte-macrophage progenitor cells (GM-CFC) and morphologically recognizable granulocyte cells in femoral marrow and a decrease in the marrow erythroid cells, can be enhanced by the combination of DP plus AMP administrated 30 minutes before G-CSF. Furthermore, it was found that the stimulatory action of DP plus AMP was expressed particularly at lower doses of G-CSF (1.5, 3, and 4.5 μg/d). In experiments with irradiated mice, when the 4-day therapeutic regimen was applied on days 3 to 6 following irradiation with the dose of 4 Gy, analogical stimulation of granulopoiesis was observed in the recovery phase on days 14 and 18 after irradiation. As example, see Fig. 1 for counts of granulocyte cells in femoral bone marrow. (authors)

  6. Actinides and rare earths complexation with adenosine phosphate nucleotides

    International Nuclear Information System (INIS)

    Organophosphorus compounds are important molecules in both nuclear industry and living systems fields. Indeed, several extractants of organophosphorus compounds (such as TBP, HDEHP) are used in the nuclear fuel cycle reprocessing and in the biological field. For instance, the nucleotides are organophosphates which play a very important role in various metabolic processes. Although the literature on the interactions of actinides with inorganic phosphate is abundant, published studies with organophosphate compounds are generally limited to macroscopic and / or physiological approaches. The objective of this thesis is to study the structure of several organophosphorus compounds with actinides to reach a better understanding and develop new specific buildings blocks. The family of the chosen molecules for this procedure consists of three adenine nucleotides mono, bi and triphosphate (AMP, adenosine monophosphate - ADP, adenosine diphosphate - ATP, adenosine triphosphate) and an amino-alkylphosphate (AEP O-phosphoryl-ethanolamine). Complexes synthesis was conducted in aqueous and weakly acidic medium (2.8-4) for several lanthanides (III) (Lu, Yb, Eu) and actinides (U (VI), Th (IV) and Am (III)). Several analytical and spectroscopic techniques have been used to describe the organization of the synthesized complexes: spectrometric analysis performed by FTIR and NMR were used to identify the functional groups involved in the complexation, analysis by ESI-MS and pH-metric titration were used to determine the solution speciation and EXAFS analyzes were performed on Mars beamline of the SOLEIL synchrotron, have described the local cation environment, for both solution and solid compounds. Some theoretical approaches of DFT were conducted to identify stable structures in purpose of completing the experimental studies. All solid complexes (AMP, ADP, ATP and AEP) have polynuclear structures, while soluble ATP complexes are mononuclear. For all synthesized complexes, it has been

  7. Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine synergize to enhance haematopoietic reconstitution in irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Pospisil, M.; Hofer, M.; Netikova, J.; Hola, J.; Vacek, A. [Academy of Sciences of the Czech Republic, Inst. of Biophysics, Brno (Czech Republic); Znojil, V.; Vacha, J. [Masaryk Univ., Medical Faculty, Brno (Czech Republic)

    1998-03-01

    The activation of adenosine receptors has recently been demonstrated to stimulate haematopoiesis. In the present study, we investigated the ability of drugs elevating extracellular adenosine to influence curative effects of granulocyte colony-stimulating factor (G-CSF) in mice exposed to a sublethal dose of 4 Gy of {sup 60}Co radiation. Elevation of extracellular adenosine in mice was induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The effects of dipyridamole plus AMP, and G-CSF, administered either alone or in combination, were evaluated. The drugs were injected to mice in a 4-d treatment regimen starting on d 3 after irradiation and the haematopoietic response was evaluated on d 7, 10, 14, 18 and 24 after irradiation. While the effects of G-CSF on the late maturation stages of blood cells, appearing shortly after the completion of the treatment, were not influenced by dipyridamole plus AMP, positive effects of the combination therapy occurred in the post-irradiation recovery phase which is dependent on the repopulation of haematopoietic stem cells. This was indicated by the significant elevation of counts of granulocyte-macrophage progenitor cells (GM-CFC) and granulocytic cells in the bone marrow (d 14), of GM-CFC (d 14), granulocytic and erythroid cells (d 14 and 18) in the spleen, and of neutrophils (d 18), monocytes (d 14 and 18) and platelets (d 18) in the peripheral blood. These effects suggest that the repopulation potential of the combination therapy lies in a common multi-lineage cell population. The results of this study implicate the promising possibility to enhance the curative effects of G-CSF under conditions of myelosuppressive state induced by radiation exposure. (au) 43 refs.

  8. Deoxypyrimidine monophosphate bypass therapy for thymidine kinase 2 deficiency

    OpenAIRE

    Garone, Caterina; Garc??a-D??az, Beatriz; Emmanuele, Valentina; L??pez Garc??a, Luis Carlos; Tadesse, Saba; Akman, Hasan O.; Tanji, Kurenai; Quinzii, Catarina M.; Hirano, Michio

    2014-01-01

    Autosomal recessive mutations in the thymidine kinase 2 gene (TK2) cause mitochondrial DNA depletion, multiple deletions, or both due to loss of TK2 enzyme activity and ensuing unbalanced deoxynucleotide triphosphate (dNTP) pools. To bypass Tk2 deficiency, we administered deoxycytidine and deoxythymidine monophosphates (dCMP+dTMP) to the Tk2 H126N (Tk2 −/− ) knock-in mouse model from postnatal day 4, when mutant mice are phenotypically normal, but biochemically affected. Assessment of 13-day-...

  9. The NAO goes to camp

    NARCIS (Netherlands)

    Wigdor, N.; Fraaije, A.; Solms, L.; Greeff, J. de; Janssen, J.; Blanson Henkemans, O.A.

    2014-01-01

    ALIZ-E is a Europe-wide project focusing on long-term child-robot interaction, specifically as a means of educating diabetic children on their condition. This video showcases a recent field study at "SugarKidsClub", a camp devoted to helping 7-12 year-olds handle type-1 diabetes. A wide range of CRI

  10. Applications of Research to Camping.

    Science.gov (United States)

    Henderson, Karla A.

    1987-01-01

    Considers contributions of basic/theoretical, applied/practical, and marketing research to the field of camping. Outlines research concerns: application of qualitative methods, practical application of marketing research, effective research dissemination, and focus on longitudinal studies using larger samples. Affirms role of research to document…

  11. Lyme Disease Comes to Camp.

    Science.gov (United States)

    Peterson, Michael

    1989-01-01

    Describes one summer camp's plan for dealing with Lyme disease. Describes the disease and the deer tick. Recommends avoiding tick exposure through clothing, frequent examination, showers, and avoiding high grass and brushy areas, and using chemical insect repellents and chemicals to kill ticks in deer mouse nests. (DHP)

  12. AVTC Hosts TechnoCamp

    Science.gov (United States)

    Miner, Brenda

    2006-01-01

    The Area Vo-Tech Center (AVTC) in Russellville, Arkansas, recently hosted its first TechnoCamp to encourage enrollment based on the aptitude and interest level of the students enrolling in the various programs. The center currently offers student enrollment in auto technology, computer engineering, cosmetology, construction technology, drafting…

  13. 36 CFR 13.1208 - Lake Camp.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Lake Camp. 13.1208 Section 13... § 13.1208 Lake Camp. Leaving a boat, trailer, or vehicle unattended for more than 72 hours at the facilities associated with the Lake Camp launching ramp is prohibited without authorization from...

  14. Camping Is Your Gift to the World.

    Science.gov (United States)

    Thurber, Christopher A.

    2002-01-01

    Many camp professionals wonder how the events of September 11 will affect their camps. Advice is given on dealing with concerns of parents, campers, staff, and directors. Stability is comforting--change only what is absolutely necessary. Compassion and inclusion, the behaviors modeled at camp, are antidotes to misunderstanding and marginalization,…

  15. Expressing Camp, Part 2: Using Key Messages.

    Science.gov (United States)

    Schultz, Bob

    1996-01-01

    Camps can play an integral part in raising a child. The American Camping Association (ACA) has developed key messages that correspond to developmental needs of children. To portray a professional image of camp, promotional materials should incorporate these key messages, the benefits of ACA accreditation, and the same language as child development…

  16. Adenosine, Energy Metabolism, and Sleep

    Directory of Open Access Journals (Sweden)

    Tarja Porkka-Heiskanen

    2003-01-01

    Full Text Available While the exact function of sleep remains unknown, it is evident that sleep was developed early in phylogenesis and represents an ancient and vital strategy for survival. Several pieces of evidence suggest that the function of sleep is associated with energy metabolism, saving of energy, and replenishment of energy stores. Prolonged wakefulness induces signs of energy depletion in the brain, while experimentally induced, local energy depletion induces increase in sleep, similarly as would a period of prolonged wakefulness. The key molecule in the induction of sleep appears to be adenosine, which induces sleep locally in the basal forebrain.

  17. An improved method for the enzymatic transformation of nucleosides into 5'-monophosphates.

    Science.gov (United States)

    Barai, Vladimir N; Kvach, Sergei V; Zinchenko, Anatoli I; Mikhailopulo, Igor A

    2004-12-01

    An improved method to transform nucleosides into 5'-monophosphates using nucleoside phosphotransferase from Erwinia herbicola is reported. The method is based on the shift in the equilibrium state of the reaction to the formation of desired product due to its precipitation by Zn2+. Under optimal conditions, the extent of nucleoside transformations into nucleoside-5'-monophosphates were 41-91% (mol). PMID:15672226

  18. Thiamine diphosphate in whole blood, thiamine and thiamine monophosphate in breast-milk in a refugee population.

    Directory of Open Access Journals (Sweden)

    Wolfgang Stuetz

    Full Text Available BACKGROUND: The provision of high doses of thiamine may prevent thiamine deficiency in the post-partum period of displaced persons. METHODOLOGY/PRINCIPAL FINDINGS: The study aimed to evaluate a supplementation regimen of thiamine mononitrate (100 mg daily at the antenatal clinics in Maela refugee camp. Women were enrolled during antenatal care and followed after delivery. Samples were collected at 12 weeks post partum. Thiamine diphosphate (TDP in whole blood and thiamine in breast-milk of 636 lactating women were measured. Thiamine in breast-milk consisted of thiamine monophosphate (TMP in addition to thiamine, with a mean TMP to total thiamine ratio of 63%. Mean whole blood TDP (130 nmol/L and total thiamine in breast-milk (755 nmol/L were within the upper range reported for well-nourished women. The prevalence of women with low whole blood TDP (<65 nmol/L was 5% and with deficient breast-milk total thiamine (<300 nmol/L was 4%. Whole blood TDP predicted both breast-milk thiamine and TMP (R(2 = 0.36 and 0.10, p<0.001. A ratio of TMP to total thiamine ≥63% was associated with a 7.5 and 4-fold higher risk of low whole blood TDP and deficient total breast-milk thiamine, respectively. Routine provision of daily 100 mg of thiamine mononitrate post-partum compared to the previous weekly 10 mg of thiamine hydrochloride resulted in significantly higher total thiamine in breast-milk. CONCLUSIONS/SIGNIFICANCE: Thiamine supplementation for lactating women in Maela refugee camp is effective and should be continued. TMP and its ratio to total thiamine in breast-milk, reported for the first time in this study, provided useful information on thiamine status and should be included in future studies of breast-milk thiamine.

  19. Huijia School Summer Camp Program

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    As an open and international educational institution, Beijing Huijia Private School is located in Changping, a scenic district in Beijing's northern suburb. In order to strengthen international cultural exchanges, promote the study of Chinese language and the spread of Chinese culture, and make the world know more about China, Huijia School regularly organizes various summer camps for students of different ages every year. Until now, we have already successfully received more than 1,000 students from hom...

  20. Optical Aptasensors for Adenosine Triphosphate

    Science.gov (United States)

    Ng, Stella; Lim, Hui Si; Ma, Qian; Gao, Zhiqiang

    2016-01-01

    Nucleic acids are among the most researched and applied biomolecules. Their diverse two- and three-dimensional structures in conjunction with their robust chemistry and ease of manipulation provide a rare opportunity for sensor applications. Moreover, their high biocompatibility has seen them being used in the construction of in vivo assays. Various nucleic acid-based devices have been extensively studied as either the principal element in discrete molecule-like sensors or as the main component in the fabrication of sensing devices. The use of aptamers in sensors - aptasensors, in particular, has led to improvements in sensitivity, selectivity, and multiplexing capacity for a wide verity of analytes like proteins, nucleic acids, as well as small biomolecules such as glucose and adenosine triphosphate (ATP). This article reviews the progress in the use of aptamers as the principal component in sensors for optical detection of ATP with an emphasis on sensing mechanism, performance, and applications with some discussion on challenges and perspectives. PMID:27446501

  1. Mast cell adenosine receptors function: a focus on the A3 adenosine receptor and inflammation

    Directory of Open Access Journals (Sweden)

    Noam eRudich

    2012-06-01

    Full Text Available Adenosine is a metabolite, which has long been implicated in a variety of inflammatory processes. Inhaled adenosine provokes bronchoconstriction in asthmatics or chronic obstructive pulmonary disease (COPD patients, but not in non-asthmatics. This hyper responsiveness to adenosine appears to be mediated by mast cell activation. These observations have marked the receptor that mediates the bronchoconstrictor effect of adenosine on mast cells, as an attractive drug candidate. Four subtypes (A1, A2a, A2b and A3 of adenosine receptors have been cloned and shown to display distinct tissue distributions and functions. Animal models have firmly established the ultimate role of the A3 adenosine receptor (A3R in mediating hyper responsiveness to adenosine in mast cells, although the influence of the A2b adenosine receptor was confirmed as well. In contrast, studies of the A3R in humans have been controversial. In this review, we summarize data on the role of different adenosine receptors in mast cell regulation of inflammation and pathology, with a focus on the common and distinct functions of the A3R in rodent and human mast cells. The relevance of mouse studies to the human is discussed.

  2. Camping: A Tool for Relationship Maintenance?

    OpenAIRE

    Morrow, Rosie; Rodriguez, Alison; King, Nigel

    2014-01-01

    Purpose - Purpose: To investigate individuals’ lived experience of camping, and to explore the effects of camping on relationships. Design/methodology/approach - Design: The research adopted a descriptive phenomenological approach (Langdridge, 2007). Guided interviews were carried out with four participants, recalling their most memorable camping experience, with the aid of photographs to elicit memories. Analysis followed Colaizzi’s (1978) seven stage analysis and findings were discussed...

  3. Adenosine triphosphate inhibition of yeast trehalase.

    Science.gov (United States)

    Panek, A D

    1969-09-01

    Yeast trehalase has been found to be inhibited non-competitively by adenosine triphosphate. Such a biological control could explain the accumulation of trehalose during the stationary phase of the growth curve. PMID:5370287

  4. Electrocardiographic profile of adenosine pharmacological stress testing

    OpenAIRE

    Sun, Hao; TIAN, YUEQIN; ZHENG, LIHUI; Pan, Qingrong; XIE, BOQIA

    2015-01-01

    Adenosine stress testing in conjunction with radionuclide myocardial perfusion imaging has become a common approach for the detection of coronary artery diseases in patients who are unable to perform adequate levels of exercise. However, specific electrocardiographic alterations during the test have been rarely described. Using a Chinese population, the aim of the present study was to provide a detailed electrocardiographic profile of adenosine stress testing. The study population included 1,...

  5. Interactions of adenosine, prostaglandins and nitric oxide in hypoxia-induced vasodilatation: in vivo and in vitro studies

    Science.gov (United States)

    Ray, Clare J; Abbas, Mark R; Coney, Andrew M; Marshall, Janice M

    2002-01-01

    Adenosine, prostaglandins (PG) and nitric oxide (NO) have all been implicated in hypoxia-evoked vasodilatation. We investigated whether their actions are interdependent. In anaesthetised rats, the PG synthesis inhibitors diclofenac or indomethacin reduced muscle vasodilatation evoked by systemic hypoxia or adenosine, but not that evoked by iloprost, a stable analogue of prostacyclin (PGI2), or by an NO donor. After diclofenac, the A1 receptor agonist CCPA evoked no vasodilatation: we previously showed that A1, but not A2A, receptors mediate the hypoxia-induced muscle vasodilatation. Further, in freshly excised rat aorta, adenosine evoked a release of NO, detected with an NO-sensitive electrode, that was abolished by NO synthesis inhibition, or endothelium removal, and reduced by ≈50 % by the A1 antagonist DPCPX, the remainder being attenuated by the A2A antagonist ZM241385. Diclofenac reduced adenosine-evoked NO release by ≈50 % under control conditions, abolished that evoked in the presence of ZM241385, but did not affect that evoked in the presence of DPCPX. Adenosine-evoked NO release was also abolished by the adenyl cyclase inhibitor 2′,5′-dideoxyadenosine, while dose-dependent NO release was evoked by iloprost. Finally, stimulation of A1, but not A2A, receptors caused a release of PGI2 from rat aorta, assessed by radioimmunoassay of its stable metabolite, 6-keto PGF1α, that was abolished by diclofenac. These results suggest that during systemic hypoxia, adenosine acts on endothelial A1 receptors to increase PG synthesis, thereby generating cAMP, which increases the synthesis and release of NO and causes muscle vasodilatation. This pathway may be important in other situations involving these autocoids. PMID:12356892

  6. Adenosine modulation of [Ca2+]i in cerebellar granular cells: multiple adenosine receptors involved.

    Science.gov (United States)

    Vacas, Javier; Fernández, Mercedes; Ros, Manuel; Blanco, Pablo

    2003-12-01

    Elimination of adenosine by addition of adenosine deaminase (ADA) to the media leads to alterations in intracellular free calcium concentration ([Ca(2+)](i)) in cerebellar granular cells. Adenosine deaminase brings about increases or decreases in [Ca(2+)](i) depending on the previous activation state of the cell. These effects are dependent on the catalytic activity of adenosine deaminase, since its previous catalytic inactivation with Hg(2+) prevents the above-mentioned changes in intracellular calcium. Extracellular calcium is required for the increase in [Ca(2+)](i) promoted by ADA. This rise is insensitive to thapsigargin, but sensitive to micromolar concentrations of Ni(2+). Toxins specific for L, N and P/Q calcium channels do not overtly reduce this effect. N(6)-Cyclopentyl adenosine (CPA), an A(1) receptor agonist, produces a partial reversion of ADA effects, while CGS21680, A(2A)/A(2B) receptor agonist, slightly enhances them. Expression of A(1), A(2A), A(2B) and A(3) adenosine receptor mRNAs was detected in cerebellar granular cell cultures. These results suggest that adenosine modulate [Ca(2+)](i) in cerebellar granule cells through different adenosine receptor subtypes which, at least in part, seem to act through R-type calcium channels.

  7. Ag(+)-mediated assembly of 5'-guanosine monophosphate.

    Science.gov (United States)

    Loo, Kristine; Degtyareva, Natalya; Park, Jihae; Sengupta, Bidisha; Reddish, Michaeal; Rogers, Christopher C; Bryant, Andrea; Petty, Jeffrey T

    2010-04-01

    Polymorphic forms of nucleic acids provide platforms for new nanomaterials, and transition metal cations give access to alternative arrangements of nucleobases by coordinating with electron-rich functional groups. Interaction of Ag(+) with 5'-guanosine monophosphate (5'-GMP) is considered in this work. Ag(+) promotes nucleotide stacking and aggregation, as indicated by the increased viscosity of 5'-GMP solutions with Ag(+), magnification of the circular dichroism response of guanine by Ag(+), and exothermic reactions between Ag(+) and guanine derivatives. Isothermal titration calorimetry studies show that the reaction is favored starting at 10 microM 5'-GMP. Utilizing the exothermic heat change associated with reaction of Ag(+) with 5'-GMP, local structure within the aggregate was assessed. On the basis of the salt dependence of the reaction and comparison with the corresponding nucleoside, the dianionic phosphate of 5'-GMP is one binding site for Ag(+), although this electrostatic interaction is not a dominant contribution to the overall heat change. Another binding site is the N7 on the nucleobase, as determined via studies with 7-deazaguanosine. Besides this binding site, Ag(+) also associates with the O6, as earlier studies deduced from the shift in the carbonyl stretching frequency associated with adduct formation. With these two binding sites on the nucleobase, the empirical stoichiometry of approximately 1 Ag(+):nucleobase derived from the calorimetry studies indicates that Ag(+) coordinates two nucleobases. The proposed structural model is a Ag(+)-mediated guanine dimer within a base stacked aggregate. PMID:20205377

  8. Teenagers and Risk-Taking at Camp.

    Science.gov (United States)

    Woods, Ann

    2002-01-01

    Teen risk-taking is normal, healthy developmental behavior. Teens act out their fantasies--good and bad--at camp because it is a safe place away from parents. Signs of unhealthy risk-taking, camp staff responses, and how the September 11 tragedy might affect risk-taking are discussed. Sidebars describe tips for understanding adolescent behavior…

  9. Dealing with World Issues in Camp.

    Science.gov (United States)

    Kujawa, Charles

    1986-01-01

    Discusses dealing with global issues in the camp setting in a way that broadens young people's world views. Topics include the educational advantages of the camp setting, desired outcomes for campers, guidelines for staff, and program ideas for dealing with issues such as environmental awareness, racism, and economic justice. (JHZ)

  10. Children with Cancer: Positive Benefits of Camp.

    Science.gov (United States)

    Winfree, Christy; Williams, Richard; Powell, Gwynn M.

    2002-01-01

    A relatively new method of helping pediatric cancer patients cope with their illness is specially designed summer camps. Camp helps children with cancer address psychological effects of the disease, bodily changes, and self-concept, and helps parents and siblings cope. Sidebars present resources and tips on incorporating children with cancer into…

  11. Adenosine stress protocols for myocardial perfusion imaging

    Directory of Open Access Journals (Sweden)

    Baškot Branislav

    2008-01-01

    Full Text Available Background/Aim. Treadmill test combined with myocardial perfusion scintigraphy (MPS is a commonly used technique in the assessment of coronary artery disease. There are many patients, however, who may not be able to undergo treadmill test. Such patients would benefit from pharmacological stress procedures combined with MPS. The most commonly used pharmacological agents for cardiac stress are coronary vasodilatators (adenosine, dipyridamol and catecholamines. Concomitant low-level treadmill exercise with adenosine pharmacologic stress (AdenoEX during MPS has become commonly used in recent years. A number of studies have demonstrated a beneficial impact of AdenoEX protocol. The aim of the study was, besides introducing into practice the two types of protocols of pharmatological stress test with adenosine, as a preparation for MPS, to compare and monitor the frequency of their side effects to quality, acquisition, as well as to standardize the onset time of acquisition (diagnostic imaging for both protocols. Methods. A total of 130 patients underwent pharmacological stress test with adenosine (vasodilatator. In 108 of the patients we performed concomitant exercise (AdenoEX of low level (50W by a bicycle ergometar. In 28 of the patients we performed Adenosine abbreviated protocol (AdenoSCAN. Side effects of adenosine were followed and compared between the two kinds of protocols AdenoEX and AdenoSCAN. Also compared were image quality and suggested time of acquisition after the stress test. Results. Numerous side effects were found, but being short-lived they did not require any active interventions. The benefit of AdenoEX versus AdenoSCAN included decreased side effects (62% vs 87%, improved safety and patients tolerance, improved target-to-background ratios because of less subdiaphragmatic activity, earlier acquisition, and improved sensitivity. Conclusion. The safety and efficacy of adenosine pharmacological stress is even better with concomitant

  12. Opening of a summer camp at CERN

    CERN Document Server

    Nursery School

    2015-01-01

    The Staff Association has the pleasure to announce the opening of a summer camp in l’EVE et Ecole de l’AP du CERN. With a capacity of 40 children, aged 4 to 6 years, it will be open from July 6 to 30. Registration Summer camp 2015 Registration for the CERN SA Summer camp for children aged 4 to 6 is open 16 to 30 April 2015 More information on the website: http://nurseryschool.web.cern.ch/ The Summer camp is open to all children of CERN Staff. An inscription per week is proposed, cost 480.-CHF/week, lunch included. The camp will be open weeks 28, 29, 30 and 31, from 8:30 am to 5:30 pm.

  13. Theophylline enhances glucose recovery after hypoglycemia in healthy man and in type I diabetic patients

    DEFF Research Database (Denmark)

    Hvidberg, A; Rasmussen, M H; Christensen, N J;

    1994-01-01

    The principal mediators of glucose counterregulation (glucagon and epinephrine) use intracellular cyclic adenosine monophosphate (cAMP) to mediate glucose release. Since theophylline increases cAMP (by inhibiting its decomposition), we investigated the effect of theophylline on glucose recovery a...

  14. Design of cAMP-CRP-activated promoters in Escherichia coli

    DEFF Research Database (Denmark)

    Valentin-Hansen, P; Holst, B; Søgaard-Andersen, L;

    1991-01-01

    We have studied the deoP2 promoter of Escherichia coli to define features that are required for optimal activation by the complex of adenosine 3',5' monophosphate (cAMP) and the cAMP receptor protein (CRP). Systematic mutagenesis of deoP2 shows that the distance between the CRP site and the -10...

  15. Subcellular localisation of Epac

    NARCIS (Netherlands)

    Zhao, Jun

    2006-01-01

    Cyclic adenosine 3', 5'- monophosphate (cAMP) is a second messenger that functions through binding to its downstream targets protein kinase A (PKA), cyclic-regulated ion channels (CNG channels) and Epac1 (exchange protein directly activated by cAMP). Epac1 is guanine nucleotide exchange factor towar

  16. Determination of adenosine effects and adenosine receptors in murine corpus cavernosum.

    Science.gov (United States)

    Tostes, Rita C; Giachini, Fernanda R C; Carneiro, Fernando S; Leite, Romulo; Inscho, Edward W; Webb, R Clinton

    2007-08-01

    This study tested the hypothesis that adenosine, in murine corpora cavernosa, produces direct relaxation of smooth muscle cells and inhibition of contractile responses mediated by sympathetic nerve stimulation. Penes were excised from anesthetized male C57BL/6 mice, dissected, and cavernosal strips were mounted to record isometric force. Adenosine, 2-chloroadenosine (stable analog of adenosine), and 2-phenylaminoadenosine (CV1808) (A2(A)/A2(B) agonist) produced concentration-dependent relaxations of phenylephrine-contracted tissues. Relaxation to 2-chloroadenosine was inhibited, in a concentration-dependent manner, by 2-(2-furanyl)-7-(2-phenylethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine (SCH58261; A2(A) antagonist; 10(-9)-10(-6) M) and N-(4-acetylphenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)phenoxy]acetamida (MRS1706; A2(B) antagonist; 10(-8)-10(-6) M). The combination of both antagonists abrogated 2-chloroadenosine-induced relaxation. Electrical field stimulation (EFS; 1-32 Hz) of adrenergic nerves produced frequency-dependent contractions that were inhibited by compounds that increase adenosine levels, such as 5'-iodotubercidin (adenosine kinase inhibitor), erythro-9-(2-hydroxy-3-nonyl)adenine (adenosine deaminase inhibitor), and dipyridamole (inhibitor of adenosine transport). The adenosine A1 receptor agonist N(6)-cyclopentyladenosine (C8031) right-shifted contractile responses to EFS, with a significant inhibitory effect at 10(-6) M. Blockade of adenosine A1 receptors with 8-cyclopentyl-1,3-dipropylxanthine (C101) (10(-7) M) enhanced contractile responses to EFS and eliminated the inhibitory effects of 5'-iodotubercidin. Dipyridamole and 5'-iodotubercidin had no effect on adenosine-mediated relaxation. In summary, adenosine directly relaxes cavernosal smooth muscle cells, by the activation of A2(A)/A2(B) receptor subtypes. In addition, adenosine negatively modulates sympathetic neurotransmission, by A1 receptor

  17. Detection of adenosine triphosphate through polymerization-induced aggregation of actin-conjugated gold/silver nanorods

    Science.gov (United States)

    Liao, Yu-Ju; Shiang, Yen-Chun; Chen, Li-Yi; Hsu, Chia-Lun; Huang, Chih-Ching; Chang, Huan-Tsung

    2013-11-01

    We have developed a simple and selective nanosensor for the optical detection of adenosine triphosphate (ATP) using globular actin-conjugated gold/silver nanorods (G-actin-Au/Ag NRs). By simply mixing G-actin and Au/Ag NRs (length ˜56 nm and diameter ˜12 nm), G-actin-Au/Ag NRs were prepared which were stable in physiological solutions (25 mM Tris-HCl, 150 mM NaCl, 5.0 mM KCl, 3.0 mM MgCl2 and 1.0 mM CaCl2; pH 7.4). Introduction of ATP into the G-actin-Au/Ag NR solutions in the presence of excess G-actin induced the formation of filamentous actin-conjugated Au/Ag NR aggregates through ATP-induced polymerization of G-actin. When compared to G-actin-modified spherical Au nanoparticles having a size of 13 nm or 56 nm, G-actin-Au/Ag NRs provided better sensitivity for ATP, mainly because the longitudinal surface plasmon absorbance of the Au/Ag NR has a more sensitive response to aggregation. This G-actin-Au/Ag NR probe provided high sensitivity (limit of detection 25 nM) for ATP with remarkable selectivity (>10-fold) over other adenine nucleotides (adenosine, adenosine monophosphate and adenosine diphosphate) and nucleoside triphosphates (guanosine triphosphate, cytidine triphosphate and uridine triphosphate). It also allowed the determination of ATP concentrations in plasma samples without conducting tedious sample pretreatments; the only necessary step was simple dilution. Our experimental results are in good agreement with those obtained from a commercial luciferin-luciferase bioluminescence assay. Our simple, sensitive and selective approach appears to have a practical potential for the clinical diagnosis of diseases (e.g. cystic fibrosis) associated with changes in ATP concentrations.

  18. "It's not Just Camp!": Understanding the Meaning of Children's Cancer Camps for Children and Families.

    Science.gov (United States)

    Laing, Catherine M; Moules, Nancy J

    2016-01-01

    The purpose of this philosophical hermeneutic inquiry was to understand the meaning of children's cancer camps for the child with cancer and the family. Six childhood cancer families and 5 cancer camp counselors were interviewed, in order to bring understanding to this topic. Findings from this research revealed that camp means different things for different families, and that much is at play in the cancer camp experience: the healing and developmental power of play, finding acceptance and fit, grief as something to live with versus "get over," storytelling as a means of reshaping and understanding traumatic experiences, and the solidarity of the community as one that creates intense, healing bonds. Children's cancer camps, we conclude, should be considered a necessity, versus a luxury, and could even be thought of as a psychosocial intervention for some children and families. Barriers such as structure of funding and access to resources are present and likely due to the separateness of camps from hospital programs. PMID:25643975

  19. Design and Development Issues for Educational Robotics Training Camps

    Science.gov (United States)

    Ucgul, Memet; Cagiltay, Kursat

    2014-01-01

    The aim of this study is to explore critical design issues for educational robotics training camps and to describe how these factors should be implemented in the development of such camps. For this purpose, two robotics training camps were organized for elementary school students. The first camp had 30 children attendees, and the second had 22. As…

  20. 2012 USGS Lidar: Brooks Camp (AK)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The U.S. Geological Survey (USGS) had a requirement for high resolution Lidar needed for mapping the Brooks Camp region of Katmai National Park in Alaska....

  1. Food Safety While Hiking, Camping and Boating

    Science.gov (United States)

    ... Standard Forms FSIS United States Department of Agriculture Food Safety and Inspection Service About FSIS District Offices ... Web Content Viewer (JSR 286) Actions ${title} Loading... Food Safety While Hiking, Camping & Boating Outdoor activities are ...

  2. Internalization and desensitization of adenosine receptors.

    NARCIS (Netherlands)

    Klaasse, E.C.; IJzerman, A.P.; Grip, W.J. de; Beukers, M.W.

    2008-01-01

    Until now, more than 800 distinct G protein-coupled receptors (GPCRs) have been identified in the human genome. The four subtypes of the adenosine receptor (A(1), A(2A), A(2B) and A(3) receptor) belong to this large family of GPCRs that represent the most widely targeted pharmacological protein clas

  3. The role of mechanical forces and adenosine in the regulation of intestinal enterochromaffin cell serotonin secretion.

    Science.gov (United States)

    Chin, A; Svejda, B; Gustafsson, B I; Granlund, A B; Sandvik, A K; Timberlake, A; Sumpio, B; Pfragner, R; Modlin, I M; Kidd, M

    2012-02-01

    Enterochromaffin (EC) cells of the diffuse neuroendocrine cell system secrete serotonin (5-HT) with activation of gut motility, secretion, and pain. These cells express adenosine (ADORA) receptors and are considered to function as mechanosensors. Physiological pathways mediating mechanosensitivity and adenosine responsiveness remain to be fully elucidated, as do their roles in inflammatory bowel disease (IBD) and neoplasia. Pure (98-99%) FACS-sorted normal and IBD human EC cells and neoplastic EC cells (KRJ-I) were studied. IBD-EC cells and KRJ-I overexpressed ADORA2B. NECA, a general ADORA receptor agonist, stimulated, whereas the A2B receptor antagonist MRS1754 inhibited, 5-HT release (EC50 = 1.8 × 10-6 M; IC50 = 3.7 × 10-8 M), which was associated with corresponding alterations in intracellular cAMP levels and pCREB (Ser133). Mechanical stimulation using a rhythmic flex model induced transcription and activation of Tph1 (tryptophan hydroxylase) and VMAT₁ (vesicular monoamine transporter 1) and the release of 5-HT, which could be inhibited by MRS1754 and amplified by NECA. Secretion was also inhibited by H-89 (PKA inhibitor) while Tph1 and VMAT₁ transcription was regulated by PKA/MAPK and PI₃K-mediated signaling. Normal and IBD-EC cells also responded to NECA and mechanical stimulation with PKA activation, cAMP production, and 5-HT release, effects reversible by MRS1754. EC cells express stimulatory ADORA2B, and rhythmic stretch induces A2B activation, PKA/MAPK/IP3-dependent transcription, and PKA-dependent secretion of 5-HT synthesis and secretion. Receptor expression is amplified in IBD and neoplasia, and 5-HT release is increased. Determination of factors that regulate EC cell function are necessary for understanding its role as a mechanosensory cell and to facilitate the development of agents that can selectively target cell function in EC cell-associated disease. PMID:22038827

  4. Adenosine: An immune modulator of inflammatory bowel diseases

    Institute of Scientific and Technical Information of China (English)

    Jeff Huaqing Ye; Vazhaikkurichi M Rajendran

    2009-01-01

    Inflammatory bowel disease (IBD) is a common and lifelong disabling gastrointestinal disease. Emerging treatments are being developed to target inflammatory cytokines which initiate and perpetuate the immune response. Adenosine is an important modulator of inflammation and its anti-inflammatory effects have been well established in humans as well as in animal models. High extracellular adenosine suppresses and resolves chronic inflammation in IBD models. High extracellular adenosine levels could be achieved by enhanced adenosine absorption and increased de novo synthesis. Increased adenosine concentration leads to activation of the A2a receptor on the cell surface of immune and epithelial cells that would be a potential therapeutic target for chronic intestinal inflammation. Adenosine is transported via concentrative nucleoside transporter and equilibrative nucleoside transporter transporters that are localized in apical and basolateral membranes of intestinal epithelial cells, respectively. Increased extracellular adenosine levels activate the A2a receptor, which would reduce cytokines responsible for chronic inflammation.

  5. Regulation of the Renin-Angiotensin System Pathways in the Human Decidua.

    Science.gov (United States)

    Wang, Yu; Lumbers, Eugenie R; Sykes, Shane D; Pringle, Kirsty G

    2015-07-01

    Pregnancy outcome is influenced, in part, by the sex of the fetus. Decidual renin messenger RNA (REN) abundance is greater in women carrying a female fetus than a male fetus. Here, we explore whether the sex of the fetus also influences the regulation of decidual RAS expression with a known stimulator of renal renin and cyclic adenosine monophosphate (cAMP). Cyclic adenosine monophosphate had no affect on decidual REN expression, since REN abundance was still greater in decidual explants from women carrying a female fetus than a male fetus after cAMP treatment. Cyclic adenosine monophosphate decreased prorenin levels in the supernatant if the fetus was female (ie, prorenin levels were no longer sexually dimorphic) and altered the fetal sex-specific differences in other RAS genes seen in vitro. Therefore, fetal sex influences the decidual renin-angiotensin system response to cAMP. This may be related to the presence of fetal cells in the maternal decidua.

  6. Adenosine receptors and asthma in humans

    OpenAIRE

    Wilson, C N

    2008-01-01

    According to an executive summary of the GINA dissemination committee report, it is now estimated that approximately 300 million people (5% of the global population or 1 in 20 persons) have asthma. Despite the scientific progress made over the past several decades toward improving our understanding of the pathophysiology of asthma, there is still a great need for improved therapies, particularly oral therapies that enhance patient compliance and that target new mechanisms of action. Adenosine...

  7. Chemoelectrical energy conversion of adenosine triphosphate

    Science.gov (United States)

    Sundaresan, Vishnu Baba; Sarles, Stephen Andrew; Leo, Donald J.

    2007-04-01

    Plant and animal cell membranes transport charged species, neutral molecules and water through ion pumps and channels. The energy required for moving species against established concentration and charge gradients is provided by the biological fuel - adenosine triphosphate (ATP) -synthesized within the cell. The adenosine triphosphatase (ATPases) in a plant cell membrane hydrolyze ATP in the cell cytoplasm to pump protons across the cell membrane. This establishes a proton gradient across the membrane from the cell exterior into the cell cytoplasm. This proton motive force stimulates ion channels that transport nutrients and other species into the cell. This article discusses a device that converts the chemical energy stored in adenosine triphosphate into electrical power using a transporter protein, ATPase. The V-type ATPase proteins used in our prototype are extracted from red beet(Beta vulgaris) tonoplast membranes and reconstituted in a bilayer lipid membrane or BLM formed from POPC and POPS lipids. A pH7 medium that can support ATP hydrolysis is provided on both sides of the membrane and ATP is dissolved in the pH7 buffer on one side of the membrane. Hydrolysis of ATP results in the formation of a phosphate ion and adenosine diphosphate. The energy from the reaction activates ATPase in the BLM and moves a proton across the membrane. The charge gradient established across the BLM due to the reaction and ion transport is converted into electrical current by half-cell reference electrodes. The prototype ATPase cell with an effective BLM area of 4.15 mm2 carrying 15 μl of ATPase proteins was observed to develop a steady state peak power output of 70 nW, which corresponds to a specific power of 1.69 μW/cm2 and a current density of 43.4 μA/cm2 of membrane area.

  8. Aminopyrimidine derivatives as adenosine antagonists / Janke Kleynhans

    OpenAIRE

    Kleynhans, Janke

    2013-01-01

    Aims of this project - The aim of this study was to design and synthesise novel 2-aminopyrimidine derivatives as potential adenosine A1 and A2A receptor antagonists. Background and rationale - Parkinson’s disease is the second most common neurodegenerative disorder (after Alzheimer’s disease) and is characterised by the selective death of the dopaminergic neurons of the nigro-striatal pathway. Distinctive motor symptoms include bradykinesia, muscle rigidity and tremor, while non-m...

  9. Physiological and Molecular Effects of the Cyclic Nucleotides cAMP and cGMP on Arabidopsis thaliana

    KAUST Repository

    Herrera, Natalia M.

    2012-12-01

    The cyclic nucleotide monophosphates (CNs), cAMP and cGMP, are second messengers that participate in the regulation of development, metabolism and adaptive responses. In plants, CNs are associated with the control of pathogen responses, pollen tube orientation, abiotic stress response, membrane transport regulation, stomatal movement and light perception. In this study, we hypothesize that cAMP and cGMP promote changes in the transcription level of genes related to photosynthesis, high light and membrane transport in Arabidopsis thaliana leaves and, that these changes at the molecular level can have functional biological consequences. For this reason we tested if CNs modulate the photosynthetic rate, responses to high light and root ion transport. Real time quantitative PCR was used to assess transcription levels of selected genes and infrared gas analyzers coupled to fluorescence sensors were used to measure the photosynthetic parameters. We present evidence that both cAMP and cGMP modulate foliar mRNA levels early after stimulation. The two CNs trigger different responses indicating that the signals have specificity. A comparison of proteomic and transcriptional changes suggest that both transcriptional and post-transcriptional mechanisms are modulated by CNs. cGMP up-regulates the mRNA levels of components of the photosynthesis and carbon metabolism. However, neither cAMP nor cGMP trigger differences in the rate of carbon assimilation, maximum efficiency of the photosystem II (PSII), or PSII operating efficiency. It was also demonstrated that CN regulate the expression of its own targets, the cyclic nucleotide gated channels - CNGC. Further studies are needed to identify the components of the signaling transduction pathway that mediate cellular changes and their respective regulatory and/or signaling roles.

  10. cAMP signalling meets mitochondrial compartments.

    Science.gov (United States)

    Lefkimmiatis, Konstantinos

    2014-04-01

    Mitochondria are highly dynamic organelles comprising at least three distinct areas, the OMM (outer mitochondrial membrane), the IMS (intermembrane space) and the mitochondrial matrix. Physical compartmentalization allows these organelles to host different functional domains and therefore participate in a variety of important cellular actions such as ATP synthesis and programmed cell death. In a surprising homology, it is now widely accepted that the ubiquitous second messenger cAMP uses the same stratagem, compartmentalization, in order to achieve the characteristic functional pleiotropy of its pathway. Accumulating evidence suggests that all the main mitochondrial compartments contain segregated cAMP cascades; however, the regulatory properties and functional significance of such domains are not fully understood and often remain controversial issues. The present mini-review discusses our current knowledge of how the marriage between mitochondrial and cAMP compartmentalization is achieved and its effects on the biology of the cell. PMID:24646228

  11. Modulatory effects of cAMP and PKC activation on gap junctional intercellular communication among thymic epithelial cells

    Directory of Open Access Journals (Sweden)

    Neves-dos-Santos Sandra

    2010-01-01

    Full Text Available Abstract Background We investigated the effects of the signaling molecules, cyclic AMP (cAMP and protein-kinase C (PKC, on gap junctional intercellular communication (GJIC between thymic epithelial cells (TEC. Results Treatment with 8-Br-cAMP, a cAMP analog; or forskolin, which stimulates cAMP production, resulted in an increase in dye transfer between adjacent TEC, inducing a three-fold enhancement in the mean fluorescence of coupled cells, ascertained by flow cytometry after calcein transfer. These treatments also increased Cx43 mRNA expression, and stimulated Cx43 protein accumulation in regions of intercellular contacts. VIP, adenosine, and epinephrine which may also signal through cyclic nucleotides were tested. The first two molecules did not mimic the effects of 8-Br-cAMP, however epinephrine was able to increase GJIC suggesting that this molecule functions as an endogenous inter-TEC GJIC modulators. Stimulation of PKC by phorbol-myristate-acetate inhibited inter-TEC GJIC. Importantly, both the enhancing and the decreasing effects, respectively induced by cAMP and PKC, were observed in both mouse and human TEC preparations. Lastly, experiments using mouse thymocyte/TEC heterocellular co-cultures suggested that the presence of thymocytes does not affect the degree of inter-TEC GJIC. Conclusions Overall, our data indicate that cAMP and PKC intracellular pathways are involved in the homeostatic control of the gap junction-mediated communication in the thymic epithelium, exerting respectively a positive and negative role upon cell coupling. This control is phylogenetically conserved in the thymus, since it was seen in both mouse and human TEC preparations. Lastly, our work provides new clues for a better understanding of how the thymic epithelial network can work as a physiological syncytium.

  12. [The involvement of adenosine and adenosine deaminase in experimental myocardial infarct].

    Science.gov (United States)

    Stratone, A; Busuioc, A; Roşca, V; Bazgan, L; Popa, M; Hăulică, I

    1989-01-01

    By the ligature of the left coronary artery in the rat anesthetized with nembutal (10 mg/100 i.p.) a significant increase of the 5'-nucleotidase activity (Wooton method) was noticed 10 minutes after the left ventricle infarction (from an average value of 1038.5 +/- 187 mU/g tissue to 1537 +/- 225 mU/g fresh tissue). The adenosine desaminase levels spectrophotometrically determined by Denstedt technique, do not appear significantly modified 10 or 30 minutes after the left ventricle infarction. The chromatographically determined adenosine levels, by HPLC technique, decrease from the average value of 11.63 +/- 1.4 micrograms/mg PT to 8.60 +/- 1.0 micrograms/mg PT 30 minutes after infarction. The observed changes are explained by the conditions of hypoxia in the infarcted ventricle which lead to the raise in adenosine levels by activating the 5'-nucleotidase and their depression by a very fast metabolism of the same substance.

  13. A specialized program for children with developmental disabilities within a "typical" overnight summer camp: Camp Ramah's Tikvah Program.

    Science.gov (United States)

    Blas, Howard I

    2007-10-01

    The Tikvah Program is an overnight camping program at Camp Ramah in New England that serves campers with a range of developmental disabilities. The program has evolved over its 37-year history and includes a camping program, vocational training program, and inclusion program. Select graduates are hired by the camp for summer employment. The Tikvah Program offers a model for serving campers with special needs within a larger "typical" summer camp. Although serving the needs of such campers offers unique challenges, the presence of such a program in a regular summer camp offers tremendous opportunities and benefits for campers with special needs and more typically developing campers. PMID:17823062

  14. N6-(2-Hydroxyethyl)-Adenosine Exhibits Insecticidal Activity against Plutella xylostella via Adenosine Receptors

    Science.gov (United States)

    Fang, Ming; Chai, Yiqiu; Chen, Guanjv; Wang, Huidong; Huang, Bo

    2016-01-01

    The diamondback moth, Plutella xylostella, is one of the most important pests of cruciferous crops. We have earlier shown that N6-(2-hydroxyethyl)-adenosine (HEA) exhibits insecticidal activity against P. xylostella. In the present study we investigated the possible mechanism of insecticidal action of HEA on P. xylostella. HEA is a derivative of adenosine, therefore, we speculated whether it acts via P. xylostella adenosine receptor (PxAdoR). We used RNAi approach to silence PxAdoR gene and used antagonist of denosine receptor (AdoR) to study the insecticidal effect of HEA. We cloned the whole sequence of PxAdoR gene. A BLAST search using NCBI protein database showed a 61% identity with the Drosophila adenosine receptor (DmAdoR) and a 32–35% identity with human AdoR. Though the amino acids sequence of PxAdoR was different compared to other adenosine receptors, most of the amino acids that are known to be important for adenosine receptor ligand binding and signaling were present. However, only 30% binding sites key residues was similar between PxAdoR and A1R. HEA, at a dose of 1 mg/mL, was found to be lethal to the second-instar larvae of P. xylostella, and a significant reduction of mortality and growth inhibition ratio were obtained when HEA was administered to the larvae along with PxAdoR-dsRNA or antagonist of AdoR (SCH58261) for 36, 48, or 60 h. Especially at 48 h, the rate of growth inhibition of the PxAdoR knockdown group was 3.5-fold less than that of the HEA group, and the corrected mortality of SCH58261 group was reduced almost 2-fold compared with the HEA group. Our findings show that HEA may exert its insecticidal activity against P. xylostella larvae via acting on PxAdoR. PMID:27668428

  15. Effects of adenosine agonist R-phenylisopropyl-adenosine on halothane anesthesia and antinociception in rats

    Institute of Scientific and Technical Information of China (English)

    Hai-chun MA; Yan-fen WANG; Chun-sheng FENG; Hua ZHAO; Shuji DOHI

    2005-01-01

    Aim: To investigate the antinociceptive effect of adenosine agonist Rphenylisopropyl-adenosine (R-PIA) given to conscious rats by intracerebroventricular (ICV) and intrathecal (IT), and identify the effect of R-PIA on minimum alveolar concentration (MAC) of halothane with pretreatment of A1 receptor an tagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) or K+ channel blocker 4-aminopyridine (4-AP). Methods: Sprague-Dawley rats were implanted with 24 gauge stainless steel guide cannula using stereotaxic apparatus and ICV method, and an IT catheter (PE-10, 8.5 cm) was inserted into the lumbar subarachnoid space, while the rats were under pentobarbital anesthesia. After one week of recovery from surgery, rats were randomly assigned to one of the following protocols: MAC of halothane, or tail-flick latency. All measurements were performed after R-PIA (0.8-2.0 μg) microinjection into ICV and IT with or without pretreatment of DPCPX or 4-AP. Results: Microinjection of adenosine agonist R PIA in doses of 0.8-2.0 μg into ICV and IT produced a significant dose- and time dependent antinociceptive action as reflected by increasing latency times and ICV administration of adenosine agonist R-PIA (0.8 μg) reducing halothane anes thetic requirements (by 29%). The antinociception and reducing halothane requirements effected by adenosine agonist R-PIA was abolished by DPCPX and 4-AP. Conclusion: ICV and IT administration of adenosine agonist R-PIA produced an antinociceptive effect in a dose-dependent manner and decreased hal othane MAC with painful stimulation through activation of A1 receptor subtype, and the underlying mechanism involves K+ channel activation.

  16. A metabolic immune checkpoint: adenosine in tumor microenvironment

    Directory of Open Access Journals (Sweden)

    Akio eOhta

    2016-03-01

    Full Text Available Within tumors, some areas are less oxygenated than others. Since their home ground is under chronic hypoxia, tumor cells adapt to this condition by activating aerobic glycolysis; however, this hypoxic environment is very harsh for incoming immune cells. Deprivation of oxygen limits availability of energy sources and induces accumulation of extracellular adenosine in tumors. Extracellular adenosine, upon binding with adenosine receptors on the surface of various immune cells, suppresses pro-inflammatory activities. In addition, signaling through adenosine receptors upregulates a number of anti-inflammatory molecules and immunoregulatory cells, leading to the establishment of a long-lasting immunosuppressive environment. Thus, due to hypoxia and adenosine, tumors can discourage anti-tumor immune responses no matter how the response was induced, whether it was spontaneous or artificially introduced with a therapeutic intention. Preclinical studies have shown the significance of adenosine in tumor survival strategy by demonstrating tumor regression after inactivation of adenosine receptors, inhibition of adenosine-producing enzymes or reversal of tissue hypoxia. These promising results indicate a potential use of the inhibitors of the hypoxia-adenosine pathway for cancer immunotherapy.

  17. Pretreatment with adenosine and adenosine A1 receptor agonist protects against intestinal ischemia-reperfusion injury in rat

    Institute of Scientific and Technical Information of China (English)

    V Haktan Ozacmak; Hale Sayan

    2007-01-01

    AIM: To examine the effects of adenosine and A1 receptor activation on reperfusion-induced small intestinal injury.METHODS: Rats were randomized into groups with sham operation, ischemia and reperfusion, and systemic treatments with either adenosine or 2-chloro-N6-cyclopentyladenosine, A1 receptor agonist or 8-cyclopentyl-1,3-dipropylxanthine, A1 receptor antagonist, plus adenosine before ischemia. Following reperfusion, contractions of ileum segments in response to KCl, carbachol and substance P were recorded. Tissue myeloperoxidase,malondialdehyde, and reduced glutathione levels were measured.RESULTS: Ischemia significantly decreased both contraction and reduced glutathione level which were ameliorated by adenosine and agonist administration. Treatment also decreased neutrophil infiltration and membrane lipid peroxidation. Beneficial effects of adenosine were abolished by pretreatment with A1 receptor antagonist.CONCLUSION: The data suggest that adenosine and A1 receptor stimulation attenuate ischemic intestinal injury via decreasing oxidative stress, lowering neutrophil infiltration, and increasing reduced glutathione content.

  18. CS Radar Imaging via Adaptive CAMP

    NARCIS (Netherlands)

    Anitori, L.; Otten, M.P.G.; Hoogeboom, P.

    2012-01-01

    In this paper we present results on application of Compressive Sensing (CS) to high resolution radar imaging and pro- pose the adaptive Complex Approximate Message Passing (CAMP) algorithm for image reconstruction. CS provides a theoretical framework that guarantees, under certain assumptions, recon

  19. Sexual Harassment at Camp: Reducing Liability.

    Science.gov (United States)

    Oakleaf, Linda; Grube, Angela Johnson

    2003-01-01

    Employers are responsible for sexual harassment perpetrated by a supervisor. Camps may be responsible for sexual harassment between campers. Steps to reduce liability include providing multiple channels for reporting sexual harassment; having written policies prohibiting sexual harassment and procedures for reporting it; posting these policies and…

  20. Seven Habits of Highly Effective Camps.

    Science.gov (United States)

    Thurber, Christopher A.

    2002-01-01

    Effective camps share seven habits that are essential elements of success: internal leadership development, explicit expectations for staff, ample camper preparation, personal relationships, supervisors-in-residence, two-way communication flow, and commitment to self-improvement. Three key outcomes for directors, staff, and campers resulting from…

  1. Camp Crisis Management: Responding to New Challenges.

    Science.gov (United States)

    Evans, Will

    2002-01-01

    Camps should have crisis management plans. Steps to formulating a plan include involving appropriate off-site agencies, identifying potential threats, gathering resources, crafting an appropriate response, training via role-playing, managing incoming and outgoing information, and writing it down. Sidebars present resources, successful response…

  2. Conduct Disorders: Are Boot Camps Effective?

    Science.gov (United States)

    Jeter, LaVaughn V.

    2010-01-01

    Youth diagnosed with "conduct disorder" are often placed in programs using forced compliance and coercive control. One type of intervention used to treat conduct disorder is the boot camp. The basic idea is that disruptive behaviors can be corrected by strict behavioral regulation and an emphasis on skills training (Weis & Toolis 2009; Weis,…

  3. The Gold Mining Camp: A Simulation Game.

    Science.gov (United States)

    Stoltman, Joseph P.; Keach, Everett T., Jr.

    This economics simulation game complements the third grade Gold Mining Unit developed by Project Social Studies at the University of Minnesota. The simulation is designed for three purposes: 1) to reinforce the prior learning which occurs in the gold mining camp unit; 2) to involve eight-year-olds in the process of solving simulated economic…

  4. The Perspective of Camping Tourism in Romania

    Directory of Open Access Journals (Sweden)

    Andreea Marin-Pantelescu

    2015-12-01

    Full Text Available The tourists, who dream of a perfect holiday, with long term positive effects, find in camping a form of tourism that diminishes the impact of urban environment, and increase the chances of return to nature in a green place without stress and technology. Nowadays, the quests for technological detoxification methods are at high level and the customers are willing to pay a price for these services. The perspective of camping tourism in Romania represents an economic study regarding the supply and the demand of the camping services in our country and the future evolution of these particular services. The camping services evolution will be forecast using the linear trend statistical method in order to see the number of the tourist willing to use and enjoy the nature, the fresh air and the self-services regarding the accommodation, food and beverage or transportation. The impact of the paper discovery will provide better understanding of a tourism market steadily increasing and producing added value for all the stakeholders involved in the tourism sector.

  5. Summer Camp and Positive Youth Development: Program with Romanian Youth

    Science.gov (United States)

    Feenstra, Jennifer S.

    2015-01-01

    A variety of activities are used in camps to help promote positive youth development, improving social skills and self-esteem in campers. I expanded on previous camp research in this study to address the influence camps have on trust, belief in the honesty of others, empowerment, and care for others in youth in Eastern Europe. Since 1999, New…

  6. 49 CFR 218.80 - Movement of occupied camp cars.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Movement of occupied camp cars. 218.80 Section 218... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD OPERATING PRACTICES Protection of Occupied Camp Cars § 218.80 Movement of occupied camp cars. Occupied cars may not be humped or flat switched unless coupled...

  7. The Effect of a Camp Experience on Self Esteem.

    Science.gov (United States)

    Dorian, Alexia Eve

    Two groups of American adolescents of Greek descent (12-15 year olds N=90 and 16-18 year olds N=166) at an Orthodox Christian Camp in Greece responded to the Rosenberg Self Esteem Scale (1965). Campers took the test on the first day of camp (pretest) and then two weeks later at the camp's conclusion (posttest). All subjects showed a significant…

  8. Trainer Guide: Business and Finance Managerial. Camp Administration Series.

    Science.gov (United States)

    Farley, Elizabeth, Ed.

    Suggested ideas on conducting a managerial workshop for camp directors are offered in this trainer's guide. Workshops must be at least one full day of training (6 hours) on each topic to be counted toward the American Camping Association (ACA) Camp Director Certification Program. Suggested topics to be addressed are: (1) basic principles and…

  9. 7 CFR 503.6 - Camping, boating, and fishing.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Camping, boating, and fishing. 503.6 Section 503.6... OF AGRICULTURE CONDUCT ON PLUM ISLAND ANIMAL DISEASE CENTER § 503.6 Camping, boating, and fishing. The use of PIADC as a recreational area for camping, boating, fishing, and picnicking is...

  10. Camp Health Aide Manual = Manual para trabajadores de salud.

    Science.gov (United States)

    Robinson, June Grube; And Others

    This bilingual manual serves as a textbook for migrant Camp Health Aides. Camp Health Aides are members of migrant labor camps enlisted to provide information about health and social services to migrant workers and their families. The manual is divided into 12 tabbed sections representing lessons. Teaching notes printed on contrasting paper…

  11. Emerging Adults' Identity Exploration: Illustrations from inside the "Camp Bubble"

    Science.gov (United States)

    Johnson, Sara K.; Goldman, Jane A.; Garey, Anita I.; Britner, Preston A.; Weaver, Shannon E.

    2011-01-01

    The study investigates the experiences of emerging adults who had worked as counselors at overnight summer camps; identity-related issues emerge as most salient in the analysis of in-depth interviews conducted with 12 women and 8 men from 8 camps. Their descriptions portray the identity exploration that took place within the camp context, through…

  12. Mechanism of protection of adenosine from sulphate radical anion and repair of adenosine radicals by caffeic acid in aqueous solution

    Indian Academy of Sciences (India)

    M Sudha Swaraga; L Charitha; M Adinarayana

    2005-07-01

    The photooxidation of adenosine in presence of peroxydisulphate (PDS) has been studied by spectrophotometrically measuring the absorbance of adenosine at 260 nm. The rates of oxidation of adenosine by sulphate radical anion have been determined in the presence of different concentrations of caffeic acid. Increase in [caffeic acid] is found to decrease the rate of oxidation of adenosine suggesting that caffeic acid acts as an efficient scavenger of $SO_{4}^{\\bullet-}$ and protects adenosine from it. Sulphate radical anion competes for adenosine as well as for caffeic acid. The quantum yields of photooxidation of adenosine have been calculated from the rates of oxidation of adenosine and the light intensity absorbed by PDS at 254 nm, the wavelength at which PDS is activated to sulphate radical anion. From the results of experimentally determined quantum yields (exptl) and the quantum yields calculated (cal) assuming caffeic acid acting only as a scavenger of $SO_{4}^{\\bullet-}$ show that exptl values are lower than cal values. The ' values, which are experimentally found quantum yield values at each caffeic acid concentration and corrected for $SO_{4}^{\\bullet-}$ scavenging by caffeic acid, are also found to be greater than exptl values. These observations suggest that the transient adenosine radicals are repaired by caffeic acid in addition to scavenging of sulphate radical anions.

  13. Electroacupuncture improves neuropathic pain Adenosine,adenosine 5'-triphosphate disodium and their receptors perhaps change simultaneously

    Institute of Scientific and Technical Information of China (English)

    Wen Ren; Wenzhan Tu; Songhe Jiang; Ruidong Cheng; Yaping Du

    2012-01-01

    Applying a stimulating current to acupoints through acupuncture needles-known as electroacupuncture-has the potential to produce analgesic effects in human subjects and experimental animals.When acupuncture was applied in a rat model,adenosine 5'-triphosphate disodium in the extracellular space was broken down into adenosine,which in turn inhibited pain transmission by means of an adenosine A1 receptor-dependent process.Direct injection of an adenosine A1 receptor agonist enhanced the analgesic effect of acupuncture.The analgesic effect of acupuncture appears to be mediated by activation of A1 receptors located on ascending nerves.In neuropathic pain,there is upregulation of P2X purinoceptor 3(P2X3)receptor expression in dorsal root ganglion neurons.Conversely,the onset of mechanical hyperalgesia was diminished and established hyperalgesia was significantly reversed when P2X3 receptor expression was downregulated.The pathways upon which electroacupuncture appear to act are interwoven with pain pathways,and electroacupuncture stimuli converge with impulses originating from painful areas.Electroacupuncture may act via purinergic A1 and P2X3 receptors simultaneously to induce an analgesic effect on neuropathic pain.

  14. Pretreatment of rats with increased bioavailable berberine attenuates cerebral ischemia-reperfusion injury via down regulation of adenosine-5'monophosphate kinase activity.

    Science.gov (United States)

    Chen, Weijia; Wei, Shengnan; Yu, Yang; Xue, Huan; Yao, Fan; Zhang, Ming; Xiao, Jun; Hatch, Grant M; Chen, Li

    2016-05-15

    Berberine (BBR) exhibits multiple beneficial biological effects. However, poor bioavailability of BBR has limited its clinical application. We previously demonstrated that solid dispersion of BBR with sodium caprate (HGSD) remarkably improves its bioavailability. We examined whether this increased bioavailability of BBR could protect the brain from ischemia-reperfusion (IR) induced injury. Rats treated with HGSD, SC and saline for 7 days then subjected to cerebral ischemia reperfusion by middle cerebral artery occlusion for 2h followed 12h reperfusion. Neurological deficit scores, infarct size, SOD, MDA and NO levels were examined. P-AMPK, Bax, cleaved-Caspase-3 in brain was determined. To further probe for the mechanism of beneficial effect of HGSD, PC12 cells were incubated with serum from control or HGSD pretreated animals, incubated with 300μM H2O2 to induce apoptosis. Caspase-3 activity and cell apoptosis was evaluated. HGSD pretreatment significantly attenuated neurological deficit scores, reduced infarct size, increased SOD and decreased MDA and NO after cerebral IR injury compared to controls. Meanwhile, HGSD pretreatment significantly reduced expression of p-AMPK, Bax, cleaved-Caspase-3 after cerebral IR injury. Sodium caprate (100mg/kg/d) pretreatment alone did not exhibit any of these beneficial effects. PC12 cell apoptosis was attenuated when cells were cultured with HGSD serum compared to control. The presence of AMPK activator (AICAR) attenuated whereas AMPK inhibitor (Compound C) augmented the protective effect of HGSD serum on PC12 cell apoptosis.The results indicate that HGSD-pretreatment of rats protects the brain from ischemia-reperfusion injury and the mechanism is due to its anti-apoptotic effect mediated by decreased activation of AMPK. PMID:26957053

  15. A tyrosine-phosphorylated 55-kilodalton motility-associated bovine sperm protein is regulated by cyclic adenosine 3',5'-monophosphates and calcium.

    Science.gov (United States)

    Vijayaraghavan, S; Trautman, K D; Goueli, S A; Carr, D W

    1997-06-01

    Sperm motility is regulated by protein phosphorylation. We have recently shown that a serine/threonine phosphatase system is involved in motility regulation. Two of the components of the phosphatase system, GSK-3 and PP1gamma2, are regulated by tyrosine phosphorylation. During our investigation of sperm tyrosine-phosphorylated proteins we discovered a 55-kDa protein whose tyrosine phosphorylation correlates closely to the motility state of sperm. This protein is tyrosine phosphorylated to a much higher degree in motile caudal than in immotile caput epididymal sperm. Motility inhibition of caudal epididymal sperm by protein kinase A (PKA) anchoring inhibition or by ionomycin-induced calcium overload led to the virtual disappearance of tyrosine phosphorylation of the 55-kDa protein. Conversely, treatment of sperm with motility activators, isobutylmethylxanthine or 8-bromo-cAMP, resulted in increased tyrosine phosphorylation of the protein. The protein was present in the soluble 100 000 x g supernatants of sperm extracts and was heat labile. Chromatography through diethylaminoethyl-cellulose and Western blot analysis showed that this 55-kDa protein is not a regulatory subunit of PKA or alpha-tubulin. Our results represent the identification of a soluble protein whose tyrosine phosphorylation varies directly with motility and suggest that motility regulation may involve cross talk between PKA, calcium, and tyrosine kinase pathways. PMID:9166697

  16. Cloning of the cDNA encoding adenosine 5'-monophosphate deaminase 1 and its mRNA expression in Japanese flounder Paralichthys olivaceus

    Science.gov (United States)

    Jiang, Keyong; Sun, Shujuan; Liu, Mei; Wang, Baojie; Meng, Xiaolin; Wang, Lei

    2013-01-01

    AMP deaminase catalyzes the conversion of AMP into IMP and ammonia. In the present study, a full-length cDNA of AMPD1 from skeletal muscle of Japanese flounder Paralichthys olivaceus was cloned and characterized. The 2 526 bp cDNA contains a 5'-UTR of 78 bp, a 3'-UTR of 237 bp and an open reading frame (ORF) of 2 211 bp, which encodes a protein of 736 amino acids. The predicted protein contains a highly conserved AMP deaminase motif (SLSTDDP) and an ATP-binding site sequence (EPLMEEYAIAAQVFK). Phylogenetic analysis showed that the AMPD1 and AMPD3 genes originate from the same branch, but are evolutionarily distant from the AMPD2 gene. RT-PCR showed that the flounder AMPD1 gene was expressed only in skeletal muscle. QRT-PCR analysis revealed a statistically significant 2.54 fold higher level of AMPD1 mRNA in adult muscle (750±40 g) compared with juvenile muscle (7.5±2 g) ( Panimals.

  17. Liver MicroRNA-291b-3p Promotes Hepatic Lipogenesis through Negative Regulation of Adenosine 5'-Monophosphate (AMP)-activated Protein Kinase α1.

    Science.gov (United States)

    Meng, Xiangyu; Guo, Jun; Fang, Weiwei; Dou, Lin; Li, Meng; Huang, Xiuqing; Zhou, Shutong; Man, Yong; Tang, Weiqing; Yu, Liqing; Li, Jian

    2016-05-13

    In a microarray study, we found that hepatic miR-291b-3p was significantly increased in leptin-receptor-deficient type 2 mice (db/db), a mouse model of diabetes. The function of miR-291b-3p is unknown. The potential role of miR-291b-3p in regulating hepatic lipid metabolism was explored in this study. High-fat diet (HFD)- and chow-fed mice were injected with an adenovirus expressing a miR-291b-3p inhibitor and a miR-291b-3p mimic through the tail vein. Hepatic lipids and lipogenic gene expression were analyzed. Additionally, gain- and loss-of-function studies were performed in vitro to identify direct targets of miR-291b-3p. MiR-291b-3p expression and the protein levels of sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FAS) were increased in the steatotic liver of db/db mice and HFD-fed mice versus their respective controls. Inhibition of hepatic miR-291b-3p expression prevented increases in hepatic lipogenesis and steatosis in HFD-fed mice. The opposite was observed when miR-291b-3p was overexpressed in the livers of chow-fed C57BL/6J wild-type mice. In vitro studies revealed that silencing of miR-291b-3p in NCTC1469 hepatic cells ameliorated oleic acid/palmitic acid mixture-induced elevation of cellular triglycerides. Importantly, we identified AMP-activated protein kinase (AMPK)-α1 as a direct target of miR-291b-3p. Using metformin, an activator of AMPK, we showed that AMPK activation-induced inhibition of hepatic lipid accumulation was accompanied by reduced expression of miR-291b-3p in the liver. Liver miR-291b-3p promoted hepatic lipogenesis and lipid accumulation in mice. AMPKα1 is a direct target of miR-291b-3p. In conclusion, our findings indicate that miR-291b-3p promotes hepatic lipogenesis by suppressing AMPKα1 expression and activity, indicating the therapeutic potential of miR-291b-3p inhibitors in fatty liver disease. PMID:27013659

  18. Body Art Comes to Camp: Tattooing and Piercing Are Becoming Mainstream; Does Your Camp Have a Policy?

    Science.gov (United States)

    Cameron, Sandy

    2000-01-01

    Tattooing and body piercing are becoming mainstream, especially among the college population that comprises camp staff. Campers often idolize their counselors and want to be like them. Piercings may present a safety hazard. Camps should develop a policy and communicate it to prospective counselors and campers as early as possible. Several camps'…

  19. High-dose adenosine overcomes the attenuation of myocardial perfusion reserve caused by caffeine.

    OpenAIRE

    Reyes, E.; Loong, C Y; Harbinson, Mark; Donovan, J; Anagnostopoulos, C.; Underwood, S. R.

    2008-01-01

    Objectives:We studied whether an increase in adenosine dose overcomes caffeine antagonism on adenosine-mediated coronary vasodilation.Background:Caffeine is a competitive antagonist at the adenosine receptors, but it is unclear whether caffeine in coffee alters the actions of exogenous adenosine, and whether the antagonism can be surmounted by increasing the adenosine dose.Methods:Myocardial perfusion scintigraphy (MPS) was used to assess adenosine-induced hyperemia in 30 patients before (bas...

  20. Changes in phosphorylation of adenosine phosphate and redox state of nicotinamide-adenine dinucleotide (phosphate) in Geobacter sulfurreducens in response to electron acceptor and anode potential variation

    KAUST Repository

    Rose, Nicholas D.

    2015-12-01

    © 2015 Elsevier B.V. Geobacter sulfurreducens is one of the dominant bacterial species found in biofilms growing on anodes in bioelectrochemical systems. The intracellular concentrations of reduced and oxidized forms of nicotinamide-adenine dinucleotide (NADH and NAD+, respectively) and nicotinamide-adenine dinucleotide phosphate (NADPH and NADP+, respectively) as well as adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) were measured in G. sulfurreducens using fumarate, Fe(III)-citrate, or anodes poised at different potentials (110, 10, -90, and -190mV (vs. SHE)) as the electron acceptor. The ratios of CNADH/CNAD+ (0.088±0.022) and CNADPH/CNADP+ (0.268±0.098) were similar under all anode potentials tested and with Fe(III)-citrate (reduced extracellularly). Both ratios significantly increased with fumarate as the electron acceptor (0.331±0.094 for NAD and 1.96±0.37 for NADP). The adenylate energy charge (the fraction of phosphorylation in intracellular adenosine phosphates) was maintained near 0.47 under almost all conditions. Anode-growing biofilms demonstrated a significantly higher molar ratio of ATP/ADP relative to suspended cultures grown on fumarate or Fe(III)-citrate. These results provide evidence that the cellular location of reduction and not the redox potential of the electron acceptor controls the intracellular redox potential in G. sulfurreducens and that biofilm growth alters adenylate phosphorylation.

  1. Comorbidities in Neurology: Is Adenosine the Common Link?

    Science.gov (United States)

    Boison, Detlev; Aronica, Eleonora

    2015-01-01

    Comorbidities in Neurology represent a major conceptual and therapeutic challenge. For example, temporal lobe epilepsy (TLE) is a syndrome comprised of epileptic seizures and comorbid symptoms including memory and psychiatric impairment, depression, and sleep dysfunction. Similarly, Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic Lateral Sclerosis (ALS) are accompanied by various degrees of memory dysfunction. Patients with AD have an increased likelihood for seizures, whereas all four conditions share certain aspects of psychosis, depression, and sleep dysfunction. This remarkable overlap suggests common pathophysiological mechanisms, which include synaptic dysfunction and synaptotoxicity, as well as glial activation and astrogliosis. Astrogliosis is linked to synapse function via the tripartite synapse, but astrocytes also control the availability of gliotransmitters and adenosine. Here we will specifically focus on the ‘adenosine hypothesis of comorbidities’ implying that astrocyte activation, via overexpression of adenosine kinase (ADK), induces a deficiency in the homeostatic tone of adenosine. We present evidence from patient-derived samples showing astrogliosis and overexpression of ADK as common pathological hallmark of epilepsy, AD, PD, and ALS. We discuss a transgenic ‘comorbidity model’, in which brain-wide overexpression of ADK and resulting adenosine deficiency produces a comorbid spectrum of seizures, altered dopaminergic function, attentional impairment, and deficits in cognitive domains and sleep regulation. We conclude that dysfunction of adenosine signaling is common in neurological conditions, that adenosine dysfunction can explain comorbid phenotypes, and that therapeutic adenosine augmentation might be effective for the treatment of comorbid symptoms in multiple neurological conditions. PMID:25979489

  2. Summer camps for children with burn injuries: a literature review.

    Science.gov (United States)

    Maslow, Gary R; Lobato, Debra

    2010-01-01

    The first summer camps for children with burn injuries started over 25 years ago, and as of 2008, there were 60 camps worldwide. This review examines the literature on summer pediatric burn camps. The authors describe common characteristics of burn camp structure, activities, and staffing and then examine the scientific evidence regarding the effect of burn camp programs on campers and camp staff volunteers. A search of Pubmed and Psychinfo databases from 1970 to 2008 for articles related to pediatric burn summer camps identified 17 articles, of which 13 fit the inclusion criteria. Existing literature consists primarily of qualitative studies, suggesting that burn camp can decrease camper isolation, improve self-esteem, and promote coping and social skills. Studies examining volunteer staff at burn camp have consistently found that there are both personal and professional benefits. Quantitative studies of self-esteem have yielded equivocal results. No studies have examined safety or the effect of burn camp on medical or rehabilitation outcomes. For the past 25 years, pediatric summer camps for children with burn injuries have played an important rehabilitation role and provided a strong community that benefits both campers and staff. Future research using more rigorous research methods and examining a broader range of outcomes (eg, safety and medical/rehabilitation outcomes) is recommended. PMID:20644489

  3. Communication Boot Camp: Discover the Speaker in You!

    Directory of Open Access Journals (Sweden)

    Zuraidah Binti Ali

    2013-07-01

    Full Text Available Learning can take place almost anywhere, and this is especially true for our undergraduates who wish to become public speakers. Besides university course and public speaking workshops on campus grounds, undergraduates are now looking for a different learning environment – communication boot camps!! This study presents a compilation of learners’ experience, fun-filled activities, insightful feedback and memorable boot camp moments as captured in camp photos and feedback surveys. It involves a total of thirty seven undergraduates who enrolled in a Communication Boot Camp at Janda Baik, Pahang. Results show that Communication Boot Camp is a successful strategy to groom public speakers with a positive correlation between camp success and camp objectives, particularly in reducing shyness, motivating participants to become public speakers and discovering their talent and skills. In short, the study adds to the promise of zest and delight in public speaking.

  4. Increased riboflavin production by manipulation of inosine 5′-monophosphate dehydrogenase in Ashbya gossypii

    OpenAIRE

    Buey, Ruben M.; Ledesma Amaro, Rodrigo; Balsera, Mónica; Revuelta Doval, José Luis

    2015-01-01

    Guanine nucleotides are the precursors of essential biomolecules including nucleic acids and vitamins such as riboflavin. The enzyme inosine-5′-monophosphate dehydrogenase (IMPDH) catalyzes the ratelimiting step in the guanine nucleotide de novo biosynthetic pathway and plays a key role in controlling the cellular nucleotide pools. Thus, IMPDH is an important metabolic bottleneck in the guanine nucleotide synthesis, susceptible of manipulation by means of metabolic engineering approaches. Her...

  5. Crystal structure, energy band and optical properties of dysprosium monophosphate DyPO{sub 4}

    Energy Technology Data Exchange (ETDEWEB)

    Khadraoui, Z.; Bouzidi, C., E-mail: bouzidtc@yahoo.fr; Horchani-Naifer, K.; Ferid, M.

    2014-12-25

    Graphical abstract: The monophosphate DyPO{sub 4} has been synthesized by high temperature solid-state reaction method and was structurally characterized by single crystal X-ray diffraction. DyPO{sub 4} crystallizes in the tetragonal system (I4{sub 1}/Iamd). The energy-band structure, density of states and the chemical bonds have been investigated by density functional methods (DFT). - Highlights: • The DyPO{sub 4} has been synthesized by high temperature solid-state reaction method. • DFT was used to determine the electronic structure and optical properties of DyPO{sub 4}. • The monophosphate DyPO{sub 4} is an insulator with direct band gap (6.38 eV). - Abstract: A rare earth monophosphate crystal of DyPO{sub 4} has been synthesized by high temperature solid-state reaction method and was structurally characterized by single crystal X-ray diffraction. Atomic arrangement of DyPO{sub 4} structure is based on corner and edge sharing PO{sub 4} tetrahedra and DyO{sub 8} polyhedra. The FTIR, Raman, Scanning electron microscopy, diffuse reflectance and emission spectra of the compound have been investigated. Density functional calculation using a Generalized Gradient Approximation was used to determine the electronic structure and optical properties. The calculated total and partial densities of states indicate that the top of valance band is mainly built upon O-2p states with P-3p states via σ (P–O) interactions, and the low conduction bands mostly originates from Dy-5d. The results show that the monophosphate DyPO{sub 4} is an insulator with a calculated band gap (5.8 eV) closer to the experimental value (6.38 eV)

  6. Targeted Disruption of the Inosine 5′-Monophosphate Dehydrogenase Type I Gene in Mice

    OpenAIRE

    Gu, Jing Jin; Tolin, Amy K.; Jain, Jugnu; Huang, Hai; Santiago, Lalaine; Mitchell, Beverly S.

    2003-01-01

    Inosine 5′-monophosphate dehydrogenase (IMPDH) is the critical, rate-limiting enzyme in the de novo biosynthesis pathway for guanine nucleotides. Two separate isoenzymes, designated IMPDH types I and II, contribute to IMPDH activity. An additional pathway salvages guanine through the activity of hypoxanthine-guanine phosphoribosyltransferase (HPRT) to supply the cell with guanine nucleotides. In order to better understand the relative contributions of IMPDH types I and II and HPRT to normal b...

  7. The CBS subdomain of inosine 5’-monophosphate dehydrogenase regulates purine nucleotide turnover†

    OpenAIRE

    Pimkin, Maxim; Markham, George D.

    2008-01-01

    Inosine 5’-monophosphate dehydrogenase (IMPDH) catalyzes the rate limiting step in guanine nucleotide biosynthesis. IMPDH has an evolutionary conserved CBS subdomain of unknown function. The subdomain can be deleted without impairing the in vitro IMPDH catalytic activity and is the site for mutations associated with human retinitis pigmentosa. A guanine-prototrophic Escherichia coli strain, MP101, was constructed with the subdomain sequence deleted from the chromosomal gene for IMPDH. The ATP...

  8. A High-Affinity Adenosine Kinase from Anopheles Gambiae

    Energy Technology Data Exchange (ETDEWEB)

    M Cassera; M Ho; E Merino; E Burgos; A Rinaldo-Matthis; S Almo; V Schramm

    2011-12-31

    Genome analysis revealed a mosquito orthologue of adenosine kinase in Anopheles gambiae (AgAK; the most important vector for the transmission of Plasmodium falciparum in Africa). P. falciparum are purine auxotrophs and do not express an adenosine kinase but rely on their hosts for purines. AgAK was kinetically characterized and found to have the highest affinity for adenosine (K{sub m} = 8.1 nM) of any known adenosine kinase. AgAK is specific for adenosine at the nucleoside site, but several nucleotide triphosphate phosphoryl donors are tolerated. The AgAK crystal structure with a bound bisubstrate analogue Ap{sub 4}A (2.0 {angstrom} resolution) reveals interactions for adenosine and ATP and the geometry for phosphoryl transfer. The polyphosphate charge is partly neutralized by a bound Mg{sup 2+} ion and an ion pair to a catalytic site Arg. The AgAK structure consists of a large catalytic core in a three-layer {alpha}/{beta}/{alpha} sandwich, and a small cap domain in contact with adenosine. The specificity and tight binding for adenosine arise from hydrogen bond interactions of Asn14, Leu16, Leu40, Leu133, Leu168, Phe168, and Thr171 and the backbone of Ile39 and Phe168 with the adenine ring as well as through hydrogen bond interactions between Asp18, Gly64, and Asn68 and the ribosyl 2'- and 3'-hydroxyl groups. The structure is more similar to that of human adenosine kinase (48% identical) than to that of AK from Toxoplasma gondii (31% identical). With this extraordinary affinity for AgAK, adenosine is efficiently captured and converted to AMP at near the diffusion limit, suggesting an important role for this enzyme in the maintenance of the adenine nucleotide pool. mRNA analysis verifies that AgAK transcripts are produced in the adult insects.

  9. Yoga camp in Ayurvedgrams of Chhattisgarh

    Directory of Open Access Journals (Sweden)

    Raghavendra Madhu

    2012-01-01

    Full Text Available The clinical and empirical health benefits of yoga and pranayam have been reiterated through research. Yoga is being adopted as a system to alleviate the burden of noncommunicable diseases (NCDs across the globe. The Directorate of AYUSH, Government of Chhattisgarh (DoA, GoCG conducts annual 5-day-yoga camp across 146 Ayurvedgrams in the State. The present article brings out the AYUSH initiatives the State is taking toward active ageing. A total of 71,096 people participated in the 5-day-yoga camp across the State. A mean participation of 5079 people over 5 days was reported across districts. Such statewide practices need to be promoted and appraised.

  10. Recipient pretransplant inosine monophosphate dehydrogenase activity in nonmyeloablative hematopoietic cell transplantation.

    Science.gov (United States)

    Bemer, Meagan J; Risler, Linda J; Phillips, Brian R; Wang, Joanne; Storer, Barry E; Sandmaier, Brenda M; Duan, Haichuan; Raccor, Brianne S; Boeckh, Michael J; McCune, Jeannine S

    2014-10-01

    Mycophenolic acid, the active metabolite of mycophenolate mofetil (MMF), inhibits inosine monophosphate dehydrogenase (IMPDH) activity. IMPDH is the rate-limiting enzyme involved in de novo synthesis of guanosine nucleotides and catalyzes the oxidation of inosine 5'-monophosphate to xanthosine 5'-monophosphate (XMP). We developed a highly sensitive liquid chromatography-mass spectrometry method to quantitate XMP concentrations in peripheral blood mononuclear cells (PMNCs) isolated from the recipient pretransplant and used this method to determine IMPDH activity in 86 nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) patients. The incubation procedure and analytical method yielded acceptable within-sample and within-individual variability. Considerable between-individual variability was observed (12.2-fold). Low recipient pretransplant IMPDH activity was associated with increased day +28 donor T cell chimerism, more acute graft-versus-host disease (GVHD), lower neutrophil nadirs, and more cytomegalovirus reactivation but not with chronic GVHD, relapse, nonrelapse mortality, or overall mortality. We conclude that quantitation of the recipient's pretransplant IMPDH activity in PMNC lysate could provide a useful biomarker to evaluate a recipient's sensitivity to MMF. Further trials should be conducted to confirm our findings and to optimize postgrafting immunosuppression in nonmyeloablative HCT recipients.

  11. Xerophthalmia clinics in rural eye camps.

    Science.gov (United States)

    Desai, N C; Desai, S; Desai, R

    1992-05-01

    Even though the primary prevention of many eye diseases can be effectively incorporated into the existing pattern of rural eye camps, efforts in this direction are restrained and insubstantial. We describe our technique and experience in the prevention of xerophthalmia by organising a distinct entity called a xerophthalmia clinic in our eye camps. The clinic consists of an Ophthalmologist or an Ophthalmic assistant who will exclusively examine children who come to the eye camp. This is perhaps, the first report on rural xerophthalmia clinics, in ophthalmic literature. Over a seven year period from 1984 to 1990 we have conducted 71 xerophthalmia clinics amongst the ninty eye camps organised. A total of 11,370 children were examined in the xerophthalmia clinic out of which 18.9% were afflicted with the disease. Therapeutic doses of Vitamin A were administered on the spot to the afflicted and prophylactic doses were administered to the rest. Intensive health education efforts are made through clinics to effectuate change in dietry habits towards consumption of locally grown DGLV (Dark Green Leafy Vegetables) like Anthenum, chenopodium and Amaranthus. A bipronged offensive consisting of mega-dosing and health education is, for the present and the foreseeable future, the best strategy to combat xerophthalmia in this desert region. A year by year breakdown of prevalence rates in the present study shows that in years of severe drought the prevalence of xerophthalmia increases three fold over the non-drought or mild drought years, thereby demonstrating that drought is a substantial risk factor in developing countries leading to vitamin A deficiency and xerophthalmia. PMID:1452416

  12. Activation of Adenosine Receptor A2A Increases HSC Proliferation and Inhibits Death and Senescence by Down-regulation of p53 and Rb

    Directory of Open Access Journals (Sweden)

    Md. Kaimul eAhsan

    2014-04-01

    Full Text Available Background & Aims: During fibrosis hepatic stellate cells (HSC undergo activation, proliferation and senescence but the regulation of these important processes is poorly understood. The adenosine A2A receptor (A2A is known to be present on HSC, and its activation results in liver fibrosis. In this study, we tested if A2A has a role in the regulation of HSC proliferation, apoptosis, senescence, and the relevant molecular mechanism.Methods: The ability of adenosine to regulate p53 and Rb protein levels, proliferation, apoptosis and senescence was tested in the human HSC cell line LX-2 and rat primary HSC.Results: Adenosine receptor activation down-regulates p53 and Rb protein levels, increases BrdU incorporation and increases cell survival in LX-2 cells and in primary rat HSC. These effects of NECA were reproduced by an adenosine A2A receptor specific agonist (CGS21680 and blocked by a specific antagonist (ZM241385. By day twenty-one of culture primary rat HSC entered senescence and expressed -gal which was significantly inhibited by NECA. Furthermore, NECA induced down regulation of p53 and Rb and Rac1, and decreased phosphorylation of p44-42 MAP Kinase in LX-2 cells and primary rat HSC. These effects were reproduced by the cAMP analog 8-Bromo-cAMP, and the adenylyl cyclase activator forskolin, and were blocked by PKA inhibitors.Conclusions: These results demonstrate that A2A receptor regulates a number of HSC fate decisions and induces greater HSC proliferation, reduces apoptosis and senescence by decreasing p53 and Rb through cAMP-PKA/Rac1/p38 MAPK pathway. This provides a mechanism for adenosine induced HSC regulation and liver fibrosis.

  13. The role of adenosine receptors and endogenous adenosine in citalopram-induced cardiovascular toxicity

    OpenAIRE

    Kubilay Oransay; Nil Hocaoglu; Mujgan Buyukdeligoz; Yesim Tuncok; Sule Kalkan

    2014-01-01

    Aim: We investigated the role of adenosine in citalopram-induced cardiotoxicity. Materials and Methods: Protocol 1: Rats were randomized into four groups. Sodium cromoglycate was administered to rats. Citalopram was infused after the 5% dextrose, 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX; A 1 receptor antagonist), 8-(-3-chlorostyryl)-caffeine (CSC; A 2a receptor antagonist), or dimethyl sulfoxide (DMSO) administrations. Protocol 2: First group received 5% dextrose intraperitoneally 1 hour...

  14. Regulatory T cells negatively affect IL-2 production of effector T cells through CD39/adenosine pathway in HIV infection.

    Directory of Open Access Journals (Sweden)

    Mohammad-Ali Jenabian

    Full Text Available The mechanisms by which Regulatory T cells suppress IL-2 production of effector CD4+ T cells in pathological conditions are unclear. A subpopulation of human Treg expresses the ectoenzyme CD39, which in association with CD73 converts ATP/ADP/AMP to adenosine. We show here that Treg/CD39+ suppress IL-2 expression of activated CD4+ T-cells more efficiently than Treg/CD39-. This inhibition is due to the demethylation of an essential CpG site of the il-2 gene promoter, which was reversed by an anti-CD39 mAb. By recapitulating the events downstream CD39/adenosine receptor (A2AR axis, we show that A2AR agonist and soluble cAMP inhibit CpG site demethylation of the il-2 gene promoter. A high frequency of Treg/CD39+ is associated with a low clinical outcome in HIV infection. We show here that CD4+ T-cells from HIV-1 infected individuals express high levels of A2AR and intracellular cAMP. Following in vitro stimulation, these cells exhibit a lower degree of demethylation of il-2 gene promoter associated with a lower expression of IL-2, compared to healthy individuals. These results extend previous data on the role of Treg in HIV infection by filling the gap between expansion of Treg/CD39+ in HIV infection and the suppression of CD4+ T-cell function through inhibition of IL-2 production.

  15. The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Uses its C-Terminus to Regulate the A2B Adenosine Receptor.

    Science.gov (United States)

    Watson, Michael J; Lee, Shernita L; Marklew, Abigail J; Gilmore, Rodney C; Gentzsch, Martina; Sassano, Maria F; Gray, Michael A; Tarran, Robert

    2016-01-01

    CFTR is an apical membrane anion channel that regulates fluid homeostasis in many organs including the airways, colon, pancreas and sweat glands. In cystic fibrosis, CFTR dysfunction causes significant morbidity/mortality. Whilst CFTR's function as an ion channel has been well described, its ability to regulate other proteins is less understood. We have previously shown that plasma membrane CFTR increases the surface density of the adenosine 2B receptor (A2BR), but not of the β2 adrenergic receptor (β2AR), leading to an enhanced, adenosine-induced cAMP response in the presence of CFTR. In this study, we have found that the C-terminal PDZ-domain of both A2BR and CFTR were crucial for this interaction, and that replacing the C-terminus of A2BR with that of β2AR removed this CFTR-dependency. This observation extended to intact epithelia and disruption of the actin cytoskeleton prevented A2BR-induced but not β2AR-induced airway surface liquid (ASL) secretion. We also found that CFTR expression altered the organization of the actin cytoskeleton and PDZ-binding proteins in both HEK293T cells and in well-differentiated human bronchial epithelia. Furthermore, removal of CFTR's PDZ binding motif (ΔTRL) prevented actin rearrangement, suggesting that CFTR insertion in the plasma membrane results in local reorganization of actin, PDZ binding proteins and certain GPCRs. PMID:27278076

  16. Communication Boot Camp: Discover the Speaker in You!

    OpenAIRE

    Zuraidah Binti Ali; Noor Hafiza Binti Nor Azmi; Alicia a/p Phillip; Mohd Zin bin Mokhtar

    2013-01-01

    Learning can take place almost anywhere, and this is especially true for our undergraduates who wish to become public speakers. Besides university course and public speaking workshops on campus grounds, undergraduates are now looking for a different learning environment – communication boot camps!! This study presents a compilation of learners’ experience, fun-filled activities, insightful feedback and memorable boot camp moments as captured in camp photos and feedback surveys. It involves a ...

  17. Modulation of bladder function by luminal adenosine turnover and A1 receptor activation

    OpenAIRE

    Prakasam, H. Sandeep; Herrington, Heather; Roppolo, James R.; Jackson, Edwin K.; Apodaca, Gerard

    2012-01-01

    The bladder uroepithelium transmits information to the underlying nervous and musculature systems, is under constant cyclical strain, expresses all four adenosine receptors (A1, A2A, A2B, and A3), and is a site of adenosine production. Although adenosine has a well-described protective effect in several organs, there is a lack of information about adenosine turnover in the uroepithelium or whether altering luminal adenosine concentrations impacts bladder function or overactivity. We observed ...

  18. Yoga camp in Ayurvedgrams of Chhattisgarh

    OpenAIRE

    Raghavendra Madhu; Nilesh Jain

    2012-01-01

    The clinical and empirical health benefits of yoga and pranayam have been reiterated through research. Yoga is being adopted as a system to alleviate the burden of noncommunicable diseases (NCDs) across the globe. The Directorate of AYUSH, Government of Chhattisgarh (DoA, GoCG) conducts annual 5-day-yoga camp across 146 Ayurvedgrams in the State. The present article brings out the AYUSH initiatives the State is taking toward active ageing. A total of 71,096 people participated in the 5-day-yo...

  19. Complexities of speech in Palestinian refugee camps

    OpenAIRE

    Hawker, Nancy

    2011-01-01

    This paper is a report on work in progress. I have recently finished my fieldwork in three refugee camps in the West Bank: Shuafat RC, which is in the Jerusalem Municipal Area, Dheisheh RC, which is in the Bethlehem Governorate, and Tulkarem RC, which is in the north of the West Bank near the Green Line. I have been recording the speech of respondents in these locations to find out whether contact with Hebrew speakers is effecting language variation and change in spoken Palestinian Arabic. So...

  20. Inhibition of uptake of adenosine into human blood platelets

    NARCIS (Netherlands)

    Lips, J.P.M.; Sixma, J.J.; Trieschnigg, A.C.

    1980-01-01

    Adenosine transport into human blood platelets is mediated by two independent systems with different affinities. Both systems transport only purine nucleosides and no pyrimidine nucleosides. In experiments with differently substituted purine nucleosides, purines and analogues, differences in carrier

  1. cAMP-dependent protein kinase A and the dynamics of epithelial cell surface domains : moving membranes to keep in shape

    NARCIS (Netherlands)

    Wojtal, Kacper A.; Hoekstra, Dick; van IJzendoorn, Sven C. D.

    2008-01-01

    Cyclic adenosine monophosphate (cAMP) and cAMP-dependent protein kinase A (PKA) are evolutionary conserved molecules with a well-established position in the complex network of signal transduction pathways. cAMP/PKA-mediated signaling pathways are implicated in many biological processes that cooperat

  2. Distribution of adenosine receptors in human sclera fibroblasts

    OpenAIRE

    Cui, Dongmei; Trier, Klaus; Chen, Xiang; Zeng, Junwen; Yang, Xiao; Hu, Jianmin; Ge, Jian

    2008-01-01

    Purpose Systemic treatment with adenosine receptor antagonists has been reported to affect the biochemistry and ultrastructure of rabbit sclera. This study was conducted to determine whether adenosine receptors (ADORs) are present in human scleral fibroblasts (HSF). Methods Primary HSF were cultured in vitro and identified with anti-vimentin, anti-keratin, anti-desmin, and anti-S-100 antibodies. Confocal fluorescence microscopy was used to study the distribution of ADORs in the HSF cell lines...

  3. Residential Grief Camps: An Initial Phenomenological Study of Staff Perspectives

    Science.gov (United States)

    Brown, Tiffany B.; Kimball, Thomas G.

    2012-01-01

    Research has focused primarily on the impact of death on family functioning and the stages and tasks of grief, though little attention has been given to grief camps or the experiences of those who work there. This study explored the experiences of staff at a four-day overnight children's grief camp. Eight participants reported their experience of…

  4. Students Become Scientists at Science Skills Boot Camp | Poster

    Science.gov (United States)

    At the 2016 Science Skills Boot Camp (SSBC), a one-day training program designed for NIH summer interns with little or no prior research experience, students gathered to learn about basic research and laboratory skills. The boot camp provided a unique opportunity for interns to expand their knowledge of simple bench techniques, scientific papers, and ways to communicate their research.

  5. Camping under Western Stars: Joan Crawford in "Johnny Guitar."

    Science.gov (United States)

    Robertson, Pamela

    1995-01-01

    Examines the dissonant and "camp" effect inherent in describing "Johnny Guitar" as a Joan Crawford western. Argues that the film's camp effect depends on its crossing of a female star vehicle with the western, a stereotypically masculine genre. Summarizes Crawford's childhood and rise to fame. Concludes by exploring the lesbian and "butch-femme"…

  6. Creating a Healthy Camp Community: A Nurse's Role.

    Science.gov (United States)

    Lishner, Kris Miller; Bruya, Margaret Auld

    This book provides an organized, systematic overview of the basic aspects of health program management, nursing practice, and human relations issues in camp nursing. A foremost assumption is that health care in most camps needs improvement. Good health is dependent upon interventions involving social, environmental, and lifestyle factors that…

  7. Socialization of Adolescents: Cultural Practices in Children's Summer Camp

    Science.gov (United States)

    Demakova, Irina D.; Valeeva, Roza A.; Shipova, Alina V.

    2016-01-01

    The article describes the relevant aspects of the adolescents' cultural practices in children's summer camp, taking into account their specific characteristics. The summer camp is considered as an educational formation and holistic socio-pedagogical body, designed to create conditions for the development of the person. The criteria for inclusion…

  8. EduCamp Colombia: Social Networked Learning for Teacher Training

    Science.gov (United States)

    Fonseca, Diego Ernesto Leal

    2011-01-01

    This paper describes a learning experience called EduCamp, which was launched by the Ministry of Education of Colombia in 2007, based on emerging concepts such as e-Learning 2.0, connectivism, and personal learning environments. An EduCamp proposes an unstructured collective learning experience, which intends to make palpable the possibilities of…

  9. "Don't Laugh at Me" Coming to Camps.

    Science.gov (United States)

    Coleman, Marla

    2000-01-01

    Describes a multimedia resource developed for camps by the American Camping Association and Peter Yarrow, of Peter, Paul, and Mary, to help children express and manage their emotions, cooperate and appreciate the individual strengths that each child brings to a group, celebrate diversity, and practice negotiating and resolving conflict creatively.…

  10. Vision, Leadership, and Change: The Case of Ramah Summer Camps

    Science.gov (United States)

    Reimer, Joseph

    2010-01-01

    In his retrospective essay, Seymour Fox (1997) identified "vision" as the essential element that shaped the Ramah camp system. I will take a critical look at Fox's main claims: (1) A particular model of vision was essential to the development of Camp Ramah; and (2) That model of vision should guide contemporary Jewish educators in creating Jewish…

  11. Structural Studies of Thiamin Monophosphate Kinase in Complex with Substrates and Products.

    Energy Technology Data Exchange (ETDEWEB)

    McCulloch, K.M.; Kinsland, C.; Begley, T.P.; Ealick, S E. (Cornell)

    2008-06-03

    Thiamin monophosphate kinase (ThiL) catalyzes the ATP-dependent phosphorylation of thiamin monophosphate (TMP) to form thiamin pyrophosphate (TPP), the active form of vitamin B1. ThiL is a member of a small ATP binding superfamily that also includes the purine biosynthetic enzymes, PurM and PurL, NiFe hydrogenase maturation protein, HypE, and selenophosphate synthase, SelD. The latter four enzymes are believed to utilize phosphorylated intermediates during catalysis. To understand the mechanism of ThiL and its relationship to the other superfamily members, we determined the structure of Aquifex aeolicus ThiL (AaThiL) with nonhydrolyzable AMP-PCP and TMP, and also with the products of the reaction, ADP and TPP. The results suggest that AaThiL utilizes a direct, inline transfer of the {gamma}-phosphate of ATP to TMP rather than a phosphorylated enzyme intermediate. The structure of ThiL is compared to those of PurM, PurL, and HypE, and the ATP binding site is compared to that of PurL, for which nucleotide complexes are available.

  12. Intracellular adenosine 3',5'-phosphate formation is essential for down-regulation of surface adenosine 3',5'-phosphate receptors in Dictyostelium

    OpenAIRE

    Van Haastert, Peter J. M.

    1994-01-01

    Dictyostelium discoideum cells contain cell surface cyclic AMP (cAMP) receptors that bind cAMP as a first messenger and intracellular cAMP receptors that bind cAMP as a second messenger. Prolonged incubation of Dictyostelium cells with cAMP induces a sequential process of phosphorylation, sequestration and down-regulation of the surface receptors. The role of intracellular cAMP in down-regulation of surface receptors was investigated. Down-regulation of receptors does not occur under conditio...

  13. Role of A3 adenosine receptor in diabetic neuropathy.

    Science.gov (United States)

    Yan, Heng; Zhang, Enshui; Feng, Chang; Zhao, Xin

    2016-10-01

    Neuropathy is the most common diabetic complication. Although the A1 and A2A adenosine receptors are important pharmacological targets in alleviating diabetic neuropathy, the role of the A3 adenosine receptor remains unknown. Because the A3 adenosine receptor regulates pain induced by chronic constriction injury or chemotherapy, its stimulation might also attenuate diabetic neuropathy. This study examines the effects of systemic treatment with the A3 adenosine receptor agonist 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-β-d-ribofuranuronamide (IB-MECA) on diabetic neuropathy and explores the putative mechanisms underlying its pharmacological effects. We show that IB-MECA alleviated mechanical hyperalgesia and thermal hypoalgesia in mice 2 weeks but not 4 weeks after streptozocin (STZ) treatment. Furthermore, IB-MECA prevented the reduction in sciatic motor nerve conduction velocity and sensory nerve conduction velocity in diabetic mice 2 weeks but not 4 weeks after STZ treatment. Similarly, IB-MECA inhibited the activation of nuclear factor-κB and decreased the generation of tumor necrosis factor-α in the spinal cord of mice 2 weeks but not 4 weeks after STZ treatment. These phenomena were associated with reduction of A3 adenosine receptor expression in the spinal cord after long-term diabetes. Our results suggest that the A3 adenosine receptor plays a critical role in regulating diabetic neuropathy and that reduction in A3 adenosine receptor expression/function might contribute to the progression of diabetic neuropathy. © 2016 Wiley Periodicals, Inc.

  14. Magnetic Cellular Switches

    OpenAIRE

    Overby, Darryl R.; Alenghat, Francis J.; Montoya-Zavala, Martín; Bei, HuCheng; Oh, Philmo; Karavitis, John; Ingber, Donald E.

    2004-01-01

    This paper focuses on the development of magnetic cellular switches to enable magnetic control of intracellular functions in living mammalian cells, including receptor signal transduction and gene transcription. Our approach takes advantage of the mechanosensitivity of adenosine 3′,5′-monophosphate (cAMP) induction and downstream transcription controlled by the cAMP regulatory element (CRE) to engineer gene constructs that optically report gene expression in living cells. We activate transcri...

  15. Hypergravity signal transduction in HeLa cells with concomitant phosphorylation of proteins immunoprecipitated with anti-microtubule-associated protein antibodies

    Science.gov (United States)

    Kumei, Yasuhiro; Whitson, Peggy A.; Sato, Atsushige; Cintron, Nitza M.

    1991-01-01

    It is shown that hypergravity (35g) stimulates the production of inositol 1,4,5-trisphosphate (IP3) and decreases adenosine 3-prime,5-prime-cyclic monophosphate (cAMP) levels in HeLa cells. It is proposed that IP3 and cAMP may act as second messengers in hypergravity signal transduction. Phosphorylation of microtubule-associated proteins in both the detergent-soluble and -insoluble fractions suggests that cytoskeletal structures may be influenced by gravity.

  16. Intracoronary adenosine improves myocardial perfusion in late reperfused myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Background Myocardial perfusion associates with clinical syndromes and prognosis.Adenosine could improve myocardial perfusion of acute myocardial infarction within 6 hours,but few data are available on late perfusion of myocardial infarction (MI).This study aimed at quantitatively evaluating the value of intracoronary adenosine improving myocardial perfusion in late reperfused MI with myocardial contrast echocardiography(MCE).Methods Twenty-six patients with anterior wall infarcts were divided randomly into 2 groups:adenosine group(n=12) and normal saline group(n=14).Their history of myocardial infarction was about 3-12 weeks.Adenosine or normalsaline was given when the guiding wire crossed the lesion through percutaneous coronary intervention(PCI),then the balloon was dilated and stent(Cypher/Cypher select)was implanted at the lesion.Contrast pulse sequencing MCE with Sonovue contrast via the coronary route was done before PCI and 30 minutes after PCI.Video densitometry and contrast filled-blank area were calculated with the CUSQ off-line software.Heart function and cardiac events were followed up within 30 days.Results Perfusion in the segments of the criminal occlusive coronary artery in the adenosine group was better than that in the saline group(5.71±0.29 vs 4.95±1.22,P<0.05).Ischemic myocardial segment was deminished significantly afterPCI,but the meliorated area was bigger in the adenosine group than in the saline group((1.56±0.60)cm2 vs(1.02±0.56) cm2,P<0.05).The video densitometry in critical segments was also improved significantly in the adenosine group (5.53±0.36 vs 5.26±0.35,P<0.05).Left ventricular ejection fraction(LVEF)was improved in all patients after PCI,but EF was not significant between the two groups((67±6)% vs(62±7)%,P>0.05).There was no in-hospital or 30-day major adverse cardiac event(MACE)in the adenosine group but 3 MACE in the saline group in 30 days after PCI.Conclusions Adenosine could improve myocardial microvascular

  17. Directed evolution of the Escherichia coli cAMP receptor protein at the cAMP pocket.

    Science.gov (United States)

    Gunasekara, Sanjiva M; Hicks, Matt N; Park, Jin; Brooks, Cory L; Serate, Jose; Saunders, Cameron V; Grover, Simranjeet K; Goto, Joy J; Lee, Jin-Won; Youn, Hwan

    2015-10-30

    The Escherichia coli cAMP receptor protein (CRP) requires cAMP binding to undergo a conformational change for DNA binding and transcriptional regulation. Two CRP residues, Thr(127) and Ser(128), are known to play important roles in cAMP binding through hydrogen bonding and in the cAMP-induced conformational change, but the connection between the two is not completely clear. Here, we simultaneously randomized the codons for these two residues and selected CRP mutants displaying high CRP activity in a cAMP-producing E. coli. Many different CRP mutants satisfied the screening condition for high CRP activity, including those that cannot form any hydrogen bonds with the incoming cAMP at the two positions. In vitro DNA-binding analysis confirmed that these selected CRP mutants indeed display high CRP activity in response to cAMP. These results indicate that the hydrogen bonding ability of the Thr(127) and Ser(128) residues is not critical for the cAMP-induced CRP activation. However, the hydrogen bonding ability of Thr(127) and Ser(128) was found to be important in attaining high cAMP affinity. Computational analysis revealed that most natural cAMP-sensing CRP homologs have Thr/Ser, Thr/Thr, or Thr/Asn at positions 127 and 128. All of these pairs are excellent hydrogen bonding partners and they do not elevate CRP activity in the absence of cAMP. Taken together, our analyses suggest that CRP evolved to have hydrogen bonding residues at the cAMP pocket residues 127 and 128 for performing dual functions: preserving high cAMP affinity and keeping CRP inactive in the absence of cAMP.

  18. Antagonism by theophylline of respiratory inhibition induced by adenosine.

    Science.gov (United States)

    Eldridge, F L; Millhorn, D E; Kiley, J P

    1985-11-01

    The effects on respiration of an analogue of adenosine, L-2-N6-(phenylisopropyl)adenosine (PIA), and of the methylxanthine, theophylline, were determined in 19 vagotomized glomectomized cats whose end-tidal PCO2 was kept constant by means of a servo-controlled ventilator. Integrated phrenic nerve activity was used to represent respiratory output. Our results show that PIA, whether given systemically or into the third cerebral ventricle, depressed respiration. Systemically administered theophylline stimulated respiration. Theophylline given intravenously, or into the third ventricle not only reversed the depressive effects of previously administered PIA but caused further increases of respiration above the control level. Prior systemic administration of theophylline blocked both respiratory and hypotensive effects of subsequently administered PIA. Effects of either agent on medullary extracellular fluid pH did not explain the results. We conclude that the adenosine analogue PIA, acts to inhibit neurons in the brain that are involved in the control of respiration and that its effects are blocked by theophylline. We suggest that adenosine acts as a tonic modulator of respiration and that theophylline stimulates breathing by competitive antagonism of adenosine at neuronal receptor sites. PMID:4066573

  19. Adenosine A1 receptor agonists inhibit trigeminovascular nociceptive transmission

    DEFF Research Database (Denmark)

    Goadsby, P J; Hoskin, K L; Storer, R J;

    2002-01-01

    There is a considerable literature to suggest that adenosine A1 receptor agonists may have anti-nociceptive effects, and we sought to explore the role of adenosine A1 receptors in a model of trigeminovascular nociceptive transmission. Cats were anaesthetized (alpha-chloralose 60 mg/kg, intraperit......There is a considerable literature to suggest that adenosine A1 receptor agonists may have anti-nociceptive effects, and we sought to explore the role of adenosine A1 receptors in a model of trigeminovascular nociceptive transmission. Cats were anaesthetized (alpha-chloralose 60 mg...... from the external jugular vein to determine levels of calcitonin gene-related peptide (CGRP) release before and after drug administration. Intravenous administration of the highly selective adenosine A1 receptor agonist, GR79236 (3-100 microg/kg) had a dose-dependent inhibitory effect on SSS...... 33 +/- 2 pmol/l (n = 6) to 64 +/- 3 pmol/l, an effect substantially reduced by pre-treatment with GR79236 (30 microg/kg; P agonist, GR190178 (30-1000 microg/kg i.v.), also inhibited SSS-evoked neuronal activity in a dose-dependent fashion...

  20. Camp Sports Injuries: Analysis of Causes, Modes and Frequencies

    Directory of Open Access Journals (Sweden)

    Panagiota Papageorgiou

    2008-12-01

    Full Text Available The purpose of this study was the description of sports injuries sustained by campers at summer camps, aged 7-15 years. A sample of 8 camps from the Greek camp population participated in this sport injury surveillance study. Doctors and camp directors completed reports detailing the number of sports injuries events sustained and provided specific information about each event. During the period of the study, 337 sport injury reports were completed. A total of 237 (70.3% boys and 100 (29.7% girls reported having a sport injury. Age of campers sustaining a sport injury was 10-12 years old (60.8%. The frequency of sports injuries was highest during the first camp season. The leading causes of sports injuries in children’s were: falls, crushed by object, collision with other person and slips. Cut/scratch injuries were the most common diagnoses (38.9%. Football, basketball and volleyball were the most frequent sport activities for injuries. Reports based surveillance systems can be successfully used to conducts sport injury surveillance among children attending summer camps. Data collected via such systems can be used to calculate sports injury rates, to describe patterns of sport injury and to identify risk factors for camper – related sport injuries. The results provide necessary information to develop prevention interventions to decrease the number of youth whose camp experiences are negatively affected by sport injury.

  1. How to run a sports camp – legally speaking

    Directory of Open Access Journals (Sweden)

    Steven Monk

    2016-04-01

    Full Text Available Camps are a great way to keep kids active throughout the summer and to make money for the program sponsoring them. Planning is needed for a sports camp to be safe for both the camp personnel and the athletes, and to minimize legal negligence.  Having a risk management plan in place is important to insure that everyone is aware of the risks of participating. Background checks on camp personnel help ensure the camp leaders and coaches do not have a criminal background.  It is important to inspect the facilities/equipment to make sure they are safe to use.  Athletic trainers help with injuries that may occur with participation.  Supervisors make sure that everyone is accounted for and camp rules help the campers behave in an appropriate manner.  When planning activities, it is important to look at the skill level of the athletes. If all of these areas are covered, camps should be legally protected if an issue were to arise.

  2. Directional sensing and streaming in Dictyostelium aggregation.

    Science.gov (United States)

    Almeida, Sofia; Dilão, Rui

    2016-05-01

    We merge the Kessler-Levine simple discrete model for Dictyostelium cyclic adenosine monophosphate (cAMP) production and diffusion with the Dilão-Hauser directional sensing aggregation mechanism. The resulting compound model describes all the known transient patterns that emerge during Dictyostelium aggregation, which include the spontaneous formation of cAMP self-sustained target and spiral waves and streaming. We show that the streaming patterns depend on the speed of the amoebae, on the relaxation time for the production of cAMP, on the cAMP degradation rate, and on directional sensing. Moreover, we show that different signaling centers emerge during Dictyostelium aggregation.

  3. Modulating effect of adenosine deaminase on function of adenosine A1receptors

    Institute of Scientific and Technical Information of China (English)

    Wan-chun SUN; Yan CAO; Lei JIN; Li-zhen WANG; Fan MENG; Xing-zu ZHU

    2005-01-01

    Aim: To study the modulating effect of adenosine deaminase (ADA) on yhe adenosine A1 receptor (A1R) in HEK293 cells stably expressing the human A1R.Methods: cDNA was amplified by RT-PCR using total RNA from human embryo brain tissue as the template. The PCR products were subcloned into the plasmid pcDNA3 and cloned into the plasmid pcDNA3.1. The cloned A1R cDNA was sequenced and stably expressed in HEK293 cells. The modulating effect of adenosine deaminase on A1R was studied by using [3H]DPCPX binding assay and an intracellular calcium assay. Results: HEK293 cells stably expressing human A1R were obtained. Saturation studies showed that the KD value and Bmax value of [3H]DPCPX were 1.6±0.2 nmol/L and 1.819±0.215 nmol/g of protein respectively, in the absence of ecto-ADA respectively, and 1.3±0.2 nmol/L and 1.992±0.130 nmol/g of protein in the presence of ecto-ADA respectively, suggesting that the KD value and Bmax value of [3H]DPCPX were unaffected by ecto-ADA. In the case of [3H]DPCPX competition curves obtained from intact cells or membranes, A1R agonist CCPA/[3H]DPCPX competition curve could be fitted well to a one-site model in the absence of ecto-ADA and a two-site model in the presence of ecto ADA with a KH value of 0.74 (0.11-4.8) nmol/L (intact cells) or 1.8 (0.25-10) nmol/L (membrane) and a KL value of 0.94 (0.62-1.41) μmol/L (intact cells) or 0.77 (0.29-0.99) μmol/L (membrane). The KL value is not significantly different from the IC50 value of 0.84(0.57-1.23) μmol/L (intact cells) or 0.84 (0.63-1.12) μmol/L (membrane) obtained in the absence of ecto-ADA. Similar results were obtained from the CPA/[3H]DPCPX competition curve in the absence or presence of ecto-ADA on intact cells or membranes. Intracellular calcium assay demonstrated that the EC50 value of CPA were 10 (5-29) nmol/L and 94 (38-229) nmol/L in the presence or absence of ecto-ADA, respectively. Conclusion: A1R stably expressed in the HEK293 cells display a low affinity for agonists in

  4. Thallium-201 scintigraphy of the myocardium in connection with adenosine

    International Nuclear Information System (INIS)

    It is shown that thallium-201 SPECT studies of the myocardium performed subsequent to intravenous infusion of adenosine provide results at least as valuable as those from exercise thallium-201 scintigraphy in the diagnosis of coronary artery disease. The infusion of adenosine offers great advantages over exercise studies in that it is a standardized procedure uninfluenced by a patient's physical fitness, which can thus be used in all cases. There are quite a number of clinically tolerable untoward reactions that may be associated with discomfort but do not warrant discontinuation of the procedure. Serious, verifiable side-effects are rare and disappear immediately on termination of the infusion. The most recent research in this field has shown that newly developed compounds of 99mTc are also suitable for radionuclide studies of the myocardium with adenosine vasodilation. (orig.)

  5. Social Meaning of Culture in a Stalinist Prison Camp

    OpenAIRE

    Aimar Ventsel; Baurzhan Zhangutin; Dinara Khamidullina

    2014-01-01

    The Stalinist prison camp system – popularly known as the Gulag archipelago – existed for a relatively short period (from 1931–1960) and became world famous as a synonym for terror, humiliation and human suffering. This article focuses on the social significance of culture in one of the biggest Stalinist prison camp – Karlag in Central Kazakhstan. The first part of the article gives an overview of the institutions of culture in prison camps and their activities. It also gives an overview of u...

  6. Increased riboflavin production by manipulation of inosine 5'-monophosphate dehydrogenase in Ashbya gossypii.

    Science.gov (United States)

    Buey, Rubén M; Ledesma-Amaro, Rodrigo; Balsera, Mónica; de Pereda, José María; Revuelta, José Luis

    2015-11-01

    Guanine nucleotides are the precursors of essential biomolecules including nucleic acids and vitamins such as riboflavin. The enzyme inosine-5'-monophosphate dehydrogenase (IMPDH) catalyzes the ratelimiting step in the guanine nucleotide de novo biosynthetic pathway and plays a key role in controlling the cellular nucleotide pools. Thus, IMPDH is an important metabolic bottleneck in the guanine nucleotide synthesis, susceptible of manipulation by means of metabolic engineering approaches. Herein, we report the functional and structural characterization of the IMPDH enzyme from the industrial fungus Ashbya gossypii. Our data show that the overexpression of the IMPDH gene increases the metabolic flux through the guanine pathway and ultimately enhances 40 % riboflavin production with respect to the wild type. Also, IMPDH disruption results in a 100-fold increase of inosine excretion to the culture media. Our results contribute to the developing metabolic engineering toolbox aiming at improving the production of metabolites with biotechnological interest in A. gossypii. PMID:26150243

  7. Osmium (VI) complexes of the 3', 5'-dinucleoside monophosphates, ApU and UpA.

    Science.gov (United States)

    Daniel, F B; Behrman, E J

    1976-02-10

    The dinucleoside monophosphates, ApU and UpA, react with potassium osmate (VI) and 2,2'-bipyridyl to form the corresponding oxo-osmium (VI) bipyridyl sugar ester in which the osmate group is bonded to the terminal 2',3'-glycol. Osmium (VIII) tetroxide and 2,2'-bipyridyl react with the dinucleosides to form the corresponding oxo-osmium (VI) bipyridyl heterocyclic esters which result from addition of the tetroxide to the 5,6-double bond of the uracil residue. Although capable of transesterification reactions, these heterocyclic esters are exceptionally stable toward exchange reactions in solution. No apparent exchange was observed after 1 month. This reaction thus seems promising for single-site osmium labeling in polynucleotides.

  8. Role of adenosine as adjunctive therapy in acute myocardial infarction.

    Science.gov (United States)

    Forman, Mervyn B; Stone, Gregg W; Jackson, Edwin K

    2006-01-01

    Although early reperfusion and maintained patency is the mainstay therapy for ST elevation myocardial infarction, experimental studies demonstrate that reperfusion per se induces deleterious effects on viable ischemic cells. Thus "myocardial reperfusion injury" may compromise the full potential of reperfusion therapy and may account for unfavorable outcomes in high-risk patients. Although the mechanisms of reperfusion injury are complex and multifactorial, neutrophil-mediated microvascular injury resulting in a progressive decrease in blood flow ("no-reflow" phenomenon) likely plays an important role. Adenosine is an endogenous nucleoside found in large quantities in myocardial and endothelial cells. It activates four well-characterized receptors producing various physiological effects that attenuate many of the proposed mechanisms of reperfusion injury. The cardio-protective effects of adenosine are supported by its role as a mediator of pre- and post-conditioning. In experimental models, administration of adenosine in the peri-reperfusion period results in a marked reduction in infarct size and improvement in ventricular function. The cardioprotective effects in the canine model have a narrow time window with the drug losing its effect following three hours of ischemia. Several small clinical studies have demonstrated that administration of adenosine with reperfusion therapy reduces infarct size and improves ventricular function. In the larger AMISTAD and AMISTAD II trials a 3-h infusion of adenosine as an adjunct to reperfusion resulted in a striking reduction in infarct size (55-65%). Post hoc analysis of AMISTAD II showed that this was associated with significantly improved early and late mortality in patients treated within 3.17 h of symptoms. An intravenous infusion of adenosine for 3 h should be considered as adjunctive therapy in high risk-patients undergoing reperfusion therapy. PMID:16961725

  9. EFFECTS OF MONOSODIUM GLUTAMATE (UMAMI TASTE) WITH AND WITHOUT GUANOSINE 5'-MONOPHOSPHATE ON RAT AUTONOMIC RESPONSES TO MEALS

    NARCIS (Netherlands)

    STEFFENS, AB; LEUVENINK, H; SCHEURINK, AJW

    1994-01-01

    Monosodium glutamate (MSG) is used as a food additive to improve the taste of food. The effect of MSG on sweet taste is enhanced by guanosine 5'-monophosphate (GMP). Because increased palatability is known to increase the vagally mediated preabsorptive insulin response (PIR), we hypothesized that MS

  10. Phosphorylation of adenosine with trimetaphosphate under simulated prebiotic conditions.

    Science.gov (United States)

    Cheng, Changmei; Fan, Chang; Wan, Rong; Tong, Chunyuan; Miao, Zhiwei; Chen, Jing; Zhao, Yufen

    2002-06-01

    The phosphorylation of adenosine with trimetaphosphate in solution, in solid phase and using wet-dry cycles was carried out and it was found that wet-dry cycles were the most efficient. The catalytic effects of some metal ions on the phosphorylation were also studied and it was discovered that Ni(II) is the most effective. The combination of wet-dry cycles (4 cycles) and catalysis by Ni(II) led to an unprecedented high conversion of adenosine to phosphorylated products (30%) near neutral pH. The main phosphorylated products were 2',3'-cyclic AMP (10.4%) and 5'-ATP (13.0%). PMID:12227426

  11. No role of interstitial adenosine in insulin-mediated vasodilation

    DEFF Research Database (Denmark)

    Dela, F; Stallknecht, B

    1999-01-01

    healthy subjects (H) and in four subjects with a complete, high (C5-C6/7) spinal cord injury (SCI) a hyperinsulinaemic (480 mU min-1 kg-1), isoglycaemic clamp was performed. SCI subjects were included as it has been proposed that adenosine and adenine nucleotides may be released from nerve endings in the...... skeletal muscle. Adenosine concentrations in the extracellular fluid (ECF) of skeletal muscle in the thigh were measured by means of the microdialysis technique. Leg blood flow (LBF) was measured by termodilution. In response to insulin infusion, LBF always increased (P < 0.05) (from 228 +/- 25 and 318...

  12. Why do premature newborn infants display elevated blood adenosine levels?

    Science.gov (United States)

    Panfoli, Isabella; Cassanello, Michela; Bruschettini, Matteo; Colella, Marina; Cerone, Roberto; Ravera, Silvia; Calzia, Daniela; Candiano, Giovanni; Ramenghi, Luca

    2016-05-01

    Our preliminary data show high levels of adenosine in the blood of very low birth weight (VLBW) infants, positively correlating to their prematurity (i.e. body weight class). This prompted us to look for a mechanism promoting such impressive adenosine increase. We hypothesized a correlation with oxygen challenge. In fact, it is recognized that either oxygen lack or its excess contribute to the pathogenesis of the injuries of prematurity, such as retinopathy (ROP) and periventricular white matter lesions (PWMI). The optimal concentration of oxygen for resuscitation of VLBW infants is currently under revision. We propose that the elevated adenosine blood concentrations of VLBW infants recognizes two sources. The first could be its activity-dependent release from unmyelinated brain axons. Adenosine in this respect would be an end-product of the hypometabolic VLBW newborn unmyelinated axon intensely firing in response to the environmental stimuli consequent to premature birth. Adenosine would be eventually found in the blood due to blood-brain barrier immaturity. In fact, adenosine is the primary activity-dependent signal promoting differentiation of premyelinating oligodendrocyte progenitor cells (OPC) into myelinating cells in the Central Nervous System, while inhibiting their proliferation and inhibiting synaptic function. The second, would be the ecto-cellular ATP synthesized by the endothelial cell plasmalemma exposed to ambient oxygen concentrations due to premature breathing, especially in lung. ATP would be rapidly transformed into adenosine by the ectonucleotidase activities such as NTPDase I (CD39), and NT5E (CD73). An ectopic extra-mitochondrial aerobic ATP synthetic ability was reported in many cell plasma-membranes, among which endothelial cells. The potential implications of the cited hypotheses for the neonatology area would be great. The amount of oxygen administration for reviving of newborns would find a molecular basis for its assessment. VLBW

  13. Tween 20-stabilized gold nanoparticles combined with adenosine triphosphate-BODIPY conjugates for the fluorescence detection of adenosine with more than 1000-fold selectivity

    Energy Technology Data Exchange (ETDEWEB)

    Hung, Szu-Ying; Shih, Ya-Chen [Department of Chemistry, National Sun Yat-sen University, Taiwan (China); Tseng, Wei-Lung, E-mail: tsengwl@mail.nsysu.edu.tw [Department of Chemistry, National Sun Yat-sen University, Taiwan (China); School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Taiwan (China); Center for Nanoscience and Nanotechnology, National Sun Yat-sen University, Taiwan (China); Center for Stem Cell Research, Kaohsiung Medical University, Taiwan (China)

    2015-02-01

    Graphical abstract: A simple, enzyme-free, label-free, sensitive and selective system was developed for detecting adenosine based on the use of Tween 20-stabilized gold nanoparticles as an efficient quencher for boron dipyrromethene-conjugated adenosine 5′-triphosphate and as a recognition element for adenosine. - Highlights: • The proposed method can detect adenosine with more than 1000-fold selectivity. • The analysis of adenosine is rapid (∼6 min) using the proposed method. • This method provided better sensitivity for adenosine as compared to aptamer-based sensors. • This method can be applied for the determination of adenosine in urine. - Abstract: This study describes the development of a simple, enzyme-free, label-free, sensitive, and selective system for detecting adenosine based on the use of Tween 20-stabilized gold nanoparticles (Tween 20-AuNPs) as an efficient fluorescence quencher for boron dipyrromethene-conjugated adenosine 5′-triphosphate (BODIPY-ATP) and as a recognition element for adenosine. BODIPY-ATP can interact with Tween 20-AuNPs through the coordination between the adenine group of BODIPY-ATP and Au atoms on the NP surface, thereby causing the fluorescence quenching of BODIPY-ATP through the nanometal surface energy transfer (NSET) effect. When adenosine attaches to the NP surface, the attached adenosine exhibits additional electrostatic attraction to BODIPY-ATP. As a result, the presence of adenosine enhances the efficiency of AuNPs in fluorescence quenching of BODIPY-ATP. The AuNP-induced fluorescence quenching of BODIPY-ATP progressively increased with an increase in the concentration of adenosine; the detection limit at a signal-to-noise ratio of 3 for adenosine was determined to be 60 nM. The selectivity of the proposed system was more than 1000-fold for adenosine over any adenosine analogs and other nucleotides. The proposed system combined with a phenylboronic acid-containing column was successfully applied to the

  14. 49 CFR 218.75 - Methods of protection for camp cars.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Methods of protection for camp cars. 218.75... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD OPERATING PRACTICES Protection of Occupied Camp Cars § 218.75 Methods of protection for camp cars. When camp cars requiring protection are on either main...

  15. It's a Small World, after All: A Look at Camp around the World.

    Science.gov (United States)

    Nicodemus, Teresa

    2000-01-01

    Camping in Malaysia, New Zealand, England, Brazil, and the United States is compared. The basic function of camp, providing a safe place for fun and discovery, seems universal. Differences discussed include camping seasons, family participation, recreational versus educational emphasis, the competitive nature of for-profit camps, and risk…

  16. Cytotoxic purine nucleoside analogues bind to A1, A2A and A3 adenosine receptors

    OpenAIRE

    Jensen, Kyle; Johnson, L’Aurelle A.; Jacobson, Pamala A.; Kachler, Sonja; Kirstein, Mark N.; Lamba, Jatinder; Klotz, Karl-Norbert

    2012-01-01

    Fludarabine, clofarabine and cladribine are anti-cancer agents which are analogues of the purine nucleoside adenosine. These agents have been associated with cardiac and neurological toxicities. Because these agents are analogues of adenosine, they may act through adenosine receptors to elicit their toxic effects. The objective of this study was to evaluate the ability of cytotoxic nucleoside analogues to bind and activate adenosine receptor subtypes (A1, A2A, A2B, and A3). Radioligand bindin...

  17. Development of coronary vasospasm during adenosine-stress myocardial perfusion CT imaging

    Energy Technology Data Exchange (ETDEWEB)

    Nam, Jeong Gu; Choi, Seong Hoon; Kang, Byeong Seong; Bang, Min Aeo; Kwon, Woon Jeong [Dept. of Radiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan (Korea, Republic of)

    2015-06-15

    Adenosine is a short-acting coronary vasodilator, and it is widely used during pharmacological stress myocardial perfusion imaging. It has a well-established safety profile, and most of its side effects are known to be mild and transient. Until now, coronary vasospasm has been rarely reported as a side effect of adenosine during or after adenosine stress test. This study reports a case of coronary vasospasm which was documented on stress myocardial perfusion CT imaging during adenosine stress test.

  18. Conditions that alter intracellular cAMP levels affect expression of the cAMP phosphodiesterase gene in Dictyostelium.

    OpenAIRE

    Riley, B B; Barclay, S L

    1990-01-01

    We examined expression of the Dictyostelium cAMP phosphodiesterase (PDE) gene under conditions that alter intracellular cAMP levels during in vitro differentiation of wild-type strain V12M2 and a sporogenous derivative, HB200. In control cultures, cellular PDE activity peaked at 6 hr and declined by 8 hr, while secreted PDE activity continued to increase through 8 hr. Lowering intracellular cAMP levels with caffeine or progesterone increased cellular and secreted PDE activities 2-fold, increa...

  19. Modulating the Cyclic Guanosine Monophosphate Substrate Selectivity of the Phosphodiesterase 3 Inhibitors by Pyridine, Pyrido[2,3-d]pyrimidine Derivatives and Their Effects upon the Growth of HT-29 Cancer Cell Line

    Science.gov (United States)

    Abadi, Ashraf Hassan; Hany, Marwa Saeed; Elsharif, Shimaa Awadain; Eissa, Amal Abdel Haleem; Gary, Bernard DeWayne; Tinsley, Heather Nicole; Piazza, Gary Anthony

    2016-01-01

    Analogues with the scaffolds of 3-cyano-4-alkoxyphenyl-6-bromoaryl-2-pyridone and 2-amino-3-cyano-4-alkoxyphenyl-6-bromoarylpyridine were synthesized. Cyclization of the 2-amino derivatives with formic acid and formamide gave the corresponding pyrido[2,3-d]pyrimidin-4(3H)-one and the pyrido[2,3-d]pyrimidin-4-amine derivatives, respectively. Active phosphodiesterase 3 (PDE3) inhibitors were identified from each of the four aforementioned scaffolds. This is the first report that pyrido[2,3-d]pyrimidin-4(3H)-one and pyrido[2,3-d]pyrimidin-4-amine derivatives can inhibit PDE3. The analogues with the pyridone and pyrido[2,3-d]pyrimidin-4(3H)-one scaffolds inhibited both cAMP and cyclic guanosine monophosphate (cGMP) hydrolysis by PDE3, while the amine containing scaffolds were more selective for cGMP hydrolysis. This observation may set the base for substrate-selective pharmacological modulation of this important class of drug targets and with less side effects, particularly tachcardia. The dual inhibitors of PDE3 were more potent inhibitor towards the growth of HT-29 cancer cell lines. PMID:23546000

  20. 14 CFR 91.1423 - CAMP: Maintenance organization.

    Science.gov (United States)

    2010-01-01

    ... Operations Program Management § 91.1423 CAMP: Maintenance organization. (a) Each program manager who... maintenance, or alterations, must organize the performance of those functions so as to separate the...

  1. Building a Successful Middle School Outreach Effort: Microscopy Camp

    Science.gov (United States)

    Penn, Lee R.; Flynn, Leslie; Johnson, Page

    2007-01-01

    Microscopy Camp program is designed to introduce acceptable representations of crystalline particles and their atomic structure to twelve-year-old middle school students at a developmental and educational stage.

  2. Nationalsozialistische Konzentrations- und Vernichtungslager National Socialist Concentration and Extermination Camps

    Directory of Open Access Journals (Sweden)

    Max Plassmann

    2000-11-01

    Full Text Available Das Buch stellt Organisationsformen, Zuständigkeiten und Politik hinter dem nationalsozialistischen Konzentrationslagersystem dar.This book presents organization, competences and policies underlying the system of National Socialist concentration camps.

  3. Camp as a Teaching Method in Health Education

    DEFF Research Database (Denmark)

    Ringby, Betina

    Background Camp as a learning activity was introduced in entrepreneurship teaching. Students were engaged to get experiences on how to cope with uncertainty, complexity and to take action in collaboration with external partners. Relevance Society calls for creative and innovative health professio......Background Camp as a learning activity was introduced in entrepreneurship teaching. Students were engaged to get experiences on how to cope with uncertainty, complexity and to take action in collaboration with external partners. Relevance Society calls for creative and innovative health...... Progression Model’ served as background theory. Evaluation Three different camps were evaluated by students in 2012 and 2013. A written individual evaluation form was filled in at the end of CAMP one; two and three. Data consisted of descriptive questionnaires with open answer alternatives. Evaluations were...

  4. The Physics of Quidditch Summer Camp: An Interdisciplinary Approach

    Science.gov (United States)

    Hammer, Donna; Uher, Tim

    The University of Maryland Physics Department has developed an innovative summer camp program that takes an interdisciplinary approach to engaging and teaching physics. The Physics of Quidditch Camp uniquely sits at the intersection of physics, sports, and literature, utilizing the real-life sport of quidditch adapted from the Harry Potter novels to stimulate critical thinking about real laws of physics and leaps of imagination, while actively engaging students in learning the sport and discussing the literature. Throughout the camp, middle school participants become immersed in fun physics experiments and exciting physical activities, which aim to build and enhance skills in problem-solving, analytical thinking, and teamwork. This camp has pioneered new ways of teaching physics to pre-college students, successfully engaged middle school students in learning physics, and grown a large demand for such activities.

  5. Thinking Big for 25 Years: Astronomy Camp Research Projects

    Science.gov (United States)

    Hooper, Eric Jon; McCarthy, D. W.; Benecchi, S. D.; Henry, T. J.; Kirkpatrick, J. D.; Kulesa, C.; Oey, M. S.; Regester, J.; Schlingman, W. M.; Camp Staff, Astronomy

    2013-01-01

    Astronomy Camp is a deep immersion educational adventure for teenagers and adults in southern Arizona that is entering its 25th year of existence. The Camp Director (McCarthy) is the winner of the 2012 AAS Education Prize. A general overview of the program is given in an accompanying contribution (McCarthy et al.). In this presentation we describe some of the research projects conducted by Astronomy Camp participants over the years. Many of the Camps contain a strong project-oriented emphasis, which reaches its pinnacle in the Advanced Camps for teenagers. High school students from around the world participate in a microcosm of the full arc of astronomy research. They plan their own projects before the start of Camp, and the staff provide a series of "key projects." Early in the Camp the students submit observing proposals to utilize time on telescopes. (The block of observing time is secured in advance by the staff.) The participants collect, reduce and analyze astronomical data with the help of staff, and they present the results to their peers on the last night of Camp, all in a span of eight days. The Camps provide research grade telescopes and instruments, in addition to amateur telescopes. Some of the Camps occur on Kitt Peak, where we use an ensemble of telescopes: the 2.3-meter (University of Arizona) with a spectrograph; the WIYN 0.9-meter; the McMath-Pierce Solar Telescope; and the 12-meter millimeter wave telescope. Additionally the Camp has one night on the 10-meter Submillimeter Telescope on Mt. Graham. Campers use these resources to study stars, galaxies, AGN, transiting planets, molecular clouds, etc. Some of the camper-initiated projects have led to very high level performances in prestigious international competitions, such as the Intel International Science and Engineering Fair. The key projects often contribute to published astronomical research (e.g., Benecchi et al. 2010, Icarus, 207, 978). Many former Campers have received Ph.D. degrees in

  6. DMPD: Shaping of monocyte and macrophage function by adenosine receptors. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17056121 Shaping of monocyte and macrophage function by adenosine receptors. Hasko ...tml) (.csml) Show Shaping of monocyte and macrophage function by adenosine receptors. PubmedID 17056121 Titl...e Shaping of monocyte and macrophage function by adenosine receptors. Authors Has

  7. Social Meaning of Culture in a Stalinist Prison Camp

    Directory of Open Access Journals (Sweden)

    Aimar Ventsel

    2014-04-01

    Full Text Available The Stalinist prison camp system – popularly known as the Gulag archipelago – existed for a relatively short period (from 1931–1960 and became world famous as a synonym for terror, humiliation and human suffering. This article focuses on the social significance of culture in one of the biggest Stalinist prison camp – Karlag in Central Kazakhstan. The first part of the article gives an overview of the institutions of culture in prison camps and their activities. It also gives an overview of unofficial cultural activities and the consequences of being engaged in the unsanctioned creation of art. In the second part of the paper, the social significance of culture in Stalinist prison camps is discussed. Official and non-official art were not separate and existed in symbiosis: people crossed the border between these spheres. Moreover, the camp administration recognised the material value of art produced in the camp and began to organise the production of pictures or handicrafts in order to sell them outside the camp. Nevertheless, both official and unofficial cultures had a deep social meaning for the people. Producing unsanctioned paintings and other objects of artistry can be seen as an act of resistance, producing sanctioned art helped the artists to create their own social and mental space and distance themselves from the everyday grind of the camp. In general, culture and its institutions in the prison failed to fulfill their original purpose – instead of re-educating and changing inmates, culture helped to maintain human dignity and integrity.

  8. Science and technology camp for girls. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1993-12-31

    This document reports on the success of Pacific University`s camp held during the summers of 1992 and 1993; ultimate goal of this summer day camp was to increase the number of women in technical and scientific fields. Some experimentation was done with the age groups (7th and 8th grade girls). The curriculum was biology, chemistry, physics, and mathematics/computer science. Laboratory work and field trips were emphasized, along with socialization.

  9. Inside the tent: Community and government in refugee camps

    OpenAIRE

    Bulley, Dan

    2014-01-01

    Refugee camps are increasingly managed through a liberal rationality of government similar to that of many industrialized societies, with security mechanisms being used to optimize the life of particular refugee populations. This governmentality has encompassed programmes introduced by the United Nations High Commissioner for Refugees (UNHCR) and various non-governmental organizations (NGOs) to build and empower communities through the spatial technology of the camp. The present article argue...

  10. Multiple facets of cAMP signalling and physiological impact : cAMP compartmentalization in the lung

    NARCIS (Netherlands)

    Oldenburger, Anouk; Maarsingh, Harm; Schmidt, Martina

    2012-01-01

    Therapies involving elevation of the endogenous suppressor cyclic AMP (cAMP) are currently used in the treatment of several chronic inflammatory disorders, including chronic obstructive pulmonary disease (COPD). Characteristics of COPD are airway obstruction, airway inflammation and airway remodelli

  11. Searching Inhibitors of Adenosine Kinase by Simulation Methods

    Institute of Scientific and Technical Information of China (English)

    ZHU Rui-Xin; ZHANG Xing-Long; DONG Xi-Cheng; CHEN Min-Bo

    2006-01-01

    Searching new inhibitors of adenosine kinase (AK) is still drawing attention of experimental scientists. A better and solid model is here proposed by means of simulation methods from different ways, the direct analysis of receptor itself, the conventional 3D-QSAR methods and the integration of docking method and the conventional QSAR analysis.

  12. 21 CFR 864.7040 - Adenosine triphosphate release assay.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Adenosine triphosphate release assay. 864.7040 Section 864.7040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... disorders. (b) Classification. Class I (general controls)....

  13. Vasoconstrictor and vasodilator effects of adenosine in the kidney

    DEFF Research Database (Denmark)

    Hansen, Pernille B; Schnermann, Jurgen

    2003-01-01

    that the steady-state response to the increase of plasma adenosine levels above normal resulting from the infusion is global renal vasorelaxation that is the result of A2AR activation in most parts of the renal vasculature, including larger renal arteries, juxtamedullary afferent arterioles, efferent arterioles...

  14. Targeting the inflammasome and adenosine type-3 receptors improves outcome of antibiotic therapy in murine anthrax

    Institute of Scientific and Technical Information of China (English)

    Serguei; G; Popov; Taissia; G; Popova; Fatah; Kashanchi; Charles; Bailey

    2011-01-01

    AIM:To establish whether activation of adenosine type-3 receptors(A3Rs)and inhibition of interleukin- 1β-induced inflammation is beneficial in combination with antibiotic therapy to increase survival of mice challenged with anthrax spores. METHODS:DBA/2 mice were challenged with Bacillus anthracis spores of the toxigenic Sterne strain 43F2. Survival of animals was monitored for 15 d.Ciprofloxacin treatment(50 mg/kg,once daily,intraperitoneally) was initiated at day+1 simultaneously with the ad- ministration of inhibitors,and continued for 10 d.Two doses(2.5 mg/kg and 12.5 mg/kg)of acetyl-tyrosylvalyl-alanyl-aspartyl-chloromethylketone(YVAD)and three doses(0.05,0.15 and 0.3 mg/kg)of 1-[2-Chloro- 6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1- deoxy-N-methyl-β-D-ribofuranuronamide(Cl-IB-MECA) were tested.Animals received YVAD on days 1-4,and Cl-IB-MECA on days 1-10 once daily,subcutaneously. Human lung epithelial cells in culture were challenged with spores or edema toxin and the effects of IB-MECAon phosphorylation of AKT and generation of cAMP were tested. RESULTS:We showed that the outcome of antibiotic treatment in a murine anthrax model could be substantially improved by co-administration of the caspase-1/4 inhibitor YVAD and the A3R agonist Cl-IB-MECA.Combination treatment with these substances and ciprofloxacin resulted in up to 90%synergistic protection.All untreated mice died,and antibiotic alone protected only 30% of animals.We conclude that both substances target the aberrant host signaling that underpins anthrax mortality. CONCLUSION:Our findings suggest new possibilities for combination therapy of anthrax with antibiotics,A3R agonists and caspase-1 inhibitors.

  15. Feed-Forward Inhibition of CD73 and Upregulation of Adenosine Deaminase Contribute to the Loss of Adenosine Neuromodulation in Postinflammatory Ileitis

    Directory of Open Access Journals (Sweden)

    Cátia Vieira

    2014-01-01

    Full Text Available Purinergic signalling is remarkably plastic during gastrointestinal inflammation. Thus, selective drugs targeting the “purinome” may be helpful for inflammatory gastrointestinal diseases. The myenteric neuromuscular transmission of healthy individuals is fine-tuned and controlled by adenosine acting on A2A excitatory receptors. Here, we investigated the neuromodulatory role of adenosine in TNBS-inflamed longitudinal muscle-myenteric plexus of the rat ileum. Seven-day postinflammation ileitis lacks adenosine neuromodulation, which may contribute to acceleration of gastrointestinal transit. The loss of adenosine neuromodulation results from deficient accumulation of the nucleoside at the myenteric synapse despite the fact that the increases in ATP release were observed. Disparity between ATP outflow and adenosine deficit in postinflammatory ileitis is ascribed to feed-forward inhibition of ecto-5′-nucleotidase/CD73 by high extracellular ATP and/or ADP. Redistribution of NTPDase2, but not of NTPDase3, from ganglion cell bodies to myenteric nerve terminals leads to preferential ADP accumulation from released ATP, thus contributing to the prolonged inhibition of muscle-bound ecto-5′-nucleotidase/CD73 and to the delay of adenosine formation at the inflamed neuromuscular synapse. On the other hand, depression of endogenous adenosine accumulation may also occur due to enhancement of adenosine deaminase activity. Both membrane-bound and soluble forms of ecto-5′-nucleotidase/CD73 and adenosine deaminase were detected in the inflamed myenteric plexus. These findings provide novel therapeutic targets for inflammatory gut motility disorders.

  16. The Rickettsia prowazekii invasion gene homolog (invA) encodes a Nudix hydrolase active on adenosine (5')-pentaphospho-(5')-adenosine.

    Science.gov (United States)

    Gaywee, Jariyanart; Xu, WenLian; Radulovic, Suzana; Bessman, Maurice J; Azad, Abdu F

    2002-03-01

    The genomic sequence of Rickettsia prowazekii, the obligate intracellular bacterium responsible for epidemic typhus, reveals an uncharacterized invasion gene homolog (invA). The deduced protein of 18,752 Da contains a Nudix signature, the specific motif found in the Nudix hydrolase family. To characterize the function of InvA, the gene was cloned and overexpressed in Escherichia coli. The expressed protein was purified to near homogeneity and subsequently tested for its enzymatic activity against a series of nucleoside diphosphate derivatives. The purified InvA exhibits hydrolytic activity toward dinucleoside oligophosphates (Np(n)N; n > or = 5), a group of cellular signaling molecules. At optimal pH 8.5, the enzyme actively degrades adenosine (5')-pentaphospho-(5')-adenosine into ATP and ADP with a K(m) of 0.1 mM and k(cat) of 1.9 s(-1). Guanosine (5')-pentaphospho-(5')-guanosine and adenosine-(5')-hexaphospho (5')-adenosine are also substrates. Similar to other Nudix hydrolases, InvA requires a divalent metal cation, Mg(2+) or Zn(2+), for optimal activity. These data suggest that the rickettsial invasion protein likely plays a role in controlling the concentration of stress-induced dinucleoside oligophosphates following bacterial invasion.

  17. Adenosine contributes to blood flow regulation in the exercising human leg by increasing prostaglandin and nitric oxide formation

    DEFF Research Database (Denmark)

    Mortensen, Stefan; Nyberg, Michael; Thaning, Pia;

    2009-01-01

    Adenosine can induce vasodilation in skeletal muscle, but to what extent adenosine exerts its effect via formation of other vasodilators and whether there is redundancy between adenosine and other vasodilators remain unclear. We tested the hypothesis that adenosine, prostaglandins, and NO act in...

  18. Students' Perceptions of the Long-Term Impact of Attending a "CSI Science Camp"

    Science.gov (United States)

    Yanowitz, Karen L.

    2016-07-01

    A science summer camp is a popular type of informal science experience for youth. While there is no one model of a science camp, these experiences typically allow for more focused and in-depth exploration of different science domains and are usually hands-on and participatory. The goal of this research was to examine the impact of a short science camp program approximately 1 year after students attended the camp. Overall, the results revealed that attending a 2-day forensic science camp had a positive and continuing influence on the participants. Students' science self-efficacy increased immediately after attending the camp and remained higher than pre-camp levels approximately 1 year later. Students were able to articulate why they believed the camp had a long-term impact on their lives. Furthermore, participants attributed a higher level of engaging in additional informal STEM-related activities during the academic year as a result of attending the camp.

  19. PHARMACOKINETIC AND PHARMACODYNAMIC ANALYSIS OF INOSINE MONOPHOSPHATE DEHYDROGENASE (IMPDH) ACTIVITY IN MMF-TREATED HCT RECIPIENTS

    Science.gov (United States)

    Li, Hong; Mager, Donald E.; Sandmaier, Brenda M.; Storer, Barry E.; Boeckh, Michael J.; Bemer, Meagan J.; Phillips, Brian R.; Risler, Linda J.; McCune, Jeannine S.

    2014-01-01

    A novel approach to personalizing postgrafting immunosuppression in hematopoietic cell transplant (HCT) recipients is evaluating inosine monophosphate dehydrogenase (IMPDH) activity as a drug-specific biomarker of mycophenolic acid (MPA)-induced immunosuppression. This prospective study evaluated total MPA, unbound MPA, and total MPA glucuronide plasma concentrations and IMPDH activity in peripheral blood mononuclear cells (PMNC) at five time points after the morning dose of oral mycophenolate mofetil (MMF) on day +21 in 56 nonmyeloablative HCT recipients. Substantial interpatient variability in the pharmacokinetics and pharmacodynamics was observed and accurately characterized by the population pharmacokinetic/dynamic model. IMPDH activity decreased with increasing MPA plasma concentration, with maximum inhibition coinciding with maximum MPA concentration in most patients. The overall relationship between MPA concentration and IMPDH activity was described by a direct inhibitory Emax model with an IC50 = 3.23 mg/L total MPA and 57.3 ng/mL unbound MPA. The day +21 IMPDH area under the effect curve (AUEC) was associated with cytomegalovirus reactivation, non-relapse mortality, and overall mortality. In conclusion, a pharmacokinetic/dynamic model was developed that relates plasma MPA concentrations with PMNC IMPDH activity after an MMF dose in HCT recipients. Future studies should validate this model and confirm that day +21 IMPDH AUEC is a predictive biomarker. PMID:24727337

  20. Study of phase transformation of guanosine 5'-monophosphate in drowning-out crystallization.

    Science.gov (United States)

    Kang, Jeongki; Tuan, Nguyen Anh; Kim, Jong-Min; Chang, Sang-Mok; Kim, Woo-Sik

    2010-01-01

    The present study used a mechanistic approach to control the phase transformation of guanosine 5'-monophosphate (GMP) via the operating conditions of agitation and feed concentration during drowning-out crystallization. First, Fourier transform infrared and UV/vis spectrophotometry were successfully applied to monitor the mass fraction of GMP polymorphs (amorphous and hydrate crystalline GMPs) and GMP supersaturation, respectively, during the crystallization. The phase transformation of amorphous GMP into hydrate crystals was significantly influenced by the agitation, which promoted the mass transfer of GMP dissolution and growth. Therefore, the phase transformation was quickly finished when increasing the agitation speed. However, a high agitation caused breakage of the hydrate crystals, resulting in a reduced crystal size with a bimodal distribution. The phase transformation was also influenced by the GMP feed concentration, as the crystal growth was promoted and the crystal size increased when increasing the feed concentration up to 61 g/l. However, a further increase in the feed concentration caused secondary nucleation due to the induction of a high supersaturation level during the phase transformation, leading to a small crystal size with a bimodal distribution. In addition, the rectangular-shaped hydrate GMP crystals exhibited a higher growth rate in the b direction rather than the a direction. Therefore, the crystal morphology shifted from a long rectangle to a square when increasing the feed concentration. PMID:19031052

  1. Ion-exclusion chromatography determination of organic acid in uridine 5'-monophosphate fermentation broth.

    Science.gov (United States)

    Niu, Huanqing; Chen, Yong; Xie, Jingjing; Chen, Xiaochun; Bai, Jianxin; Wu, Jinglan; Liu, Dong; Ying, Hanjie

    2012-09-01

    Simultaneous determination of organic acids using ion-exclusion liquid chromatography and ultraviolet detection is described. The chromatographic conditions are optimized when an Aminex HPX-87H column (300 × 7.8 mm) is employed, with a solution of 3 mmol/L sulfuric acid as eluent, a flow rate of 0.4 mL/min and a column temperature of 60°C. Eight organic acids (including orotic acid, α-ketoglutaric acid, citric acid, pyruvic acid, malic acid, succinic acid, lactic acid and acetic acid) and one nucleotide are successfully quantified. The calibration curves for these analytes are linear, with correlation coefficients exceeding 0.999. The average recovery of organic acids is in the range of 97.6% ∼ 103.1%, and the relative standard deviation is in the range of 0.037% ∼ 0.38%. The method is subsequently applied to obtain organic acid profiles of uridine 5'-monophosphate culture broth fermented from orotic acid by Saccharomyces cerevisiae. These data demonstrate the quantitative accuracy for nucleotide fermentation mixtures, and suggest that the method may also be applicable to other biological samples. PMID:22634191

  2. Post-translational Analysis of Arabidopsis thaliana Proteins in Response to Cyclic Guanosine Monophosphate Treatment

    KAUST Repository

    Parrott, Brian

    2011-12-12

    The introduction of mass spectrometry techniques to the field of biology has made possible the exploration of the proteome as a whole system as opposed to prior techniques, such as anti-body based assays or yeast two-hybrid studies, which were strictly limited to the study of a few proteins at a time. This practice has allowed for a systems biology approach of exploring the proteome, with the possibility of viewing entire pathways over increments of time. In this study, the effect of treating Arabidopsis thaliana suspension culture cells with 3’,5’-cyclic guanosine monophosphate (cGMP), which is a native second messenger, was examined. Samples were collected at four time points and proteins were extracted and enriched for both oxidation and phosphorylation before analysis via mass spectrometry. Preliminary results suggest a tendency towards an increased number of phosphorylated proteins as a result of cGMP treatment. The data also showed a sharp increase in methionine oxidation in response to the treatment, occurring within the first ten minutes. This finding suggests that cGMP may utilize methionine oxidation as a mechanism of signal transduction. As such, this study corroborates a growing body of evidence supporting the inclusion of methionine oxidation in intracellular signaling pathways.

  3. Target validation of the inosine monophosphate dehydrogenase (IMPDH) gene in Cryptosporidium using Phylomer(®) peptides.

    Science.gov (United States)

    Jefferies, R; Yang, R; Woh, C K; Weldt, T; Milech, N; Estcourt, A; Armstrong, T; Hopkins, R; Watt, P; Reid, S; Armson, A; Ryan, U M

    2015-01-01

    Cryptosporidiosis, a gastroenteric disease characterised mainly by diarrheal illnesses in humans and mammals is caused by infection with the protozoan parasite Cryptosporidium. Treatment options for cryptosporidiosis are limited, with the current therapeutic nitazoxanide, only partly efficacious in immunocompetent individuals. The parasite lacks de novo purine synthesis, and is exclusively dependant on purine salvage from its host. Inhibition of the inosine 5' monophosphate dehydrogenase (IMPDH), a purine salvage enzyme that is essential for DNA synthesis, thereby offers a potential drug target against this parasite. In the present study, a yeast-two-hybrid system was used to identify Phylomer peptides within a library constructed from the genomes of 25 phylogenetically diverse bacteria that targeted the IMPDH of Cryptosporidium parvum (IMPcp) and Cryptosporidium hominis (IMPch). We identified 38 unique interacting Phylomers, of which, 12 were synthesised and screened against C. parvum in vitro. Two Phylomers exhibited significant growth inhibition (81.2-83.8% inhibition; P < 0.05), one of which consistently exhibited positive interactions with IMPcp and IMPch during primary and recapitulation yeast two-hybrid screening and did not interact with either of the human IMPDH proteins. The present study highlightsthe potential of Phylomer peptides as target validation tools for Cryptosporidium and other organisms and diseases because of their ability to bind with high affinity to target proteins and disrupt function. PMID:25447124

  4. Myricetin is a novel inhibitor of human inosine 5'-monophosphate dehydrogenase with anti-leukemia activity.

    Science.gov (United States)

    Pan, Huiling; Hu, Qian; Wang, Jingyuan; Liu, Zehui; Wu, Dang; Lu, Weiqiang; Huang, Jin

    2016-09-01

    Human inosine 5'-monophosphate dehydrogenase (hIMPDH) is a rate-limiting enzyme in the de novo biosynthetic pathway of purine nucleotides, playing crucial roles in cellular proliferation, differentiation, and transformation. Dysregulation of hIMPDH expression and activity have been found in a variety of human cancers including leukemia. In this study, we found that myricetin, a naturally occurring phytochemical existed in berries, wine and tea, was a novel inhibitor of human type 1 and type 2 IMPDH (hIMPDH1/2) with IC50 values of 6.98 ± 0.22 μM and 4.10 ± 0.14 μM, respectively. Enzyme kinetic analysis using Lineweaver-Burk plot revealed that myricetin is a mix-type inhibitor for hIMPDH1/2. Differential scanning fluorimetry and molecular docking simulation data demonstrate that myricetin is capable of binding with hIMPDH1/2. Myricetin treatment exerts potent anti-proliferative and pro-apoptotic effects on K562 human leukemia cells in a dose-dependent manner. Importantly, cytotoxicity of myricetin on K562 cells were markedly attenuated by exogenous addition of guanosine, a salvage pathway of maintaining intracellular pool of guanine nucleotides. Taking together, these results indicate that natural product myricetin exhibits potent anti-leukemia activity by interfering with purine nucleotides biosynthetic pathway through the suppression of hIMPDH1/2 catalytic activity. PMID:27378425

  5. Turning an antiviral into an anticancer drug: nanoparticle delivery of acyclovir monophosphate.

    Science.gov (United States)

    Yao, Jing; Zhang, Yuan; Ramishetti, Srinivas; Wang, Yuhua; Huang, Leaf

    2013-09-28

    Anti-herpes simplex virus (HSV) drug acyclovir (ACV) is phosphorylated by the viral thymidine kinase (TK), but not the cellular TK. Phosphorylated ACV inhibits cellular DNA synthesis and kills the infected cells. We hypothesize that ACV monophosphate (ACVP), which is an activated metabolite of ACV, should be efficient in killing cells independent of HSV-TK. If so, ACVP should be a cytotoxic agent if properly delivered to the cancer cells. The Lipid/Calcium/Phosphate (LCP) nanoparticles (NPs) with a membrane/core structure were used to encapsulate ACVP to facilitate the targeted delivery of ACVP to the tumor. The LCP NPs showed entrapment efficiency of ~70%, the nano-scaled particle size and positive zeta potential. Moreover, ACVP-loaded LCP NPs (A-LCP NPs) exhibited concentration-dependent cytotoxicity against H460 cells and increased S-phase arrest. More importantly, a significant reduction of the tumor volume over 4 days following administration (pACV and ACVP) and blank LCP NPs showed little or no therapeutic effect. It was also found that the high efficacy of A-LCP NPs was associated with the ability to induce dramatic apoptosis of the tumor cells, as well as significantly inhibit tumor cell proliferation and cell cycle progression. In conclusion, with the help of LCP NPs, monophosphorylation modification of ACV can successfully modify an HSV-TK-dependent antiviral drug into an anti-tumor drug.

  6. HPLC–MS/MS method for the intracellular determination of ribavirin monophosphate and ribavirin triphosphate in CEMss cells

    OpenAIRE

    Meléndez, Margarita; Rosario, Osvaldo; Zayas, Beatriz; Rodríguez, José F.

    2009-01-01

    A sensitive and specific method using high performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) for the determination of ribavirin monophosphate (RBV-MP) and ribavirin triphosphate (RBV-TP) in cells has been developed and validated. In this method, ribavirin phosphorylated metabolites were extracted and separated by anion exchange solid phase extraction (SPE). The RBV-MP and RBV-TP fractions were dephosphorylated using acid phosphatase and further purified by phenyl boronat...

  7. Effects of intragastric infusion of inosine monophosphate and l-glutamate on vagal gastric afferent activity and subsequent autonomic reflexes

    OpenAIRE

    Kitamura, Akihiko; Sato, Wataru; Uneyama, Hisayuki; Torii, Kunio; NIIJIMA, Akira

    2010-01-01

    In this study we investigated the effects of intragastric infusion of palatable basic taste substances (umami, sweet, and salty) on the activity of the vagal gastric afferent nerve (VGA), the vagal celiac efferent nerve (VCE), and the splanchnic adrenal efferent nerve (SAE) in anesthetized rats. To test the three selected taste groups, rats were infused with inosine monophosphate (IMP) and l-glutamate (GLU) for umami, with glucose and sucrose for sweet, and with sodium chloride (NaCl) for sal...

  8. Caffeine inhibits the activation of hepatic stellate cells induced by acetaldehyde via adenosine A2A receptor mediated by the cAMP/PKA/SRC/ERK1/2/P38 MAPK signal pathway.

    Directory of Open Access Journals (Sweden)

    He Wang

    Full Text Available Hepatic stellate cell (HSC activation is an essential event during alcoholic liver fibrosis. Evidence suggests that adenosine aggravates liver fibrosis via the adenosine A2A receptor (A2AR. Caffeine, which is being widely consumed during daily life, inhibits the action of adenosine. In this study, we attempted to validate the hypothesis that caffeine influences acetaldehyde-induced HSC activation by acting on A2AR. Acetaldehyde at 50, 100, 200, and 400 μM significantly increased HSC-T6 cells proliferation, and cell proliferation reached a maximum at 48 h after exposure to 200 μM acetaldehyde. Caffeine and the A2AR antagonist ZM241385 decreased the cell viability and inhibited the expression of procollagen type I and type III in acetaldehyde-induced HSC-T6 cells. In addition, the inhibitory effect of caffeine on the expression of procollagen type I was regulated by A2AR-mediated signal pathway involving cAMP, PKA, SRC, and ERK1/2. Interestingly, caffeine's inhibitory effect on the expression of procollagen type III may depend upon the A2AR-mediated P38 MAPK-dependent pathway.Caffeine significantly inhibited acetaldehyde-induced HSC-T6 cells activation by distinct A2AR mediated signal pathway via inhibition of cAMP-PKA-SRC-ERK1/2 for procollagen type I and via P38 MAPK for procollagen type III.

  9. Investigation of Sylvatic Typhus at a Wilderness Camp

    Centers for Disease Control (CDC) Podcasts

    2009-06-30

    In this podcast, Dr. Greg Dasch discusses an outbreak of four cases of sylvatic typhus that occurred at a wilderness camp in Pennsylvania. Sylvatic typhus is very rare in the United States, with only 41 cases since it was discovered in the United States in 1975. Lab work at CDC and the discovery that all four camp counselors who became ill had slept in the same bunk at the camp between 2004 and 2006 ultimately led to confirmation that flying squirrels living in the wall of the cabin were to blame for the illnesses.  Created: 6/30/2009 by Emerging Infectious Diseases.   Date Released: 6/30/2009.

  10. Adenosine-mediated modulation of ventral horn interneurons and spinal motoneurons in neonatal mice.

    Science.gov (United States)

    Witts, Emily C; Nascimento, Filipe; Miles, Gareth B

    2015-10-01

    Neuromodulation allows neural networks to adapt to varying environmental and biomechanical demands. Purinergic signaling is known to be an important modulatory system in many parts of the CNS, including motor control circuitry. We have recently shown that adenosine modulates the output of mammalian spinal locomotor control circuitry (Witts EC, Panetta KM, Miles GB. J Neurophysiol 107: 1925-1934, 2012). Here we investigated the cellular mechanisms underlying this adenosine-mediated modulation. Whole cell patch-clamp recordings were performed on ventral horn interneurons and motoneurons within in vitro mouse spinal cord slice preparations. We found that adenosine hyperpolarized interneurons and reduced the frequency and amplitude of synaptic inputs to interneurons. Both effects were blocked by the A1-type adenosine receptor antagonist DPCPX. Analysis of miniature postsynaptic currents recorded from interneurons revealed that adenosine reduced their frequency but not amplitude, suggesting that adenosine acts on presynaptic receptors to modulate synaptic transmission. In contrast to interneurons, recordings from motoneurons revealed an adenosine-mediated depolarization. The frequency and amplitude of synaptic inputs to motoneurons were again reduced by adenosine, but we saw no effect on miniature postsynaptic currents. Again these effects on motoneurons were blocked by DPCPX. Taken together, these results demonstrate differential effects of adenosine, acting via A1 receptors, in the mouse spinal cord. Adenosine has a general inhibitory action on ventral horn interneurons while potentially maintaining motoneuron excitability. This may allow for adaptation of the locomotor pattern generated by interneuronal networks while helping to ensure the maintenance of overall motor output. PMID:26311185

  11. Adenosine receptors and stress : Studies using methylmercury, caffeine and hypoxia

    OpenAIRE

    Björklund, Olga

    2008-01-01

    Brain development is a precisely organized process that can be disturbed by various stress factors present in the diet (e.g. exposure to xenobiotics) as well as insults such as decreased oxygen supply. The consequent adverse changes in nervous system function may not necessarily be apparent until a critical age when neurodevelopmental defects may be unmasked by a subsequent challenge. Adenosine and its receptors (AR) (A1, A2A, A2B and A3) which participate in the brain stres...

  12. Myocardial energy metabolism in ischemic preconditioning, role of adenosine catabolism

    OpenAIRE

    Kavianipour, Mohammad

    2002-01-01

    Brief episodes of ischemia and reperfusion render the myocardium more resistant to necrosis from a subsequent, otherwise lethal ischemic insult. This phenomenon is called ischemic preconditioning(IP). Today, much is known about the signalling pathways involved in IP; however, the details of the final steps leading to cardioprotection, remain elusive. Adenosine (a catabolite of ATP) plays a major role in the signalling pathways of IP. Following IP there is an unexplained discrepancy between an...

  13. Pharmacology of the Adenosine A3 Receptor in the Vasculature and Essential Hypertension

    Science.gov (United States)

    Ho, Ming-Fen; Low, Leanne M.; Rose’Meyer, Roselyn B.

    2016-01-01

    Background Essential hypertension is considered to be a multifactorial disorder and its aetiology has yet to be clearly identified. As the adenosine receptors have a significant role in mediating vasodilation, alterations in their structures or signalling pathways may be involved in the development of hypertension. This study aimed to measure the expression of adenosine A3 receptors in a range of cardiovascular tissues and determine whether they could be altered with essential hypertension, and to functionally test responses to adenosine A3 receptor agonists in coronary blood vessels using the isolated perfused heart preparation. Methods mRNA samples from cardiovascular tissues and a range of blood vessels were collected from 10 week old male spontaneously hypertensive rats and age-gender matched Wistar rats (n = 8). The Langendorff heart perfusion preparation was used to characterise adenosine A3 receptor mediated coronary vasodilation in the rat heart. Results Adenosine A3 receptor agonists induced coronary vasodilation. The expression of adenosine A3 receptors in cardiovascular tissues was altered in a tissue-specific pattern. Specifically, down-regulation of adenosine A3 receptor expression occurred in hypertensive hearts, which might be associated with attenuated vasodilator responses observed in coronary vessels to adenosine A3 receptor agonists. Conclusions This study demonstrated alterations in the expression of adenosine A3 receptors occurred in a tissue specific mode, and reduced adenosine A3 receptor mediated coronary vasodilation in hearts from spontaneously hypertensive rats. Our findings with regard to changes in the adenosine A3 receptor in hypertensive hearts suggest that adenosine A3 receptor might play a role in the physiopathology of essential hypertension and potentially open the way to pharmacologic manipulation of vasomotor activity by the use of adenosine A3 receptor agonists. PMID:26907173

  14. Adenosine and Prostaglandin E2 Production by Human Inducible Regulatory T cells (iTreg in Health and Disease

    Directory of Open Access Journals (Sweden)

    Theresa L Whiteside

    2013-07-01

    Full Text Available Regulatory T cells (Treg play a key role in maintaining the balance of immune responses in human health and in disease. Treg come in many flavors and can utilize a variety of mechanisms to modulate immune responses. In cancer, inducible (i or adaptive Treg expand, accumulate in tissues and peripheral blood of patients and represent a functionally-prominent component of CD4+ T lymphocytes. Phenotypically and functionally, iTreg are distinct from natural (n Treg. A subset of iTreg expressing ectonucleotidases CD39 and CD73 is able to hydrolyze ATP to 5’-AMP and adenosine (ADO and thus mediate suppression of those immune cells which express ADO receptors. iTeg can also produce prostaglandin E2 (PGE2. The mechanisms responsible for iTeg-mediated suppression involve binding of ADO and PGE2 produced by iTreg to their respective receptors expressed on Teff, leading to the up-regulation of adenylate cyclase and cAMP activities in Teff and to their functional inhibition. The potential for regulating these mechanisms by the use of pharmacologic inhibitors to relieve iTreg-mediated suppression in cancer suggests the development of therapeutic strategies targeting the ADO and PGE2 pathways.

  15. Science Camp - lystigt eller lærerigt

    DEFF Research Database (Denmark)

    Ahrenkiel, Linda; Albrechtsen, Thomas S. R.

    2013-01-01

    I oplægget vil vi undersøge fænomenet Science Camps nærmere ved at fortælle om dets historiske udvikling og ikke mindst lægge op til en diskussion af en definition. Derudover vil vi præsentere en case, hvor der med udgangspunkt i et aktuelt ph.d.-projekt er blevet undersøgt, hvad deltagerne får ud...... af at deltage i en science camp: Kan man både vække begejstring og medvirke til læring?...

  16. EduCamp Colombia: Social Networked Learning for Teacher Training

    Directory of Open Access Journals (Sweden)

    Diego Ernesto Leal Fonseca

    2011-03-01

    Full Text Available This paper describes a learning experience called EduCamp, which was launched by the Ministry of Education of Colombia in 2007, based on emerging concepts such as e-Learning 2.0, connectivism, and personal learning environments. An EduCamp proposes an unstructured collective learning experience, which intends to make palpable the possibilities of social software tools in learning and interaction processes while demonstrating face-to-face organizational forms that reflect social networked learning ideas. The experience opens new perspectives for the design of technology training workshops and for the development of lifelong learning experiences.

  17. Rebuilding Jewish identities in Displaced Persons Camps in Germany

    Directory of Open Access Journals (Sweden)

    Françoise Ouzan

    2007-10-01

    Full Text Available In the summer 1945, Displaced Persons camps in Germany epitomized a place of contrasts and paradoxes. DPs still languished behind barbed wires after the Allied armies had liberated the concentration camps. The military had assumed that practically all of the Displaced Persons would be sent to their countries of origin. In the spring and summer 1945, 65 000 DPs were sent back home every day and almost six million were repatriated in September 1945. Accurate statistics are impossible, yet, acco...

  18. Science Skills Boot Camp Gets Interns Ready for Research | Poster

    Science.gov (United States)

    By Ashley DeVine, Staff Writer Summer interns learned how to read a scientific paper, present a poster, maintain a laboratory notebook, and much more, at the Science Skills Boot Camp in June. “It was a great experience, and it was a great opportunity to meet some of the other interns also working on the campus,” said Alyssa Klein, a Werner H. Kirsten student intern in the Cellular Immunology Group, Laboratory of Molecular Immunoregulation. “The boot camp covered many topics essential to being a good scientist and science researcher.”

  19. Promoting independence in adolescent paraplegics: a 2-week "camping" experience.

    Science.gov (United States)

    Bodzioch, J; Roach, J W; Schkade, J

    1986-01-01

    In the summer of 1982, Texas Scottish Rite Hospital (Dallas, TX, U.S.A.) sponsored a camp for paraplegic adolescents. Six patients, three boys and three girls 14-17 years of age, participated in a 2-week program that was designed to improve their self-esteem, independence, and eventual employability. In their pre- and postcamp psychological evaluations, the campers demonstrated improvement in social skills and self-concept testing as compared with the scores of a matched control group, although this improvement did not reach statistical significance. We believe the camp was immensely successful, an opinion that was shared by both the campers and their parents. PMID:3514667

  20. Winter Camp: A Blog from the Greenland Summit, Part II

    Science.gov (United States)

    Koenig, Lora

    2009-01-01

    An earlier issue presents the first half of the author's experience living and working at the National Science Foundation's (NSF) Greenland Summit Camp. The author is a remote-sensing glaciologist at NASA s Goddard Space Flight Center. She took measurements that will be used to validate data collected by NASA s Aqua, Terra, and Ice, Clouds, and land Elevation Satellite (ICESat) satellites with ground-truth measurements of the Greenland Ice Sheet she made at Summit Camp from November 2008-February 2009. This article presents excerpts from the second half of her stay and work at the Greenland Summit.

  1. Promoting independence in adolescent paraplegics: a 2-week "camping" experience.

    Science.gov (United States)

    Bodzioch, J; Roach, J W; Schkade, J

    1986-01-01

    In the summer of 1982, Texas Scottish Rite Hospital (Dallas, TX, U.S.A.) sponsored a camp for paraplegic adolescents. Six patients, three boys and three girls 14-17 years of age, participated in a 2-week program that was designed to improve their self-esteem, independence, and eventual employability. In their pre- and postcamp psychological evaluations, the campers demonstrated improvement in social skills and self-concept testing as compared with the scores of a matched control group, although this improvement did not reach statistical significance. We believe the camp was immensely successful, an opinion that was shared by both the campers and their parents.

  2. High-throughput assay of adenosine in fermentation broth based on enzyme catalysis%酶法高通量测定发酵液中的腺苷含量

    Institute of Scientific and Technical Information of China (English)

    李宁; 董会娜; 祖昕; 张大伟; 吴勇杰

    2015-01-01

    腺苷是合成阿糖腺苷、腺苷酸(AMP)、三磷酸腺苷(ATP)的主要原料,是一种重要的医药原料.目前,微生物发酵生产腺苷越来越受到重视,会产生大量的发酵液样品需要检测.基于腺苷脱氨酶(ADA)建立了一种快速、高通量检测发酵液腺苷的方法.实验结果表明,响应面方法优化检测试剂浓度为碳酸钠-碳酸氢钠34.20mmol/L-27.40 mmol/L,亚硝基铁氰化钠3.35 g/L,次氯酸钠的有效氯为0.172 5%,百里香酚6.64 g/L.该方法检测灵敏,检测限为0.025~6 mmol/L,能够满足发酵检测和高通量筛选的需要.%Adenosine is the main raw material for the production of vidarabine,adenosine monophosphate (AMP) and adenosinetriphosphate (ATP).Adenosine is also an important pharmaceutical raw materials.At present,microbial fermentation production of adenosoine will produce large amounts of fermentation samples to be detected A rapid high -throughput method for detecting adenosine in fermentation broth based on adenosine deaminase (ADA)was estabished.Using response surface model analysis to determine the optimum concentration of four substances,the results showed sodium carbonate-sodium bicarbonate 34.20 mmol/L-27.40 mmol/L,sodium nitropmssid 3.35 g/L,the effective chlorine of sodium hypochlorite 0.172 5%,thymol 6.64 g/L.The limit of detection was between 0.025 mmo1/L and 6 mmo1/L,this method is sensitive and can meet the needs of the fermentation detection and high-throughput screening.

  3. Changes of nitric oxide synthase and cyclic guanosine monophosphate in form deprivation myopia in guinea pigs

    Institute of Scientific and Technical Information of China (English)

    WU Jie; LIU Qiong; YANG Xiao; YANG Hui; WANG Xin-mei; ZENG Jun-wen

    2007-01-01

    Background The form deprivation(FD)reduces spatial contrasts and induces myopia. Nitric oxide and cyclic guanosine monophosphate(cGMP)are involved in visual signal transmission.This study investigated changes in nitric oxide synthase(NOS)activity and cGMP concentration in ocular tissues in acute and chronic form deprivation myopia.Methods Guinea pigs had one eye covered by translucent glass for 7,14 or 21 days.Untreated litter mates were used as controls.NOS activity and cGMP concentrations in the retinal,choroidal and scleral tissues of FD eyes and controleyes were analyzed by radioimmunoassay after various durations of FD.The expression of NOS subtypes was identified by immunohistochemistry.Results Myopia was successfully induced in FD eyes after 14 days.Compared with control groups,the retinal NOS activity and cGMP concentrations in the FD eyes significantly increased after 14 and 21 days while the retinal NOS activity in the FD eyes was transiently suppressed by 7 days of FD.The NOS activity and cGMP concentrations of choroid and sclera in the FD eyes were higher than in the control groups at 21 days.The three isoenzymes of nitric oxide synthase were detected in the ocular tissues of guinea pigs.Conclusions The NOS activity and cGMP concentrations were upregulated after chronic FD and the retinal NOS activity was transiently suppressed at acute FD.The function of elevated NOS activity may be mediated by cGMP.

  4. Different characteristics and nucleotide binding properties of inosine monophosphate dehydrogenase (IMPDH isoforms.

    Directory of Open Access Journals (Sweden)

    Elaine C Thomas

    Full Text Available We recently reported that Inosine Monophosphate Dehydrogenase (IMPDH, a rate-limiting enzyme in de novo guanine nucleotide biosynthesis, clustered into macrostructures in response to decreased nucleotide levels and that there were differences between the IMPDH isoforms, IMPDH1 and IMPDH2. We hypothesised that the Bateman domains, which are present in both isoforms and serve as energy-sensing/allosteric modules in unrelated proteins, would contribute to isoform-specific differences and that mutations situated in and around this domain in IMPDH1 which give rise to retinitis pigmentosa (RP would compromise regulation. We employed immuno-electron microscopy to investigate the ultrastructure of IMPDH macrostructures and live-cell imaging to follow clustering of an IMPDH2-GFP chimera in real-time. Using a series of IMPDH1/IMPDH2 chimera we demonstrated that the propensity to cluster was conferred by the N-terminal 244 amino acids, which includes the Bateman domain. A protease protection assay suggested isoform-specific purine nucleotide binding characteristics, with ATP protecting IMPDH1 and AMP protecting IMPDH2, via a mechanism involving conformational changes upon nucleotide binding to the Bateman domain without affecting IMPDH catalytic activity. ATP binding to IMPDH1 was confirmed in a nucleotide binding assay. The RP-causing mutation, R224P, abolished ATP binding and nucleotide protection and this correlated with an altered propensity to cluster. Collectively these data demonstrate that (i the isoforms are differentially regulated by AMP and ATP by a mechanism involving the Bateman domain, (ii communication occurs between the Bateman and catalytic domains and (iii the RP-causing mutations compromise such regulation. These findings support the idea that the IMPDH isoforms are subject to distinct regulation and that regulatory defects contribute to human disease.

  5. Recognition of Nucleoside Monophosphate Substrates by Haemophilus influenzae Class C Acid Phosphatase

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Harkewal; Schuermann, Jonathan P.; Reilly, Thomas J.; Calcutt, Michael J.; Tanner, John J. (Cornell); (UMC)

    2010-12-08

    The e (P4) phosphatase from Haemophilus influenzae functions in a vestigial NAD{sup +} utilization pathway by dephosphorylating nicotinamide mononucleotide to nicotinamide riboside. P4 is also the prototype of class C acid phosphatases (CCAPs), which are nonspecific 5{prime},3{prime}-nucleotidases localized to the bacterial outer membrane. To understand substrate recognition by P4 and other class C phosphatases, we have determined the crystal structures of a substrate-trapping mutant P4 enzyme complexed with nicotinamide mononucleotide, 5{prime}-AMP, 3{prime}-AMP, and 2{prime}-AMP. The structures reveal an anchor-shaped substrate-binding cavity comprising a conserved hydrophobic box that clamps the nucleotide base, a buried phosphoryl binding site, and three solvent-filled pockets that contact the ribose and the hydrogen-bonding edge of the base. The span between the hydrophobic box and the phosphoryl site is optimal for recognizing nucleoside monophosphates, explaining the general preference for this class of substrate. The base makes no hydrogen bonds with the enzyme, consistent with an observed lack of base specificity. Two solvent-filled pockets flanking the ribose are key to the dual recognition of 5{prime}-nucleotides and 3{prime}-nucleotides. These pockets minimize the enzyme's direct interactions with the ribose and provide sufficient space to accommodate 5{prime} substrates in an anti conformation and 3{prime} substrates in a syn conformation. Finally, the structures suggest that class B acid phosphatases and CCAPs share a common strategy for nucleotide recognition.

  6. Seafloor Science and Remotely Operated Vehicle (SSROV) Day Camp: A Week-Long, Hands-On STEM Summer Camp

    Science.gov (United States)

    Wheat, C. G.; Fournier, T.; Monahan, K.; Paul, C.

    2015-12-01

    RETINA (Robotic Exploration Technologies IN Astrobiology) has developed a program geared towards stimulating our youth with innovative and relevant hands-on learning modules under a STEM umbrella. Given the breadth of potential science and engineering topics that excite children, the RETINA Program focuses on interactive participation in the design and development of simple robotic and sensor systems, providing a range of challenges to engage students through project-based learning (PBL). Thus, young students experience scientific discovery through the use and understanding of technology. This groundwork serves as the foundation for SSROV Camp, a week-long, summer day camp for 6th-8th grade students. The camp is centered on the sensors and platforms that guide seafloor exploration and discovery and builds upon the notion that transformative discoveries in the deep sea result from either sampling new environments or making new measurements with sensors adapted to this extreme environment. These technical and scientific needs are folded into the curriculum. Each of the first four days of the camp includes four team-based, hands-on technical challenges, communication among peer groups, and competition. The fifth day includes additional activities, culminating in camper-led presentations to describe a planned mission based on a given geologic setting. Presentations include hypotheses, operational requirements and expected data products. SSROV Camp was initiated last summer for three sessions, two in Monterey, CA and one in Oxford, MS. Campers from both regions grasped key elements of the program, based on written responses to questions before and after the camp. On average, 32% of the pre-test questions were answered correctly compared with 80% of the post-test questions. Additional confirmation of gains in campers' knowledge, skills, and critical thinking on environmental issues and engineering problems were apparent during the "jeopardy" competition, nightly homework

  7. Intracellular signalling pathways in the vasoconstrictor response of mouse afferent arterioles to adenosine

    DEFF Research Database (Denmark)

    Hansen, Pernille B. Lærkegaard; Friis, Ulla Glenert; Uhrenholt, Torben Rene;

    2007-01-01

    calcium from the sarcoplasmic reticulum (SR), stimulated presumably by IP(3), is involved in the adenosine contraction mechanism of the afferent arteriole. In agreement with this notion is the observation that 2 aminoethoxydiphenyl borate (100 microM) blocked the adenosine-induced constriction whereas the...... protein kinase C inhibitor calphostin C had no effect. The calcium-activated chloride channel inhibitor IAA-94 (30 microM) inhibited the adenosine-mediated constriction. Patch clamp experiments showed that adenosine treatment induced a depolarizing current in preglomerular smooth muscle cells which was....... METHODS AND RESULTS: Adenosine (10(-7) M) significantly increased the intracellular calcium concentration in mouse isolated afferent arterioles measured by fura-2 fluorescence. Pre-treatment with thapsigargin (2 microM) blocked the vasoconstrictor action of adenosine (10(-7) M) indicating that release of...

  8. [Effects of dopamine and adenosine on regulation of water-electrolyte exchange in Amoeba proteus].

    Science.gov (United States)

    Bagrov, Ia Iu; Manusova, N B

    2014-01-01

    Dopamine and adenosine both regulate transport of sodium chloride in the renal tubules in mammals. We have studied the effect of dopamine and adenosine on spontaneous activity of contractile vacuole of Amoeba proteous. Both substances stimulated contractile vacuole. The effect of dopamine was suppressed by D2 receptor antagonist, haloperidol, but not by D1 antagonist, SCH 39166. Adenylate cyclase inhibitor, 2.5-dideoxyadenosine, suppressed the effect of dopamine, but not of adenosine. Inhibitor of protein kinase C, staurosporine, in contrast, blocked the effect of adenosine, but not dopamine. Notably, dopamine opposed effect of adenosine and vice versa. These results suggest that similar effects of dopamine and adenosine could be mediated by different intracellulare mechanisms.

  9. Acute hyperammonemia and systemic inflammation is associated with increased extracellular brain adenosine in rats

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Dale, Nicholas; Larsen, Fin Stolze

    2015-01-01

    Acute liver failure (ALF) can lead to brain edema, cerebral hyperperfusion and intracranial hypertension. These complications are thought to be mediated by hyperammonemia and inflammation leading to altered brain metabolism. As increased levels of adenosine degradation products have been found...... in brain tissue of patients with ALF we investigated whether hyperammonemia could induce adenosine release in brain tissue. Since adenosine is a potent vasodilator and modulator of cerebral metabolism we furthermore studied the effect of adenosine receptor ligands on intracranial pressure (ICP......) and cerebral blood flow (CBF). We measured the adenosine concentration with biosensors in rat brain slices exposed to ammonia and in a rat model with hyperammonemia and systemic inflammation. Exposure to ammonia in concentrations from 0.15-10 mM led to increases in the cortical adenosine concentration up to 18...

  10. Contraction induced secretion of VEGF from skeletal muscle cells is mediated by adenosine

    DEFF Research Database (Denmark)

    Høier, Birgitte; Olsen, Karina; Nyberg, Michael Permin;

    2010-01-01

    The role of adenosine and contraction for secretion of VEGF in skeletal muscle was investigated in human subjects and rat primary skeletal muscle cells. Microdialysis probes were inserted into the thigh muscle of seven male subjects and dialysate was collected at rest, during infusion of adenosine...... and contraction caused secretion of VEGF (pcontraction induced secretion of VEGF protein was abolished by the A(2B) antagonist enprofyllin and markedly reduced by inhibition of PKA or MAPK. The results demonstrate that adenosine causes secretion of VEGF from human skeletal muscle cells...... and that the contraction induced secretion of VEGF is partially mediated via adenosine acting on A(2B) adenosine receptors. Moreover, the contraction induced secretion of VEGF protein from muscle is dependent on both PKA and MAPK activation, but only the MAPK pathway appears to be adenosine dependent....

  11. A kinase-anchoring proteins and adenylyl cyclase in cardiovascular physiology and pathology.

    Science.gov (United States)

    Efendiev, Riad; Dessauer, Carmen W

    2011-10-01

    3'-5'-Cyclic adenosine monophosphate (cAMP), generated by adenylyl cyclase (AC), serves as a second messenger in signaling pathways regulating many aspects of cardiac physiology, including contraction rate and action potential duration, and in the pathophysiology of hypertrophy and heart failure. A kinase-anchoring proteins localize the effect of cAMP in space and time by organizing receptors, AC, protein kinase A, and other components of the cAMP cascade into multiprotein complexes. In this review, we discuss how the interaction of A kinase-anchoring proteins with distinct AC isoforms affects cardiovascular physiology.

  12. Snakes Have Feelings, Too: Elements of a Camp Snake Program.

    Science.gov (United States)

    Allen, Robert Ross

    2001-01-01

    A camp snake program can help campers overcome their fear of snakes, and people cannot truly enjoy nature when they carry a phobia about any one part of it. It can also help overcome prejudice by teaching truth and respect, instilling compassion, and helping campers develop empathy. Advice on catching, handling, identifying, keeping, and feeding…

  13. Criticality for Global Citizenship in Korean English Immersion Camps

    Science.gov (United States)

    Ahn, So-Yeon

    2015-01-01

    Given a heavy social, ideological pressure for parents to pursue better English education for their children in the globalized world, short-term English immersion camp programs have emerged as an educational option in South Korea, promoted as environments for intercultural communication between native English-speaking teachers and local Korean…

  14. Participant Perspectives on the ESO Astronomy Camp Programme

    Science.gov (United States)

    Olivotto, C.; Cenadelli, D.; Gamal, M.; Grossmann, D.; Teller, L. A. I.; Marta, A. S.; Matoni, C. L.; Taillard, A.

    2015-09-01

    This article describes the experience of attending the European Southern Observatory (ESO) Astronomy Camp from the perspective of its participants - students aged between 16 and 18 years old from around the world. The students shared a week together during the winter of 2014 in the Alpine village of Saint-Barthelemy, Italy. The camp was organised by ESO in collaboration with Sterrenlab and the Astronomical Observatory of the Autonomous Region of the Aosta Valley and offered a rich programme of astronomy and leisure activities. This article focuses on the concept of astronomy camps, and their role as a unique tool to complement formal classroom education, rather than on the astronomy activities and the scientific programme. Thus, it is not an academic review of the implemented methodologies, but rather a reflection on the overall experience. The article was brought together from collaborative accounts by some of the participants who were asked to reflect on the experience. The participants who contributed to this article represent the diversity of the ESO Astronomy Camp's alumni community.

  15. Gender Differences in the Perceived Severity of Boot Camp

    Science.gov (United States)

    Wood, Peter B.; May, David C.; Grasmick, Harold G.

    2005-01-01

    We analyze survey data from 181 male and 224 female inmates serving brief prison terms for nonviolent offenses to examine offenders' perceptions of the severity of boot camp compared to prison. Building on the limited work in this area, we present reasons those offenders feel are important to both avoid and participate in alternative sanctions.…

  16. Novel H1N1 Flu and Camp

    Centers for Disease Control (CDC) Podcasts

    2009-06-30

    This podcast gives tips to stay healthy and help prevent infection with novel H1N1 flu if your child or someone you know is going to camp.  Created: 6/30/2009 by Centers for Disease Control and Prevention (CDC).   Date Released: 6/30/2009.

  17. Addressing Nature Deficit Disorder through Primitive Camping Experiences

    Science.gov (United States)

    Allen, Kevin; Varner, Keegan; Sallee, Jeff

    2011-01-01

    Today's youth suffer from Nature Deficit Disorder, a condition that has been connected to ADHD, shortage of creativity, and general lack of knowledge about the outdoors. A team of educators and specialists are addressing this issue with primitive camping. County educators were trained using experiential learning and train-the-trainer techniques.…

  18. Credit-based livelihood interventions in a Zambian refugee camp

    Directory of Open Access Journals (Sweden)

    Jane Travis

    2004-05-01

    Full Text Available Establishing community credit facilities has become an important developmental tool for building livelihood strategies. In the refugee camps where the British NGO Christian Outreach Relief andDevelopment (CORD has worked, programmes have provided credit in the form of cash, agricultural inputs or livestock.

  19. Camp stability predicts patterns of hunter–gatherer cooperation

    Science.gov (United States)

    2016-01-01

    Humans regularly cooperate with non-kin, which has been theorized to require reciprocity between repeatedly interacting and trusting individuals. However, the role of repeated interactions has not previously been demonstrated in explaining real-world patterns of hunter–gatherer cooperation. Here we explore cooperation among the Agta, a population of Filipino hunter–gatherers, using data from both actual resource transfers and two experimental games across multiple camps. Patterns of cooperation vary greatly between camps and depend on socio-ecological context. Stable camps (with fewer changes in membership over time) were associated with greater reciprocal sharing, indicating that an increased likelihood of future interactions facilitates reciprocity. This is the first study reporting an association between reciprocal cooperation and hunter–gatherer band stability. Under conditions of low camp stability individuals still acquire resources from others, but do so via demand sharing (taking from others), rather than based on reciprocal considerations. Hunter–gatherer cooperation may either be characterized as reciprocity or demand sharing depending on socio-ecological conditions. PMID:27493770

  20. Phun Physics 4 Phemales: Physics Camp for High School Girls

    Science.gov (United States)

    Kwon, Chuhee; Gu, Jiyeong; Henriquez, Laura

    2014-03-01

    The department of Physics and Astronomy with the department of Science Education at California State University, Long Beach hosted summer program of ``Phun Physics 4 Phemales (PP4P)'' during summer 2012 and summer 2013 with the support from APS public outreach program. PP4P summer camp was hosted along with a two-week summer science camp, Young Scientists Camp, which has been institutionalized for the last 14 years since 1999. More than 2,500 3rd -8th grade students and 250 teachers have participated in the program. PP4P program provided the tools and support that female high school students need to pursue careers in physics and/or science, technology, engineering and math (STEM) field. This girls-only camp created connections among the girls and built confidence. In addition PP4P program introduced students to key principles in physics by a hands-on lab environment and demonstrated the real-world social impact of physics. In summer 2012, high school girls worked on physics experimental project on electronics and in summer 2013 they worked on the mechanics. I would share our experience in this program and the impact on the female high school students. This work was supported by 2012 Public Outreach and Informing the Public Grants from American Physical Society.

  1. Vietnamese in America, Part Four: Life in the Refugee Camps

    Science.gov (United States)

    Liu, William T.; Murata, Alice K.

    1978-01-01

    The experiences of Vietnamese refugees in transitional camps in the summer and fall of 1975 are described in this paper. The data show that the mental health needs of the refugees were not taken seriously and that it was assumed that assimilation would be problem-free. (Author/AM)

  2. 14 CFR 91.1415 - CAMP: Mechanical reliability reports.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false CAMP: Mechanical reliability reports. 91.1415 Section 91.1415 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF... certificate (including a supplemental type certificate), a Parts Manufacturer Approval, or a...

  3. Academic Boot Camp for the Writing of Psychology Research Reports

    Science.gov (United States)

    Skues, Jason L.; Wise, Lisa

    2014-01-01

    Herein, we describe the implementation of, and responses to, a structured writing workshop in the form of an academic boot camp. Participants were 42 undergraduate psychology students from a medium-sized Australian university who were completing their major assignment for the semester. A majority of the students expressed satisfaction with the…

  4. Graying America Presents Golden Opportunities for Camp Directors.

    Science.gov (United States)

    Cosky, Alicia C.

    1989-01-01

    Discusses quality-of-life issues for ever-increasing population of American elderly, emphasizing value of recreation. Offers organized camping as way of exposing older adults to enjoyable physical activities. Cites evidence supporting beneficial effects of regular exercise for elderly, beginning at any age. (TES)

  5. Reflections on Refugee Students' Major Perceptions of Education in Kakuma Refugee Camp, Kenya

    Science.gov (United States)

    Mareng, Chuei D.

    2010-01-01

    This reflective study explores refugee students' perceptions of the educational approach used in Kakuma Refugee Camp in Kenya. The study focuses on my personal reflections as a teacher and a student in this camp, and as a refugee. My goal of writing this narrative is to reflect fully on the refugee students' life in a camp and then contribute to…

  6. The accidental city : violence, economy and humanitarianism in Kakuma refugee camp Kenya

    NARCIS (Netherlands)

    Jansen, B.J.

    2011-01-01

    In this research I examine social ordering processes in Kakuma refugee camp in Kenya. I view the camp as an accidental city, by which I challenge the image of the camp as a temporary and artificial waiting space or a protracted refugee crisis per se. The reference to the city is both metaphorical

  7. A Multidisciplinary Science Summer Camp for Students with Emphasis on Environmental and Analytical Chemistry

    Science.gov (United States)

    Schwarz, Gunnar; Frenzel, Wolfgang; Richter, Wolfgang M.; Ta¨uscher, Lothar; Kubsch, Georg

    2016-01-01

    This paper presents the course of events of a five-day summer camp on environmental chemistry with high emphasis on chemical analysis. The annual camp was optional and open for students of all disciplines and levels. The duration of the summer camp was five and a half days in the Feldberg Lake District in northeast Germany (federal state of…

  8. Impact of Attending Jump Start Literacy Camp on Reading Achievement among Third and Fourth Grade Students

    Science.gov (United States)

    Padgett, Carrie B.

    2010-01-01

    The Jump Start Literacy Camp was developed as a means to combat summer learning loss. The camp utilized high-energy activities to target phonemic awareness, phonics, vocabulary, fluency, and comprehension. This study examined the effects of the Jump Start Literacy Camp on reading achievement for rising third and fourth grade students in an urban…

  9. 14 CFR 91.1425 - CAMP: Maintenance, preventive maintenance, and alteration programs.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false CAMP: Maintenance, preventive maintenance... RULES Fractional Ownership Operations Program Management § 91.1425 CAMP: Maintenance, preventive maintenance, and alteration programs. Each program manager who maintains program aircraft under a CAMP...

  10. Strengthening Families: Exploring the Impacts of Family Camp Experiences on Family Functioning and Parenting

    Science.gov (United States)

    Garst, Barry A.; Baughman, Sarah; Franz, Nancy K.; Seidel, Richard W.

    2013-01-01

    Research suggests that family camp experiences can enhance family relationships. Families often participate in family camp experiences for a vacation, as part of a therapeutic and/or intervention strategy, or to gain general enrichment or engagement. To better understand the impacts of family camp experiences on family functioning, a mixed-methods…

  11. Culture Camp, Ethnic Identity, and Adoption Socialization for Korean Adoptees: A Pretest and Posttest Study

    Science.gov (United States)

    Baden, Amanda L.

    2015-01-01

    This study explores the impact of racial-ethnic socialization on adopted South Korean children and adolescents who attended a sleepaway Korean culture camp for one week. This camp provided racial-ethnic socialization experiences via exposure to camp counselors, staff, and teachers who were Korean Americans, Korean nationals, and Korean adult…

  12. 77 FR 56174 - Proposed Establishment of Class D and Class E Airspace; Camp Guernsey, WY

    Science.gov (United States)

    2012-09-12

    ... 14 CFR Part 71 Proposed Establishment of Class D and Class E Airspace; Camp Guernsey, WY AGENCY... action proposes to establish Class D airspace and Class E airspace at Camp Guernsey Airport, Camp... holidays. An informal docket may also be examined during normal business hours at the Northwest...

  13. Metabolites of an Epac-selective cAMP analog induce cortisol synthesis by adrenocortical cells through a cAMP-independent pathway.

    Directory of Open Access Journals (Sweden)

    Judith A Enyeart

    Full Text Available Adrenal zona fasciculata (AZF cells express a cAMP-activated guanine nucleotide exchange protein (Epac2 that may function in ACTH-stimulated cortisol synthesis. Experiments were done to determine whether cAMP analogs that selectively activate Epacs could induce cortisol synthesis and the expression of genes coding for steroidogenic proteins in bovine AZF cells. Treatment of AZF cells with the Epac-selective cAMP analog (ESCA 8CPT-2'-OMe-cAMP induced large (>100 fold, concentration-dependent, delayed increases in cortisol synthesis and the expression of mRNAs coding for the steroid hydroxylases CYP11a1, CYP17, CYP21, and the steroid acute regulatory protein (StAR. However, a non-hydrolyzable analog of this ESCA, Sp-8CPT-2'-OMe-cAMP, failed to stimulate cortisol production even at concentrations that activated Rap1, a downstream effector of Epac2. Accordingly, putative metabolites of 8CPT-2'-OMe-cAMP, including 8CPT-2'-OMe-5'AMP, 8CPT-2'-OMe-adenosine, and 8CPT-adenine all induced cortisol synthesis and steroid hydroxylase mRNA expression with a temporal pattern, potency, and effectiveness similar to the parent compound. At concentrations that markedly stimulated cortisol production, none of these metabolites significantly activated cAMP-dependent protein kinase (PKA. These results show that one or more metabolites of the ESCA 8CPT-2'-OMe-cAMP induce cortico-steroidogenesis by activating a panel of genes that code for steroidogenic proteins. The remarkable increases in cortisol synthesis observed in this study appear to be mediated by a novel cAMP-, Epac- and PKA-independent signaling pathway.

  14. Topical adenosine increases the proportion of thick hair in Caucasian men with androgenetic alopecia.

    Science.gov (United States)

    Iwabuchi, Tokuro; Ideta, Ritsuro; Ehama, Ritsuko; Yamanishi, Haruyo; Iino, Masato; Nakazawa, Yosuke; Kobayashi, Takashi; Ohyama, Manabu; Kishimoto, Jiro

    2016-05-01

    Adenosine is an effective treatment for androgenetic alopecia (AGA) in Japanese men and women. Adenosine exerts its effects by significantly increasing the proportion of thick hair. In this study, we assessed the clinical outcome of adenosine treatment for 6 months in 38 Caucasian men. The change in proportion of thick hair (≥60 μm) compared with baseline in the adenosine group was significantly higher than that in the placebo group (P thick hair in Caucasian men with AGA as well as in Japanese men and women.

  15. Comparison of the novel vasodilator uridine triphosphate and adenosine for the measurement of fractional flow reserve

    DEFF Research Database (Denmark)

    Sivertsen, Jacob; Jensen, Jan Skov; Galatius, Søren;

    2014-01-01

    AIM: Examination of the fractional flow reserve (FFR) responses of intravenous (IV) adenosine with increasing doses of intracoronary (IC) adenosine versus IC uridine triphosphate (UTP) in patients with coronary artery disease. METHODS AND RESULTS: We measured FFR in 25 patients during continuous IV...... and IC infusion (using a microcatheter in the coronary ostium). Standard IV adenosine infusion (140 μg/kg/min) was compared to 8 equimolar incremental doses of IC UTP and IC adenosine (20, 40, 60, 80, 160, 240, 320 and 640 μg/min) in a randomized order. Across all doses, ΔFFR[IC UTP - IC adenosine......] was -0.038 ± 0.008, Pdose of IC UTP, FFR was significantly lower (FFR[IC UTP] = 0.62 ± 0.04) than during IV adenosine (FFR[IV adenosine] = 0.72 ± 0.05; P=.02) and IC adenosine (FFR[IC adenosine] = 0.68 ± 0.05; P=.03). Furthermore, UTP had significantly fewer side effects compared...

  16. cAMP and in vivo hypoxia induce tob, ifr1, and fos expression in erythroid cells of the chick embryo.

    Science.gov (United States)

    Dragon, Stefanie; Offenhäuser, Nina; Baumann, Rosemarie

    2002-04-01

    During avian embryonic development, terminal erythroid differentiation occurs in the circulation. Some of the key events, such as the induction of erythroid 2,3-bisphosphoglycerate (2,3-BPG), carbonic anhydrase (CAII), and pyrimidine 5'-nucleotidase (P5N) synthesis are oxygen dependent (Baumann R, Haller EA, Schöning U, and Weber M, Dev Biol 116: 548-551, 1986; Dragon S and Baumann R, Am J Physiol Regulatory Integrative Comp Physiol 280: R870-R878, 2001; Dragon S, Carey C, Martin K, and Baumann R, J Exp Biol 202: 2787-2795, 1999; Dragon S, Glombitza S, Götz R, and Baumann R, Am J Physiol Regulatory Integrative Comp Physiol 271: R982-R989, 1996; Dragon S, Hille R, Götz R, and Baumann R, Blood 91: 3052-3058, 1998; Million D, Zillner P, and Baumann R, Am J Physiol Regulatory Integrative Comp Physiol 261: R1188-R1196, 1991) in an indirect way: hypoxia stimulates the release of norepinephrine (NE)/adenosine into the circulation (Dragon et al., J Exp Biol 202: 2787-2795, 1999; Dragon et al., Am J Physiol Regulatory Integrative Comp Physiol 271: R982-R989, 1996). This leads via erythroid beta-adrenergic/adenosine A(2) receptor activation to a cAMP signal inducing several proteins in a transcription-dependent manner (Dragon et al., Am J Physiol Regulatory Integrative Comp Physiol 271: R982-R989, 1996; Dragon et al., Blood 91: 3052-3058, 1998; Glombitza S, Dragon S, Berghammer M, Pannermayr M, and Baumann R, Am J Physiol Regulatory Integrative Comp Physiol 271: R973-R981, 1996). To understand how the cAMP-dependent processes are initiated, we screened an erythroid cDNA library for cAMP-regulated genes. We detected three genes that were strongly upregulated (>5-fold) by cAMP in definitive and primitive red blood cells. They are homologous to the mammalian Tob, Ifr1, and Fos proteins. In addition, the genes are induced in the intact embryo during short-term hypoxia. Because the genes are regulators of proliferation and differentiation in other cell types, we suggest that cAMP

  17. Using Science Camps to Develop Understandings about Scientific Inquiry--Taiwanese Students in a U.S. Summer Science Camp

    Science.gov (United States)

    Antink-Meyer, Allison; Bartos, Stephen; Lederman, Judith S.; Lederman, Norman G.

    2016-01-01

    Recent years have witnessed a dramatic rise in the number of middle and high school students from Asian countries participating in U.S.-based summer experiences (Perlez & Gao, 2013). Although summer science camps have been shown to improve students' attitudes and interests related to science and science learning (Bhattacharyya, Mead &…

  18. The camp analogue, dbcAMP can stimulate rabbit reproductive functions: I. Effect on ovarian folliculogenesis, ovulation and embryo production

    Directory of Open Access Journals (Sweden)

    Chrenek P.

    2012-01-01

    Full Text Available The aim of our study was to examine the influence of administration of N6,2’-dibutyryladenosine 3’5’-cyclic monophosphate (dbcAMP, a cAMP agonist, on ovarian folliculogenesis and atresia, as well as on reproductive efficiency in rabbits, whose ovarian cycle and ovulation was induced by gonadotropins. Ovarian cycle and ovulation of control rabbits were induced by 20 IU/kg PMSG followed by 35 IU/kg hCG administration. Experimental animals received PMSG and hCG together with dbcAMP (at 5, 25 or 50 μg/animal. After ovulation and insemination, the animals were sacrificed. Ovaries were weighted, histological sections of ovaries were prepared, and the presence of ovulated and not ovulated follicles and different stages of atresia was evaluated by light microscopy. The eggs were flushed from the oviducts after insemination and cultured up to blastocyst cell stage. Numbers of ovarian Corpora lutea, ovulated oocytes and oocyte-derived zygotes and embryos reaching hatched blastocyst stage were determined. Administration of dbcAMP (at doses 25 or 50 μg/animal, but not at 5 μg/animal was able to increase the proportion of follicles with cystic and luteinization-related atresia. Furthermore, dbcAMP (50 μg/animal, but not lower doses increased the ovarian mass, number of Corpora lutea, number of harvested oocytes, zygotes and embryos at blastocyst stage derived from these zygotes after culture. These data demonstrate that dbcAMP can stimulate rabbit ovarian follicle atresia, ovulation, oocyte, zygote and embryo yield and development. Furthermore, they confirm in the involvement of cyclic nucleotide-dependent intracellular mechanisms in the control of rabbit reproductive functions and potential practical usefulness of dbcAMP in improving animal reproduction and fertility.

  19. Elevated nitric oxide and 3',5' cyclic guanosine monophosphate levels in patients with alcoholic cirrhosis

    Institute of Scientific and Technical Information of China (English)

    C(i)ntia Siqueira; Miguel Carneiro de Moura; Ana J(u)lia Pedro; Paula Rocha

    2008-01-01

    AIM: To evaluate whether serum levels of nitric oxide (NO') and plasma levels of cyclic guanosine monophosphate (Cgmp) and total glutathione (GSH) are altered in patients with alcoholic cirrhosis and to examine their correlation with the severity of liver disease.METHODS: Twenty-six patients with alcoholic liver cirrhosis were studied. Serum levels of NO· and plasma levels of cGMP and GSH were measured in 7 patients with compensated alcoholic cirrhosis (Child-Pugh A) and 19 patients with advanced cirrhosis (Child-Pugh B and C).The model for end-stage liver disease (MELD) score was evaluated. Sixteen healthy volunteers served as controls.Liver enzymes and creatinine levels were also tested.RESULTS: NO· and cGMP levels were higher in patients with Child-Pugh B and C cirrhosis than in Child-Pugh A cirrhosis or controls (NO·: 21.70 ± 8.07 vs 11.70 ± 2.74; 21.70 ± 8.07 vs 7.26 ± 2.47 μmol/L, respectively;P < 0.001) and (cGMP: 20.12 ± 6.62 vs 10.14 ± 2.78;20.12 ± 6.62 vs 4.95 ± 1.21 pmol/L, respectively; P <0.001). Total glutathione levels were lower in patients with Child-Pugh B and C cirrhosis than in patients with Child-Pugh A cirrhosis or controls (16.04 ± 6.06 vs 23.01 ± 4.38 or 16.04 ± 6.06 vs 66.57 ± 26.23 μmol/L,respectively; P < 0.001). There was a significant correlation between NO· and cGMP levels in all patients with alcoholic cirrhosis. A significant negative correlation between reduced glutathione/glutathione disulfide and the MELD score was found in all cirrhotic patients. CONCLUSION: Our results suggest a role for oxidative stress in alcoholic liver cirrhosis, which is more significant in decompensated patients with higher levels of NO· and cGMP and lower GSH levels than in compensated and control patients. Altered mediator levels in decompensated patients may influence the hemodynamic changes in and progression of liver disease.

  20. Multiple Facets of cAMP Signalling and Physiological Impact: cAMP Compartmentalization in the Lung

    Directory of Open Access Journals (Sweden)

    Martina Schmidt

    2012-11-01

    Full Text Available Therapies involving elevation of the endogenous suppressor cyclic AMP (cAMP are currently used in the treatment of several chronic inflammatory disorders, including chronic obstructive pulmonary disease (COPD. Characteristics of COPD are airway obstruction, airway inflammation and airway remodelling, processes encompassed by increased airway smooth muscle mass, epithelial changes, goblet cell and submucosal gland hyperplasia. In addition to inflammatory cells, airway smooth muscle cells and (myofibroblasts, epithelial cells underpin a variety of key responses in the airways such as inflammatory cytokine release, airway remodelling, mucus hypersecretion and airway barrier function. Cigarette smoke, being next to environmental pollution the main cause of COPD, is believed to cause epithelial hyperpermeability by disrupting the barrier function. Here we will focus on the most recent progress on compartmentalized signalling by cAMP. In addition to G protein-coupled receptors, adenylyl cyclases, cAMP-specific phospho-diesterases (PDEs maintain compartmentalized cAMP signalling. Intriguingly, spatially discrete cAMP-sensing signalling complexes seem also to involve distinct members of the A-kinase anchoring (AKAP superfamily and IQ motif containing GTPase activating protein (IQGAPs. In this review, we will highlight the interaction between cAMP and the epithelial barrier to retain proper lung function and to alleviate COPD symptoms and focus on the possible molecular mechanisms involved in this process. Future studies should include the development of cAMP-sensing multiprotein complex specific disruptors and/or stabilizers to orchestrate cellular functions. Compartmentalized cAMP signalling regulates important cellular processes in the lung and may serve as a therapeutic target.

  1. [Medicine in the concentration camps of the Third Reich].

    Science.gov (United States)

    Shasha, Shaul M

    2005-04-01

    Between 1942 and 1944 millions of prisoners were subjected to forced labor in concentration camps throughout the Third Reich, all the while being the victims of a systematic and "scientific" extermination policy. Though the policy was directed mainly against Jews, it was implemented against other "inferior races" as well. The prisoners, stripped of all rights, experienced constant humiliation, uncertain survival and terror. The harsh living condition, characterized by crowding, absent sanitation and poor personal hygiene led to considerable morbidity, mainly due to injuries, infectious diseases and famine, and to high mortality rates. Medical care in the camps was the responsibility of the S.S. Each camp had a chief S.S. physician accompanied by a number of assistants and orderlies. There was also a parallel system of "prisoner-physicians." There was a chief prisoner-physician in every camp, and each block was assigned a "block doctor" who was responsible for sanitation, the removal of corpses, setting up the sick- call and authorizing sick leave. Work teams were accompanied by "mobile doctors" (Streckenpfleger), who dispensed first aid for work injuries. Prisoner-physicians were also charged with disinfecting the blocks and maintaining hygienic conditions in the camp. Every camp had one or more blocks, called "Reviers", that were used for treatment and hospitalization. In the larger camps a number of blocks were designated to function as a sort of hospital (Krankenbau). At times one camp out of a group of camps would be set aside as quarantine, primarily for patients with infectious diseases. Officially, the "Revier" was the responsibility of an S.S. physicians', assisted by a chief prisoner-physician, his assistants and, at times, nurses. But in actuality the Reviers were managed by prisoners (Capos) who did not have medical training but were authorized to make decisions in medical matters such as operations and, on occasion, even performed them. The Reviers

  2. Musik in Konzentrationslagern The Role of Music in Concentration Camps

    Directory of Open Access Journals (Sweden)

    Gabriele Knapp

    2002-03-01

    Full Text Available Die Holocaust-Forschung hat sich jahrzehntelang vorwiegend mit den Verbrechen in den Konzentrationslagern beschäftigt, während Fragen nach dem „Alltag“ der Häftlinge und ihren Strategien des Überlebens nebensächlich erschienen. Untersuchungen zum (ÜberLeben im KZ können aber gerade die Brutalität des Systems deutlich machen. So war Musik ein integraler Bestandteil des Lageralltags und diente keineswegs nur der Erbauung der Häftlinge, sondern bedeutete für sie häufig eine zusätzliche Tortur, wie Forschungsarbeiten für die Zeit von 1939 bis 1945 bereits belegt haben. Inwieweit dies für die frühen Lager von 1933 bis 1936 zutraf, untersucht Guido Fackler in seiner Studie. Darüber hinaus versucht er, musikalische Kontinuitätslinien von den frühen Lagern bis in die späte Phase (1937–1945 zu zeichnen. Eine Gesamtdarstellung zu KZ-Musik von 1933 bis 1945 konnte dem Autor indes nicht gelingen, wenn er auch einzelne Zusammenhänge zwischen musikalischen Phänomenen in unterschiedlichen Lagern aufzeigt. Facklers Buch lässt sich eher als Quellensammlung für Musik in unterschiedlichsten Konzentrationslagern verstehen und gebrauchen – wenn auch fast ausschließlich begrenzt auf Männerlager.In the past decades, Holocaust studies have focused on researching the annihilating structures of concentration camps, while the study of the inmates’ everyday lives and their strategies for survival was not included in this field of work. However, studying aspects of daily life and survival in the concentration camps can serve to truly bring out the brutality of the Holocaust. Music, for example, was an integral part of everyday life in the camps and did not solely serve to entertain the inmates, but also represented an additional form of torture for them, as previous studies for the time period between 1939 and 1945 have documented. Fackler’s study investigates the extent to which this was the case in the early concentration camps between

  3. Vascular effects and cyclic AMP production produced by VIP, PHM, PHV, PACAP-27, PACAP-38, and NPY on rabbit ovarian artery

    DEFF Research Database (Denmark)

    Yao, W; Sheikh, S P; Ottesen, B;

    1996-01-01

    The relationship between vessel tone and cAMP production induced by vasoactive intestinal polypeptide (VIP), peptide histidine methionine (PHM), peptide histidine valine (PHV), pituitary adenylate cyclase activating polypeptide (PACAP-27 and PACAP-38), and neuropeptide Y (NPY) was investigated......-38 all increased cyclic adenosine monophosphate (cAMP) accumulation. The cAMP accumulation induced by PACAP-27 and PACAP-38 was five times higher than the cAMP content induced by the other three peptides. The peptide-induced smooth muscle relaxation did not correlate to the cAMP accumulation. NPY (10......(-7) M) markedly reversed the relaxations induced by VIP, PHM, PHV, PACAP-27, and PACAP-38, but did not influence the cAMP production induced by these peptides. In conclusion, the relaxation induced by VIP, PHM, PHV, PACAP-27, and PACAP-38 and the contraction induced by NPY are not solely related...

  4. Genetically Controlled Upregulation of Adenosine A(1) Receptor Expression Enhances the Survival of Primary Cortical Neurons

    NARCIS (Netherlands)

    Serchov, Tsvetan; Atas, Hasan-Cem; Normann, Claus; van Calker, Dietrich; Biber, Knut

    2012-01-01

    Adenosine has a key endogenous neuroprotective role in the brain, predominantly mediated by the adenosine A(1) receptor (A(1)R). This has been mainly explored using pharmacological tools and/or receptor knockout mice strains. It has long been suggested that the neuroprotective effects of A(1)R are i

  5. Activation of A(2) adenosine receptors dilates cortical efferent arterioles in mouse

    DEFF Research Database (Denmark)

    Al-Mashhadi, Rozh H; Skøtt, Ole; Vanhoutte, Paul M;

    2009-01-01

    that the adenosine-induced vasodilatation was inhibited by the A(2)-specific receptor blocker 3,7-dimethyl-1-propargylxanthine. In the presence of this inhibitor, adenosine failed to alter the basal vessel diameter of quiescent efferent arterioles. Using primer-specific polymerase chain reaction we found...

  6. Adenosine receptors in COPD and asymptomatic smokers : effects of smoking cessation

    NARCIS (Netherlands)

    Versluis, Mieke; ten Hacken, Nick; Postma, Dirkje; Barroso, Begona; Rutgers, Bea; Geerlings, Marie; Willemse, Brigitte; Timens, Wim; Hylkema, Machteld

    2009-01-01

    Our group has shown that 1-year smoking cessation persisted or increased airway inflammation in chronic obstructive pulmonary disease (COPD). We compared adenosine and adenosine receptor (AR) expression in COPD and asymptomatic smokers (AS) before and after 1-year smoking cessation. Sputum cytospins

  7. Treatment of paroxysmal supraventricular tachycardia with intravenous injection of adenosine triphosphate.

    OpenAIRE

    Saito, D.; Ueeda, M; Abe, Y.; Tani, H; Nakatsu, T.; Yoshida, H.; Haraoka, S; Nagashima, H

    1986-01-01

    Intravenous adenosine triphosphate rapidly terminated all 11 episodes of paroxysmal supraventricular tachycardia in 10 patients. Eight patients reported side effects but these resolved within 20 seconds and did not require treatment. Adenosine triphosphate is a suitable agent for the rapid termination of paroxysmal supraventricular tachycardia.

  8. Role of adenosine in regulating the heterogeneity of skeletal muscle blood flow during exercise in humans

    DEFF Research Database (Denmark)

    Heinonen, Ilkka; Nesterov, Sergey V; Kemppainen, Jukka;

    2007-01-01

    Evidence from both animal and human studies suggests that adenosine plays a role in the regulation of exercise hyperemia in skeletal muscle. We tested whether adenosine also plays a role in the regulation of blood flow (BF) distribution and heterogeneity among and within quadriceps femoris (QF...

  9. Adenosine signaling and the energetic costs of induced immunity.

    Directory of Open Access Journals (Sweden)

    Brian P Lazzaro

    2015-04-01

    Full Text Available Life history theory predicts that trait evolution should be constrained by competing physiological demands on an organism. Immune defense provides a classic example in which immune responses are presumed to be costly and therefore come at the expense of other traits related to fitness. One strategy for mitigating the costs of expensive traits is to render them inducible, such that the cost is paid only when the trait is utilized. In the current issue of PLOS Biology, Bajgar and colleagues elegantly demonstrate the energetic and life history cost of the immune response that Drosophila melanogaster larvae induce after infection by the parasitoid wasp Leptopilina boulardi. These authors show that infection-induced proliferation of defensive blood cells commands a diversion of dietary carbon away from somatic growth and development, with simple sugars instead being shunted to the hematopoetic organ for rapid conversion into the raw energy required for cell proliferation. This metabolic shift results in a 15% delay in the development of the infected larva and is mediated by adenosine signaling between the hematopoietic organ and the central metabolic control organ of the host fly. The adenosine signal thus allows D. melanogaster to rapidly marshal the energy needed for effective defense and to pay the cost of immunity only when infected.

  10. Adenosine Amine Congener as a Cochlear Rescue Agent

    Directory of Open Access Journals (Sweden)

    Srdjan M. Vlajkovic

    2014-01-01

    Full Text Available We have previously shown that adenosine amine congener (ADAC, a selective A1 adenosine receptor agonist, can ameliorate noise- and cisplatin-induced cochlear injury. Here we demonstrate the dose-dependent rescue effects of ADAC on noise-induced cochlear injury in a rat model and establish the time window for treatment. Methods. ADAC (25–300 μg/kg was administered intraperitoneally to Wistar rats (8–10 weeks old at intervals (6–72 hours after exposure to traumatic noise (8–16 kHz, 110 dB sound pressure level, 2 hours. Hearing sensitivity was assessed using auditory brainstem responses (ABR before and 12 days after noise exposure. Pharmacokinetic studies investigated ADAC concentrations in plasma after systemic (intravenous administration. Results. ADAC was most effective in the first 24 hours after noise exposure at doses >50 μg/kg, providing up to 21 dB protection (averaged across 8–28 kHz. Pharmacokinetic studies demonstrated a short (5 min half-life of ADAC in plasma after intravenous administration without detection of degradation products. Conclusion. Our data show that ADAC mitigates noise-induced hearing loss in a dose- and time-dependent manner, but further studies are required to establish its translation as a clinical otological treatment.

  11. Novel trypanocidal analogs of 5'-(methylthio)-adenosine.

    Science.gov (United States)

    Sufrin, Janice R; Spiess, Arthur J; Marasco, Canio J; Rattendi, Donna; Bacchi, Cyrus J

    2008-01-01

    The purine nucleoside 5'-deoxy-5'-(hydroxyethylthio)-adenosine (HETA) is an analog of the polyamine pathway metabolite 5'-deoxy-5'-(methylthio)-adenosine (MTA). HETA is a lead structure for the ongoing development of selectively targeted trypanocidal agents. Thirteen novel HETA analogs were synthesized and examined for their in vitro trypanocidal activities against bloodstream forms of Trypanosoma brucei brucei LAB 110 EATRO and at least one drug-resistant Trypanosoma brucei rhodesiense clinical isolate. New compounds were also assessed in a cell-free assay for their activities as substrates of trypanosome MTA phosphorylase. The most potent analog in this group was 5'-deoxy-5'-(hydroxyethylthio)-tubercidin, whose in vitro cytotoxicity (50% inhibitory concentration [IC50], 10 nM) is 45 times greater than that of HETA (IC50, 450 nM) against pentamidine-resistant clinical isolate KETRI 269. Structure-activity analyses indicate that the enzymatic cleavage of HETA analogs by trypanosome MTA phosphorylase is not an absolute requirement for trypanocidal activity. This suggests that additional biochemical mechanisms are associated with the trypanocidal effects of HETA and its analogs.

  12. Distribution of adenosine receptors in human sclera fibroblasts

    Science.gov (United States)

    Cui, Dongmei; Trier, Klaus; Chen, Xiang; Zeng, Junwen; Yang, Xiao; Hu, Jianmin

    2008-01-01

    Purpose Systemic treatment with adenosine receptor antagonists has been reported to affect the biochemistry and ultrastructure of rabbit sclera. This study was conducted to determine whether adenosine receptors (ADORs) are present in human scleral fibroblasts (HSF). Methods Primary HSF were cultured in vitro and identified with anti-vimentin, anti-keratin, anti-desmin, and anti-S-100 antibodies. Confocal fluorescence microscopy was used to study the distribution of ADORs in the HSF cell lines and in the frozen human scleral sections. ADOR protein expression in HSF and human sclera was confirmed by western blot analysis of cell lysates. Results ADORs were expressed in both HSF and human sclera. This was confirmed by western blot. ADORA1 expression was concentrated in the nucleus. ADORA2A was concentrated mainly in one side of the cytoplasm, and ADORA2B was found both in the nucleus and the cytoplasm. ADORA3 was expressed weakly in the cytoplasm. Conclusions All four subtypes of ADOR were found in HSF and may play a role in scleral remodeling. PMID:18385786

  13. Feed-Forward Inhibition of CD73 and Upregulation of Adenosine Deaminase Contribute to the Loss of Adenosine Neuromodulation in Postinflammatory Ileitis

    OpenAIRE

    Cátia Vieira; Maria Teresa Magalhães-Cardoso; Fátima Ferreirinha; Isabel Silva; Ana Sofia Dias; Julie Pelletier; Jean Sévigny; Paulo Correia-de-Sá

    2014-01-01

    Purinergic signalling is remarkably plastic during gastrointestinal inflammation. Thus, selective drugs targeting the “purinome” may be helpful for inflammatory gastrointestinal diseases. The myenteric neuromuscular transmission of healthy individuals is fine-tuned and controlled by adenosine acting on A2A excitatory receptors. Here, we investigated the neuromodulatory role of adenosine in TNBS-inflamed longitudinal muscle-myenteric plexus of the rat ileum. Seven-day postinflammation ileitis ...

  14. Cloning, expression and pharmacological characterization of rabbit adenosine A1 and A3 receptors.

    Science.gov (United States)

    Hill, R J; Oleynek, J J; Hoth, C F; Kiron, M A; Weng, W; Wester, R T; Tracey, W R; Knight, D R; Buchholz, R A; Kennedy, S P

    1997-01-01

    The role of adenosine A1 and A3 receptors in mediating cardioprotection has been studied predominantly in rabbits, yet the pharmacological characteristics of rabbit adenosine A1 and A3 receptor subtypes are unknown. Thus, the rabbit adenosine A3 receptor was cloned and expressed, and its pharmacology was compared with that of cloned adenosine A1 receptors. Stable transfection of rabbit A1 or A3 cDNAs in Chinese hamster ovary-K1 cells resulted in high levels of expression of each of the receptors, as demonstrated by high-affinity binding of the A1/A3 adenosine receptor agonist N6-(4-amino-3-[125I]iodobenzyl)adenosine (125I-ABA). For both receptors, binding of 125I-ABA was inhibited by the GTP analog 5'-guanylimidodiphosphate, and forskolin-stimulated cyclic AMP accumulation was inhibited by the adenosine receptor agonist (R)-phenylisopropyladenosine. The rank orders of potency of adenosine receptor agonists for inhibition of 125I-ABA binding were as follows: rabbit A1, N6-cyclopentyladenosine = (R)-phenylisopropyladenosine > N-ethylcarboxamidoadenosine > or = I-ABA > or = N6-2-(4-aminophenyl) ethyladenosine > > N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide > N6-(4-amino-3-benzyl)adenosine; rabbit A3, N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide > or = I-ABA > > N-ethylcarboxamidoadenosine > N6-2-(4-aminophenyl) ethyladenosine = N6-cyclopentyladenosine = (R)-phenylisopropyladenosine > N6-(4-amino-3-benzyl)adenosine. The adenosine receptor antagonist rank orders were as follow: rabbit A1, 8-cyclopentyl-1,3-dipropylxanthine > 1,3- dipropyl-8-(4-acrylate)phenylxanthine > or = xanthine amine congener > > 8-(p-sulfophenyl)theophylline; rabbit A3, xanthine amine congener > 1,3-dipropyl-8-(4-acrylate)phenylxanthine > or = 8-cyclopentyl-1,3-dipropylxanthine > > 8-(p-sulfophenyl)theophylline. These observations confirm the identity of the expressed proteins as A1 and A3 receptors. The results will facilitate further in-depth studies of the roles of A1 and A3 receptors in

  15. From camp to kitsch: A queer eye on console fandom

    Directory of Open Access Journals (Sweden)

    Rob Gallagher

    2014-03-01

    Full Text Available Offering a queer perspective on video game fandom, this article considers the factors that fostered a subculture of Western devotees of Japanese video games in the 1990s. Focused on readers of the English publication Sega Saturn Magazine, it shows how, for these players, Japanese games became the basis of a collective identity founded on precisely the kinds of perverse over-attachment, projective identification and hermeneutic ingenuity that Eve Kosofsky Sedgwick identifies with camp. Citing this subculture as an example of how fans transform the texts they put to use, the article also addresses its implications for our understanding of fandom today, at a time when the proliferation of quantitative analysis techniques is transforming the production and consumption of games. Such techniques, I argue, threaten to compromise the contingency and ambiguity on which camp thrives, instead fostering the kinds of cynical calculation Sedgwick associates with kitsch.

  16. Yoga cAMP in ayurvedgrams of chhattisgarh.

    Science.gov (United States)

    Madhu, Raghavendra; Jain, Nilesh

    2012-04-01

    The clinical and empirical health benefits of yoga and pranayam have been reiterated through research. Yoga is being adopted as a system to alleviate the burden of noncommunicable diseases (NCDs) across the globe. The Directorate of AYUSH, Government of Chhattisgarh (DoA, GoCG) conducts annual 5-day-yoga camp across 146 Ayurvedgrams in the State. The present article brings out the AYUSH initiatives the State is taking toward active ageing. A total of 71,096 people participated in the 5-day-yoga camp across the State. A mean participation of 5079 people over 5 days was reported across districts. Such statewide practices need to be promoted and appraised. PMID:22707860

  17. Distinct Roles for the A2B Adenosine Receptor in Acute and Chronic Stages of Bleomycin-Induced Lung Injury

    OpenAIRE

    Yang ZHOU; Schneider, Daniel J.; Morschl, Eva; Song, Ling; Pedroza, Mesias; Karmouty-Quintana, Harry; Le, Thuy.; Sun, Chun-Xiao; Blackburn, Michael R.

    2010-01-01

    Adenosine is an extracellular signaling molecule that is generated in response to cell injury where it orchestrates tissue protection and repair. Whereas adenosine is best known for promoting anti-inflammatory activities during acute injury responses, prolonged elevations can enhance destructive tissue remodeling processes associated with chronic disease states. The generation of adenosine and the subsequent activation of the adenosine 2B receptor (A2BR) is an important processes in the regul...

  18. Reconstruction of the adenosine system by bone marrow-derived mesenchymal stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Huicong Kang; Qi Hu; Xiaoyan Liu; Yinhe Liu; Feng Xu; Xiang Li; Suiqiang Zhu

    2012-01-01

    In the present study, we transplanted bone marrow-derived mesenchymal stem cells into the CA3 area of the hippocampus of chronic epilepsy rats kindled by lithium chloride-pilocarpine. Immunofluorescence and western blotting revealed an increase in adenosine A1 receptor expression and a decrease in adenosine A2a receptor expression in the brain tissues of epileptic rats 3 months after transplantation. Moreover, the imbalance in the A1 adenosine receptor/A2a adenosine receptor ratio was improved. Electroencephalograms showed that frequency and amplitude of spikes in the hippocampus and frontal lobe were reduced. These results suggested that mesenchymal stem cell transplantation can reconstruct the normal function of the adenosine system in the brain and greatly improve epileptiform discharges.

  19. Comparison of exogenous adenosine and voluntary exercise on human skeletal muscle perfusion and perfusion heterogeneity

    DEFF Research Database (Denmark)

    Heinonen, Ilkka H.A.; Kemppainen, Jukka; Kaskinoro, Kimmo;

    2010-01-01

    Adenosine is a widely used pharmacological agent to induce a 'high flow' control condition to study the mechanisms of exercise hyperemia, but it is not known how well adenosine infusion depicts exercise-induced hyperemia especially in terms of blood flow distribution at the capillary level in human...... muscle. Additionally, it remains to be determined what proportion of adenosine-induced flow elevation is specifically directed to muscle only. In the present study we measured thigh muscle capillary nutritive blood flow in nine healthy young men using positron emission tomography at rest and during...... femoral artery infusion of adenosine (1 mg * min(-1) * litre thigh volume(-1)), which has previously been shown to induce maximal whole thigh blood flow of ~8 L/min. This response was compared to the blood flow induced by moderate-high intensity one-leg dynamic knee extension exercise. Adenosine increased...

  20. Adenosine formation in contracting primary rat skeletal muscle cells and endothelial cells in culture

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Frandsen, Ulrik

    1997-01-01

    in the extracellular adenosine concentration (421 +/- 91 and 235 +/- 30 nmol (g protein)-1, respectively; P muscle cells (161 +/- 20 nmol (g protein)-1). The ATP concentration was lower (18%; P muscle cells...... found to have ecto-forms of several enzymes involved in nucleotide metabolism, including ATPases capable of converting extracellular ATP to ADP and AMP. 5. Adenosine added to the cell medium was taken up by muscle cells and incorporated into the adenine nucleotide pool so that after 30 min of incubation......, over 95% of the adenosine label was present in ATP, ADP and AMP. A similar extent of incorporation of adenosine into the nucleotide pool was evident in the endothelial cells. 6. The present data suggest that contracting muscle cells induce an elevation in the extracellular adenosine concentration...

  1. 2-(1-Hexyn-1-yl)adenosine-induced intraocular hypertension is mediated via K+ channel opening through adenosine A2A receptor in rabbits.

    Science.gov (United States)

    Konno, Takashi; Uchibori, Takehiro; Nagai, Akihiko; Kogi, Kentaro; Nakahata, Norimichi

    2005-08-22

    The present study was performed to clarify the mechanism of change in intraocular pressure by 2-(1-hexyn-1-yl)adenosine (2-H-Ado), a selective adenosine A2 receptor agonist, in rabbits. 2-H-Ado (0.1%, 50 microl)-induced ocular hypertension (E(max): 7.7 mm Hg) was inhibited by an adenosine A2A receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine, ATP-sensitive K+ channel blocker glibenclamide or 5-hydroxydecanoic acid, but not by an adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A2B receptor antagonist alloxazine or a cyclooxygenase inhibitor indomethacin. The outflow facility induced by 2-H-Ado seems to be independent of increase in intraocular pressure or ATP-sensitive K+ channel. In contrast, the recovery rate in intraocular pressure decreased by hypertonic saline was accelerated by 2-H-Ado, and this response was dependent on ATP-sensitive K+ channel. These results suggest that 2-H-Ado-induced ocular hypertension is mediated via K+ channel opening through adenosine A2A receptor, and this is probably due to aqueous formation, but independent of change in outflow facility or prostaglandin production.

  2. Autophagy occurs within an hour of adenosine triphosphate treatment after nerve cell damage:the neuroprotective effects of adenosine triphosphate against apoptosis

    Institute of Scientific and Technical Information of China (English)

    Na Lu; Baoying Wang; Xiaohui Deng; Honggang Zhao; Yong Wang; Dongliang Li

    2014-01-01

    After hypoxia, ischemia, or inlfammatory injuries to the central nervous system, the damaged cells release a large amount of adenosine triphosphate, which may cause secondary neuronal death. Autophagy is a form of cell death that also has neuroprotective effects. Cell Counting Kit assay, monodansylcadaverine staining, lfow cytometry, western blotting, and real-time PCR were used to determine the effects of exogenous adenosine triphosphate treatment at different concentrations (2, 4, 6, 8, 10 mmol/L) over time (1, 2, 3, and 6 hours) on the apoptosis and autophagy of SH-SY5Y cells. High concentrations of extracellular adenosine triphosphate induced autophagy and apoptosis of SH-SY5Y cells. The enhanced autophagy ifrst appeared, and peaked at 1 hour after treatment with adenosine triphosphate. Cell apoptosis peaked at 3 hours, and persisted through 6 hours. With prolonged exposure to the adenosine triphosphate treatment, the fraction of apoptotic cells increased. These data suggest that the SH-SY5Y neural cells initiated autophagy against apoptosis within an hour of adenosine triphosphate treatment to protect themselves against injury.

  3. 2-(1-Hexyn-1-yl)adenosine-induced intraocular hypertension is mediated via K+ channel opening through adenosine A2A receptor in rabbits.

    Science.gov (United States)

    Konno, Takashi; Uchibori, Takehiro; Nagai, Akihiko; Kogi, Kentaro; Nakahata, Norimichi

    2005-08-22

    The present study was performed to clarify the mechanism of change in intraocular pressure by 2-(1-hexyn-1-yl)adenosine (2-H-Ado), a selective adenosine A2 receptor agonist, in rabbits. 2-H-Ado (0.1%, 50 microl)-induced ocular hypertension (E(max): 7.7 mm Hg) was inhibited by an adenosine A2A receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine, ATP-sensitive K+ channel blocker glibenclamide or 5-hydroxydecanoic acid, but not by an adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A2B receptor antagonist alloxazine or a cyclooxygenase inhibitor indomethacin. The outflow facility induced by 2-H-Ado seems to be independent of increase in intraocular pressure or ATP-sensitive K+ channel. In contrast, the recovery rate in intraocular pressure decreased by hypertonic saline was accelerated by 2-H-Ado, and this response was dependent on ATP-sensitive K+ channel. These results suggest that 2-H-Ado-induced ocular hypertension is mediated via K+ channel opening through adenosine A2A receptor, and this is probably due to aqueous formation, but independent of change in outflow facility or prostaglandin production. PMID:16023100

  4. CORRECTIVE SURGERY IN CONGENITAL TALIPES EQUINOVARUS DEFORMITY: A CAMP APPROACH

    Directory of Open Access Journals (Sweden)

    Antony R.

    2015-09-01

    Full Text Available The study was intended to assess the results of soft tissue release and bony corrective surgery in patients of moderate to severe deformed rigid club foot (CTEV and neglected clubfoot (CTEV at free disabled surgical camps at Chhattisgarh state . MATERIAL AND METHODS : In our study 50 patients were included with 70% male and 30% female with 4 - 16 years of age grou p and 70% unilateral and 30% bilateral foot involvement. Patients were admitted and operated in different free disabled surgical camps at Chhattisgarh state over the period of 36 months (1 may 2004 to 30 th April 2007. Improvement in functional ability and locomotion of all operated patients were assessed by physical and clinical examination. RESULTS : All patients who were operated in our study showed significant improvement in functional ability and locomotion after surgery. All patients were maintaining f unctional ability at follow up duration of 12 months (1 year. 75% patients were walking normally, 10% cases were walking with internal rotation of leg and 5% cases were walking with midtarsal varus foot with AFO with medial bar support. CONCLUSION : Our st udy showed and established that excellent results can be obtained in congenital talipes equinovarus (CTEV patients by soft tissue release with bony corrective surgery. The team work of devoted surgeons, paramedical and rehabilitation staff in whole durati on of camps to achieve the goal. With an aim to help more number of CTEV cases by surgery, our team has started doing surgeries in small institutions, and organize charity camps to help poor patients and mankind even in small clinics

  5. Smart and Green Energy (SAGE) for Base Camps Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Engels, Matthias; Boyd, Paul A.; Koehler, Theresa M.; Goel, Supriya; Sisk, Daniel R.; Hatley, Darrel D.; Mendon, Vrushali V.; Hail, John C.

    2014-02-11

    The U.S. Army Logistics Innovation Agency’s (LIA’s) Smart and Green Energy (SAGE) for Base Camps project was to investigate how base camps’ fuel consumption can be reduced by 30% to 60% using commercial off-the-shelf (COTS) technologies for power generation, renewables, and energy efficient building systems. Field tests and calibrated energy models successfully demonstrated that the fuel reductions are achievable.

  6. Building Energy Audit Report for Camp Smith, HI

    Energy Technology Data Exchange (ETDEWEB)

    Chvala, William D.; De La Rosa, Marcus I.; Brown, Daryl R.; Dixon, Douglas R.

    2010-09-30

    A detailed energy assessment was performed by a team of engineers from Pacific Northwest National Laboratory (PNNL) under contract to the Department of Energy/Federal Energy Management program (FEMP). The effort used the Facility Energy Decision System (FEDS) model to determine how energy is consumed at Camp Smith, identify the most cost-effective energy retrofit measures, and calculate the potential energy and cost savings. This report documents the results of that assessment.

  7. Camp Pendleton Saves 91% in Parking Lot Lighting

    Energy Technology Data Exchange (ETDEWEB)

    None

    2016-01-01

    Case study describes how Camp Pendleton Marine Corps Base replaced high-pressure sodium (HPS) fixtures in one parking lot with high-efficiency induction fixtures for 91% savings in energy use and $5,700 in cost savings annually. This parking lot is estimated to have a simple payback of 2.9 years. Sitewide up-grades yielded annual savings of 1 million kWh.

  8. Real-time monitoring of extracellular adenosine using enzyme-linked microelectrode arrays.

    Science.gov (United States)

    Hinzman, Jason M; Gibson, Justin L; Tackla, Ryan D; Costello, Mark S; Burmeister, Jason J; Quintero, Jorge E; Gerhardt, Greg A; Hartings, Jed A

    2015-12-15

    Throughout the central nervous system extracellular adenosine serves important neuroprotective and neuromodulatory functions. However, current understanding of the in vivo regulation and effects of adenosine is limited by the spatial and temporal resolution of available measurement techniques. Here, we describe an enzyme-linked microelectrode array (MEA) with high spatial (7500 µm(2)) and temporal (4 Hz) resolution that can selectively measure extracellular adenosine through the use of self-referenced coating scheme that accounts for interfering substances and the enzymatic breakdown products of adenosine. In vitro, the MEAs selectively measured adenosine in a linear fashion (r(2)=0.98±0.01, concentration range=0-15 µM, limit of detection =0.96±0.5 µM). In vivo the limit of detection was 0.04±0.02 µM, which permitted real-time monitoring of the basal extracellular concentration in rat cerebral cortex (4.3±1.5 µM). Local cortical injection of adenosine through a micropipette produced dose-dependent transient increases in the measured extracellular concentration (200 nL: 6.8±1.8 µM; 400 nL: 19.4±5.3 µM) [P<0.001]. Lastly, local injection of dipyridamole, which inhibits transport of adenosine through equilibrative nucleoside transporter, raised the measured extracellular concentration of adenosine by 120% (5.6→12.3 µM) [P<0.001]. These studies demonstrate that MEAs can selectively measure adenosine on temporal and spatial scales relevant to adenosine signaling and regulation in normal and pathologic states. PMID:26183072

  9. Specificity of synergistic coronary flow enhancement by adenosine and pulsatile perfusion in the dog.

    Science.gov (United States)

    Pagliaro, P; Senzaki, H; Paolocci, N; Isoda, T; Sunagawa, G; Recchia, F A; Kass, D A

    1999-10-01

    1. Coronary flow elevation from enhanced perfusion pulsatility is synergistically amplified by adenosine. This study determined the specificity of this interaction and its potential mechanisms. 2. Mean and phasic coronary flow responses to increasing pulsatile perfusion were assessed in anaesthetized dogs, with the anterior descending coronary artery servoperfused to regulate real-time physiological flow pulsatility at constant mean pressure. Pulsatility was varied between 40 and 100 mmHg. Hearts ejected into the native aorta whilst maintaining stable loading. 3. Increasing pulsatility elevated mean coronary flow +11.5 +/- 1.7 % under basal conditions. Co-infusion of adenosine sufficient to raise baseline flow 66 % markedly amplified this pulsatile perfusion response (+82. 6 +/- 14.3 % increase in mean flow above adenosine baseline), due to a leftward shift of the adenosine-coronary flow response curve at higher pulsatility. Flow augmentation with pulsatility was not linked to higher regional oxygen consumption, supporting direct rather than metabolically driven mechanisms. 4. Neither bradykinin, acetylcholine nor verapamil reproduced the synergistic amplification of mean flow by adenosine and higher pulsatility, despite being administered at doses matching basal flow change with adenosine. 5. ATP-sensitive potassium (KATP) activation (pinacidil) amplified the pulse-flow response 3-fold, although this remained significantly less than with adenosine. Co-administration of the phospholipase A2 inhibitor quinacrine virtually eliminated adenosine-induced vasodilatation, yet synergistic interaction between adenosine and pulse perfusion persisted, albeit at a reduced level. 6. Thus, adenosine and perfusion pulsatility specifically interact to enhance coronary flow. This synergy is partially explained by KATP agonist action and additional non-flow-dependent mechanisms, and may be important for modulating flow reserve during exercise or other high output states where

  10. Outbreak of chickenpox in a refugee camp of northern Thailand

    Directory of Open Access Journals (Sweden)

    Camélique Olivier

    2010-02-01

    Full Text Available Abstract Although chickenpox is a generally mild, self-limited illness of children, it can cause fatal disease in adults. Accumulating reports from tropical countries showed a high prevalence of seronegativity among the adults, implying that varicella diseases could become a heavy burden in tropical countries. However, in the situation of humanitarian emergencies in tropical areas, chickenpox has largely been ignored as a serious communicable disease, due to lack of data regarding varicella mortality and hospital admissions in such a context. This is the first report describing an outbreak of chickenpox in a refugee camp of tropical region. In 2008, we experienced a varicella outbreak in ethnic Lao Hmong refugee camp in Phetchabun Province, northern Thailand. The attack rate was 4.0% (309/7,815 and this caused 3 hospitalizations including one who developed severe varicella pneumonia with respiratory failure. All hospitalizations were exclusively seen in adults, and the proportion of patients ≥15 years old was 13.6% (42/309. Because less exposure to varicella-zoster virus due to low population density has previously been suggested to be one of the reasons behind higher prevalence of susceptible adults in tropics, the influx of displaced people from rural areas to a densely populated asylum might result in many severe adult cases once a varicella outbreak occurs. Control interventions such as vaccination should be considered even in refugee camp, if the confluence of the risk factors present in this situation.

  11. Exchange Protein Directly Activated by cAMP (epac) : A Multidomain cAMP Mediator in the Regulation of Diverse Biological Functions

    NARCIS (Netherlands)

    Schmidt, Martina; Dekker, Frank J.; Maarsingh, Harm

    2013-01-01

    Since the discovery nearly 60 years ago, cAMP is envisioned as one of the most universal and versatile second messengers. The tremendous feature of cAMP to tightly control highly diverse physiologic processes, including calcium homeostasis, metabolism, secretion, muscle contraction, cell fate, and g

  12. The Effect of a Disability Camp Program on Attitudes towards the Inclusion of Children with Disabilities in a Summer Sport and Leisure Activity Camp

    Science.gov (United States)

    Papaioannou, Christina; Evaggelinou, Christina

    2014-01-01

    The aim of the present study was to examine the impact of a specific Disability Camp Program (DCP) in the attitudes of children without disabilities toward the inclusion of children with disabilities in a summer sport and leisure activity camp. Three hundred eighty-seven campers without disabilities participated in the study and were divided into…

  13. Effect of adenosine and adenosine receptor antagonist on Müller cell potassium channel in Rat chronic ocular hypertension models.

    Science.gov (United States)

    Yang, Zijian; Huang, Ping; Liu, Xiaohong; Huang, Shouyue; Deng, Lianfu; Jin, Zhe; Xu, Shuo; Shen, Xi; Luo, Xunda; Zhong, Yisheng

    2015-01-01

    Müller cells are principal glial cells in rat retina and have attracted much attention in glaucoma studies. However, it is not clear whether adenosine and adenosine receptor (AR) antagonists play any roles in the regulation of potassium channels in Müller cells and subsequently in the promotion of glutamine synthetase (GS) and L-Glutamate/L-Aspartate Transporter (GLAST) functions. We found that chronic ocular hypertension (COH) in rat down-regulated Müller cells Kir2.1, Kir4.1, TASK-1, GS and GLAST expressions and attenuated the peak of inward potassium current. Retinal ganglion cells (RGC) count was lower in the COH rats than that in the sham operation animals. Intravitreal injection of selective A2A AR antagonist SCH442416 up-regulated Müller cell Kir4.1, TASK-1, GS and GLAST expressions and enhanced inward potassium currents compared with those in the COH rats with vehicle control. Meanwhile, the RGC count was higher following intravitreal injection of SCH442416 in the COH rats than that after vehicle injection. The fact that PKA inhibitor H-89 blocked these SCH442416 effects suggested that the PKA signaling pathway was involved in the observed ocular responses following the intravitreal SCH442416 injection. PMID:26063641

  14. Chlorella intake attenuates reduced salivary SIgA secretion in kendo training camp participants

    Directory of Open Access Journals (Sweden)

    Otsuki Takeshi

    2012-12-01

    Full Text Available Abstract Background The green alga Chlorella contains high levels of proteins, vitamins, and minerals. We previously reported that a chlorella-derived multicomponent supplement increased the secretion rate of salivary secretory immunoglobulin A (SIgA in humans. Here, we investigated whether intake of this chlorella-derived supplement attenuated the reduced salivary SIgA secretion rate during a kendo training camp. Methods Ten female kendo athletes participated in inter-university 6-day spring and 4-day summer camps. They were randomized into two groups; one took placebo tablets during the spring camp and chlorella tablets during the summer camp, while the other took chlorella tablets during the spring camp and placebo tablets during the summer camp. Subjects took these tablets starting 4 weeks before the camp until post-camp saliva sampling. Salivary SIgA concentrations were measured by ELISA. Results All subjects participated in nearly all training programs, and body-mass changes and subjective physical well-being scores during the camps were comparable between the groups. However, salivary SIgA secretion rate changes were different between these groups. Salivary SIgA secretion rates decreased during the camp in the placebo group (before vs. second, middle, and final day of camp, and after the camp: 146 ± 89 vs. 87 ± 56, 70 ± 45, 94 ± 58, and 116 ± 71 μg/min, whereas no such decreases were observed in the chlorella group (121 ± 53 vs. 113 ± 68, 98 ± 69,115 ± 80, and 128 ± 59 μg/min. Conclusion Our results suggest that a use of a chlorella-derived dietary supplement attenuates reduced salivary SIgA secretion during a training camp for a competitive sport.

  15. A Computational Modeling and Simulation Approach to Investigate Mechanisms of Subcellular cAMP Compartmentation.

    Directory of Open Access Journals (Sweden)

    Pei-Chi Yang

    2016-07-01

    Full Text Available Subcellular compartmentation of the ubiquitous second messenger cAMP has been widely proposed as a mechanism to explain unique receptor-dependent functional responses. How exactly compartmentation is achieved, however, has remained a mystery for more than 40 years. In this study, we developed computational and mathematical models to represent a subcellular sarcomeric space in a cardiac myocyte with varying detail. We then used these models to predict the contributions of various mechanisms that establish subcellular cAMP microdomains. We used the models to test the hypothesis that phosphodiesterases act as functional barriers to diffusion, creating discrete cAMP signaling domains. We also used the models to predict the effect of a range of experimentally measured diffusion rates on cAMP compartmentation. Finally, we modeled the anatomical structures in a cardiac myocyte diad, to predict the effects of anatomical diffusion barriers on cAMP compartmentation. When we incorporated experimentally informed model parameters to reconstruct an in silico subcellular sarcomeric space with spatially distinct cAMP production sites linked to caveloar domains, the models predict that under realistic conditions phosphodiesterases alone were insufficient to generate significant cAMP gradients. This prediction persisted even when combined with slow cAMP diffusion. When we additionally considered the effects of anatomic barriers to diffusion that are expected in the cardiac myocyte dyadic space, cAMP compartmentation did occur, but only when diffusion was slow. Our model simulations suggest that additional mechanisms likely contribute to cAMP gradients occurring in submicroscopic domains. The difference between the physiological and pathological effects resulting from the production of cAMP may be a function of appropriate compartmentation of cAMP signaling. Therefore, understanding the contribution of factors that are responsible for coordinating the spatial and

  16. A Computational Modeling and Simulation Approach to Investigate Mechanisms of Subcellular cAMP Compartmentation.

    Science.gov (United States)

    Yang, Pei-Chi; Boras, Britton W; Jeng, Mao-Tsuen; Docken, Steffen S; Lewis, Timothy J; McCulloch, Andrew D; Harvey, Robert D; Clancy, Colleen E

    2016-07-01

    Subcellular compartmentation of the ubiquitous second messenger cAMP has been widely proposed as a mechanism to explain unique receptor-dependent functional responses. How exactly compartmentation is achieved, however, has remained a mystery for more than 40 years. In this study, we developed computational and mathematical models to represent a subcellular sarcomeric space in a cardiac myocyte with varying detail. We then used these models to predict the contributions of various mechanisms that establish subcellular cAMP microdomains. We used the models to test the hypothesis that phosphodiesterases act as functional barriers to diffusion, creating discrete cAMP signaling domains. We also used the models to predict the effect of a range of experimentally measured diffusion rates on cAMP compartmentation. Finally, we modeled the anatomical structures in a cardiac myocyte diad, to predict the effects of anatomical diffusion barriers on cAMP compartmentation. When we incorporated experimentally informed model parameters to reconstruct an in silico subcellular sarcomeric space with spatially distinct cAMP production sites linked to caveloar domains, the models predict that under realistic conditions phosphodiesterases alone were insufficient to generate significant cAMP gradients. This prediction persisted even when combined with slow cAMP diffusion. When we additionally considered the effects of anatomic barriers to diffusion that are expected in the cardiac myocyte dyadic space, cAMP compartmentation did occur, but only when diffusion was slow. Our model simulations suggest that additional mechanisms likely contribute to cAMP gradients occurring in submicroscopic domains. The difference between the physiological and pathological effects resulting from the production of cAMP may be a function of appropriate compartmentation of cAMP signaling. Therefore, understanding the contribution of factors that are responsible for coordinating the spatial and temporal

  17. Three-dimensional measurement of cAMP gradients using hyperspectral confocal microscopy

    Science.gov (United States)

    Rich, Thomas C.; Annamdevula, Naga; Britain, Andrea L.; Mayes, Samuel; Favreau, Peter F.; Leavesley, Silas J.

    2016-03-01

    Cyclic AMP (cAMP) is a ubiquitous second messenger known to differentially regulate many cellular functions over a wide range of timescales. Several lines of evidence have suggested that the distribution of cAMP within cells is not uniform, and that cAMP compartmentalization is largely responsible for signaling specificity within the cAMP signaling pathway. However, to date, no studies have experimentally measured three dimensional (3D) cAMP distributions within cells. Here we use both 2D and 3D hyperspectral microscopy to visualize cAMP gradients in endothelial cells from the pulmonary microvasculature (PMVECs). cAMP levels were measured using a FRETbased cAMP sensor comprised of a cAMP binding domain from EPAC sandwiched between FRET donors and acceptors -- Turquoise and Venus fluorescent proteins. Data were acquired using either a Nikon A1R spectral confocal microscope or custom spectral microscopy system. Analysis of hyperspectral image stacks from a single confocal slice or from summed images of all slices (2D analysis) indicated little or no cAMP gradients were formed within PMVECs under basal conditions or following agonist treatment. However, analysis of hyperspectral image stacks from 3D cellular geometries (z stacks) demonstrate marked cAMP gradients from the apical to basolateral membrane of PMVECs. These results strongly suggest that 2D imaging studies of cAMP compartmentalization -- whether epifluorescence or confocal microscopy -- may lead to erroneous conclusions about the existence of cAMP gradients, and that 3D studies are required to assess mechanisms of signaling specificity.

  18. Corticotropin-Releasing Factor in the Basolateral Amygdala Enhances Memory Consolidation via an Interaction with the β-Adrenoceptor-cAMP Pathway: Dependence on Glucocorticoid Receptor Activation

    OpenAIRE

    Roozendaal, Benno; Schelling, Gustav; McGaugh, James L.

    2008-01-01

    Extensive evidence indicates that stress hormone effects on the consolidation of emotionally influenced memory involve noradrenergic activation of the basolateral complex of the amygdala (BLA). The present experiments examined whether corticotropin-releasing factor (CRF) modulates memory consolidation via an interaction with the β-adrenoceptor-adenosine 3′,5′-cyclic monophosphate (cAMP) system in the BLA. In a first experiment, male Sprague-Dawley rats received bilateral infusions of the CRF-...

  19. Epistatic Interactions between CREB and CREM Variants in Affective Disorder

    OpenAIRE

    Chiesa, Alberto; Marsano, Agnese; Han, Changsu; Lee, Soo-Jung; Patkar, Ashwin A.; Pae, Chi-Un; Serretti, Alessandro

    2014-01-01

    The aim of the present work is to investigate the existence of epistatic interactions possibly influencing psychotropic agents' response between rs6740584 within Cyclic adenosine monophosphate Response Element Binding (CREB) and rs12775799 within cAMP response element-modulator (CREM) variants in bipolar disorder (BD) and major depressive disorder (MDD). All BD and MDD patients were administered with the Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HAMD) at baseline a...

  20. Phosphodiesterase 8B gene polymorphism in women with recurrent miscarriage: A retrospective case control study

    OpenAIRE

    Granfors Michaela; Karypidis Helena; Hosseini Frida; Skjöldebrand-Sparre Lottie; Stavreus-Evers Anneli; Bremme Katarina; Landgren Britth-Marie; Sundström-Poromaa Inger; Wikström Anna-Karin; Åkerud Helena

    2012-01-01

    Abstract Background Recurrent miscarriage affects approximately 1% of all couples. There is a known relation between hypothyroidism and recurrent miscarriage. Phosphodiesterase 8B (PDE8B) is a regulator of cyclic adenosine monophosphate (cAMP) with important influence on human thyroid metabolism. Single nucleotide polymorphism (SNP) rs 4704397 in the PDE8B gene has been shown to be associated with variations in serum Thyroid Stimulating Hormone (TSH) and thyroxine (T4) levels. The aim of this...

  1. Genetic association of cyclic AMP signaling genes with bipolar disorder

    OpenAIRE

    McDonald, M-L; MacMullen, C.; Liu, D. J.; Leal, S M; Davis, R L

    2012-01-01

    The genetic basis for bipolar disorder (BPD) is complex with the involvement of multiple genes. As it is well established that cyclic adenosine monophosphate (cAMP) signaling regulates behavior, we tested variants in 29 genes that encode components of this signaling pathway for associations with BPD type I (BPD I) and BPD type II (BPD II). A total of 1172 individuals with BPD I, 516 individuals with BPD II and 1728 controls were analyzed. Single SNP (single-nucleotide polymorphism), haplotype...

  2. Optogenetic activation of intracellular adenosine A2A receptor signaling in the hippocampus is sufficient to trigger CREB phosphorylation and impair memory.

    Science.gov (United States)

    Li, P; Rial, D; Canas, P M; Yoo, J-H; Li, W; Zhou, X; Wang, Y; van Westen, G J P; Payen, M-P; Augusto, E; Gonçalves, N; Tomé, A R; Li, Z; Wu, Z; Hou, X; Zhou, Y; IJzerman, A P; PIJzerman, Ad; Boyden, E S; Cunha, R A; Qu, J; Chen, J-F

    2015-11-01

    Human and animal studies have converged to suggest that caffeine consumption prevents memory deficits in aging and Alzheimer's disease through the antagonism of adenosine A2A receptors (A2ARs). To test if A2AR activation in the hippocampus is actually sufficient to impair memory function and to begin elucidating the intracellular pathways operated by A2AR, we have developed a chimeric rhodopsin-A2AR protein (optoA2AR), which retains the extracellular and transmembrane domains of rhodopsin (conferring light responsiveness and eliminating adenosine-binding pockets) fused to the intracellular loop of A2AR to confer specific A2AR signaling. The specificity of the optoA2AR signaling was confirmed by light-induced selective enhancement of cAMP and phospho-mitogen-activated protein kinase (p-MAPK) (but not cGMP) levels in human embryonic kidney 293 (HEK293) cells, which was abolished by a point mutation at the C terminal of A2AR. Supporting its physiological relevance, optoA2AR activation and the A2AR agonist CGS21680 produced similar activation of cAMP and p-MAPK signaling in HEK293 cells, of p-MAPK in the nucleus accumbens and of c-Fos/phosphorylated-CREB (p-CREB) in the hippocampus, and similarly enhanced long-term potentiation in the hippocampus. Remarkably, optoA2AR activation triggered a preferential p-CREB signaling in the hippocampus and impaired spatial memory performance, while optoA2AR activation in the nucleus accumbens triggered MAPK signaling and modulated locomotor activity. This shows that the recruitment of intracellular A2AR signaling in the hippocampus is sufficient to trigger memory dysfunction. Furthermore, the demonstration that the biased A2AR signaling and functions depend on intracellular A2AR loops prompts the possibility of targeting the intracellular A2AR-interacting partners to selectively control different neuropsychiatric behaviors. PMID:25687775

  3. Use of potato tuber nucleotide pyrophosphatase to synthesize adenosine 5'-monophosphate methyl ester: evidence that the solvolytic preferences of the enzyme are regulated by pH and temperature.

    Science.gov (United States)

    Agudo, A; Ribeiro, J M; Canales, J; Cameselle, J C

    1998-07-01

    Nucleotide alkyl esters are pharmacologically important as potential (ant)agonists of purinoceptors and inhibitors of enzymes. Potato nucleotide pyrophosphatase (PNP) was compared with snake venom phosphodiesterase (SVP) as a catalyst to synthesize nucleotide alkyl esters. In methanol-water mixtures, the methanolysis/hydrolysis ratio of PNP, but not SVP, changed with pH and temperature, being optimal at high pH and low temperature. In a semi-preparative experiment, a crude PNP preparation produced 0.17 mM AMP-O-methyl ester (AMP-OMe) from 1 mM diadenosine 5',5"'-P1,P2-diphosphate (AppA) and 5M methanol, at pH 9 and 0 degrees C. Drawbacks to large-scale use are: low rates inherent to low temperatures, ATP unsuitability as a substrate for alcoholysis, and high cost of AppA. Advantages of PNP vs. SVP are cheapness, non-toxicity, and availability of the enzyme source.

  4. Developmental and Diurnal Dynamics of Pax4 Expression in the Mammalian Pineal Gland: Nocturnal Down-Regulation Is Mediated by Adrenergic-Cyclic Adenosine 3′,5′-Monophosphate Signaling

    OpenAIRE

    Rath, Martin F.; Bailey, Michael J; Kim, Jong-So; Ho, Anthony K.; Gaildrat, Pascaline; Steven L Coon; Møller, Morten; Klein, David C.

    2008-01-01

    Pax4 is a homeobox gene that is known to be involved in embryonic development of the endocrine pancreas. In this tissue, Pax4 counters the effects of the related protein, Pax6. Pax6 is essential for development of the pineal gland. In this study we report that Pax4 is strongly expressed in the pineal gland and retina of the rat. Pineal Pax4 transcripts are low in the fetus and increase postnatally; Pax6 exhibits an inverse pattern of expression, being more strongly expressed in the fetus. In ...

  5. Developmental and diurnal dynamics of Pax4 expression in the mammalian pineal gland: nocturnal down-regulation is mediated by adrenergic-cyclic adenosine 3',5'-monophosphate signaling

    DEFF Research Database (Denmark)

    Rath, Martin F; Bailey, Michael J; Kim, Jong-So;

    2009-01-01

    Pax4 is a homeobox gene that is known to be involved in embryonic development of the endocrine pancreas. In this tissue, Pax4 counters the effects of the related protein, Pax6. Pax6 is essential for development of the pineal gland. In this study we report that Pax4 is strongly expressed in the pi...... findings suggest that the nocturnal decrease in pineal Pax4 mRNA is controlled by the sympathetic neural pathway that controls pineal function acting via an adrenergic-cAMP mechanism. The daily changes in Pax4 expression may influence gene expression in the pineal gland....

  6. Post-Meal Responses of Elongation Factor 2 (eEF2) and Adenosine Monophosphate-Activated Protein Kinase (AMPK) to Leucine and Carbohydrate Supplements for Regulating Protein Synthesis Duration and Energy Homeostasis in Rat Skeletal Muscle

    OpenAIRE

    Layman, Donald K; Anthony, Tracy G.; Garlick, Peter J.; Wilson, Gabriel J; Moulton, Christopher J

    2012-01-01

    Previous research demonstrates that the anabolic response of muscle protein synthesis (MPS) to a meal is regulated at the level of translation initiation with signals derived from leucine (Leu) and insulin to activate mTORC1 signaling. Recent evidence suggests that the duration of the meal response is limited by energy status of the cell and inhibition of translation elongation factor 2 (eEF2). This study evaluates the potential to extend the anabolic meal response with post-meal supplements ...

  7. Enhancing the efficiency of direct reprogramming of human mesenchymal stem cells into mature neuronal-like cells with the combination of small molecule modulators of chromatin modifying enzymes, SMAD signaling and cyclic adenosine monophosphate levels.

    Science.gov (United States)

    Alexanian, Arshak R; Liu, Qing-song; Zhang, Zhiying

    2013-08-01

    Advances in cell reprogramming technologies to generate patient-specific cells of a desired type will revolutionize the field of regenerative medicine. While several cell reprogramming methods have been developed over the last decades, the majority of these technologies require the exposure of cell nuclei to reprogramming large molecules via transfection, transduction, cell fusion or nuclear transfer. This raises several technical, safety and ethical issues. Chemical genetics is an alternative approach for cell reprogramming that uses small, cell membrane penetrable substances to regulate multiple cellular processes including cell plasticity. Recently, using the combination of small molecules that are involved in the regulation chromatin structure and function and agents that favor neural differentiation we have been able to generate neural-like cells from human mesenchymal stem cells. In this study, to improve the efficiency of neuronal differentiation and maturation, two specific inhibitors of SMAD signaling (SMAD1/3 and SMAD3/5/8) that play an important role in neuronal differentiation of embryonic stem cells, were added to our previous neural induction recipe. Results demonstrated that human mesenchymal stem cells grown in this culture conditions exhibited higher expression of several mature neuronal genes, formed synapse-like structures and exerted electrophysiological properties of differentiating neural stem cells. Thus, an efficient method for production of mature neuronal-like cells from human adult bone marrow derived mesenchymal stem cells has been developed. We concluded that specific combinations of small molecules that target specific cell signaling pathways and chromatin modifying enzymes could be a promising approach for manipulation of adult stem cell plasticity.

  8. Adenosine, ketogenic diet and epilepsy: the emerging therapeutic relationship between metabolism and brain activity.

    Science.gov (United States)

    Masino, S A; Kawamura, M; Wasser, C D; Wasser, C A; Pomeroy, L T; Ruskin, D N

    2009-09-01

    For many years the neuromodulator adenosine has been recognized as an endogenous anticonvulsant molecule and termed a "retaliatory metabolite." As the core molecule of ATP, adenosine forms a unique link between cell energy and neuronal excitability. In parallel, a ketogenic (high-fat, low-carbohydrate) diet is a metabolic therapy that influences neuronal activity significantly, and ketogenic diets have been used successfully to treat medically-refractory epilepsy, particularly in children, for decades. To date the key neural mechanisms underlying the success of dietary therapy are unclear, hindering development of analogous pharmacological solutions. Similarly, adenosine receptor-based therapies for epilepsy and myriad other disorders remain elusive. In this review we explore the physiological regulation of adenosine as an anticonvulsant strategy and suggest a critical role for adenosine in the success of ketogenic diet therapy for epilepsy. While the current focus is on the regulation of adenosine, ketogenic metabolism and epilepsy, the therapeutic implications extend to acute and chronic neurological disorders as diverse as brain injury, inflammatory and neuropathic pain, autism and hyperdopaminergic disorders. Emerging evidence for broad clinical relevance of the metabolic regulation of adenosine will be discussed. PMID:20190967

  9. Role of adenosine signalling and metabolism in β-cell regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, Olov, E-mail: olov.andersson@ki.se

    2014-02-01

    Glucose homeostasis, which is controlled by the endocrine cells of the pancreas, is disrupted in both type I and type II diabetes. Deficiency in the number of insulin-producing β cells – a primary cause of type I diabetes and a secondary contributor of type II diabetes – leads to hyperglycemia and hence an increase in the need for insulin. Although diabetes can be controlled with insulin injections, a curative approach is needed. A potential approach to curing diabetes involves regenerating the β-cell mass, e.g. by increasing β-cell proliferation, survival, neogenesis or transdifferentiation. The nucleoside adenosine and its cognate nucleotide ATP have long been known to affect insulin secretion, but have more recently been shown to increase β-cell proliferation during homeostatic control and regeneration of the β-cell mass. Adenosine is also known to have anti-inflammatory properties, and agonism of adenosine receptors can promote the survival of β-cells in an inflammatory microenvironment. In this review, both intracellular and extracellular mechanisms of adenosine and ATP are discussed in terms of their established and putative effects on β-cell regeneration. - Highlights: • A potential way to cure diabetes is to regenerate the β-cell mass by promoting cell survival, proliferation or neogenesis. • Adenosine may promote β-cell regeneration through several cellular mechanisms. • Adenosine and its cognate nucleotide ATP can each promote β-cell proliferation. • Do adenosine and ATP interact in promoting β-cell proliferation?.

  10. Susceptibility to seizure-induced sudden death in DBA/2 mice is altered by adenosine.

    Science.gov (United States)

    Faingold, Carl L; Randall, Marc; Kommajosyula, Srinivasa P

    2016-08-01

    Sudden unexpected death in epilepsy (SUDEP) is rare but is an important public health burden due to the number of patient years lost. Respiratory dysfunction following generalized convulsive seizure is a common sequence of events in witnessed SUDEP cases. The DBA/2 mouse model of SUDEP exhibits generalized convulsive audiogenic seizures (AGSz), which result in seizure-induced respiratory arrest (S-IRA) in ∼75% of these animals, while the remaining DBA/2 mice exhibit AGSz without S-IRA. SUDEP induction may involve actions of adenosine, which is released during generalized seizures in animals and patients and is known to depress respiration. This study examined the effects of systemic administration of agents that alter the actions of adenosine on the incidence of S-IRA in DBA/2 mice. DBA/2 mice that consistently exhibited AGSz without S-IRA showed a significantly increased incidence of S-IRA following treatment with 5-iodotubercidin, which blocks adenosine metabolism. Treatment of DBA/2 mice that consistently exhibited AGSz followed by S-IRA with a non-selective adenosine antagonist, caffeine, or an A2A adenosine receptor subtype-selective antagonist (SCH 442416) significantly reduced S-IRA incidence. By contrast, an A1 adenosine receptor antagonist (DPCPX) was not effective in reducing S-IRA incidence. These findings suggest that preventative approaches for SUDEP should consider agents that reduce the actions of adenosine. PMID:27259068

  11. How Women Work: The Symbolic and Material Reproduction of Migrant Labor Camps in United States Agribusiness

    Directory of Open Access Journals (Sweden)

    Robert CARLEY

    2011-05-01

    Full Text Available This article analyzes gender exploitation in Mexican and Central American migrant farm worker camps in the U.S through small group interactions. We describe how gender exploitation and oppression is transmitted through the social fabric of the camp. We argue that the camp produces an endogenous system of social interaction, which maintains uneven gender relationships. Our data is based on observations of twenty-five women and girls in three labor camps in North Carolina. Research was conducted over a period of six weeks. We found that women who served as the primary bearers of patrimonial authority best maintained the camp community. We conclude that women who successfully reproduce the authority structure gain social status in the camps and are more likely to stay.

  12. Barriers and Facilitators for Generalizing Cycling Skills Learned at Camp to Home.

    Science.gov (United States)

    Temple, Viviene A; Purves, P Lynn; Misovic, Robyn; Lewis, Coral J; DeBoer, Carrie

    2016-01-01

    Many children with disabling conditions do not acquire the skills to successfully ride a 2-wheeled bicycle. The aim was to describe cycling patterns before and after an innovative learn-to-ride bike camp and factors that facilitate or hinder the generalization of skills developed at camp to home. Parents and children participated in semistructured interviews 3-4 mo postcamp. Transcripts were examined deductively for participation and contextual influences using a template of codes approach. None of the children were successfully riding a 2-wheeled bicycle before camp. Two patterns of participation were evident from narrative descriptions of postcamp riding: "riders" and "not there yet." Major facilitating factors were the camp itself, the interaction between the camp and the health service, and continued parent involvement. The program transferred well to home for children who were riding independently on the last day of camp. Ongoing support is needed for children "not there yet."

  13. Vasodilator effects of adenosine on retinal arterioles in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Nakazawa, Taisuke; Mori, Asami; Saito, Maki; Sakamoto, Kenji; Nakahara, Tsutomu; Ishii, Kunio

    2008-02-01

    Adenosine is a potent vasodilator of retinal blood vessels and is implicated to be a major regulator of retinal blood flow during metabolic stress, but little is known about the impact of diabetes on the role of adenosine in regulation of retinal hemodynamics. Therefore, we examined how diabetes affects adenosine-induced vasodilation of retinal arterioles. Male Wistar rats were treated with streptozotocin (80 mg/kg, intraperitoneally), and experiments were performed 6-8 weeks later. Rats were treated with tetrodotoxin (50 microg/kg, intravenously [i.v.]) to eliminate any nerve activity and prevent movement of the eye and infused with methoxamine continuously to maintain adequate systemic circulation. Fundus images were captured with a digital camera that was equipped with a special objective lens, and diameters of retinal arterioles were measured. Adenosine increased diameters of retinal arterioles and decreased systemic blood pressure. These responses were significantly attenuated by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (30 mg/kg, i.v.) and the adenosine triphosphate-dependent K+ (K(ATP)) channel blocker glibenclamide (20 mg/kg, i.v.). The depressor responses to adenosine were reduced in diabetic rats, whereas diabetes did not alter vasodilation of retinal arterioles to adenosine. In contrast, both depressor response and vasodilation of retinal arteriole to acetylcholine were reduced in diabetic rats. The retinal vasodilator responses to adenosine and acetylcholine observed in diabetic rats were diminished by N(G)-nitro-L-arginine methyl ester. There were no differences in the responses to pinacidil, a K(ATP) channel opener, between the diabetic and nondiabetic rats. These results suggest that both the activation of nitric oxide synthase and opening of K(ATP) channels contribute to the vasodilator effects of adenosine in rats in vivo. However, diabetes has no significant impact on the vasodilation mediated by these mechanisms in

  14. Severe hemorrhage attenuates cardiopulmonary chemoreflex control of regional sympathetic outputs via NTS adenosine receptors.

    Science.gov (United States)

    Minic, Zeljka; Li, Cailian; O'Leary, Donal S; Scislo, Tadeusz J

    2014-09-15

    Selective stimulation of inhibitory A1 and facilitatory A2a adenosine receptor subtypes located in the nucleus of the solitary tract (NTS) powerfully inhibits cardiopulmonary chemoreflex (CCR) control of regional sympathetic outputs via different mechanisms: direct inhibition of glutamate release and facilitation of an inhibitory neurotransmitter release, respectively. However, it remains unknown whether adenosine naturally released into the NTS has similar inhibitory effects on the CCR as the exogenous agonists do. Our previous study showed that adenosine is released into the NTS during severe hemorrhage and contributes to reciprocal changes of renal (decreases) and adrenal (increases) sympathetic nerve activity observed in this setting. Both A1 and A2a adenosine receptors are involved. Therefore, we tested the hypothesis that, during severe hemorrhage, CCR control of the two sympathetic outputs is attenuated by adenosine naturally released into the NTS. We compared renal and adrenal sympathoinhibitory responses evoked by right atrial injections of 5HT3 receptor agonist phenylbiguanide (2-8 μg/kg) under control conditions, during hemorrhage, and during hemorrhage preceded by blockade of NTS adenosine receptors with bilateral microinjections of 8-(p-sulfophenyl) theophylline (1 nmol/100 nl) in urethane/chloralose anesthetized rats. CCR-mediated inhibition of renal and adrenal sympathetic activity was significantly attenuated during severe hemorrhage despite reciprocal changes in the baseline activity levels, and this attenuation was removed by bilateral blockade of adenosine receptors in the caudal NTS. This confirmed that adenosine endogenously released into the NTS has a similar modulatory effect on integration of cardiovascular reflexes as stimulation of NTS adenosine receptors with exogenous agonists. PMID:25063794

  15. Adenosine Modulates the Oocyte Developmental Competence by Exposing Stages and Synthetic Blocking during In Vitro Maturation.

    Science.gov (United States)

    Cheon, Yong-Pil

    2016-06-01

    Purine metabolism is known factor for nuclear maturation of oocytes through both follicle cells and oocyte itself. However, it is largely unknown the roles of purine metabolism in the oocyte competence for fertilization and early development. In this study, the effects of adenosine in oocyte competence for development were examined using adenosine and its synthetic inhibitors. Adenosine treatment from GV intact stage for 18 hr (fGV) caused of decrease the fertilization rate but of increase the cleavage rate compared from the other stage treatment groups. Hadacidin did not effect on fertilization rate but increased cleavage rate without stage specificity. Adenosine did not block the effects of hadacidin with the exception of fGV group. By the inhibition of purine synthetic pathways the fertilization rate was decreased in the fGV and fGVB groups but increased in the fMII group. Exogenous adenosine caused of decrease fertilization rate in the fGVB group but increase in the fMII group. Cleavage rate was dramatically increased in the adenosine treatment with synthetic inhibitors. It means that the metabolism of purine has stage specific effects on fertilization and cleavage. Exogenous adenosine had only can improve oocyte developmental competence when it treated at GV intact stage. On the other hand, endogenous synthesis in all maturation stage caused of increase the cleavage rate without effects on fertilization. These data suggest that adenosine at GV stage as a paracrine fashion and inhibitions of endogenous adenosine in all stage improve oocyte developmental competence.. PMID:27660830

  16. Severe hemorrhage attenuates cardiopulmonary chemoreflex control of regional sympathetic outputs via NTS adenosine receptors.

    Science.gov (United States)

    Minic, Zeljka; Li, Cailian; O'Leary, Donal S; Scislo, Tadeusz J

    2014-09-15

    Selective stimulation of inhibitory A1 and facilitatory A2a adenosine receptor subtypes located in the nucleus of the solitary tract (NTS) powerfully inhibits cardiopulmonary chemoreflex (CCR) control of regional sympathetic outputs via different mechanisms: direct inhibition of glutamate release and facilitation of an inhibitory neurotransmitter release, respectively. However, it remains unknown whether adenosine naturally released into the NTS has similar inhibitory effects on the CCR as the exogenous agonists do. Our previous study showed that adenosine is released into the NTS during severe hemorrhage and contributes to reciprocal changes of renal (decreases) and adrenal (increases) sympathetic nerve activity observed in this setting. Both A1 and A2a adenosine receptors are involved. Therefore, we tested the hypothesis that, during severe hemorrhage, CCR control of the two sympathetic outputs is attenuated by adenosine naturally released into the NTS. We compared renal and adrenal sympathoinhibitory responses evoked by right atrial injections of 5HT3 receptor agonist phenylbiguanide (2-8 μg/kg) under control conditions, during hemorrhage, and during hemorrhage preceded by blockade of NTS adenosine receptors with bilateral microinjections of 8-(p-sulfophenyl) theophylline (1 nmol/100 nl) in urethane/chloralose anesthetized rats. CCR-mediated inhibition of renal and adrenal sympathetic activity was significantly attenuated during severe hemorrhage despite reciprocal changes in the baseline activity levels, and this attenuation was removed by bilateral blockade of adenosine receptors in the caudal NTS. This confirmed that adenosine endogenously released into the NTS has a similar modulatory effect on integration of cardiovascular reflexes as stimulation of NTS adenosine receptors with exogenous agonists.

  17. Possible therapeutic benefits of adenosine-potentiating drugs in reducing age-related degenerative disease in dogs and cats.

    Science.gov (United States)

    Scaramuzzi, R J; Baker, D J

    2003-10-01

    Adenosine is a ubiquitous, biologically important molecule that is a precursor of other biologically active molecules. It also is a component of some co-factors and has distinct physiological actions in its own right. Levels are maintained by synthesis from dietary precursors and re-cycling. The daily turnover of adenosine is very high. Adenosine can act either as a hormone by binding to adenosine receptors, four adenosine receptor subtypes have been identified, and as an intracellular modulator, after transport into the cell by membrane transporter proteins. One of the principal intracellular actions of adenosine is inhibition of the enzyme phosphodiesterase. Extracellular adenosine also has specific neuromodulatory actions on dopamine and glutamate. Selective and nonselective agonists and antagonists of adenosine are available. The tasks of developing, evaluating and exploiting the therapeutic potential of these compounds is still in its infancy. Adenosine has actions in the central nervous system (CNS), heart and vascular system, skeletal muscle and the immune system and the presence of receptors suggests potential actions in the gonads and other organs. Adenosine agonists improve tissue perfusion through actions on vascular smooth muscle and erythrocyte fluidity and they can be used to improve the quality of life in aged dogs. This article reviews the therapeutic potential of adenosine-potentiating drugs in the treatment of age-related conditions in companion animals, some of which may be exacerbated by castration or spaying at an early age. PMID:14633184

  18. Modeling Soil Loss to Determine Water Erosion Risk at Camp Williams National Guard Base, Utah

    OpenAIRE

    Bartsch, Kevin P.

    1998-01-01

    Soil erosion was assessed at Camp Williams National Guard Base by creating an erosion risk classification map and comparing the erosion impact of disturbance regimes on different hillslopes. Soil erosion does not appear to be a problem for most of Camp Williams. The Revised Universal Soil Loss Equation was applied using GIS to create a soil erosion risk map for the entire Camp Williams facility. The map indicated where problem areas occurred and showed relative erosion risk, but its lack o...

  19. The effectiveness of an American science camp for Taiwanese high school students

    Science.gov (United States)

    Kuo, Pi-Chu

    The purposes of this study were: (1) to evaluate the effectiveness of an American science camp for Taiwanese high school students in terms of student attitudes toward science; (2) to understand the factors that affect student attitudes toward science in the American science camp. Qualitative and quantitative data were collected and analyzed to answer my research questions: (1) How did the influence of the abroad science camp differ from the local one in terms of student attitudes toward science? (2) How did gender, grade level, and personality affect student attitudes toward science in the abroad science camp? An Attitudes toward Science Inventory was used in this study to measure student attitudes. The results of factor analysis suggested that the attitudes measured in this study include five common factors: science as school subjects (SC), science in society (SS), value of science (VS), science in laboratory (SL), and nature of science (NS). Significant improvements were found in SS, VS, and NS after the experiences of the abroad science camp. In the local science camp, only NS was non-significant comparing before and after the camp. The results from the comparisons between the two science camps show that different program designs have different impacts on student attitudes toward science. Furthermore, whether the science camps are designed based on learning theory or not, and regardless of how much time the campers spend in science-related activities during science camps, science camps can motivate students' interests in learning science. The results of mixed-design ANOVA for gender, grade level, and personality suggest that most of these personal factors did not significantly affect student attitudes. However, extraversion/introversion and sensing/intuition had impacts on the persuasibility of the abroad science camp.

  20. WEBSITE AS A MARKETING TOOL IN TOURISM : Website Design for Svanen Camping Site

    OpenAIRE

    Paudel, Binaya

    2012-01-01

    The aim of this thesis was to a give little introduction into modern marketing tools in tourism, such as, websites, Facebook, YouTube, Twitter and Google Plus, and to modify the existing website of Svanen camping, Pietarsaari/ Jakobstad attractively. The Svanen camping is run during the summer by Central Ostrobothnia University of Applied Sciences (COU) since 2004. It is owned by the town of Pietarsaari. The camping is managed by Centria – Research and Development. Jennie Elfving, who is a re...

  1. Brain-natriuretic peptide and cyclic guanosine monophosphate as biomarkers of myxomatous mitral valve disease in dogs

    DEFF Research Database (Denmark)

    Moesgaard, Sophia Gry; Falk, Bo Torkel; Teerlink, Tom;

    2011-01-01

    Elevations in the plasma concentrations of natriuretic peptides correlate with increased severity of myxomatous mitral valve disease (MMVD) in dogs. This study correlates the severity of MMVD with the plasma concentrations of the biomarkers N-terminal fragment of the pro-brain-natriuretic peptide...... (NT-proBNP) and its second messenger, cyclic guanosine monophosphate (cGMP). Furthermore, the l-arginine:asymmetric dimethylarginine (ADMA) ratio was measured as an index of nitric oxide availability. The study included 75 dogs sub-divided into five groups based on severity of MMVD as assessed...... by clinical examination and echocardiography. Plasma NT-proBNP and cGMP concentrations increased with increasing valve dysfunction and were significantly elevated in dogs with heart failure. The cGMP:NT-proBNP ratio decreased significantly in dogs with heart failure, suggesting the development of natriuretic...

  2. Photo-cycle dynamics of LOV1-His domain of phototropin from Chlamydomonas reinhardtii with roseoflavin monophosphate cofactor

    Science.gov (United States)

    Tyagi, A.; Penzkofer, A.; Mathes, T.; Hegemann, P.

    2010-09-01

    The wild-type phototropin protein phot from the green alga Chlamydomonas reinhardtii consists of two N-terminal LOV domains LOV1 and LOV2 with flavin mononucleotide (FMN) cofactor and a C-terminal serine-threonine kinase domain. It controls multiple steps in the sexual lifecycle of the alga. Here the LOV1-His domain of phot with modified cofactor is studied. FMN is replaced by roseoflavin monophosphate (8-dimethylamino-8-demethyl-FMN, RoFMN). The modified LOV1 domain is called RoLOV1. The photo-dynamics consequences of the cofactor change are studied. The absorption, emission, and photo-cyclic behaviour of LOV1-His and RoLOV1-His are compared. A spectroscopic characterisation of the cofactors FMN and RoFMN (roseoflavin) is given.

  3. Receptor crosstalk: haloperidol treatment enhances A2A adenosine receptor functioning in a transfected cell model

    OpenAIRE

    Trincavelli, Maria Letizia; Cuboni, Serena; Catena Dell’Osso, Mario; Maggio, Roberto; Klotz, Karl-Norbert; Novi, Francesca; Panighini, Anna; Daniele, Simona; Martini, Claudia

    2010-01-01

    A2A adenosine receptors are considered an excellent target for drug development in several neurological and psychiatric disorders. It is noteworthy that the responses evoked by A2A adenosine receptors are regulated by D2 dopamine receptor ligands. These two receptors are co-expressed at the level of the basal ganglia and interact to form functional heterodimers. In this context, possible changes in A2A adenosine receptor functional responses caused by the chronic blockade/activation of D2 dop...

  4. Adenosine concentrations in the interstitium of resting and contracting human skeletal muscle

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Maclean, D.; Rådegran, G.;

    1998-01-01

    BACKGROUND: Adenosine has been proposed to be a locally produced regulator of blood flow in skeletal muscle. However, the fundamental questions of to what extent adenosine is formed in skeletal muscle tissue of humans, whether it is present in the interstitium, and where it exerts its vasodilatory...... effect remain unanswered. METHODS AND RESULTS: The interstitial adenosine concentration was determined in the vastus lateralis muscle of healthy humans via dialysis probes inserted in the muscle. The probes were perfused with buffer, and the dialysate samples were collected at rest and during graded knee...... concentration and a higher FaBF (2.22+/-0.18 L/min; PATP, ADP, and AMP increased from...

  5. The role of adenosine A2A receptors on neuromuscular transmission upon ageing

    OpenAIRE

    Pousinha, Paula Isabel Antunes, 1978-

    2012-01-01

    Tese de doutoramento, Ciências Biomédicas (Neurociências), Universidade de Lisboa, Faculdade de Medicina, 2012 Adenosine is a neuromodulator with important actions in the nervous system. The activation of adenosine A2A receptors has been shown to modulate the action of other receptors. Considering that it was observed an interaction between adenosine A2A receptors and TrkB receptors in hippocampus, I hypothesized that the activation of A2A receptors could also facilitate BDNF actions on ne...

  6. The adenosine A2B receptor is involved in anion secretion in human pancreatic duct Capan-1 epithelial cells

    DEFF Research Database (Denmark)

    Hayashi, M.; Inagaki, A.; Novak, Ivana;

    2016-01-01

    Adenosine modulates a wide variety of biological processes via adenosine receptors. In the exocrine pancreas, adenosine regulates transepithelial anion secretion in duct cells and is considered to play a role in acini-to-duct signaling. To identify the functional adenosine receptors and Cl− chann...

  7. Adenosine A2A receptor binding profile of two antagonists, ST1535 and KW6002: consideration on the presence of atypical adenosine A2A binding sites

    Directory of Open Access Journals (Sweden)

    Teresa Riccioni

    2010-08-01

    Full Text Available Adenosine A2A receptors seem to exist in typical (more in striatum and atypical (more in hippocampus and cortex subtypes. In the present study, we investigated the affinity of two adenosine A2A receptor antagonists, ST1535 [2 butyl -9-methyl-8-(2H-1,2,3-triazol 2-yl-9H-purin-6-xylamine] and KW6002 [(E-1,3-diethyl-8-(3,4-dimethoxystyryl-7-methyl-3,7-dihydro-1H-purine-2,6,dione] to the “typical” and “atypical” A2A binding sites. Affinity was determined by radioligand competition experiments in membranes from rat striatum and hippocampus. Displacement of the adenosine analog [3H]CGS21680 [2-p-(2-carboxyethylphenethyl-amino-5’-N-ethylcarbox-amidoadenosine] was evaluated in the absence or in the presence of either CSC [8-(3-chlorostyryl-caffeine], an adenosine A2A antagonist that pharmacologically isolates atypical binding sites, or DPCPX (8-cyclopentyl-1,3-dipropylxanthine, an adenosine A1 receptor antagonist that pharmacologically isolates typical binding site. ZM241385 [84-(2-[7-amino-2-(2-furyl [1,2,4]-triazol[2,3-a][1,3,5]triazin-5-yl amino]ethyl phenol] and SCH58261 [(5-amino-7-(β-phenylethyl-2-(8-furylpyrazolo(4,3-e-1,2,4-triazolo(1,5-c pyrimidine], two other adenosine A2A receptor antagonists, which were reported to differently bind to atypical and typical A2A receptors, were used as reference compounds. ST1535, KW6002, ZM241385 and SCH58261 displaced [3H]CGS21680 with higher affinity in striatum than in hippocampus. In hippocampus, no typical adenosine A2A binding was detected, and ST1535 was the only compound that occupied atypical A2A adenosine receptors. Present data are explained in terms of heteromeric association among adenosine A2A, A2B and A1 receptors, rather than with the presence of atypical A2A receptor subtype.

  8. Regulation and function of transaldolase isoenzymes involved in sugar and one-carbon metabolism in the ribulose monophosphate cycle methylotroph Arthrobacter P1

    NARCIS (Netherlands)

    Levering, P.R.; Dijkhuizen, Lubbert

    1986-01-01

    In the facultative methylotroph Arthrobacter P1 the enzyme transaldolase plays an important role in both the pentose phosphate pathway and in the ribulose monophosphate cycle of formaldehyde fixation. Among gluconate-negative mutants of Arthrobacter P1 strains occurred which also were unable to grow

  9. cAMP diffusion in Dictyostelium discoideum: A Green's function method

    Science.gov (United States)

    Calovi, Daniel S.; Brunnet, Leonardo G.; de Almeida, Rita M. C.

    2010-07-01

    A Green’s function method is developed to approach the spatiotemporal equations describing the cAMP production in Dictyostelium discoideum, markedly reducing numerical calculations times: cAMP concentrations and gradients are calculated just at the amoeba locations. A single set of parameters is capable of reproducing the different observed behaviors, from cAMP synchronization, spiral waves and reaction-diffusion patterns to streaming and mound formation. After aggregation, the emergence of a circular motion of amoebas, breaking the radial cAMP field symmetry, is observed.

  10. USE OF MODIFIED CAMP TEST FOR PRELIMINARY NONSEROLOGIC IDENTIFICATION OF VIBRIO CHOLERAE IN STOOL SPECIMENS

    Directory of Open Access Journals (Sweden)

    Murad Lesmana

    2012-09-01

    Full Text Available Suatu modifikasi uji CAMP digunakan bersama dengan reaksi biokimiawi untuk identifikasi Vibrio cholerae pada sampel klinis. Dari 579 usap dubur penderita diare, 92 (16% memberikan hasil isolasi V. cholerae 01 biotipe El Tor dan 34 (6% V. cholerae non-01. Semua isolat V. cholerae 01 El Tor menunjukkan reaksi CAMP positif kuat dengan gambaran hemolisis sinergistik lengkap berbentuk sosis; sedangkan V. cholerae non-01 memberikan reaksi CAMP yang sempit dengan pola hemolisis menyerupai bulan sabit. Hasil uji CAMP yang dilakukan bersama dengan reaksi biokimiawi sesuai dengan metode biakan konvensional yang menyertakan tes aglutinasi dengan antiserum V. cholerae 01 untuk mengidentifikasi V. cholerae.

  11. RESULTS OF PROPHYLACTIC VACCINATION AGAINST PNEUMONIA AT CAMP WHEELER.

    Science.gov (United States)

    Cecil, R L; Vaughan, H F

    1919-05-01

    1. 13,460 men, or about 80 per cent of the entire camp strength, were vaccinated against pneumonia with pneumococcus lipovaccine. 2. The dosage employed in all cases was 1 cc. of the lipovaccine containing approximately 10 billion each of Pneumococcus Types I, II, and III. 3. Both the local and general reactions produced by the vaccine were usually mild. Only 0.7 per cent of those who received the vaccine were sufficiently affected to need hospital care. None of these was seriously ill, and a majority of them returned to duty on the 2nd or 3rd day after admission. 4. Most of the troops inoculated were under observation for 2 or 3 months after vaccination. During this period there were 32 cases of Pneumococcus Type I, II, and III pneumonia among the vaccinated four-fifths of camp, and 42 cases of pneumonia of these types among the unvaccinated one-fifth of camp. If, however, all cases of pneumonia that developed within 1 week after vaccination are excluded from the vaccinated group, there remain only 8 cases of pneumonia produced by fixed types, and these were all secondary to severe attacks of influenza. This exclusion is justified by the fact that protective bodies do not begin to appear in the serum until the 8th day after injection of pneumococcus lipovaccine. 5. There is no evidence whatever that pneumococcus vaccine predisposes the individual even temporarily toward either pneumococcus or streptococcus pneumonia. 6. The weekly incidence rate for pneumonia (all types) among the vaccinated troops was conspicuously lower than that for the unvaccinated troops. 7. The pneumonia incidence rate per 1,000 men during the period of the experiment was twice as high for unvaccinated recruits as for vaccinated recruits, and nearly seven times as high for unvaccinated seasoned men as for vaccinated seasoned men. 8. Influenza causes a marked reduction in resistance to pneumonia even among vaccinated men. Of the 155 cases of pneumonia (all types) developing 1 week or more

  12. Classification of MEC with the ALLTEM at Camp Stanley, Texas

    Science.gov (United States)

    Asch, T.; Moulton, C.; Smith, D.V.

    2011-01-01

    The ALLTEM is a multi-axis electromagnetic induction system designed for unexploded ordnance UXO applications. It uses a continuous triangle-wave excitation and provides good late-time signal-to-noise ratio SNR especially for ferrous targets. Multi-axis transmitter Tx and receiver Rx systems such as ALLTEM provide a richer data set from which to invert for the target parameters required to distinguish between clutter and UXO. Inversions of field data acquired between 2006 and 2010 over the Army's UXO Standardized Test sites at the Yuma Proving Ground YPG in Arizona and at the Aberdeen Proving Ground APG in Maryland have produced reasonable and generally repeatable results for many UXO items buried at different orientations and depths. In February-March 2011 ALLTEM data was acquired at two locations on the Camp Stanley Storage Activity CSSA just north of San Antonio, Texas. Camp Stanley is used to store munitions as well as test, fire, and overhaul munitions components. Site B-20 is an open burn/open detonation OBOD area and Site B-27 consists of narrow trenches blasted into limestone containing buried range and munitions debris and possibly MEC. The processing, analysis, and classification techniques developed at the controlled environments of YPG and APG have been applied to these two "live" sites at Camp Stanley. ALLTEM data analysis includes both classical numerical inversion of data from each anomaly and clustering of the raw data by means of a self-organizing map SOM via generalized neural network algorithms. Final classification consists of an integration of both the numerical and SOM results. ?? 2011 Society of Exploration Geophysicists.

  13. Ion-Pairing Liquid Chromatography Coupled with Mass Spectrometry for the Simultaneous Determination of Nucleosides and Nucleotides%离子对液相色谱-质谱应用于核苷和核苷酸的同时测定

    Institute of Scientific and Technical Information of China (English)

    蔡宗苇; 钱天秀; 杨斯敏

    2004-01-01

    Adenosine and its corresponding nucleotides adenosine 5'-monophosphate (AMP), adenosine 5'-diphosphate ( ADP ) and adenosine 5'-triphos-phate (ATP) are important biomolecules that provide energy and substrates for various cellular bio-chemical processes. There have been strong

  14. The role of carotid chemoreceptors in the sympathetic activation by adenosine in humans.

    NARCIS (Netherlands)

    Timmers, H.J.L.M.; Rongen, G.A.P.J.M.; Karemaker, J.M.; Wieling, W.; Marres, H.A.M.; Lenders, J.W.M.

    2004-01-01

    The direct vasodilatory and negative chronotropic effects of adenosine in humans are counterbalanced by a reflex increase in sympathetic nerve traffic. A suggested mechanism for this reflex includes peripheral chemoreceptor activation. We, therefore, assessed the contribution of carotid chemorecepto

  15. Influence of the adenosine A1 receptor on blood pressure regulation and renin release

    DEFF Research Database (Denmark)

    Brown, Russell D.; Thorén, Peter; Steege, Andreas;

    2006-01-01

    The present study was performed to investigate the role of adenosine A1 receptors in regulating blood pressure in conscious mice. Adenosine A1-receptor knockout (A1R-/-) mice and their wild-type (A1R+/+) littermates were placed on standardized normal-salt (NS), high-salt (HS), or salt-deficient (SD...... in sodium excretion between the two genotypes on the HS diet. Even on the SD diet, A1R-/- mice had an increased sodium excretion compared with A1R+/+ mice. An abolished tubuloglomerular feedback response and reduced tubular reabsorption can account for the elevated salt excretion found in A1R-/- animals....... The elevated plasma renin concentrations found in the A1R-/- mice could also result in increased blood pressure. Our results confirm that adenosine, acting through the adenosine A1 receptor, plays an important role in regulating blood pressure, renin release, and sodium excretion....

  16. The effect of circulating adenosine on cerebral haemodynamics and headache generation in healthy subjects

    DEFF Research Database (Denmark)

    Birk, S; Petersen, K.A.; Kruuse, Christina Rostrup;

    2005-01-01

    Adenosine is an endogenous neurotransmitter that is released from the brain during hypoxia and relaxes isolated human cerebral arteries. Many cerebral artery dilators cause migraine attacks. However, the effect of intravenous adenosine on headache and cerebral artery diameter has not previously...... been investigated in man and reports regarding the effect of intravenous adenosine on cerebral blood flow are conflicting. Twelve healthy participants received adenosine 80, 120 microg kg(-1) min(-1) and placebo intravenously for 20 min, in a double-blind, three-way, crossover, randomized design....... Headache was rated on a verbal scale (0-10). Regional cerebral blood flow (rCBF) with 133Xe inhalation and single-photon emission computed tomography (SPECT) and MCA flow velocity (V(MCA)) with transcranial Doppler, were measured in direct sequence. Six participants developed headache during 80 microg kg...

  17. Laboratory procedures manual for the firefly luciferase assay for adenosine triphosphate (ATP)

    Science.gov (United States)

    Chappelle, E. W.; Picciolo, G. L.; Curtis, C. A.; Knust, E. A.; Nibley, D. A.; Vance, R. B.

    1975-01-01

    A manual on the procedures and instruments developed for the adenosine triphosphate (ATP) luciferase assay is presented. Data cover, laboratory maintenance, maintenance of bacterial cultures, bacteria measurement, reagents, luciferase procedures, and determination of microbal susceptibility to antibiotics.

  18. Reduced striatal ecto-nucleotidase activity in schizophrenia patients supports the “adenosine hypothesis”

    OpenAIRE

    Aliagas, Elisabet; Villar-Menéndez, Izaskun; Sévigny, Jean; Roca, Mercedes; Romeu, Miriam; Ferrer, Isidre; Martín-Satué, Mireia; Barrachina, Marta

    2013-01-01

    Schizophrenia (SZ) is a major chronic neuropsychiatric disorder characterized by a hyperdopaminergic state. The hypoadenosinergic hypothesis proposes that reduced extracellular adenosine levels contribute to dopamine D2 receptor hyperactivity. ATP, through the action of ecto-nucleotidases, constitutes a main source of extracellular adenosine. In the present study, we examined the activity of ecto-nucleotidases (NTPDases, ecto-5′-nucleotidase, and alkaline phosphatase) in the postmortem putame...

  19. Severe hemorrhage attenuates cardiopulmonary chemoreflex control of regional sympathetic outputs via NTS adenosine receptors

    OpenAIRE

    Minic, Zeljka; Li, Cailian; O'Leary, Donal S.; Scislo, Tadeusz J.

    2014-01-01

    Selective stimulation of inhibitory A1 and facilitatory A2a adenosine receptor subtypes located in the nucleus of the solitary tract (NTS) powerfully inhibits cardiopulmonary chemoreflex (CCR) control of regional sympathetic outputs via different mechanisms: direct inhibition of glutamate release and facilitation of an inhibitory neurotransmitter release, respectively. However, it remains unknown whether adenosine naturally released into the NTS has similar inhibitory effects on the CCR as th...

  20. Effect of insulin and glucose on adenosine metabolizing enzymes in human B lymphocytes.

    Science.gov (United States)

    Kocbuch, Katarzyna; Sakowicz-Burkiewicz, Monika; Grden, Marzena; Szutowicz, Andrzej; Pawelczyk, Tadeusz

    2009-01-01

    In diabetes several aspects of immunity are altered, including the immunomodulatory action of adenosine. Our study was undertaken to investigate the effect of different glucose and insulin concentrations on activities of adenosine metabolizing enzymes in human B lymphocytes line SKW 6.4. The activity of adenosine deaminase in the cytosolic fraction was very low and was not affected by different glucose concentration, but in the membrane fraction of cells cultured with 25 mM glucose it was decreased by about 35% comparing to the activity in cells maintained in 5 mM glucose, irrespective of insulin concentration. The activities of 5'-nucleotidase (5'-NT) and ecto-5'-NT in SKW 6.4 cells depended on insulin concentration, but not on glucose. Cells cultured with 10(-8) M insulin displayed an about 60% lower activity of cytosolic 5'-NT comparing to cells maintained at 10(-11) M insulin. The activity of ecto-5'-NT was decreased by about 70% in cells cultured with 10(-8) M insulin comparing to cells grown in 10(-11) M insulin. Neither insulin nor glucose had an effect on adenosine kinase (AK) activity in SKW 6.4 cells or in human B cells isolated from peripheral blood. The extracellular level of adenosine and inosine during accelerated catabolism of cellular ATP depended on glucose, but not on insulin concentration. Concluding, our study demonstrates that glucose and insulin differentially affect the activities of adenosine metabolizing enzymes in human B lymphocytes, but changes in those activities do not correlate with the adenosine level in cell media during accelerated ATP catabolism, implying that nucleoside transport is the primary factor determining the extracellular level of adenosine.

  1. Cyclization of the phosphate side chain of adenosine triphosphate: formation of monoadenosine 5'-trimetaphosphate.

    Science.gov (United States)

    Glonek, T; Kleps, R A; Myers, T C

    1974-07-26

    Monoadenosine 5'-trimetaphosphate has been prepared from adeno-sine 5'-triphosphate by a carbodiimide-mediated condensation. The molecule was characterized by (3l)P nuclear magnetic resonance, and its (31)P spectrum was simulated through the assumption of a three-phosphorus spin system. The molecule is highly reactive and is rapidly converted to adenosine triphosphate upon contact with water. PMID:4834364

  2. Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells.

    OpenAIRE

    Cronstein, B. N.; Eberle, M A; Gruber, H E; Levin, R I

    1991-01-01

    Although commonly used to control a variety of inflammatory diseases, the mechanism of action of a low dose of methotrexate remains a mystery. Methotrexate accumulates intracellularly where it may interfere with purine metabolism. Therefore, we determined whether a 48-hr pretreatment with methotrexate affected adenosine release from [14C]adenine-labeled human fibroblasts and umbilical vein endothelial cells. Methotrexate significantly increased adenosine release by fibroblasts from 4 +/- 1% t...

  3. Regulation of aggregate size and pattern by adenosine and caffeine in cellular slime molds

    OpenAIRE

    Jaiswal Pundrik; Soldati Thierry; Thewes Sascha; Baskar Ramamurthy

    2012-01-01

    Abstract Background Multicellularity in cellular slime molds is achieved by aggregation of several hundreds to thousands of cells. In the model slime mold Dictyostelium discoideum, adenosine is known to increase the aggregate size and its antagonist caffeine reduces the aggregate size. However, it is not clear if the actions of adenosine and caffeine are evolutionarily conserved among other slime molds known to use structurally unrelated chemoattractants. We have examined how the known factor...

  4. Photovoltaic Technology of Electricity Generation for Desert Camping

    Directory of Open Access Journals (Sweden)

    Shafiqur Rehman

    2005-01-01

    Full Text Available This study presents a case study on the utilization of global solar radiation data on horizontal surface to perform economical feasibility of using Photovoltaic (PV panels with battery backup to meet a small load for a camping site in Saudi Arabia. The analysis considers three scenarios with daily average energy demands of: (i full load, (ii 75% load and (iii half load with annual peak load of 3.84, 3.06 and 2.27 kW, respectively. Each of these loads is further studied economically to investigate the effect of battery storage for 1 to 5 days. The study also compares the cost of electricity generation in $/kWh from PV system and diesel generating systems. The lower mean temperature (~20°C and high intensity of radiation (~ 6.3 kWh m2/day in Abha make it a promising site for the usage of PV systems for desert camping. Analysis of the data indicates that the battery storage capacity cost plays an important role in the overall cost of the PV system. The economical indicators suggest that larger PV systems be preferred over the smaller ones with minimal storage option. The energy generation cost analysis indicated that the diesel generating cost was found to be 29, 56 and 116% higher than the PV system for full, 75% and half load systems, respectively.

  5. Rapid Assessment of Seismic Vulnerability in Palestinian Refugee Camps

    Science.gov (United States)

    Al-Dabbeek, Jalal N.; El-Kelani, Radwan J.

    Studies of historical and recorded earthquakes in Palestine demonstrate that damaging earthquakes are occurring frequently along the Dead Sea Transform: Earthquake of 11 July 1927 (ML 6.2), Earthquake of 11 February 2004 (ML 5.2). In order to reduce seismic vulnerability of buildings, losses in lives, properties and infrastructures, an attempt was made to estimate the percentage of damage degrees and losses at selected refugee camps: Al Ama`ri, Balata and Dhaishe. Assessing the vulnerability classes of building structures was carried out according to the European Macro-Seismic Scale 1998 (EMS-98) and the Fedral Emergency Management Agency (FEMA). The rapid assessment results showed that very heavy structural and non structural damages will occur in the common buildings of the investigated Refugee Camps (many buildings will suffer from damages grades 4 and 5). Bad quality of buildings in terms of design and construction, lack of uniformity, absence of spaces between the building and the limited width of roads will definitely increase the seismic vulnerability under the influence of moderate-strong (M 6-7) earthquakes in the future.

  6. Aptamer-based Electrochemical Biosensors for Highly Selective and Quantitative Detection of Adenosine

    Institute of Scientific and Technical Information of China (English)

    ZHENG Fan; WU Zai-sheng; ZHANG Song-bai; GUO Meng-meng; CHEN Chen-rui; SHEN Guo-li; YU Ru-qin

    2008-01-01

    A new adenosine biosensor based on aptamer probe is introduced in this article.An amino-labeled aptamer probe was immobilized on the gold electrode modified with an o-phenylenediamine electropolymerized film.When adenosine is bound specifically to the aptamer probe,the interface of the biosensor is changed,resulting in the decrement of the peak current.The response current is proportional to the amount of adenosine in sample.The used electrode can be easily regenerated in hot water.The proposed biosensor represents a linear response to adenosine over a concentration range of 1.0×10-7-1.0×10-4 mol/L with a detection limit of 1.0×10-8 mol/L.The presented biosensor exhibits a nice specificity towards adenosine.It offers a promising approach for adenosine assay due to its excellent electrochemical properties that are believed to be very attractive for electrochemical studies and electroanalytical applications.

  7. Label-Free Sensing of Adenosine Based on Force Variations Induced by Molecular Recognition

    Directory of Open Access Journals (Sweden)

    Jingfeng Li

    2015-03-01

    Full Text Available We demonstrate a simple force-based label-free strategy for the highly sensitive sensing of adenosine. An adenosine ssDNA aptamer was bound onto an atomic force microscopy (AFM probe by covalent modification, and the molecular-interface adsorption force between the aptamer and a flat graphite surface was measured by single-molecule force spectroscopy (SMFS. In the presence of adenosine, the molecular recognition between adenosine and the aptamer resulted in the formation of a folded, hairpin-like DNA structure and hence caused a variation of the adsorption force at the graphite/water interface. The sensitive force response to molecular recognition provided an adenosine detection limit in the range of 0.1 to 1 nM. The addition of guanosine, cytidine, and uridine had no significant interference with the sensing of adenosine, indicating a strong selectivity of this sensor architecture. In addition, operational parameters that may affect the sensor, such as loading rate and solution ionic strength, were investigated.

  8. Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells

    International Nuclear Information System (INIS)

    Although commonly used to control a variety of inflammatory diseases, the mechanism of action of a low dose of methotrexate remains a mystery. Methotrexate accumulates intracellularly where it may interfere with purine metabolism. Therefore, the authors determined whether a 48-hr pretreatment with methotrexate affected adenosine release from [14C]adenine-labeled human fibroblasts and umbilical vein endothelial cells. Methotrexate significantly increased adenosine release by fibroblasts. The effect of methotrexate on adenosine release was not due to cytotoxicity since cells treated with maximal concentrations of methotrexate took up [14C]adenine and released 14C-labeled purine (a measure of cell injury) in a manner identical to control cells. Methotrexate treatment of fibroblasts dramatically inhibited adherence to fibroblasts by both unstimulated neutrophils and stimulated neutrophils. One hypothesis that explains the effect of methotrexate on adenosine release is that, by inhibition of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase, methotrexate induces the accumulation of AICAR, the nucleoside precursor of which has previously been shown to cause adenosine release from ischemic cardiac tissue. The observation that the antiinflammatory actions of methotrexate are due to the capacity of methotrexate to induce adenosine release may form the basis for the development of an additional class of antiinflammatory drugs

  9. Serum adenosine deaminase as oxidative stress marker in type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Shashikala Magadi Dasegowda

    2015-05-01

    Results: The study observed an increased level of serum adenosine deaminase, malondialdehyde and decreased levels of total antioxidant capacity in type 2 diabetes mellitus compared to controls. Serum adenosine deaminase levels in type 2 diabetics were 50.77 +/- 6.95 and in controls was 17.86 +/- 4.04. Serum Malondialdehyde levels in type 2 diabetics was 512.13 +/- 70.15 and in controls was 239.32 +/- 23.97. Serum total antioxidant levels in type 2 diabetics was 0.39+/-0.15 and in controls was 1.66+/-0.25. Positive correlation was seen between serum adenosine deaminase and malondialdehyde and it was statistically significant. Statistically significant negative correlation was seen between serum adenosine deaminase and total antioxidant capacity. Conclusion: Adenosine deaminase can be used as oxidative stress marker. Their increased levels indicate oxidative stress in type 2 diabetes mellitus. Therefore, estimation of serum adenosine deaminase levels help in early prediction and prevention of long term complications occurring due to oxidative stress in diabetics, thereby decreasing the mortality and morbidity in them. [Int J Res Med Sci 2015; 3(5.000: 1195-1198

  10. Functional proteomics of adenosine triphosphatase system in the rat striatum during aging

    Institute of Scientific and Technical Information of China (English)

    Roberto Federico Villa; Federica Ferrari; Antonella Gorini

    2012-01-01

    The maximum rates of adenosine triphosphatase (ATPase) systems related to energy consumption were systematically evaluated in synaptic plasma membranes isolated from the striata of male Wistar rats aged 2, 6, 12, 18, and 24 months, because of their key role in presynaptic nerve ending homeostasis. The following enzyme activities were evaluated: sodium-potassium-magnesium adenosine triphosphatase (Na+, K+, Mg2+-ATPase); ouabain-insensitive magnesium adenosine triphosphatase (Mg2+-ATPase); sodium-potassium adenosine triphosphatase (Na+, K+-ATPase); direct magnesium adenosine triphosphatase (Mg2+-ATPase); calcium-magnesium adenosine triphosphatase (Ca2+, Mg2+-ATPase); and acetylcholinesterase. The results showed that Na+, K+-ATPase decreased at 18 and 24 months, Ca2+, Mg2+-ATPase and acetylcholinesterase decreased from 6 months, while Mg2+-ATPase was unmodified. Therefore, ATPases vary independently during aging, suggesting that the ATPase enzyme systems are of neuropathological and pharmacological importance. This could be considered as an experimental model to study regeneration processes, because of the age-dependent modifications of specific synaptic plasma membranes. ATPases cause selective changes in some cerebral functions, especially bioenergetic systems. This could be of physiopathological significance, particularly in many central nervous system diseases, where, during regenerative processes, energy availability is essential.

  11. The progressive nature of concentration camp syndrome in former prisoners of Nazi concentration camps--Not just history, but the important issue of contemporary medicine.

    Science.gov (United States)

    Jabłoński, Robert; Rosińczuk, Joanna; Leszek, Jerzy; Uchmanowicz, Izabella; Panaszek, Bernard

    2016-04-01

    Constant stress, slave labor, tortures, and starvation all affected the health of concentration camp prisoners, contributing to multimorbidities, increased mortality and accelerated development of chronic illnesses, what we have shown in an earlier publication. The interrelated somatic and psychological symptoms gave rise to concentration camp syndrome (KZ-syndrome), which has many features of PTSD, occurring frequently nowadays. The paper attempts at assessing the influence of concentration camp conditions on functional disorders in each system of the human body, occurring in KZ-syndrome, and at demonstrating the progressive nature of the syndrome. A retrospective assessment of the former prisoners' health after 5 and 30 years following their leaving camps was performed based on medical records and surveys. The materials included 250 former prisoners who underwent medical examination in 1950, i.e. 5 years after leaving the camp, of whom 120 former prisoners survived and were examined and surveyed in 1975, i.e. 30 years after leaving the camp. KZ-syndrome was shown to occur in 58.8% of former prisoners 5 years after leaving the camp, and in 77.5% after 30 years (p < 0.001), which confirms the syndrome's chronic and progressive nature. Pathological sequels of internment in concentration camps, in the form of KZ-syndrome, were observed in most former prisoners. Over time, the number of morbidities and the intensity of symptoms increased, which indicates that the syndrome has a chronic and progressive nature. KZ-syndrome is a multi-organ disorder, with numerous chronic comorbidities exacerbating the progression. PMID:26783727

  12. Camp Read-a-Rama® and Fully-Engaged Literacy Learning: Implications for LIS Education

    Science.gov (United States)

    Copeland, Clayton A.; Martin, Michelle H.

    2016-01-01

    Literacy and literacy skill development remain critical concerns in the U.S. "Two of every three students in the U.S. do not have the necessary reading proficiencies to successfully complete grade-level work" (Allington, 2011). Camp Read-a-Rama, a summer day camp in South Carolina for 4- to 11-year-olds, creates innovative programming…

  13. The modulation of cell surface cAMP receptors from Dictyostelium disscoideum by ammonium sulfate

    NARCIS (Netherlands)

    Haastert, Peter J.M. van

    1985-01-01

    Dictyostelium discoideum cells contain a heterogeneous population of cell surface cAMP receptors with components possessing different affinities (Kd between 15 and 450 nM) and different off-rates of the cAMP-receptor complex (t½ between 0.7 and 150 s). The association of cAMP to the receptor and the

  14. Camper learning and friendship at pediatric oncology camps in North America.

    Science.gov (United States)

    Martiniuk, Alexandra L C; Amylon, Michael D; Briery, Brandon G; Shea-Perry, Marci; Kelsey, Kathleen P; Lam, Gary W; Körver, Sarah

    2014-01-01

    Children with cancer and their families often attend specialized camps (therapeutic recreation) through their cancer treatment journey, yet little is known about the effects of these camps. A qualitative cohort study was used to assess learning and friendship development by campers attending one of four pediatric oncology summer camps during 2010 in North America. Standardized perceived change questionnaires developed by the American Camp Association were administered following camp attendance. Five-hundred and eighteen campers were enrolled: 120 (age 6-9 years) and 398 (age 10 and older). The largest positive response from the younger campers was observed for the question, "At camp did you learn to look forward to trying new activities?" For the older campers' survey, the items "Becoming better at enjoying being with my friends," "Becoming better at helping my friends have a good time when they are with me," and "Becoming better at getting to know more things about my friends" were perceived to increase the most for the majority of campers compared to other questions. Items for which older campers most often perceived little change were "Becoming better at choosing people who would be good friends to be with" and "Becoming better at understanding friends' emotions." Camp helps children learn new activities as well as enjoy good times with friends. Dealing with one's own mistakes and understanding others' emotions are areas for improvement. Ultimately it is hoped that these skills gained at camp will help build coping and resiliency for children/siblings affected by pediatric cancers. PMID:24364990

  15. Science Camps in Europe--Collaboration with Companies and School, Implications and Results on Scientific Literacy

    Science.gov (United States)

    Lindner, M.; Kubat, C.

    2014-01-01

    The paper informs on the characteristics of a Comenius Network of seven organizations, who are collaborating in exchanging best practice on science camps. This exchange includes evaluation results on more science camps of European organizations, which will deliver information on organization, collaboration with companies, pedagogical aspects, as…

  16. 14 CFR 91.1437 - CAMP: Authority to perform and approve maintenance.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false CAMP: Authority to perform and approve maintenance. 91.1437 Section 91.1437 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF... Ownership Operations Program Management § 91.1437 CAMP: Authority to perform and approve maintenance....

  17. Distancing Students from Nature: Science Camp and the Representation of the Human-Nature Relationship

    Science.gov (United States)

    Terrill, Laura Anne

    2015-01-01

    This study investigated the curricular representations of the environment and the human-environment relationship at one residential school sponsored science camp. Data gathered included field notes from observational time at the camp, interviews with staff and classroom teachers, and documents from the site's website, guides, manuals, and…

  18. Assessment of the Psychosocial Development of Children Attending Nursery Schools in Karen Refugee Camps in Thailand

    Science.gov (United States)

    Tanaka, Akiko

    2013-01-01

    The Karen, an ethnic minority group in Burma, have experienced a prolonged state of exile in refugee camps in neighboring Thailand because of ethnic conflict in their home country. Nursery schools in the three largest Karen refugee camps aim to promote the psychosocial development of young children by providing a child-centered, creative,…

  19. Alexander Pechersky Testifies: an Open Page of Sobibor Death Camp History

    Directory of Open Access Journals (Sweden)

    Lev S. Simkin

    2013-01-01

    Full Text Available Here, the author introduces the interrogation of the witness Alexander Aronovich Pechersky, the leader of the German death camp Sobibor Revolt during the World War II. Special attention is attached to the daily life of the death camp. The picture of revolt preparation was completed

  20. Offering a Forensic Science Camp to Introduce and Engage High School Students in Interdisciplinary Science Topics

    Science.gov (United States)

    Ahrenkiel, Linda; Worm-Leonhard, Martin

    2014-01-01

    In this article, we present details of a one-week interdisciplinary science camp for high school students in Denmark, "Criminal Camp". We describe the use of forensic science and simulated crimes as a common foundation for teaching the theory and practice of concepts in chemistry, physics, and medicine or biology. The main goal of the…

  1. Which Social Emotional Competencies Are Enhanced at a Social Emotional Learning Camp?

    Science.gov (United States)

    Ee, Jessie; Ong, Chew Wei

    2014-01-01

    Research studies have shown that educational programmes such as camps and field trips can develop affective and social relationships through personal exposure to outdoor experiences among students. This study will illustrate the outcome of a social emotional learning camp organized for 93 Secondary Two students (mean age 14.1) in Singapore. Both…

  2. Neuroeconomics: Two camps gradually converging: What can economics gain from it?

    NARCIS (Netherlands)

    J.J. Vromen (Jack)

    2011-01-01

    textabstractNeuroeconomics started off as a hybrid project. Two camps, behavioral economics in the scanner (BES) and Glimcher's economics of neural activity (ENA), could be clearly distinguished. The camps disagreed not only about substantive issues but also about what neuroeconomics ultimately aims

  3. The Efficacy of Mammography Boot Camp to Improve the Performance of Radiologists

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Hye [Dept. of Radiology, Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon (Korea, Republic of); Jun, Jae Kwan [National Cancer Control Institute, National Cancer Center, Goyang (Korea, Republic of); Jung, Seung Eun [Dept. of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Kim, You Me [Dept. of Radiology, Dankook University Hospital, Cheonan (Korea, Republic of); Choi, Nami [Dept. of Radiology, Konkuk University Medical Center, Seoul (Korea, Republic of)

    2014-10-15

    To evaluate the efficacy of a mammography boot camp (MBC) to improve radiologists' performance in interpreting mammograms in the National Cancer Screening Program (NCSP) in Korea. Between January and July of 2013, 141 radiologists were invited to a 3-day educational program composed of lectures and group practice readings using 250 digital mammography cases. The radiologists' performance in interpreting mammograms were evaluated using a pre- and post-camp test set of 25 cases validated prior to the camp by experienced breast radiologists. Factors affecting the radiologists' performance, including age, type of attending institution, and type of test set cases, were analyzed. The average scores of the pre- and post-camp tests were 56.0 ± 12.2 and 78.3 ± 9.2, respectively (p < 0.001). The post-camp test scores were higher than the pre-camp test scores for all age groups and all types of attending institutions (p < 0.001). The rate of incorrect answers in the post-camp test decreased compared to the pre-camp test for all suspicious cases, but not for negative cases (p > 0.05). The MBC improves radiologists' performance in interpreting mammograms irrespective of age and type of attending institution. Improved interpretation is observed for suspicious cases, but not for negative cases.

  4. The effect of neuropeptides on vessel tone and cAMP production

    DEFF Research Database (Denmark)

    Yao, W; Sheikh, S P; Ottesen, B;

    1996-01-01

    The effect of VIP, PHM, PHV, PACAP-27, and PACAP-38 on vessel tone and cAMP production was investigated in rabbit ovarian arteries in vitro. The peptides (10(-7)M) induced a significant relaxation on NA-precontracted vessels and displayed similar potencies. The cAMP accumulation induced by PACAP-...

  5. The Efficacy of Family Camp Experience for Families Who Have Children with Visual Impairments. Research Report

    Science.gov (United States)

    Day, Janice Neibaur; Kleinschmidt, Julia

    2005-01-01

    This study was designed to address the paucity of research on the efficacy of camps for children with visual impairments and their families. The study evaluated the performance of a two-day camp for families with young visually impaired children at the Utah Schools for the Deaf and the Blind whose program was based on perceived family needs and…

  6. Better Camping for All: A Beginning Look at the Americans with Disabilities Act.

    Science.gov (United States)

    Scanlin, Margery M.

    1992-01-01

    Provides a brief overview of the Americans with Disabilities Act (ADA) and schedule for phasing in the law. Discusses general features of the law that apply to camps including provisions of employment and public accommodation and requirements for making camp facilities and programs accessible. Provides key definitions included in the ADA and…

  7. Les novel·les dels camps de concentració

    Directory of Open Access Journals (Sweden)

    Vicent Simbor Roig

    2014-11-01

    novelistic fiction, the elaboration of a rather peculiar conception of time and space that makes up the true chronotope of the concentration camp, narrative options with regard to the narrator, etc. The final conclusion is that the testimonial novel describing life in a concentration camp is a model with very clear characteristics.

  8. Global and local missions of cAMP signaling in neural plasticity, learning and memory

    Directory of Open Access Journals (Sweden)

    Daewoo eLee

    2015-08-01

    Full Text Available The fruit fly Drosophila melanogaster has been a popular model to study cAMP signaling and resultant behaviors due to its powerful genetic approaches. All molecular components (AC, PDE, PKA, CREB, etc essential for cAMP signaling have been identified in the fly. Among them, adenylyl cyclase (AC gene rutabaga and phosphodiesterase (PDE gene dunce have been intensively studied to understand the role of cAMP signaling. Interestingly, these two mutant genes were originally identified on the basis of associative learning deficits. This commentary summarizes findings on the role of cAMP in Drosophila neuronal excitability, synaptic plasticity and memory. It mainly focuses on two distinct mechanisms (global versus local regulating excitatory and inhibitory synaptic plasticity related to cAMP homeostasis. This dual regulatory role of cAMP is to increase the strength of excitatory neural circuits on one hand, but to act locally on postsynaptic GABA receptors to decrease inhibitory synaptic plasticity on the other. Thus the action of cAMP could result in a global increase in the neural circuit excitability and memory. Implications of this cAMP signaling related to drug discovery for neural diseases are also described.

  9. Adenosine Deaminase Activity in Chronic Lymphocytic Leukemia and Healthy Subjects

    Science.gov (United States)

    Ghaderi, Bayazid; Amini, Sabrieh; Maroofi, Farzad; Jalali, Chiya; Javanmardi, Mitra; Roshani, Daem; Abdi, Mohammad

    2016-01-01

    Background B cell chronic lymphocytic leukemia is one of the most frequent hematologic malignancies in the world. Cellular surface CD markers and serum Beta-2-microglobulin may be used as a prognostic tool in CLL patients. Objectives In the present study we introduce serum adenosine deaminase as a diagnostic marker in CLL. Materials and Methods Blood samples were collected from B-CLL and healthy subjects. White blood cell, red blood cell and platelet count and blood Erythrocyte sedimentation rate was recorded and serum Beta-2-microglobulin, Lactate dehydrogenase and total ADA enzyme activity were determined. Results Serum ADA activity was significantly higher in patients group than that of controls. ADA had a significant and direct correlation with B2M, WBC, LDH and ESR. However, there was not any relation between ADA and the stages of disease. Diagnostic cut-off, sensitivity and specificity of the serum ADA test were 27.97 U/L, 91% and 94%, respectively. Conclusions A higher ADA activity in patients group and its correlation with CLL markers were seen in our study. High diagnostic value of serum ADA in our study suggests that it might be considered as a useful screening tool among the other markers in CLL.

  10. An adenosine nucleoside analogue NITD008 inhibits EV71 proliferation.

    Science.gov (United States)

    Shang, Luqing; Wang, Yaxin; Qing, Jie; Shu, Bo; Cao, Lin; Lou, Zhiyong; Gong, Peng; Sun, Yuna; Yin, Zheng

    2014-12-01

    Enterovirus 71 (EV71), one of the major causative agents of Hand-Foot-Mouth Disease (HFMD), causes severe pandemics and hundreds of deaths in the Asia-Pacific region annually and is an enormous public health threat. However, effective therapeutic antiviral drugs against EV71 are rare. Nucleoside analogues have been successfully used in the clinic for the treatment of various viral infections. We evaluated a total of 27 nucleoside analogues and discovered that an adenosine nucleoside analogue NITD008, which has been reported to be an antiviral reagent that specifically inhibits flaviviruses, effectively suppressed the propagation of different strains of EV71 in RD, 293T and Vero cells with a relatively high selectivity index. Triphosphorylated NITD008 (ppp-NITD008) functions as a chain terminator to directly inhibit the RNA-dependent RNA polymerase activity of EV71, and it does not affect the EV71 VPg uridylylation process. A significant synergistic anti-EV71 effect of NITD008 with rupintrivir (AG7088) (a protease inhibitor) was documented, supporting the potential combination therapy of NITD008 with other inhibitors for the treatment of EV71 infections.

  11. Adenosine deaminase complexing protein (ADCP) immunoreactivity in colorectal adenocarcinoma.

    Science.gov (United States)

    ten Kate, J; van den Ingh, H F; Khan, P M; Bosman, F T

    1986-04-15

    Immunoreactive adenosine deaminase complexing protein (ADCP) was studied in 91 human colorectal adenocarcinomas. The expression of ADCP was correlated with that of secretory component (SC) and carcinoembryonic antigen (CEA), with the histological grade and the Dukes' stage of the carcinomas. The histological grade was scored semi-quantitatively according to 5 structural and 4 cytological variables. ADCP expression was observed in 3 different staining patterns, namely: (1) diffuse cytoplasmic (77% of the carcinomas); (2) granular cytoplasmic (13%); and (3) membrane-associated (66%). These patterns were observed alone or in combination. Eleven percent of the carcinomas exhibited no ADCP immunoreactivity. Linear regression analysis showed that the expression of ADCP correlates with that of SC and CEA. However, no significant correlation emerged between the histological parameters or the Dukes' stage and any of the immunohistological parameters. Comparison of the histological characteristics of carcinomas exhibiting little or no ADCP immunoreactivity with those showing extensive immunoreactivity, showed that membranous ADCP immunoreactivity occurs more frequently in well-differentiated carcinomas. Structural parameters showed a better correlation with membranous ADCP expression than the cytological variables. It is concluded that membranous expression of ADCP and CEA are indicators of a high level of differentiation as reflected primarily in the structural characteristics of the tumor. PMID:3957458

  12. Distribution of adenosine deaminase complexing protein (ADCP) in human tissues.

    Science.gov (United States)

    Dinjens, W N; ten Kate, J; van der Linden, E P; Wijnen, J T; Khan, P M; Bosman, F T

    1989-12-01

    The normal distribution of adenosine deaminase complexing protein (ADCP) in the human body was investigated quantitatively by ADCP-specific radioimmunoassay (RIA) and qualitatively by immunohistochemistry. In these studies we used a specific rabbit anti-human ADCP antiserum. In all 19 investigated tissues, except erythrocytes, ADCP was found by RIA in the soluble and membrane fractions. From all tissues the membrane fractions contained more ADCP (expressed per mg protein) than the soluble fractions. High membrane ADCP concentrations were found in skin, renal cortex, gastrointestinal tract, and prostate. Immunoperoxidase staining confirmed the predominant membrane-associated localization of the protein. In serous sweat glands, convoluted tubules of renal cortex, bile canaliculi, gastrointestinal tract, lung, pancreas, prostate gland, salivary gland, gallbladder, mammary gland, and uterus, ADCP immunoreactivity was found confined to the luminal membranes of the epithelial cells. These data demonstrate that ADCP is present predominantly in exocrine glands and absorptive epithelia. The localization of ADCP at the secretory or absorptive apex of the cells suggests that the function of ADCP is related to the secretory and/or absorptive process. PMID:2573631

  13. Adenosine to Inosine editing frequency controlled by splicing efficiency.

    Science.gov (United States)

    Licht, Konstantin; Kapoor, Utkarsh; Mayrhofer, Elisa; Jantsch, Michael F

    2016-07-27

    Alternative splicing and adenosine to inosine (A to I) RNA-editing are major factors leading to co- and post-transcriptional modification of genetic information. Both, A to I editing and splicing occur in the nucleus. As editing sites are frequently defined by exon-intron basepairing, mRNA splicing efficiency should affect editing levels. Moreover, splicing rates affect nuclear retention and will therefore also influence the exposure of pre-mRNAs to the editing-competent nuclear environment. Here, we systematically test the influence of splice rates on RNA-editing using reporter genes but also endogenous substrates. We demonstrate for the first time that the extent of editing is controlled by splicing kinetics when editing is guided by intronic elements. In contrast, editing sites that are exclusively defined by exonic structures are almost unaffected by the splicing efficiency of nearby introns. In addition, we show that editing levels in pre- and mature mRNAs do not match. This phenomenon can in part be explained by the editing state of an RNA influencing its splicing rate but also by the binding of the editing enzyme ADAR that interferes with splicing. PMID:27112566

  14. Adenosine, type 1 receptors: role in proximal tubule Na+ reabsorption.

    Science.gov (United States)

    Welch, W J

    2015-01-01

    Adenosine type 1 receptor (A1 -AR) antagonists induce diuresis and natriuresis in experimental animals and humans. Much of this effect is due to inhibition of A1 -ARs in the proximal tubule, which is responsible for 60-70% of the reabsorption of filtered Na(+) and fluid. Intratubular application of receptor antagonists indicates that A1 -AR mediates a portion of Na(+) uptake in PT and PT cells, via multiple transport systems, including Na(+) /H(+) exchanger-3 (NHE3), Na(+) /PO4(-) co-transporter and Na(+) -dependent glucose transporter, SGLT. Renal microperfusion and recollection studies have shown that fluid reabsorption is reduced by A1 -AR antagonists and is lower in A1 -AR KO mice, compared to WT mice. Absolute proximal reabsorption (APR) measured by free-flow micropuncture is equivocal, with studies that show either lower APR or similar APR in A1 -AR KO mice, compared to WT mice. Inhibition of A1 -ARs lowers elevated blood pressure in models of salt-sensitive hypertension, partially due to their effects in the proximal tubule. PMID:25345761

  15. In Vitro Functional Study of Rice Adenosine 5'-Phosphosulfate Kinase

    Institute of Scientific and Technical Information of China (English)

    WANG De-zhen; CHEN Guo-guo; LU Lu-jia; JIANG Zhao-jun; RAO Yu-chun; SUN Mei-hao

    2016-01-01

    Sulfate can be activated by ATP sulfurylase and adenosine 5'-phosphosulfate kinase (APSK)in vivo. Recent studies suggested that APSK inArabidopsis thaliana regulated the partition between APS reduction and phosphorylation and its activity can be modulated by cellular redox status. In order to study regulation of APSK in rice (OsAPSK),OsAPSK1 gene was cloned and its activity was analyzed. OsAPSK1 C36 and C69 were found to be the conserved counterparts of C86 and C119, which involved in disulfide formation in AtAPSK.C36A/C69A OsAPSK1 double mutation was made by site directed mutagenesis. OsAPSK1 and its mutant were prokaryotically over-expressed and purified, and then assayed for APS phosphorylation activity. OsAPSK1 activity was depressed by oxidized glutathione, while the activity of its mutantwas not. Further studies in the case that oxidative stress will fluctuatein vivo3'-phosphoadenosine-5'-phosphosulfate content, and all APSK isoenzymes have similar regulation patterns are necessary to be performed.

  16. 77 FR 32986 - Notice of Inventory Completion: Marine Corps Base Camp Pendleton, U.S. Marine Corps, San Diego...

    Science.gov (United States)

    2012-06-04

    ... removed from the construction site of the San Onofre Nuclear Generating Station (SONGS) on MCB Camp... San Onofre Nuclear Generating Station (SONGS) at MCB Camp Pendleton. Bechtel relocated the...

  17. Free will in total institutions: The case of choice inside Nazi death camps.

    Science.gov (United States)

    Davidov, Jonathan; Eisikovits, Zvi

    2015-07-01

    Nazi death camps, as any total institutions, were designed to deny any free will or choice from inmates. Furthermore, former inmates in such extreme conditions often account for their own actions and behavior in such settings as inevitable ("I had no other choice"). This study examines the questions of free will vs. determinism in death camps from a descriptive-phenomenological perspective. Data was collected through in-depth interviews with 20 former death camp inmates. The following themes emerged from the qualitative analysis of the data: the 'selection' experience; 'borrowed time' perception; and the experience of 'nothingness'. A conceptual model grounded in these data was developed to illustrate the inmate's lived experience of choice in the reality of the camps. Analysis of the model indicates that under the extreme conditions of the death camp, free will and existence are interchangeable: "I choose - therefore I am". PMID:25881235

  18. Free will in total institutions: The case of choice inside Nazi death camps.

    Science.gov (United States)

    Davidov, Jonathan; Eisikovits, Zvi

    2015-07-01

    Nazi death camps, as any total institutions, were designed to deny any free will or choice from inmates. Furthermore, former inmates in such extreme conditions often account for their own actions and behavior in such settings as inevitable ("I had no other choice"). This study examines the questions of free will vs. determinism in death camps from a descriptive-phenomenological perspective. Data was collected through in-depth interviews with 20 former death camp inmates. The following themes emerged from the qualitative analysis of the data: the 'selection' experience; 'borrowed time' perception; and the experience of 'nothingness'. A conceptual model grounded in these data was developed to illustrate the inmate's lived experience of choice in the reality of the camps. Analysis of the model indicates that under the extreme conditions of the death camp, free will and existence are interchangeable: "I choose - therefore I am".

  19. Evaluation of undergraduate nursing students' clinical confidence following a mental health recovery camp.

    Science.gov (United States)

    Cowley, Thomas; Sumskis, Sue; Moxham, Lorna; Taylor, Ellie; Brighton, Renee; Patterson, Chris; Halcomb, Elizabeth

    2016-02-01

    In the present study, we evaluate the impact of participation in a mental health recovery camp on the clinical confidence of undergraduate nursing students in dealing with individuals with mental illness. Twenty undergraduate nursing students who participated in the recovery camp completed the Mental Health Nursing Clinical Confidence Scale both before and directly after attending the camp. Data were analysed using descriptive and inferential statistics. Participation in the recovery camp was associated with a statistically-significant increase in students' level of overall confidence between the pretest and post-test data (P students over the age of 25 years and who do not have a family history of mental illness are more likely to self-report a higher level of confidence in both the pre- and post-results. The clinical confidence of undergraduate nursing students improved through participation in an immersive clinical experience within the recovery camp.

  20. Use of a token reinforcement system to promote appropriate behavior at a pediatric burn summer camp.

    Science.gov (United States)

    Adams, C D; Girolami, P A; Joseph, K E; Sauvageot, S A; Slater, H

    2002-01-01

    Child behavior management can be an important concern in conducting summer camps for pediatric burn patients, because many of these patients have a history of significant behavioral difficulties. To be efficient, a flexible camp-wide behavior management system, such as a token economy, would be ideal. In this article we discuss the concept and principles of a token reinforcement system and outline how this intervention was applied to our pediatric burn summer camp across 2 consecutive years. We also provide a description of modifications made for the second camp, based on counselor ratings of and our experience with the token system during the first camp. Results from counselor assessments indicated that after using the token system, counselors' perceptions of its utility (eg, effective in decreasing problem behavior in campers, useful in making behavior management easier) increased significantly across both years.