WorldWideScience

Sample records for cholecystokinin receptor exists

  1. Carbobenzoxy amino acids: Structural requirements for cholecystokinin receptor antagonist activity

    International Nuclear Information System (INIS)

    Maton, P.N.; Sutliff, V.E.; Jensen, R.T.; Gardner, J.D.

    1985-01-01

    The authors used dispersed acini prepared from guinea pig pancreas to examine 28 carbobenzoxy (CBZ) amino acids for their abilities to function as cholecystokinin receptor antagonists. All amino acid derivatives tested, except for CBZ-alanine, CBZ-glycine, and N alpha-CBZ- lysine, were able to inhibit the stimulation of amylase secretion caused by the C-terminal octapeptide of cholecystokinin. In general, there was a good correlation between the ability of a carbobenzoxy amino acid to inhibit stimulated amylase secretion and the ability of the amino acid derivative to inhibit binding of 125 I-cholecystokinin. The inhibition of cholecystokinin-stimulated amylase secretion was competitive, fully reversible, and specific for those secretagogues that interact with the cholecystokinin receptor. The potencies with which the various carbobenzoxy amino acids inhibited the action of cholecystokinin varied 100-fold and CBZ-cystine was the most potent cholecystokinin receptor antagonist. This variation in potency was primarily but not exclusively a function of the hydrophobicity of the amino acid side chain

  2. Cholecystokinin receptor-1 mediates the inhibitory effects of exogenous cholecystokinin octapeptide on cellular morphine dependence

    Directory of Open Access Journals (Sweden)

    Wen Di

    2012-06-01

    Full Text Available Abstract Background Cholecystokinin octapeptide (CCK-8, the most potent endogenous anti-opioid peptide, has been shown to regulate the processes of morphine dependence. In our previous study, we found that exogenous CCK-8 attenuated naloxone induced withdrawal symptoms. To investigate the precise effect of exogenous CCK-8 and the role of cholecystokinin (CCK 1 and/or 2 receptors in morphine dependence, a SH-SY5Y cell model was employed, in which the μ-opioid receptor, CCK1/2 receptors, and endogenous CCK are co-expressed. Results Forty-eight hours after treating SH-SY5Y cells with morphine (10 μM, naloxone (10 μM induced a cAMP overshoot, indicating that cellular morphine dependence had been induced. The CCK receptor and endogenous CCK were up-regulated after chronic morphine exposure. The CCK2 receptor antagonist (LY-288,513 at 1–10 μM inhibited the naloxone-precipitated cAMP overshoot, but the CCK1 receptor antagonist (L-364,718 did not. Interestingly, CCK-8 (0.1-1 μM, a strong CCK receptor agonist, dose-dependently inhibited the naloxone-precipitated cAMP overshoot in SH-SY5Y cells when co-pretreated with morphine. The L-364,718 significantly blocked the inhibitory effect of exogenous CCK-8 on the cAMP overshoot at 1–10 μM, while the LY-288,513 did not. Therefore, the CCK2 receptor appears to be necessary for low concentrations of endogenous CCK to potentiate morphine dependence in SH-SY5Y cells. An additional inhibitory effect of CCK-8 at higher concentrations appears to involve the CCK1 receptor. Conclusions This study reveals the difference between exogenous CCK-8 and endogenous CCK effects on the development of morphine dependence, and provides the first evidence for the participation of the CCK1 receptor in the inhibitory effects of exogenous CCK-8 on morphine dependence.

  3. Cyclic cholecystokinin analogues with high selectivity for central receptors

    International Nuclear Information System (INIS)

    Charpentier, B.; Pelaprat, D.; Durieux, C.; Dor, A.; Roques, B.P.; Reibaud, M.; Blanchard, J.C.

    1988-01-01

    Taking as a model the N-terminal folding of the cholecystokinin tyrosine-sulfated octapeptide deduced from conformational studies, two cyclic cholecystokinin (CCK) analogues were synthesized by conventional peptide synthesis. The binding characteristics of these peptides were investigated on brain cortex membranes and pancreatic acini of guinea pig. Compounds I and II were competitive inhibitors of [ 3 H]Boc[Ahx 28,31 ]CCK-(27-33) binding to central CCK receptors and showed a high degree of selectivity for these binding sites. This high selectivity was associated with a high affinity for central CCK receptors. Similar affinities and selectivities were found when 125 I Bolton-Hunter-labeled CCK-8 was used as a ligand. Moreover, these compounds were only weakly active in the stimulation of amylase release from guinea pig pancreatic acini and were unable to induce contractions in the guinea pig ileum. The two cyclic CCK analogues, therefore, appear to be synthetic ligands exhibiting both high affinity and high selectivity for central CCK binding sites. These compounds could help clarify the respective role of central and peripheral receptors for various CCK-8-induced pharmacological effects

  4. Preclinical evaluation of radiolabeled DOTA-derivatized cyclic minigastrin analogs for targeting cholecystokinin receptor expressing malignancies.

    NARCIS (Netherlands)

    Guggenberg, E. von; Rangger, C.; Sosabowski, J.; Laverman, P.; Reubi, J.C.; Virgolini, I.J.; Decristoforo, C.

    2012-01-01

    PURPOSE: Targeting of cholecystokinin receptor expressing malignancies such as medullary thyroid carcinoma is currently limited by low in vivo stability of radioligands. To increase the stability, we have developed and preclinically evaluated two cyclic

  5. Characterization of cholecystokinin receptors on guinea pig gastric chief cell membranes

    International Nuclear Information System (INIS)

    Matozaki, T.; Sakamoto, C.; Nagao, M.; Nishisaki, H.; Konda, Y.; Nakano, O.; Matsuda, K.; Wada, K.; Suzuki, T.; Kasuga, M.

    1991-01-01

    The binding of cholecystokinin (CCK) to its receptors on guinea pig gastric chief cell membranes were characterized by the use of 125 I-CCK-octapeptide (CCK8). At 30 degrees C optimal binding was obtained at acidic pH in the presence of Mg2+, while Na+ reduced the binding. In contrast to reports on pancreatic and brain CCK receptors, scatchard analysis of CCK binding to chief cell membranes revealed two classes of binding sites. Whereas, in the presence of a non-hydrolyzable GTP analog, GTP gamma S, only a low affinity site of CCK binding was observed. Chief cell receptors recognized CCK analogs, with an order of potency of: CCK8 greater than gastrin-I greater than CCK4. Although all CCK receptor antagonists tested (dibutyryl cyclic GMP, L-364718 and CR1409) inhibited labeled CCK binding to chief cell membranes, the relative potencies of these antagonists in terms of inhibiting labeled CCK binding were different from those observed in either pancreatic membranes or brain membranes. The results indicate, therefore, that on gastric chief cell membranes there exist specific CCK receptors, which are coupled to G protein. Furthermore, chief cell CCK receptors may be distinct from pancreatic or brain type CCK receptors

  6. Use of a specific cholecystokinin receptor antagonist (L-364,718) to determine the role of cholecystokinin on feeding and body weight in rats with obstructive jaundice.

    Science.gov (United States)

    Tangoku, A; Doi, R; Chowdhury, P; Pasley, J N; McKay, D W; Rayford, P L

    1992-01-01

    We conducted a study to examine the role of cholecystokinin in feeding behavior and weight change in rats with obstructive jaundice. Daily food and water intake, body weight, and short-term food intake were determined in two groups of rats with surgically induced obstructive jaundice and in control rats. One group of rats with obstructive jaundice was given L-364,718, a selective cholecystokinin receptor antagonist. Plasma bilirubin and cholecystokinin levels were measured in each rat before and 7 days after surgery. Daily food intake and body weight were decreased in obstructive jaundice rats compared with control rats during the first week after surgery (P less than .05); however, obstructive jaundice rats treated with L-364,718 had increased food intake and body weight (P less than .05). Short-term food intake measured for 30 minutes and 120 minutes in food-deprived obstructive jaundice rats was decreased when compared with control rats (P less than .05), but the obstructive jaundice rats given L-364,718 had increased short-term food intake (P less than .05). Water intake was similar between the two groups of rats. Plasma levels of cholecystokinin and bilirubin were increased in obstructive jaundice rats with and without L-364,718 treatment (P less than .05). The results support the concept that endogenously elevated levels of plasma cholecystokinin play an important role in decreased food intake and subsequent loss of body weight in rats with obstructive jaundice.

  7. Cholecystokinin receptors: Biochemical demonstration and autoradiographical localization in rat brain and pancreas using [3H] cholecystokinin8 as radioligand

    International Nuclear Information System (INIS)

    Van Dijk, A.; Richards, J.G.; Trzeciak, A.; Gillessen, D.; Moehler, H.

    1984-01-01

    Since cholecystokinin8 (CCK8) seems to be the physiological ligand of CCK receptors in the brain, it would be the most suitable probe for the characterization of CCK receptors in radioligand binding studies. [ 3 H]CCK8 was synthetized with a specific radioactivity sufficient for the detection of high affinity binding sites. [ 3 H]CCK8 binds saturably and reversibly to distinct sites in rat brain and pancreas with nanomolar affinity. While the C-terminal tetrapeptide of CCK is the minimal structure required for nanomolar affinity in the brain, the entire octapeptide sequence is required for binding affinity in pancreas. Desulfated CCK8 and several gastrin-I peptides, which are likewise unsulfated, show virtually no affinity to the binding sites in pancreas but high affinity in cerebral cortex. The ligand specificity of the CCK peptides corresponds to their electrophysiological potency in the brain and their stimulation of secretion in pancreas, respectively. Autoradiographically, high densities of [ 3 H]CCK8 binding sites were found in cerebral cortex and olfactory bulb, medium levels in nucleus accumbens, hippocampus, dentate gyrus, and striatum with virtually no labeling in cerebellum. This pattern is similar to the distribution of CCK-like immunoreactivity in the brain. In pancreas, equally high levels of [ 3 H]CCK8 labeling were found in the exocrine and endocrine region. [ 3 H]CCK8 binding sites differ from those identified previously with [ 125 I]Bolton-Hunter-CCK33 by their sensitivity to guanyl nucleotides in the brain, their ion dependency in the brain, and pancreas, and their different autoradiographical localization in some parts of the brain. The distribution of CCK binding sites labeled with [ 3 H]CCK8 appears to correlate better with the CCK immunoreactivity than those labeled with [ 125 I]Bolton-Hunter-CCK33. Thus, [ 3 H]CCK8 appears to be the radioligand of choice for the investigation of CCK receptors

  8. Expression of cholecystokinin receptors in colon cancer and the clinical correlation in Taiwan.

    Science.gov (United States)

    Huang, Bee-Piao; Lin, Chun-Hsiang; Chen, Yi-Ching; Kao, Shao-Hsuan

    2016-04-01

    Cholecystokinin and gastrin receptors are upregulated in many human digestive malignancies; however, the correlation of their expressions with severity of colon carcinoma remains sketchy. Here, we determined the expression of cholecystokinin-1 and cholecystokinin-2 receptor, CCK1R and CCK2R, in colon carcinomas and investigated their correlations with clinicopathological characteristics and 1-year survival rate. Expression of CCK1R and CCK2R was determined by immunohistochemical assay in tissue samples obtained from 97 surgical specimens. Clinicopathological character analysis revealed that higher expression of cytoplasmic CCK1R and CCK2R was significantly associated with several variables including the depth of tumor invasion (P = 0.001), venous invasion (P = 0.023), and progression stage (P = 0.013). In addition, immunohistochemical staining revealed statistically significant associations of nuclear CCK1R expression with higher lymphatic invasion (P = 0.042), progression stage (P = 0.025), and unfavorable survival (P = 0.025). Interestingly, we found no link between nuclear CCK2R expression and all the clinicopathological characteristics examined. Taken these, our findings indicate that nuclear CCK1R represents a potential biomarker for poor prognosis, and CCK1R may play a role differing from CCK2R in colon carcinogenesis.

  9. Cholecystokinin A receptor (CCKAR gene variation is associated with language lateralization.

    Directory of Open Access Journals (Sweden)

    Sebastian Ocklenburg

    Full Text Available Schizophrenia is a psychiatric disorder associated with atypical handedness and language lateralization. However, the molecular mechanisms underlying these functional changes are still poorly understood. Therefore, the present study was aimed at investigating whether variation in schizophrenia-related genes modulates individual lateralization patterns. To this end, we genotyped 16 single nucleotide polymorphisms that have previously been linked to schizophrenia on a meta-analysis level in a sample of 444 genetically unrelated healthy participants and examined the association of these polymorphisms with handedness, footedness and language lateralization. We found a significant association of the cholecystokinin-A receptor (CCKAR gene variation rs1800857 and language lateralization assessed using the dichotic listening task. Individuals carrying the schizophrenia risk allele C of this polymorphism showed a marked reduction of the typical left-hemispheric dominance for language processing. Since the cholecystokinin A receptor is involved in dopamine release in the central nervous system, these findings suggest that genetic variation in this receptor may modulate language lateralization due to its impact on dopaminergic pathways.

  10. An intron 1 polymorphism in the cholecystokinin-A receptor gene associated with schizophrenia in males

    DEFF Research Database (Denmark)

    Koefoed, P; Hansen, T V O; Woldbye, D P D

    2009-01-01

    OBJECTIVE: To identify whether a genetic variation (rs1800857; IVS1-5T>C) in the neuropeptide cholecystokinin-A receptor (CCKAR) gene is a risk factor in the pathogenesis of schizophrenia. METhod: The variation was analysed in a case-control design comprising 508 patients with schizophrenia...... and 1619 control subjects. A possible functional impact of this variant on CCKAR protein synthesis through alterations in splicing was analysed in an exon-trapping assay. RESULTS: In males only, the risk variant, IVS1-5C, was associated with a significantly increased risk of schizophrenia. Carrying one...... risk allele was associated with an increased risk of 1.74 (Odds Ratio, OR) and homozygosity (CC) was associated with an OR of 3.19. The variation had no impact on protein synthesis of CCKAR. CONCLUSION: This is the first report associating the CCKAR gene variant with schizophrenia specifically in men...

  11. CHOLECYSTOKININ RECEPTOR ANTAGONIST HALTS PROGRESSION OF PANCREATIC CANCER PRECURSOR LESIONS AND FIBROSIS IN MICE

    Science.gov (United States)

    Smith, Jill P.; Cooper, Timothy K.; McGovern, Christopher O.; Gilius, Evan L.; Zhong, Qing; Liao, Jiangang; Molinolo, Alfredo A.; Gutkind, J. Silvio; Matters, Gail L.

    2014-01-01

    Objectives Exogenous administration of cholecystokinin (CCK) induces hypertrophy and hyperplasia of the pancreas with an increase in DNA content. We hypothesized that endogenous CCK is involved with the malignant progression of pancreatic intraepithelial neoplasia (PanIN) lesions and the fibrosis associated with pancreatic cancer. Methods The presence of CCK receptors in early PanIN lesions was examined by immunohistochemistry in mouse and human pancreas. Pdx1-Cre/LSL-KrasG12D transgenic mice were randomized to receive either untreated drinking water or water supplemented with a CCK-receptor antagonist (proglumide, 0.1mg/ml). Pancreas from mice were removed and examined histologically for number and grade of PanINs after 1, 2 or 4 months of antagonist therapy. Results Both CCK-A and CCK-B receptors were identified in early stage PanINs from mouse and human pancreas. The grade of PanIN lesions was reversed and progression to advanced lesions arrested in mice treated with proglumide compared to controls (p=0.004). Furthermore, pancreatic fibrosis was significantly reduced in antagonist-treated animals compared to vehicle (pitalic>0.001). Conclusions These findings demonstrate that endogenous CCK is in part responsible for the development and progression of pancreatic cancer. Use of CCK-receptor antagonists may have a role in cancer prophylaxis in high risk subjects, and may reduce fibrosis in the microenvironment. PMID:25058882

  12. Use of a nitrotryptophan-containing peptide for photoaffinity labeling the pancreatic cholecystokinin receptor

    International Nuclear Information System (INIS)

    Klueppelberg, U.G.; Gaisano, H.Y.; Powers, S.P.; Miller, L.J.

    1989-01-01

    The authors report the preparation and characterization of a new type of intrinsic photoaffinity labeling probe, on the basis of the incorporation of a photolabile nitrotryptophan into a biologically relevant domain of a peptide. The model system used was the pancreatic cholecystokinin (CCK) receptor, previously affinity labeled with a variety of probes. Those studies have suggested that an M r = 85,000-95,000 protein is more likely to be labeled as the site of covalent attachment approaches the receptor-binding domain of this hormone. Indeed, CCK has a Trp in the center of its receptor-binding region, and replacement of that residue with 6-nitrotryptophan resulted in a photolabile probe which affinity labeled the same M r = 85,000-95,000 pancreatic membrane protein. This probe, 125 I-D-Tyr-Gly-[(Nle 28,31 ,6-NO 2 -Trp 30 )CCK-26-33], was synthesized by solid-phase and solution techniques and characterized by mass spectrometry. Following oxidative iodination, it was purified on HPLC to 2000 Ci/mmol. Binding to pancreatic membranes was rapid, temperature dependent, reversible, saturable, and specific and was with high affinity. While its binding affinity was only 3-fold lower than that of native CCK-8, this probe was 70-fold less potent than native hormone in stimulating amylase secretion and equally efficacious to native hormone

  13. Biochemical characterization of the pancreatic cholecystokinin receptor using monofunctional photoactivatable probes

    International Nuclear Information System (INIS)

    Pearson, R.K.; Miller, L.J.; Powers, S.P.; Hadac, E.M.

    1987-01-01

    Receptor characterization by affinity labeling can be enhanced by taking multiple complementary approaches. To extend our observations on the subunit structure of the rat pancreatic cholecystokinin (CCK) receptor (made using bifunctional cross-linking reagents), we synthesized two monofunctional photoactivatable receptor probes. CCK-8 was acylated with the iodinated aryl azide derivatives, methyl-3-azido-4-hydroxy-5-[ 125 I]iodobenzimidate and N-[4-(4'-azido-3'-[ 125 I]iodophenylazo)benzoyl]-3-aminopropionyl-N- oxy- succinimide. The products were purified by reverse-phase HPLC to a specific radioactivity of 2000 Ci/mmol. Both analogs demonstrated saturable and specific binding to rat pancreatic plasma membranes. Photoaffinity labeling of pancreatic membranes with these monofunctional probes identified an Mr 85,000-95,000 protein that was not part of a larger disulfide-linked complex. High affinity for CCK was demonstrated by the concentration-dependent inhibition of labeling observed with competing CCK-8 (IC50 = 1 nM). On sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) this protein co-migrates with the major component we identified using a series of cross-linkable, iodinated decapeptide analogs of CCK, and is different from the major protein labeled using 125 I-Bolton Hunter-CCK-33. Thus, these results support the presence of an Mr 85,000-95,000 subunit in the pancreatic CCK receptor, while the small size of these photoaffinity probes and their monovalency suggest that this subunit may contain or be spatially apposed to the active binding site. These probes should be very useful in the further characterization of this and other receptors for this hormone

  14. Cholecystokinin receptors: disparity between phosphoinositide breakdown and amylase releasing activity of CCK analogues in pancreas

    International Nuclear Information System (INIS)

    Lin, C.W.; Grant, D.; Bianchi, B.; Miller, T.; Witte, D.; Shue, Y.K.; Nadzan, A.

    1986-01-01

    Cholecystokinin (CCK) peptides are a family of hormones which also occur in brain. In pancreas CCK stimulates the release of amylase, a process that is dependent on the mobilization of intracellular Ca 2+ . Recent evidence suggests that inositol 1,4,5-trisphosphate, the breakdown product of phosphatidylinositol 4,5-bisphosphate, is responsible for the rise in intracellular Ca 2+ . Their laboratory has developed assays to study synthetic CCK analogues using radioligand binding, PI breakdown and amylase release. They have shown that there are good correlations among these three assay systems for the carboxy terminal fragments of CCK 8 . Recently, they have discovered synthetic analogues of CCK 4 that are full agonists in amylase release but are ineffective in causing PI breakdown. In particular, A-61576, Boc-5-amino-2-indolemethylene-pent-2-ene-1-oyl-Leu-Asp-Phe-NH 2 , is a full agonist in the amylase releasing assay, but is devoid of PI stimulating activity. A-61576 completely reverses the stimulation of PI response induced by CCK 8 , indicative of an antagonist. Since a mechanism other than the PI breakdown is responsible for amylase release by A-61576, they suggest that separate receptors are responsible for PI breakdown and amylase release

  15. Cholecystokinin receptors on gallbladder muscle and pancreatic acinar cells: a comparative study

    International Nuclear Information System (INIS)

    von Schrenck, T.; Moran, T.H.; Heinz-Erian, P.; Gardner, J.D.; Jensen, R.T.

    1988-01-01

    To compare receptors for cholecystokinin (CCK) in pancreas and gallbladder, we measured binding of 125I-Bolton-Hunter-labeled CCK-8 (125I-BH-CCK-8) to tissue sections from guinea pig gallbladder and pancreas under identical conditions. In both tissues, binding had similar time-, temperature-, and pH dependence, was reversible, saturable and inhibited only by CCK related peptides or CCK receptor antagonists. Autoradiography localized 125I-BH-CCK-8 binding to the smooth muscle layer in the gallbladder. Binding of 125I-BH-CCK-8 to gallbladder sections was inhibited by various agonists with the following potencies (IC50):CCK-8 (0.4 nM) greater than des(SO3)CCK-8 (0.07 microM) greater than gastrin-17-I (1.7 +/- 0.3 microM) and by various receptor antagonists with the following potencies: L364,718 (1.5 nM) greater than CR 1409 (0.19 microM) greater than asperlicin = CBZ-CCK-(27-32)-NH2 (1 microM) greater than Bt2cGMP (120 microM). Similar potencies were found for the agonists and antagonists for pancreas sections. Inhibition of binding of 125I-BH-CCK-8 by 11 different analogues of proglumide gave similar potencies for both pancreas and gallbladder. The potencies of agonists in stimulating and antagonists in inhibiting CCK-stimulated contraction or amylase release correlated closely with their abilities to inhibit 125I-BH-CCK-8 binding to gallbladder or pancreas sections or acini, respectively. The present results demonstrate and characterize a method that can be used to compare the CCK receptors in guinea pig gallbladder and pancreas under identical conditions. Moreover, this study demonstrates that gallbladder and pancreatic CCK receptors have similar affinities for the various agonists and antagonists tested and, therefore, provides no evidence that they represent different subtypes of CCK receptors that can be distinguished pharmacologically

  16. Quantitative autoradiographic localization of cholecystokinin receptors in rat and guinea pig brain using 125I-Bolton-Hunter-CCK8

    International Nuclear Information System (INIS)

    Niehoff, D.L.

    1989-01-01

    The autoradiographic localization of receptors for the brain-gut peptide cholecystokinin (CCK) has shown differences in receptor distribution between rat and guinea pig brain. However the full anatomical extent of the differences has not been determined quantitatively. In the present study, 125 I-Bolton-Hunter-CCK8 ( 125 I-BH-CCK8) was employed in a comparative quantitative autoradiographic analysis of the distribution of CCK receptors in these two species. The pharmacological profile of 125 I-BH-CCK8 binding in guinea pig forebrain sections was comparable to those previously reported for rat and human. Statistically significant differences in receptor binding between rat and guinea pig occurred in olfactory bulb, caudate-putamen, amygdala, several cortical areas, ventromedial hypothalamus, cerebellum, and a number of midbrain and brainstem nuclei. The results of this study confirm the presence of extensive species-specific variation in the distribution of CCK receptors, suggesting possible differences in the physiological roles of this peptide in different mammalian species

  17. Characterization of the three different states of the cholecystokinin (CCK) receptor in pancreatic acini.

    Science.gov (United States)

    Talkad, V D; Patto, R J; Metz, D C; Turner, R J; Fortune, K P; Bhat, S T; Gardner, J D

    1994-10-20

    By measuring binding of [125I]CCK-8 and [3H]L-364,718 to rat pancreatic acini we demonstrated directly that the pancreatic CCK receptor can exist in three different affinity states with respect to CCK--high affinity, low affinity and very low affinity. Binding of [125I]CCK-8 reflects interaction of the tracer with the high and low affinity states, whereas binding of [3H]L-364,718 reflects interaction of the tracer with the low and very low affinity states. Treating acini with carbachol abolished the high affinity state of the CCK receptor and converted approximately 25% of the low affinity receptors to the very low affinity state. Carbachol treatment was particularly useful in establishing the values of Kd for the high and low affinity states for different CCK receptor agonists and antagonists. Of the various CCK receptor agonists tested, CCK-8 had the highest affinity for the high affinity state (Kd approximately 1 nM), whereas CCK-JMV-180 had the highest affinity for the low (Kd 7 nM) and very low affinity (Kd 200 nM) states. Gastrin and de(SO4)CCK-8 had affinities for the high and low affinity states of the receptor that were 100- to 400-fold less than those of CCK-8 but had affinities for the very low affinity state that were only 3- to 10-fold less than that of CCK-8. CCK receptor antagonists showed several patterns in interacting with the different states of the CCK receptor. L-364,718 had the same affinity for each state of the CCK receptor. CR1409 and Bt2cGMP each had similar affinities for the high and low affinity states and lower affinity for the very low affinity state. L-365,260 and CCK-JMV-179 had the highest affinity for the low affinity state and lower affinities for the high and very low affinity states. Different CCK receptor agonists caused the same maximal stimulation of amylase secretion but showed different degrees of amplification in terms of the relationship between their abilities to stimulate amylase secretion and their abilities to occupy

  18. Preclinical Evaluation of 68Ga-DOTA-Minigastrin for the Detection of Cholecystokinin-2/Gastrin Receptor-Positive Tumors

    Directory of Open Access Journals (Sweden)

    Maarten Brom

    2011-03-01

    Full Text Available In comparison to somatostatin receptor scintigraphy, gastrin receptor scintigraphy using 111In-DTPA-minigastrin (MG0 showed added value in diagnosing neuroendocrine tumors. We investigated whether the 68Ga-labeled gastrin analogue DOTA-MG0 is suited for positron emission tomography (PET, which could improve image quality. Targeting of cholecystokinin-2 (CCK2/gastrin receptor-positive tumor cells with DOTA-MG0 labeled with either 111In or 68Ga in vitro was investigated using the AR42J rat tumor cell line. Biodistribution was examined in BALB/c nude mice with a subcutaneous AR42J tumor. In vivo PET imaging was performed using a preclinical PET-computed tomographic scanner. DOTA-MG0 showed high receptor affinity in vitro. Biodistribution studies revealed high tumor uptake of 68Ga-DOTA-MG0: 4.4 ± 1.3 %ID/g at 1 hour postinjection. Coadministration of an excess unlabeled peptide blocked the tumor uptake (0.7 ± 0.1 %ID/g, indicating CCK2/gastrin receptor-mediated uptake (p = .0005. The biodistribution of 68Ga-DOTA-MG0 was similar to that of 111In-DOTA-MG0. Subcutaneous and intraperitoneal tumors were clearly visualized by small-animal PET imaging with 5 MBq 68Ga-DOTA-MG0. 111In- and 68Ga-labeled DOTA-MG0 specifically accumulate in CCK2/gastrin receptor-positive AR42J tumors with similar biodistribution apart from the kidneys. AR42J tumors were clearly visualized by microPET. Therefore, 68Ga-DOTA-MG0 is a promising tracer for PET imaging of CCK2/gastrin receptor-positive tumors in humans.

  19. The gastrin/cholecystokinin-B receptor on prostate cells--a novel target for bifunctional prostate cancer imaging.

    Science.gov (United States)

    Sturzu, Alexander; Klose, Uwe; Sheikh, Sumbla; Echner, Hartmut; Kalbacher, Hubert; Deeg, Martin; Nägele, Thomas; Schwentner, Christian; Ernemann, Ulrike; Heckl, Stefan

    2014-02-14

    The means of identifying prostate carcinoma and its metastases are limited. The contrast agents used in magnetic resonance imaging clinical diagnostics are not taken up into the tumor cells, but only accumulate in the interstitial space of the highly vasculated tumor. We examined the gastrin/cholecystokinin-B receptor as a possible target for prostate-specific detection using the C-terminal seven amino acid sequence of the gastrin peptide hormone. The correct sequence and a scrambled control sequence were coupled to the fluorescent dye rhodamine and the magnetic resonance imaging contrast agent gadolinium (Gd)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Expression analysis of the gastrin receptor mRNA was performed by reverse transcriptase polymerase chain reaction on PC3 prostate carcinoma cells, U373 glioma, U2OS osteosarcoma and Colo205 colon carcinoma cells. After having confirmed elevated expression of gastrin receptor in PC3 cells and very low expression of the receptor in Colo205 cells, these two cell lines were used to create tumor xenografts on nude mice for in vivo experiments. Confocal lasers scanning microscopy and magnetic resonance imaging showed a high specificity of the correct conjugate for the PC3 xenografts. Staining of the PC3 xenografts was much weaker with the scrambled conjugate while the Colo205 xenografts showed no marked staining with any of the conjugates. In vitro experiments comparing the correct and scrambled conjugates on PC3 cells by magnetic resonance relaxometry and fluorescence-activated cell sorting confirmed markedly higher specificity of the correct conjugate. The investigations show that the gastrin receptor is a promising tumor cell surface target for future prostate-cancer-specific imaging applications. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. An assessment tumor targeting ability of 177Lu labeled cyclic CCK analogue peptide by binding with cholecystokinin receptor

    Directory of Open Access Journals (Sweden)

    Eun-Ha Cho

    2016-07-01

    Full Text Available The cholecystokinin (CCK receptor is known as a receptor that is overexpressed in many human tumors. The present study was designed to investigate the targeting ability of cyclic CCK analogue in AR42J pancreatic cells. The CCK analogues, DOTA-K(glucose-Gly-Trp-Nle-Asp-Phe (DOTA-glucose-CCK and DOTA-Nle-cyclo(Glu-Trp-Nle-Asp-Phe-Lys-NH2 (DOTA-[Nle]-cCCK, were synthesized and radiolabeled with 177Lu, and competitive binding was evaluated. The binding appearance of synthesized peptide with AR42J cells was evaluated by confocal microscopy. And bio-distribution was performed in AR42J xenografted mice. Synthesized peptides were prepared by a solid phase synthesis method, and their purity was over 98%. DOTA is the chelating agent for 177Lu-labeling, in which the peptides were radiolabeled with 177Lu by a high radiolabeling yield. A competitive displacement of 125I-CCK8 on the AR42J cells revealed that the 50% inhibitory concentration value (IC50 was 12.3 nM of DOTA-glucose-CCK and 1.7 nM of DOTA-[Nle]-cCCK. Radio-labeled peptides were accumulated in AR42J tumor in vivo, and %ID/g of the tumor was 0.4 and 0.9 at 2 h p.i. It was concluded that 177Lu-DOTA-[Nle]-cCCK has higher binding affinity than 177Lu-DOTA-glucose-CCK and can be a potential candidate as a targeting modality for a CCK receptor over-expressing tumors.

  1. Characterization and visualization of cholecystokinin receptors in rat brain using [3H]pentagastrin

    International Nuclear Information System (INIS)

    Gaudreau, P.; Quirion, R.; St Pierre, S.; Pert, C.B.

    1983-01-01

    [ 3 H]Pentagastrin binds specifically to an apparent single class of CCK receptors on slide-mounted sections of rat brain (KD . 5.6 nM; Bmax . 36.6 fmol/mg protein). This specific binding is temperature-dependent and regulated by ions and nucleotides. The relative potencies of C-terminal fragments of CCK-8(SO 3 H), benzotript and proglumide in inhibiting specific [ 3 H]pentagastrin binding to CCK brain receptors reinforce the concept of different brain and pancreas CCK receptors. CCK receptors were visualized by using tritium-sensitive LKB film analyzed by computerized densitometry. CCK receptors are highly concentrated in the cortex, dentate gyrus, granular and external plexiform layers of the olfactory bulb, anterior olfactory nuclei, olfactory tubercle, claustrum, accumbens nucleus, some nuclei of the amygdala, thalamus and hypothalamus

  2. Cholecystokinin Receptor-Targeted Polyplex Nanoparticle Inhibits Growth and Metastasis of Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Julian Burks

    2018-01-01

    Conclusions: Our polyplex nanoparticle platform establishes both a strong foundation for the development of receptor-targeted therapeutics and a unique approach for the delivery of siRNA in vivo, thus warranting further exploration of this approach in other types of cancers.

  3. Pituitary tumors containing cholecystokinin

    DEFF Research Database (Denmark)

    Rehfeld, J F; Lindholm, J; Andersen, B N

    1987-01-01

    We found small amounts of cholecystokinin in the normal human adenohypophysis and therefore examined pituitary tumors from 87 patients with acromegaly, Cushing's disease, Nelson's syndrome, prolactinoma, or inactive pituitary adenomas. Five adenomas associated with Nelson's syndrome contained......'s disease and 7 acromegaly with adenomas containing ACTH. The cholecystokinin peptides from the tumors were smaller and less sulfated than cholecystokinin from normal pituitary glands. We conclude that ACTH-producing pituitary cells may also produce an altered form of cholecystokinin....

  4. Cholecystokinin-8 suppressed /sup 3/H-etorphine binding to rat brain opiate receptors

    Energy Technology Data Exchange (ETDEWEB)

    Wang, X.J.; Fan, S.G.; Ren, M.F.; Han, J.S.

    1989-01-01

    Radioreceptor assay (RRA) was adopted to analyze the influence of CCK-8 on /sup 3/H-etorphine binding to opiate receptors in rat brain synaptosomal membranes (P2). In the competition experiment CCK-8 suppressed the binding of /sup 3/H-etorphine. This effect was completely reversed by proglumide at 1/mu/M. Rosenthal analysis for saturation revealed two populations of /sup 3/H-etorphine binding sites. CCK-8 inhibited /sup 3/H-etorphine binding to the high affinity sites by an increase in Kd and decrease in Bmax without significant changes in the Kd and Bmax of the low affinity sites. This effect of CCK-8 was also completely reversed by proglumide at 1/mu/M. Unsulfated CCK-8 produced only a slight increase in Kd of the high affinity sites without affecting Bmax. The results suggest that CCK-8 might be capable of suppressing the high affinity opioid binding sites via the activation of CCK receptor.

  5. Cholecystokinin-2 receptor mediated gene expression in neuronal PC12 cells

    DEFF Research Database (Denmark)

    Hansen, Thomas v O; Borup, Rehannah; Marstrand, Troels

    2007-01-01

    could be identified. Comparison with forskolin- and nerve growth factor (NGF)-treated PC12 cells showed that CCK induced a separate set of target genes. Taken together, we propose that neuronal CCK may have a role in the regulation of the circadian rhythm, the metabolism of cerebral cholesterol...... of neuronal CCK are incompletely understood. To identify genes regulated by neuronal CCK, we generated neuronal PC12 cells stably expressing the CCK-2 receptor (CCK-2R) and treated the cells with sulphated CCK-8 for 2-16 h, before the global expression profile was examined. The changes in gene expression...... peaked after 2 h, with 67 differentially expressed transcripts identified. A pathway analysis indicated that CCK was implicated in the regulation of the circadian clock system, the plasminogen system and cholesterol metabolism. But transcripts encoding proteins involved in dopamine signaling, ornithine...

  6. Female mice lacking cholecystokinin 1 receptors have compromised neurogenesis, and fewer dopaminergic cells in the olfactory bulb

    Directory of Open Access Journals (Sweden)

    Yi eSui

    2013-03-01

    Full Text Available Neurogenesis in the adult rodent brain is largely restricted to the subependymal zone (SVZ of the lateral ventricle and subgranular zone (SGZ of the dentate gyrus (DG. We examined whether cholecystokinin (CCK through actions mediated by CCK1 receptors (CCK1R is involved in regulating neurogenesis. Proliferating cells in the SVZ, measured by 5-bromo-2-deoxyuridine (BrdU injected 2 hours prior to death or by immunoreactivity against Ki67, were reduced by 37% and 42%, respectively, in female (but not male mice lacking CCK1Rs (CCK1R-/- compared to wild-type (WT. Generation of neuroblasts in the SVZ and rostral migratory stream was also affected, since the number of doublecortin (DCX-immunoreactive (ir neuroblasts in these regions decreased by 29%. In the SGZ of female CCK1R-/- mice, BrdU-positive (+ and Ki67-ir cells were reduced by 38% and 56%, respectively, while DCX-ir neuroblasts were down 80%. Subsequently, the effect of reduced SVZ/SGZ proliferation on the generation and survival of mature adult-born cells in female CCK1R-/- mice was examined. In the OB granule cell layer (GCL, the number of neuronal nuclei (NeuN-ir and calretinin-ir cells was stable compared to WT, and 42 days after BrdU injections, the number of BrdU+ cells co-expressing GABA- or NeuN-like immunoreactivity (LI was similar. Compared to WT, the granule cell layer of the DG in female CCK1R-/- mice had a similar number of calbindin-ir cells and BrdU+ cells co-expressing calbindin-LI 42 days after BrdU injections. However, the OB glomerular layer (GL of CCK1R-/- female mice had 11% fewer NeuN-ir cells, 23% less TH-ir cells, and a 38% and 29% reduction in BrdU+ cells that co-expressed TH-LI or GABA-LI, respectively. We conclude that CCK, via CCK1Rs, is involved in regulating the generation of proliferating cells and neuroblasts in the adult female mouse brain, and mechanisms are in place to maintain steady neuronal populations in the OB and DG when the rate of proliferation is

  7. Quantitative autoradiographic localization of cholecystokinin receptors in rat and guinea pig brain using sup 125 I-Bolton-Hunter-CCK8

    Energy Technology Data Exchange (ETDEWEB)

    Niehoff, D.L. (Abbott Laboratories, Abbott Park, IL (USA))

    1989-03-01

    The autoradiographic localization of receptors for the brain-gut peptide cholecystokinin (CCK) has shown differences in receptor distribution between rat and guinea pig brain. However the full anatomical extent of the differences has not been determined quantitatively. In the present study, {sup 125}I-Bolton-Hunter-CCK8 ({sup 125}I-BH-CCK8) was employed in a comparative quantitative autoradiographic analysis of the distribution of CCK receptors in these two species. The pharmacological profile of {sup 125}I-BH-CCK8 binding in guinea pig forebrain sections was comparable to those previously reported for rat and human. Statistically significant differences in receptor binding between rat and guinea pig occurred in olfactory bulb, caudate-putamen, amygdala, several cortical areas, ventromedial hypothalamus, cerebellum, and a number of midbrain and brainstem nuclei. The results of this study confirm the presence of extensive species-specific variation in the distribution of CCK receptors, suggesting possible differences in the physiological roles of this peptide in different mammalian species.

  8. Activation of neural cholecystokinin-1 receptors induces relaxation of the isolated rat duodenum which is reduced by nitric oxide synthase inhibitors

    Directory of Open Access Journals (Sweden)

    S.R. Martins

    2006-02-01

    Full Text Available Cholecystokinin (CCK influences gastrointestinal motility, by acting on central and peripheral receptors. The aim of the present study was to determine whether CCK has any effect on isolated duodenum longitudinal muscle activity and to characterize the mechanisms involved. Isolated segments of the rat proximal duodenum were mounted for the recording of isometric contractions of longitudinal muscle in the presence of atropine and guanethidine. CCK-8S (EC50: 39; 95% CI: 4.1-152 nM and cerulein (EC50: 58; 95% CI: 18-281 nM induced a concentration-dependent and tetrodotoxin-sensitive relaxation. Nomeganitro-L-arginine (L-NOARG reduced CCK-8S- and cerulein-induced relaxation (IC50: 5.2; 95% CI: 2.5-18 µM in a concentration-dependent manner. The magnitude of 300 nM CCK-8S-induced relaxation was reduced by 100 µM L-NOARG from 73 ± 5.1 to 19 ± 3.5% in an L-arginine but not D-arginine preventable manner. The CCK-1 receptor antagonists proglumide, lorglumide and devazepide, but not the CCK-2 receptor antagonist L-365,260, antagonized CCK-8S-induced relaxation in a concentration-dependent manner. These findings suggest that CCK-8S and cerulein activate intrinsic nitrergic nerves acting on CCK-1 receptors in order to cause relaxation of the rat duodenum longitudinal muscle.

  9. Autoradiographical detection of cholecystokinin-A receptors in primate brain using 125I-Bolton Hunter CCK-8 and 3H-MK-329

    International Nuclear Information System (INIS)

    Hill, D.R.; Shaw, T.M.; Graham, W.; Woodruff, G.N.

    1990-01-01

    In vitro autoradiography was performed in order to visualize cholecystokinin-A (CCK-A) receptors in sections of Cynomolgus monkey brain. CCK-A receptors were defined as those which displayed high affinity for the selective non-peptide antagonist MK-329 (L-364,718) and were detected in several regions by selective inhibition of 125I-Bolton Hunter CCK using MK-329 or direct labeling with 3H-MK-329. In the caudal medulla, high densities of CCK-A sites were present in the nucleus tractus solitarius, especially the caudal and medial aspects, and also the dorsal motor nucleus of the vagus. CCK-A sites were localized to a number of hypothalamic nuclei such as the supraoptic and paraventricular nuclei, the dorsomedial and infundibular nuclei as well as the neurohypophysis. The mammillary bodies and supramammillary nuclei also contained CCK-A receptor sites. High concentrations of CCK-A receptors were present in the substantia nigra zona compacta and also the ventral tegmental area and may be associated with dopamine cell bodies. Binding of 3H-MK-329 was also detected in parts of the caudate nucleus and ventral putamen. The detection, by autoradiographical means, of CCK-A receptors throughout the Cynomolgus monkey brain contrasts with similar studies performed using rodents and suggests differences in the density and, perhaps, the importance of CCK-A receptors in the primate as opposed to the rodent. The data suggest the possibility that CCK-A receptors may be involved in a number of important brain functions as diverse as the processing of sensory information from the gut, the regulation of hormone secretion, and the activity of dopamine cell activity

  10. Role of sulfate ester in influencing biological activity of cholecystokinin-related peptides

    International Nuclear Information System (INIS)

    Vinayek, R.; Jensen, R.T.; Gardner, J.D.

    1987-01-01

    In dispersed acini from guinea pig, mouse, or rat pancreas cholecystokinin-(27-33) is a full agonist, and removing the sulfate ester from the tyrosine residue in position 27 caused a 100- to 300-fold decrease in potency with no change in efficacy. In dispersed acini from mouse or rat pancreas, cholecystokinin-(27-32)-NH 2 is a partial agonist, and removing the sulfate ester from the tyrosine in position 27 abolished the efficacy. The desulfated peptide was able, however, to interact with [ 125 I] CCK receptors with a potency that was threefold less than that of cholecystokinin-(27-32)-NH 2 and therefore functioned as a cholecystokinin receptor antagonist. In dispersed acini from guinea pig pancreas cholecystokinin-(27-32)-NH 2 is a cholecystokinin receptor antagonist. Removing the sulfate ester from the tyrosine residue in position 27 of cholecystokinin-(27-32)-NH 2 caused a fourfold decrease in potency but did not abolish the ability of the peptide to interact with cholecystokinin receptors; therefore, desulfated cholecystokinin-(27-32)-NH 2 functioned as a cholecystokinin receptor antagonist

  11. Characterization of the binding of [3H]-(+/-)-L-364,718: a new potent, nonpeptide cholecystokinin antagonist radioligand selective for peripheral receptors

    International Nuclear Information System (INIS)

    Chang, R.S.; Lotti, V.J.; Chen, T.B.; Kunkel, K.A.

    1986-01-01

    [3H]-(+/-)-L-364,718 a new, potent and selective nonpeptide peripheral cholecystokinin (CCK) antagonist bound saturably and reversibly to rat pancreatic membranes. The radioligand recognized a single class of binding sites with a high affinity (Kd = 0.23 nM). The binding of [ 3 H]-(+/-)-L-364,718 was stereospecific in that the more biologically active (-)-enantiomer demonstrated greater potency than the (+)-enantiomer. The rank order of potency of various CCK agonists and antagonists in displacing [ 3 H]-(+/-)-L-364,718 correlated with their ability to displace [ 125 I]CCK-8 and their known pharmacological activities in peripheral tissues. However, the absolute potencies of agonists were greater in displacing [ 125 I]CCK-8 than [ 3 H]-(+/-)-L-364,718. As described for other physiologically relevant receptor systems, the potency for displacement of [ 3 H]-(+/-)-L-364,718 binding by CCK agonists, but not antagonists, was reduced by guanosine 5'-(beta, gamma-imido)triphosphate and NaCl and enhanced by MgCl 2 . [ 3 H]-(+/-)-L-364,718 also demonstrated specific binding to bovine gall bladder tissue but not guinea pig brain or gastric glands, consistent with its selectivity as a peripheral CCK antagonist. [ 3 H]-(+/-)-L-364,718 binding to pancreatic membranes was not affected by various pharmacological agents known to interact with other common peptide and nonpeptide receptor systems. These data indicate that [ 3 H]-(+/-)-L-364,718 represents a new potent nonpeptide antagonist radioligand for the study of peripheral CCK receptors which may allow differentiation of agonist and antagonist interactions

  12. The Synergistic Roles of Cholecystokinin B and Dopamine D5 Receptors on the Regulation of Renal Sodium Excretion.

    Directory of Open Access Journals (Sweden)

    Xiaoliang Jiang

    Full Text Available Renal dopamine D1-like receptors (D1R and D5R and the gastrin receptor (CCKBR are involved in the maintenance of sodium homeostasis. The D1R has been found to interact synergistically with CCKBR in renal proximal tubule (RPT cells to promote natriuresis and diuresis. D5R, which has a higher affinity for dopamine than D1R, has some constitutive activity. Hence, we sought to investigate the interaction between D5R and CCKBR in the regulation of renal sodium excretion. In present study, we found D5R and CCKBR increase each other's expression in a concentration- and time-dependent manner in the HK-2 cell, the specificity of which was verified in HEK293 cells heterologously expressing both human D5R and CCKBR and in RPT cells from a male normotensive human. The specificity of D5R in the D5R and CCKBR interaction was verified further using a selective D5R antagonist, LE-PM436. Also, D5R and CCKBR colocalize and co-immunoprecipitate in BALB/c mouse RPTs and human RPT cells. CCKBR protein expression in plasma membrane-enriched fractions of renal cortex (PMFs is greater in D5R-/- mice than D5R+/+ littermates and D5R protein expression in PMFs is also greater in CCKBR-/- mice than CCKBR+/+ littermates. High salt diet, relative to normal salt diet, increased the expression of CCKBR and D5R proteins in PMFs. Disruption of CCKBR in mice caused hypertension and decreased sodium excretion. The natriuresis in salt-loaded BALB/c mice was decreased by YF476, a CCKBR antagonist and Sch23390, a D1R/D5R antagonist. Furthermore, the natriuresis caused by gastrin was blocked by Sch23390 while the natriuresis caused by fenoldopam, a D1R/D5R agonist, was blocked by YF476. Taken together, our findings indicate that CCKBR and D5R synergistically interact in the kidney, which may contribute to the maintenance of normal sodium balance following an increase in sodium intake.

  13. The stomach, cholecystokinin, and satiety.

    Science.gov (United States)

    McHugh, P R; Moran, T H

    1986-04-01

    The stomach of the rhesus monkey empties liquids in a fashion that varies with the character of the solutions. Physiological saline empties exponentially. Glucose solutions empty biphasically--rapidly for the first minutes, then slowly and proportionately to glucose concentration to deliver glucose calories through the pylorus at a regulated rate (0.4 kcal/min). This prolonged and regulated second phase of gastric emptying depends on intestinal inhibition of the stomach. Cholecystokinin (CCK), a hormone released by food in the intestine, is an inhibitor of gastric emptying. In vitro receptor autoradiography demonstrates CCK receptors to be clustered on the circular muscle of the pylorus. Exogenous CCK, in doses that inhibit gastric emptying, will reduce food intake only if combined with an infusion of saline in the stomach. These observations indicate how gastric distension can be a means for provoking satiety. The variably sustained distension produced by the stomach's slow, calorically regulated emptying could prolong intermeal intervals and thus permit high-calorie meals to inhibit further caloric intake over time. CCK, by directly inhibiting gastric emptying during a meal, could promote gastric distension and so restrict the duration and size of individual meals.

  14. Cholecystokinin-From Local Gut Hormone to Ubiquitous Messenger

    DEFF Research Database (Denmark)

    Rehfeld, Jens F

    2017-01-01

    Cholecystokinin (CCK) was discovered in 1928 in jejunal extracts as a gallbladder contraction factor. It was later shown to be member of a peptide family, which are all ligands for the CCK1 and CCK2 receptors. CCK peptides are known to be synthetized in small intestinal endocrine I-cells and cere...

  15. Lack of Analgesic Synergy of the Cholecystokinin Receptor Antagonist Proglumide and Spinal Cord Stimulation for the Treatment of Neuropathic Pain in Rats.

    Science.gov (United States)

    Inoue, Shinsuke; Johanek, Lisa M; Sluka, Kathleen A

    2017-08-01

    Neuropathic pain is difficult to manage and treat. Spinal cord stimulation (SCS) has become an established procedure for treating chronic neuropathic pain that is refractory to pharmacological therapy. In order to achieve better analgesia, a number of studies have evaluated the effectiveness of combining drug therapy with SCS. Cholecystokinin antagonists, such as proglumide, enhance the analgesic efficacy of endogenous opioids in animal models of pain. We previously reported that both systemic and spinal administration of proglumide enhances analgesia produced by both low- and high-frequency transcutaneous electrical nerve stimulation (TENS). Since SCS produces analgesia through endogenous opioids, we hypothesized that the analgesic effect of SCS would be enhanced through co-administration with proglumide in animals with neuropathic pain. Male Sprague-Dawley rats (n = 40) with spared nerve injury were given proglumide (20 mg/kg, i.p.) or saline prior to treatment with SCS (sham, 4 Hz, and 60 Hz). Mechanical withdrawal thresholds of the paw were measured before and after induction of nerve injury, and after SCS. Physical activity levels were measured after SCS. Both proglumide and SCS when given independently significantly increased withdrawal thresholds two weeks after nerve injury. However, there was no additional effect of combining proglumide and SCS on mechanical withdrawal thresholds or activity levels in animals with nerve injury. Proglumide may be a candidate for achieving analgesia for patients with refractory neuropathic pain conditions, but does not enhance analgesia produced by SCS. © 2017 International Neuromodulation Society.

  16. Occupation of low-affinity cholecystokinin (CCK) receptors by CCK activates signal transduction and stimulates amylase secretion in pancreatic acinar cells.

    Science.gov (United States)

    Vinayek, R; Patto, R J; Menozzi, D; Gregory, J; Mrozinski, J E; Jensen, R T; Gardner, J D

    1993-03-10

    Based on the effects of monensin on binding of 125I-CCK-8 and its lack of effect on CCK-8-stimulated amylase secretion we previously proposed that pancreatic acinar cells possess three classes of CCK receptors: high-affinity receptors, low-affinity receptors and very low-affinity receptors [1]. In the present study we treated pancreatic acini with carbachol to induce a complete loss of high-affinity CCK receptors and then examined the action of CCK-8 on inositol trisphosphate IP3(1,4,5), cytosolic calcium and amylase secretion in an effort to confirm and extend our previous hypothesis. We found that first incubating pancreatic acini with 10 mM carbachol decreased binding of 125I-CCK-8 measured during a second incubation by causing a complete loss of high-affinity CCK receptors with no change in the low-affinity CCK receptors. Carbachol treatment of acini, however, did not alter the action of CCK-8 on IP3(1,4,5), cytosolic calcium or amylase secretion or the action of CCK-JMV-180 on amylase secretion or on the supramaximal inhibition of amylase secretion caused by CCK-8. The present findings support our previous hypothesis that pancreatic acinar cells possess three classes of CCK receptors and suggest that high-affinity CCK receptors do not mediate the action of CCK-8 on enzyme secretion, that low-affinity CCK receptors may mediate the action of CCK on cytosolic calcium that does not involve IP3(1,4,5) and produce the upstroke of the dose-response curve for CCK-8-stimulated amylase secretion and that very low-affinity CCK receptors mediate the actions of CCK on IP3(1,4,5) and cytosolic calcium and produce the downstroke of the dose-response curve for CCK-8-stimulated amylase secretion. Moreover, CCK-JMV-180 is a full agonist for stimulating amylase secretion by acting at low-affinity CCK receptors and is an antagonist at very low-affinity CCK receptors.

  17. Radioimmunoassay of cholecystokinin in tissue and plasma

    International Nuclear Information System (INIS)

    Jansen, J.B.M.J.

    1984-01-01

    The physiological and pathophysiological role of the pancreas hormone, the polypeptide 'cholecystokinin' (CCK) is not well-established yet. This is due to the lack of specific and reliable radioimmunoassays for CCK. The aim of this thesis is to develop such an assay meeting the requirements of high specificity and sensitivity. Several problems were faced, such as (1) the cross-reactivity of existing antibodies with the stomach hormone gastrin and (2) changes in immunoreactivity caused by the introduction of the labelling isotope 125 I and various labels (prepared according to the Bolton-Hunter method) into the polypeptide. The reliability of the assay for the measurement in human tissue and blood is extensively evaluated, inter alia, in patients with pancreas insufficiency (alcohol, cystic fibrosis) and with coeliac disease. (Auth.)

  18. Cysteamine induces cholecystokinin release from the duodenum. Evidence for somatostatin as an inhibitory paracrine regulator of cholecystokinin secretion in the rat

    International Nuclear Information System (INIS)

    Abucham, J.; Reichlin, S.

    1990-01-01

    To determine whether cholecystokinin secretion is regulated by endogenous somatostatin, somatostatin deficiency was induced in vivo with cysteamine (250 mg/kg body wt, IV) or anti-somatostatin antiserum in anaesthetized rats and in vitro with cysteamine (30 micrograms/mL) in a rat duodenum-incubation system. Cholecystokinin secretion was assessed in vivo by measuring amylase in duodenal perfusates collected at 10-minute intervals for 1 hour and in vitro by a carboxy-terminal radioimmunoassay. Cysteamine induced a marked decrease in duodenal immunoreactive somatostatin both in vivo (50%) and in vitro (60%). The rate of amylase secretion increased from 9.7 +/- 2.1 U (mean +/- SE) to 28.0 +/- 4.8 U at 20 minutes (P less than 0.001). The cholecystokinin-receptor antagonist CR-1392 abolished amylase response for 30 minutes, whereas the more potent antagonists Asperlicin (18.0 mg/kg body wt, IV) and L-364,718 (0.25 mg/kg body wt, IV) caused prolonged blockade. The rate of amylase secretion in gastrectomized animals increased from 7.2 +/- 2.0 U to 15.0 +/- 2.2 U 20 minutes after cysteamine administration (P less than 0.01), indicating that the effect was not due to the presence of gastrin. In vitro, cysteamine caused a nearly fourfold increase in cholecystokinin secretion compared with controls (63.1 +/- 4.9 vs. 15.2 +/- 3.7, respectively; P less than 0.001). In vivo immunoneutralization of circulating somatostatin with a high-affinity and high-capacity antiserum produced no significant change in the rate of amylase secretion. These results suggest that cholecystokinin secretion is tonically inhibited by somatostatin and that this effect is mediated by locally secreted (paracrine) but not by circulating somatostatin

  19. On the existence and function of galanin receptor heteromers in the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Kjell eFuxe

    2012-10-01

    Full Text Available Galanin receptor (GalR subtypes1-3 linked to central galanin neurons may form heteromers with each other and other types of G protein coupled receptors (GPCRs in the Central Nervous System (CNS. These heteromers may be one molecular mechanism for galanin peptides and their N-terminal fragments (gal 1-15 to modulate the function of different types of glia-neuronal networks in the CNS, especially the emotional and the cardiovascular networks. GalR-5-HT1A heteromers likely exist with antagonistic GalR-5-HT1A receptor-receptor interactions in the ascending midbrain raphe 5-HT neuron systems and their target regions. They represent a novel target for antidepressant drugs. Evidence is given for the existence of GalR1-5-HT1A heteromers in cellular models with transinhibition of the protomer signaling. A GalR1-GalR2 heteromer is proposed to be a galanin N-terminal fragment preferring receptor (1-15 in the CNS. Furthermore, a GalR1-GalR2-5-HT1A heterotrimer is postulated to explain why only galanin (1-15 but not galanin (1-29 can antagonistically modulate the 5-HT1A receptors in the dorsal hippocampus rich in gal fragment binding sites. The results underline a putative role of different types of GalR-5-HT1A heteroreceptor complexes in depression. GalR antagonists may also have therapeutic actions in depression by blocking the antagonistic GalR-NPYY1 receptor interactions in putative GalR-NPYY1 receptor heteromers in the CNS resulting in increases in NPYY1 transmission and antidepressant effects. In contrast the galanin fragment receptor (a postulated GalR1-GalR2 heteromer appears to be linked to the NPYY2 receptor enhancing the affinity of the NPYY2 binding sites in a putative GalR1-GalR2-NPYY2 heterotrimer. Finally, putative GalR-α2-adrenoreceptor heteromers with antagonistic receptor-receptor interactions may be a widespread mechanism in the CNS for integration of galanin and noradrenaline signals also of likely relevance for depression.

  20. Fenofibrate reduces food intake via cholecystokinin

    Directory of Open Access Journals (Sweden)

    S Yu Vorotnikova

    2012-12-01

    Full Text Available Реферат по статье: Park MK, Han Y, Kim MS, Seo E, Kang S, Park SY, Koh H, Kim DK, Lee HJ. Reduction of Food Intake by Fenofibrate is Associated with Cholecystokinin Release in Long-Evans Tokushima Rats. Korean J Physiol Pharmacol. 2012 Jun;16(3:181-6.

  1. The Role of Cholecystokinin in Peripheral Taste Signaling in Mice

    Directory of Open Access Journals (Sweden)

    Ryusuke Yoshida

    2017-10-01

    Full Text Available Cholecystokinin (CCK is a gut hormone released from enteroendocrine cells. CCK functions as an anorexigenic factor by acting on CCK receptors expressed on the vagal afferent nerve and hypothalamus with a synergistic interaction between leptin. In the gut, tastants such as amino acids and bitter compounds stimulate CCK release from enteroendocrine cells via activation of taste transduction pathways. CCK is also expressed in taste buds, suggesting potential roles of CCK in taste signaling in the peripheral taste organ. In the present study, we focused on the function of CCK in the initial responses to taste stimulation. CCK was coexpressed with type II taste cell markers such as Gα-gustducin, phospholipase Cβ2, and transient receptor potential channel M5. Furthermore, a small subset (~30% of CCK-expressing taste cells expressed a sweet/umami taste receptor component, taste receptor type 1 member 3, in taste buds. Because type II taste cells are sweet, umami or bitter taste cells, the majority of CCK-expressing taste cells may be bitter taste cells. CCK-A and -B receptors were expressed in both taste cells and gustatory neurons. CCK receptor knockout mice showed reduced neural responses to bitter compounds compared with wild-type mice. Consistently, intravenous injection of CCK-Ar antagonist lorglumide selectively suppressed gustatory nerve responses to bitter compounds. Intravenous injection of CCK-8 transiently increased gustatory nerve activities in a dose-dependent manner whereas administration of CCK-8 did not affect activities of bitter-sensitive taste cells. Collectively, CCK may be a functionally important neurotransmitter or neuromodulator to activate bitter nerve fibers in peripheral taste tissues.

  2. Radioimmunoassay of cholecystokinin in human plasma

    International Nuclear Information System (INIS)

    Byrnes, D.J.; Henderson, L.; Borody, T.; Rehfeld, J.F.

    1981-01-01

    A sensitive radioimmunoassay for cholecystokinin (CCK) has been developed. Porcine CCK-33 was labelled by conjugation with 125 I-hydroxyphenyl-propionic acid succinimide ester. Antibodies were raised against porcine CCK-33 covalently coupled to egg albumin. Plasma samples were extracted with 96% ethanol prior to assay. Free and bound hormone were separated by dextran-coated charcoal. The antibodies bound CCK-8 and CCK-33 with equimolar potency. The assay detection limit was 1 pmol/l plasma. Within and between assay coefficients of variation were +-12.7 and 13.0% at mean plasma CCK concentrations of 13.2 and 13.6 pmol/l. The concentration of CCK in 47 normal fasting subjects ranged from undetectable to 22 pmol/l. Ingestion of a mixed meal in 9 normal subjects increased the plasma concentration from 8.3 +- 2.5 S.E. to 24.4 +- 6.5 pmol/l. (Auth.)

  3. The predominant cholecystokinin in human plasma and intestine is cholecystokinin-33

    DEFF Research Database (Denmark)

    Rehfeld, J F; Sun, G; Christensen, T

    2001-01-01

    Cholecystokinin (CCK) occurs in multiple molecular forms; the major ones are CCK-58, -33, -22, and -8. Their relative abundance in human plasma and intestine, however, is debated. To settle the issue, extracts of intestinal biopsies and plasma from 10 human subjects have been examined by chromato......Cholecystokinin (CCK) occurs in multiple molecular forms; the major ones are CCK-58, -33, -22, and -8. Their relative abundance in human plasma and intestine, however, is debated. To settle the issue, extracts of intestinal biopsies and plasma from 10 human subjects have been examined...... by chromatography, enzyme cleavages, and measurements using a library of sequence-specific RIAs. Plasma samples were drawn in the fasting state and at intervals after a meal. The abundance of the larger forms varied with the 8 C-terminal assays in the library, as 2 assays overestimated and 3 underestimated...... the amounts present. One assay, however, measured carboxyamidated and O:-sulfated CCKs with equimolar potency before and after tryptic cleavage. This assay showed that the predominant plasma form is CCK-33, both in the fasting state ( approximately 51%) and postprandially ( approximately 57%), whereas CCK-22...

  4. CCK-5: sequence analysis of a small cholecystokinin from canine brain and intestine

    International Nuclear Information System (INIS)

    Shively, J.; Reeve, J.R. Jr.; Eysselein, V.E.; Ben-Avram, C.; Vigna, S.R.; Walsh, J.H.

    1987-01-01

    The purpose of this study is to purify and to characterize chemically cholecystokinin (CCK)-like peptides present in brain and gut extracts that elute from gel filtration after the octapeptide. Canine small intestinal mucosa and brain were boiled in water and then extracted in cold trifluoroacetic acid, and cholecystokinin-like immunoreactivity was determined by carboxyl-terminal specific radioimmunoassay. Gel permeation chromatography on Sephadex G-50 revealed a form of CCK apparently smaller than CCK-8. Microsequence analysis showed that the amino terminal primary sequence of this small CCK was Gly-Trp-Met-Asp. Immunochemical and chromatographic analysis indicated that the carboxyl-terminal residue was Phe-NH 2 and thus the full sequence is Gly-Trp-Met-Asp-Phe-NH 2 . An antibody that recognizes synthetic CCK-8, CCK-5, and CCK-equally did not reveal the presence of significant amounts of CCK-4. These results indicate that CCK-5 is the major CCK form smaller than the octapeptide present in brain and small intestine. This finding, coupled with the demonstration by others that CCK-5 interacts with high-affinity brain CCK receptors, indicates that CCK-5 may play a physiological role in brain function

  5. Measurement and characterization of neuronal cholecystokinin using a novel radioreceptor assay

    International Nuclear Information System (INIS)

    Beresford, I.J.M.; Clark, C.R.; Hughes, J.

    1986-01-01

    This study describes a novel radioreceptor assay (RRA) for cholecystokinin (CCK) which is the first to measure and characterize brain CCK using a technique not dependent on the generation of peptide antibodies. The CCK RRA utilizes the mouse cerebral cortex CCK receptor as the binding source and [ 125 I]BH-CCK-8 as the radiolabelled probe. CCK was extracted (90% methanol) from discrete brain regions (mouse) and quantified using the CCK RRA. The amygdala contained the highest concentration of CCK, followed by the olfactory bulbs and cerebral cortex. Moderate levels of CCK were found in the hippocampus, striatum and hypothalamus. Low levels of CCK were recorded in the pons, medulla and spinal cord, whilst no CCK was detected in the cerebellum. The molecular forms of CCK in amygdala, cerebral cortex and hypothalamus were characterized using RRA in conjunction with HPLC. CCK-8 was identified as the major molecular form with a smaller component attributable to CCK-4. (Auth.)

  6. Postsynaptic Depolarization Enhances GABA Drive to Dorsomedial Hypothalamic Neurons through Somatodendritic Cholecystokinin Release.

    Science.gov (United States)

    Crosby, Karen M; Baimoukhametova, Dinara V; Bains, Jaideep S; Pittman, Quentin J

    2015-09-23

    Somatodendritically released peptides alter synaptic function through a variety of mechanisms, including autocrine actions that liberate retrograde transmitters. Cholecystokinin (CCK) is a neuropeptide expressed in neurons in the dorsomedial hypothalamic nucleus (DMH), a region implicated in satiety and stress. There are clear demonstrations that exogenous CCK modulates food intake and neuropeptide expression in the DMH, but there is no information on how endogenous CCK alters synaptic properties. Here, we provide the first report of somatodendritic release of CCK in the brain in male Sprague Dawley rats. CCK is released from DMH neurons in response to repeated postsynaptic depolarizations, and acts in an autocrine fashion on CCK2 receptors to enhance postsynaptic NMDA receptor function and liberate the retrograde transmitter, nitric oxide (NO). NO subsequently acts presynaptically to enhance GABA release through a soluble guanylate cyclase-mediated pathway. These data provide the first demonstration of synaptic actions of somatodendritically released CCK in the hypothalamus and reveal a new form of retrograde plasticity, depolarization-induced potentiation of inhibition. Significance statement: Somatodendritic signaling using endocannabinoids or nitric oxide to alter the efficacy of afferent transmission is well established. Despite early convincing evidence for somatodendritic release of neurohypophysial peptides in the hypothalamus, there is only limited evidence for this mode of release for other peptides. Here, we provide the first evidence for somatodendritic release of the satiety peptide cholecystokinin (CCK) in the brain. We also reveal a new form of synaptic plasticity in which postsynaptic depolarization results in enhancement of inhibition through the somatodendritic release of CCK. Copyright © 2015 the authors 0270-6474/15/3513160-11$15.00/0.

  7. Comprehensive gene expression analysis of rice aleurone cells: probing the existence of an alternative gibberellin receptor.

    Science.gov (United States)

    Yano, Kenji; Aya, Koichiro; Hirano, Ko; Ordonio, Reynante Lacsamana; Ueguchi-Tanaka, Miyako; Matsuoka, Makoto

    2015-02-01

    Current gibberellin (GA) research indicates that GA must be perceived in plant nuclei by its cognate receptor, GIBBERELLIN INSENSITIVE DWARF1 (GID1). Recognition of GA by GID1 relieves the repression mediated by the DELLA protein, a model known as the GID1-DELLA GA perception system. There have been reports of potential GA-binding proteins in the plasma membrane that perceive GA and induce α-amylase expression in cereal aleurone cells, which is mechanistically different from the GID1-DELLA system. Therefore, we examined the expression of the rice (Oryza sativa) α-amylase genes in rice mutants impaired in the GA receptor (gid1) and the DELLA repressor (slender rice1; slr1) and confirmed their lack of response to GA in gid1 mutants and constitutive expression in slr1 mutants. We also examined the expression of GA-regulated genes by genome-wide microarray and quantitative reverse transcription-polymerase chain reaction analyses and confirmed that all GA-regulated genes are modulated by the GID1-DELLA system. Furthermore, we studied the regulatory network involved in GA signaling by using a set of mutants defective in genes involved in GA perception and gene expression, namely gid1, slr1, gid2 (a GA-related F-box protein mutant), and gamyb (a GA-related trans-acting factor mutant). Almost all GA up-regulated genes were regulated by the four named GA-signaling components. On the other hand, GA down-regulated genes showed different expression patterns with respect to GID2 and GAMYB (e.g. a considerable number of genes are not controlled by GAMYB or GID2 and GAMYB). Based on these observations, we present a comprehensive discussion of the intricate network of GA-regulated genes in rice aleurone cells. © 2015 American Society of Plant Biologists. All Rights Reserved.

  8. Development of cholecystokinin binding sites in rat upper gastrointestinal tract

    International Nuclear Information System (INIS)

    Robinson, P.H.; Moran, T.H.; Goldrich, M.; McHugh, P.R.

    1987-01-01

    Autoradiography using 125 I-labeled Bolton Hunter-CCK-33 was used to study the distribution of cholecystokinin binding sites at different stages of development in the rat upper gastrointestinal tract. Cholecystokinin (CCK) binding was present in the distal stomach, esophagus, and gastroduodenal junction in the rat fetus of gestational age of 17 days. In the 20-day fetus, specific binding was found in the gastric mucosa, antral circular muscle, and pyloric sphincter. Mucosal binding declined during postnatal development and had disappeared by day 15. Antral binding declined sharply between day 10 and day 15 and disappeared by day 50. Pyloric muscle binding was present in fetal stomach and persisted in the adult. Pancreatic CCK binding was not observed before day 10. These results suggest that CCK may have a role in the control of gastric emptying and ingestive behavior in the neonatal rat

  9. Development of cholecystokinin binding sites in rat upper gastrointestinal tract

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, P.H.; Moran, T.H.; Goldrich, M.; McHugh, P.R.

    1987-04-01

    Autoradiography using /sup 125/I-labeled Bolton Hunter-CCK-33 was used to study the distribution of cholecystokinin binding sites at different stages of development in the rat upper gastrointestinal tract. Cholecystokinin (CCK) binding was present in the distal stomach, esophagus, and gastroduodenal junction in the rat fetus of gestational age of 17 days. In the 20-day fetus, specific binding was found in the gastric mucosa, antral circular muscle, and pyloric sphincter. Mucosal binding declined during postnatal development and had disappeared by day 15. Antral binding declined sharply between day 10 and day 15 and disappeared by day 50. Pyloric muscle binding was present in fetal stomach and persisted in the adult. Pancreatic CCK binding was not observed before day 10. These results suggest that CCK may have a role in the control of gastric emptying and ingestive behavior in the neonatal rat.

  10. Cholecystokinin octapeptide induces endogenous opioid-dependent anxiolytic effects in morphine-withdrawal rats.

    Science.gov (United States)

    Wen, D; Sun, D; Zang, G; Hao, L; Liu, X; Yu, F; Ma, C; Cong, B

    2014-09-26

    Cholecystokinin octapeptide (CCK-8), a brain-gut peptide, plays an important role in several opioid addictive behaviors. We previously reported that CCK-8 attenuated the expression and reinstatement of morphine-induced conditioned place preference. The possible effects of CCK-8 on the negative affective components of drug abstinence are not clear. There are no studies evaluating the effect of CCK-8 on emotional symptoms, such as anxiety, in morphine-withdrawal animals. We investigated the effects of CCK-8 on the anxiety-like behavior in morphine-withdrawal rats using an elevated plus-maze. Morphine withdrawal elicited time-dependent anxiety-like behaviors with peak effects on day 10 (5 days after induction of morphine dependence). Treatment with CCK-8 (0.1 and 1 μg, i.c.v.) blocked this anxiety in a dose-dependent fashion. A CCK1 receptor antagonist (L-364,718, 10 μg, i.c.v.) blocked the effect of CCK-8. Mu-opioid receptor antagonism with CTAP (10 μg, i.c.v.) decreased the 'anxiolytic' effect. CCK-8 inhibited anxiety-like behaviors in morphine-withdrawal rats by up-regulating endogenous opioids via the CCK1 receptor in rats. This study clearly identifies a distinct function of CCK-8 and a potential medication target of central CCK1 receptors for drugs aimed at ameliorating drug addiction. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Internalization and cellular processing of cholecystokinin in rat pancreatic acinar cells

    International Nuclear Information System (INIS)

    Izzo, R.S.; Pellecchia, C.; Praissman, M.

    1988-01-01

    To evaluate the internalization of cholecystokinin, monoiodinated imidoester of cholecystokinin octapeptide [ 125 I-(IE)-CCK-8] was bound to dispersed pancreatic acinar cells, and surface-bound and internalized radioligand were differentiated by treating with an acidified glycine buffer. The amount of internalized radioligand was four- and sevenfold greater at 24 and 37 degree C than at 4 degree C between 5 and 60 min of association. Specific binding of radioligand to cell surface receptors was not significantly different at these temperatures. Chloroquine, a lysosomotropic agent that blocks intracellular proteolysis, significantly increased the amount of CCK-8 internalized by 18 and 16% at 30 and 60 min of binding, respectively, compared with control. Dithiothreitol (DTT), a sulfhydryl reducing agent, also augmented the amount of CCK-8 radioligand internalized by 25 and 29% at 30 and 60 min, respectively. The effect of chloroquine and DTT on the processing of internalized radioligand was also considered after an initial 60 min of binding of radioligand to acinar cells. After 180 min of processing, the amount of radioligand internalized was significantly greater in the presence of chloroquine compared with controls, whereas the amount of radioligand declined in acinar cells treated with DTT. Internalized and released radioactivity from acinar cells was rebound to pancreatic membrane homogenates to determine the amount of intact radioligand during intracellular processing. Chloroquine significantly increased the amount of intact 125 I-(IE)-CCK-8 radioligand in released and internalized radioactivity while DTT increased the amount of intact radioligand only in internalized samples. This study shows that pancreatic acinar cells rapidly internalize large amounts of CCK-8 and that chloroquine and DTT inhibit intracellular degradation

  12. Effects of growth hormone deficiency and recombinant growth hormone therapy on postprandial gallbladder motility and cholecystokinin release.

    NARCIS (Netherlands)

    Moschetta, A.; Twickler, M.; Rehfeld, J.F.; Ooteghem, N.A. van; Castro Cabezas, M.; Portincasa, P.; Berge-Henegouwen, G.P. van; Erpecum, K.J. van

    2004-01-01

    In addition to cholecystokinin, other hormones have been suggested to be involved in regulation of postprandial gallbladder contraction. We aimed to evaluate effects of growth hormone (GH) on gallbladder contractility and cholecystokinin release. Gallbladder and gastric emptying (by ultrasound) and

  13. Functional characteristics of parvalbumin- and cholecystokinin-expressing basket cells.

    Science.gov (United States)

    Bartos, Marlene; Elgueta, Claudio

    2012-02-15

    Cortical neuronal network operations depend critically on the recruitment of GABAergic interneurons and the properties of their inhibitory output signals. Recent evidence indicates a marked difference in the signalling properties of two major types of perisomatic inhibitory interneurons, the parvalbumin- and the cholecystokinin-containing basket cells. Parvalbumin-expressing basket cells are rapidly recruited by excitatory synaptic inputs, generate high-frequency trains of action potentials, discharge single action potentials phase-locked to fast network oscillations and provide fast, stable and timed inhibitory output onto their target cells. In contrast, cholecystokinin-containing basket cells are recruited in a less reliable manner, discharge at moderate frequencies with single action potentials weakly coupled to the phases of fast network oscillations and generate an asynchronous, fluctuating and less timed inhibitory output. These signalling modes are based on cell type-dependent differences in the functional and plastic properties of excitatory input synapses, integrative qualities and in the kinetics and dynamics of inhibitory output synapses. Thus, the two perisomatic inhibitory interneuron types operate with different speed and precision and may therefore contribute differently to the operations of neuronal networks.

  14. Cholecystokinin in plasma predicts cardiovascular mortality in elderly females

    DEFF Research Database (Denmark)

    Gøtze, Jens P.; Rehfeld, Jens F; Alehagen, Urban

    2016-01-01

    BACKGROUND: Cholecystokinin (CCK) and gastrin are related gastrointestinal hormones with documented cardiovascular effects of exogenous administration. It is unknown whether measurement of endogenous CCK or gastrin in plasma contains information regarding cardiovascular mortality. METHODS......: Mortality risk was evaluated using Cox proportional hazard regression and Kaplan-Meier analyses. Elderly patients in a primary care setting with symptoms of cardiac disease, i.e. shortness of breath, peripheral edema, and/or fatigue, were evaluated (n=470). Primary care patients were followed for 13years...... information was obtained from 4th quartile gastrin concentrations on 5-year cardiovascular mortality risk. CONCLUSIONS: CCK in plasma is an independent marker of cardiovascular mortality in elderly female patients. The study thus introduces measurement of plasma CCK in gender-specific cardiovascular risk...

  15. G protein in stimulation of PI hydrolysis by CCK [cholecystokinin] in isolated rat pancreatic acinar cells

    International Nuclear Information System (INIS)

    Matozaki, Takashi; Sakamoto, Choitsu; Nagao, Munehiko; Nishizaki, Hogara; Baba, Shigeaki

    1988-01-01

    To clarify the possible role of a guanine nucleotide-binding protein (G protein) in the signal transducing system activated by cholecystokinin (CCK), actions of CCK on rat pancreatic acini were compared with those of fluoride, a well-known activator of stimulatory (G s ) or inhibitory (G i ) G protein. When acini were incubated with increasing concentrations of either CCK-octapeptide (CCK8) or NaF, a maximal stimulation of amylase release from acini occurred at 100 pM CCK8 or 10 mM NaF, respectively; this secretory rate decreased as CCK8 or NaF concentration was increased. NaF caused an increase in cytoplasmic Ca 2+ concentration from the internal Ca 2+ store and stimulated accumulation of inositol phosphates in acini, as observed with CCK. Guanylimidodiphosphate activated the generation of inositol phosphates in the [ 3 H]inositol-labeled pancreatic acinar cell membrane preparation, with half-maximal and maximal stimulation at 1 and 10 μM, respectively. Furthermore, the effects of submaximal CCK concentrations on inositol phosphate accumulation in membranes were markedly potentiated in the presence of 100 μM GTP, which alone was ineffective. Combined findings of the present study strongly suggest that pancreatic CCK receptors are probably coupled to the activation of polyphosphoinositide (PI) breakdown by a G protein, which appears to be fluoride sensitive but is other than G s - or G i -like protein

  16. Radioimmunoassay of cholecystokinin in human tissue and plasma

    International Nuclear Information System (INIS)

    Jansen, J.B.M.J.; Lamers, C.B.H.W.

    1983-01-01

    A highly sensitive radioimmunoassay for cholecystokinin (CCK) without any cross-reactivity with gastrin is described. The antibody was raised in a rabbit by immunisation with 30% CCK and bound to all COOH-terminal CCK-peptides containing at least 14 amino acid residues. The affinity constant of the antibody was 59.4 x 10 10 l/mol. CCK 33 conjugated to [ 125 I]hydroxyphenylpropionic acid-succinimide ester was used as label. The binding between label and antibody was inhibited by 50% (ID 50 ) at a concentration of 2.8 pmol/l cholecystokinin 33. The detection limit of the assay was between 0.5 and 1.0 pmol/l plasma. Concentrations of CCK in aqueous acid extracts of human upper small intestine were 36.5 +- 9.8 pmol/g and of human cerebral cortex 28.2 +- 2.5 pmol/g tissue. Plasma samples were extracted in 96% ethanol prior to assay. No advantage was obtained by adding aprotinin to the tubes. When frozen at -20 0 C plasma CCK was stable for at least 6 months. Basal plasma CCK concentrations in 30 normal subjects were very low, 0.9 +- 0.1 pmol/l, range 0.5 to 3.1 pmol/l. Intraduodenal administration of fat induced significant increases in plasma CCK from 1.1 +- 0.1 to 8.2 +- 1.3 pmol/l (p = 0.01). Infusion of exogenous CCK, resulting in plasma CCK levels slightly lower than those measured during administration of fat, induced pancreatic enzyme secretion and gallbladder contraction. The reliability of this radioimmunoassay for measurements of CCK in human plasma was extensively evaluated. (Auth.)

  17. Development of new methods for the radioactive labelling of compounds useful in biology. Application to the study of digestive tract hormones and their analogues (gastrine, pentagastrine, cholecystokinine, pancreozymine, caeruleine, somatostatine)

    International Nuclear Information System (INIS)

    Girma, J.-P.

    1976-01-01

    To establish the kinetics of fixation on receptor sites, tissular distribution and metabolism of hormones, it is necessary to obtain high specific activity labelled hormones possessing biological activities identical with those of the originals. In this context two aims were pursued: hormonal peptide labelling at high specific radioactivity; research on the biological fate of the intermediate compounds involved in the preparations. This research was centred chiefly on gastrine, caeruleine, cholecystokinine and pentagastrine, structural analogues representing one of the two groups of digestive tract hormones (the gastrine family). After a brief review of present knowledge on the gastro-intestinal system; the hormones selected are situated in their biological context. Part two is devoted mainly to the study of iodine and tritium labelling of peptides and includes the adaptation of an existing method to the problem of gastrine labelling and the development of two new tritium-labelling methods, one specific to tryptophanyl residues and the other to tyrosyl residues. Finally the separation of modified hormones during the preparations offered the occasion to develop a study of the biological behavior of these analogues [fr

  18. Cholecystokinin cholescintigraphic findings in the cystic duct syndrome

    International Nuclear Information System (INIS)

    Fink-Bennett, D.; DeRidder, P.; Kolozsi, W.; Gordon, R.; Rapp, J.

    1985-01-01

    Fourteen patients with a cystic duct syndrome (CDS) underwent cholecystokinin (CCK) cholescintigraphy. All patients presented with persistent postprandial right upper quadrant pain and biliary colic. None of the patients had an abnormal oral cholecystography, gallbladder (GB) ultrasound exam or upper GI series. Each patient received 5 mCi of technetium-99m disofenin. When the GB maximally filled, 0.02 microgram/kg CCK was administered (3 min) intravenously. Background corrected gallbladder ejection fractions (GBEFs) were determined every 5 min X 4 by rationing the pre-CCK GB counts minus post-CCK GB counts to pre-CCK GB counts. GBEFs were: 12% (3 patients), 17% (2), 0%, 1.3%, 3%, 4%, 6%, 11%, 14%, 18.5%, and 22% (1 each). All patients underwent a surgical exploration and all had macro- or microscopically abnormal cystic ducts with (12 patients) or without (2 patients) concomitant chronic cholecystitis. No patient with a partially occluded cystic duct with or without concomitant chronic cholecystitis had an ejection fraction that exceeded 22%. In an appropriate clinical setting, a low EF response to CCK should alert the physician to the presence of either chronic acalculous cholecystitis, CDS, or the combination of both

  19. In vivo sulfation of cholecystokinin octapeptide. Possible interactions of the two forms of cholecystokinin with dopamine in the brain

    International Nuclear Information System (INIS)

    Penke, B.; Kovacs, G.L.; Zsigo, J.; Kadar, T.; Szabo, G.; Kovacs, K.; Telegdy, G.

    1985-01-01

    In most laboratories CCK-8(s) has been found to be the biologically active form of CCK-8 in the CNS. The role of CCK-8(ns) has scarcely been investigated and is poorly understood. These results point to the equivalence of CCK-8(s) and CCK-8(ns) in the CNS in most biological tests. It is most likely that a brain receptor population exists which can bind both forms of CCK-8 and even CCK-4. Nevertheless, the CNS could contain binding sites which bind only CCK-8(s) as a ligand. The authors have found that an unidentified sulfotransferase of the brain can sulfate CCK-8(ns) and thereby provide a ligand for the special receptors of CCK-8(s). The authors have focused their investigations on the enzymic sulfation-desulfation processes of both CCK-8 and DA and have devised a hypothetical model for the possible interactions. Both CCK-8(ns) and DA could be sulfated in vivo, this enzymic reaction generally requiring active sulfate (PAPS). These two compounds could compete for the limited pool of PAPS, and thus CCK-8 and DA could mutually regulate their levels in the same cell by influencing one of the metabolic (DA) or synthetic (CCK-8(s)) pathways

  20. Cholecystokinin revisited: CCK and the hunger trap in anorexia nervosa.

    Directory of Open Access Journals (Sweden)

    Ulrich Cuntz

    Full Text Available OBJECTIVE: Despite a number of studies in the past decades, the role of Cholecystokinin (CCK in anorexia nervosa (AN has remained uncertain. In this study a highly specific assay for the biologically active part of CCK was used in patients with bulimic as well as with the restricting type of AN who were followed over the course of weight gain. METHODS: Ten patients with restricting and 13 with bulimic AN were investigated upon admission (T0, after a weight gain of at least 2 kg on two consecutive weighting dates (T1, and during the last week before discharge (T2 from inpatient treatment in a specialized clinic. Blood samples were drawn under fasting conditions and 20 and 60 minutes following a standard meal (250 kcal. Data were compared to those of eight controls matched for sex and age. Gastrointestinal complaints of patients were measured by a questionnaire at each of the follow-up time points. RESULTS: At admission, AN patients exhibited CCK-levels similar to controls both prior to and after a test meal. Pre and post-meal CCK levels increased significantly after an initial weight gain but decreased again with further weight improvement. CCK release was somewhat lower in bulimic than in restricting type AN but both subgroups showed a similar profile. There was no significant association of CCK release to either initial weight or BMI, or their changes, but CCK levels at admission predicted gastrointestinal symptom improvement during therapy. CONCLUSIONS: Normal CCK profiles in AN at admission indicates hormonal responses adapted to low food intake while change of eating habits and weight gain results in initially increased CCK release (counteracting the attempts to alter eating behavior that returns towards normal levels with continuous therapy.

  1. Stimulation of (3H) spiroperidol binding after prolonged neuroleptic therapy by the cholecystokinin octapeptide analog cerulein

    International Nuclear Information System (INIS)

    Vasar, E.E.; Allikmets, L.K.; Maimets, O.O.; Nurk, A.M.

    1985-01-01

    Evidence has recently been obtained that cholecystokinin and its analog cerulein have marked antipsychotic action on patients with schizophrenia who are resistant to neuroleptics; this is the basis for interest in this study of the effect of cerulein, a high-affinity analog of the octapeptide cholecystokinin, on binding of tritium-spiroperidol in vivo. Considering the apormorphine-like action of cerulein, this biochemical analysis was undertaken in the form of a comparative study with N-propyl-norapomorphine, a high-affinity analogy of apomorphine

  2. Fiber mediated receptor masking in non-infected bystander cells restricts adenovirus cell killing effect but promotes adenovirus host co-existence.

    Directory of Open Access Journals (Sweden)

    Johan Rebetz

    Full Text Available The basic concept of conditionally replicating adenoviruses (CRAD as oncolytic agents is that progenies generated from each round of infection will disperse, infect and kill new cancer cells. However, CRAD has only inhibited, but not eradicated tumor growth in xenograft tumor therapy, and CRAD therapy has had only marginal clinical benefit to cancer patients. Here, we found that CRAD propagation and cancer cell survival co-existed for long periods of time when infection was initiated at low multiplicity of infection (MOI, and cancer cell killing was inefficient and slow compared to the assumed cell killing effect upon infection at high MOI. Excessive production of fiber molecules from initial CRAD infection of only 1 to 2% cancer cells and their release prior to the viral particle itself caused a tropism-specific receptor masking in both infected and non-infected bystander cells. Consequently, the non-infected bystander cells were inefficiently bound and infected by CRAD progenies. Further, fiber overproduction with concomitant restriction of adenovirus spread was observed in xenograft cancer therapy models. Besides the CAR-binding Ad4, Ad5, and Ad37, infection with CD46-binding Ad35 and Ad11 also caused receptor masking. Fiber overproduction and its resulting receptor masking thus play a key role in limiting CRAD functionality, but potentially promote adenovirus and host cell co-existence. These findings also give important clues for understanding mechanisms underlying the natural infection course of various adenoviruses.

  3. Comprehensive Gene Expression Analysis of Rice Aleurone Cells: Probing the Existence of an Alternative Gibberellin Receptor1

    Science.gov (United States)

    Yano, Kenji; Aya, Koichiro; Hirano, Ko; Ordonio, Reynante Lacsamana; Ueguchi-Tanaka, Miyako; Matsuoka, Makoto

    2015-01-01

    Current gibberellin (GA) research indicates that GA must be perceived in plant nuclei by its cognate receptor, GIBBERELLIN INSENSITIVE DWARF1 (GID1). Recognition of GA by GID1 relieves the repression mediated by the DELLA protein, a model known as the GID1-DELLA GA perception system. There have been reports of potential GA-binding proteins in the plasma membrane that perceive GA and induce α-amylase expression in cereal aleurone cells, which is mechanistically different from the GID1-DELLA system. Therefore, we examined the expression of the rice (Oryza sativa) α-amylase genes in rice mutants impaired in the GA receptor (gid1) and the DELLA repressor (slender rice1; slr1) and confirmed their lack of response to GA in gid1 mutants and constitutive expression in slr1 mutants. We also examined the expression of GA-regulated genes by genome-wide microarray and quantitative reverse transcription-polymerase chain reaction analyses and confirmed that all GA-regulated genes are modulated by the GID1-DELLA system. Furthermore, we studied the regulatory network involved in GA signaling by using a set of mutants defective in genes involved in GA perception and gene expression, namely gid1, slr1, gid2 (a GA-related F-box protein mutant), and gamyb (a GA-related trans-acting factor mutant). Almost all GA up-regulated genes were regulated by the four named GA-signaling components. On the other hand, GA down-regulated genes showed different expression patterns with respect to GID2 and GAMYB (e.g. a considerable number of genes are not controlled by GAMYB or GID2 and GAMYB). Based on these observations, we present a comprehensive discussion of the intricate network of GA-regulated genes in rice aleurone cells. PMID:25511432

  4. An electrophysiological investigation of the effects of cholecystokinin on enteric neurons

    NARCIS (Netherlands)

    Schutte, I.W.M.

    1998-01-01


    Cholecystokinin (CCK) is a peptide, which is present in the gastrointestinat tract in endocrine cells and in the enteric nervous system (ENS). A possible function in the control of motility of the small intestine has been attributed to neuronal CCK. The aim of this thesis was to obtain a

  5. Time-resolved quantitative analysis of CCK1 receptor-induced intracellular calcium increase.

    NARCIS (Netherlands)

    Staljanssens, D.; Vos, W.H. De; Willems, P.H.; Camp, J. Van; Smagghe, G.

    2012-01-01

    Cholecystokinin (CCK) is a gastrointestinal hormone, which regulates many physiological functions such as satiety by binding to the CCK receptor (CCKR). Molecules, which recognize this receptor can mimic or block CCK signaling and thereby influence CCKR-mediated processes. We have set up a

  6. Comparative biodistribution of 12 111In-labelled gastrin/CCK2 receptor-targeting peptides

    NARCIS (Netherlands)

    P. Laverman (Peter); L. Joosten; A. Eek (Annemarie); S. Roosenburg (Susan); P.K. Peitl; T. Maina (Theodosia); H.R. Mäcke (Helmut); L. Aloj (Luigi); E. von Guggenber (Elisabeth); J.K. Sosabowski (Jane); M. de Jong (Marion); J.-C. Reubi (Jean-Claude); W.J.G. Oyen (Wim); O.C. Boerman (Otto)

    2011-01-01

    textabstractPurpose Cholecystokinin 2 (CCK-2) receptor overexpression has been demonstrated in various tumours such as medullary thyroid carcinomas and small-cell lung cancers. Due to this high expression, CCK-2 receptors might be suitable targets for radionuclide imaging and/or radionuclide

  7. Preclinical Evaluation of 68Ga-DOTA-Minigastrin for the Detection of Cholecystokinin-2/Gastrin Receptor–Positive Tumors

    Science.gov (United States)

    Brom, Maarten; Joosten, Lieke; Laverman, Peter; Oyen, Wim J.G.; Béhé, Martin; Gotthardt, Martin; Boerman, Otto C.

    2011-01-01

    In comparison to somatostatin receptor scintigraphy, gastrin receptor scintigraphy using 111In-DTPA-minigastrin (MG0) showed added value in diagnosing neuroendocrine tumors. We investigated whether the 68Ga-labeled gastrin analogue DOTA-MG0 is suited for positron emission tomography (PET), which could improve image quality. Targeting of cholecystokinin-2 (CCK2)/gastrin receptor–positive tumor cells with DOTA-MG0 labeled with either 111In or 68Ga in vitro was investigated using the AR42J rat tumor cell line. Biodistribution was examined in BALB/c nude mice with a subcutaneous AR42J tumor. In vivo PET imaging was performed using a preclinical PET–computed tomographic scanner. DOTA-MG0 showed high receptor affinity in vitro. Biodistribution studies revealed high tumor uptake of 68Ga-DOTA-MG0: 4.4 ± 1.3 %ID/g at 1 hour postinjection. Coadministration of an excess unlabeled peptide blocked the tumor uptake (0.7 ± 0.1 %ID/g), indicating CCK2/gastrin receptor–mediated uptake (p = .0005). The biodistribution of 68Ga-DOTA-MG0 was similar to that of 111In-DOTA-MG0. Subcutaneous and intraperitoneal tumors were clearly visualized by small-animal PET imaging with 5 MBq 68Ga-DOTA-MG0. 111In- and 68Ga-labeled DOTA-MG0 specifically accumulate in CCK2/gastrin receptor–positive AR42J tumors with similar biodistribution apart from the kidneys. AR42J tumors were clearly visualized by microPET. Therefore, 68Ga-DOTA-MG0 is a promising tracer for PET imaging of CCK2/gastrin receptor–positive tumors in humans. PMID:21439259

  8. Cholecystokinin enhances visceral pain-related affective memory via vagal afferent pathway in rats

    Directory of Open Access Journals (Sweden)

    Cao Bing

    2012-06-01

    Full Text Available Abstract Background Pain contains both sensory and affective dimensions. Using a rodent visceral pain assay that combines the colorectal distension (CRD model with the conditioned place avoidance (CPA paradigms, we measured a learned behavior that directly reflects the affective component of visceral pain, and showed that perigenual anterior cingulate cortex (pACC activation is critical for memory processing involved in long-term visceral affective state and prediction of aversive stimuli by contextual cue. Progress has been made and suggested that activation of vagal afferents plays a role in the behavioral control nociception and memory storage processes. In human patients, electrical vagus nerve stimulation enhanced retention of verbal learning performance. Cholecystokinin-octapeptide (CCK, which is a gastrointestinal hormone released during feeding, has been shown to enhance memory retention. Mice access to food immediately after training session enhanced memory retention. It has been well demonstrated that CCK acting on vagal afferent fibers mediates various physiological functions. We hypothesize that CCK activation of vagal afferent enhances visceral pain-related affective memory. Results In the presented study, infusion of CCK-8 at physiological concentration combining with conditional training significantly increased the CRD-induced CPA scores, and enhanced the pain affective memory retention. In contrast, CCK had no effect on CPA induced by non-nociceptive aversive stimulus (U69,593. The physiological implications were further strengthened by the similar effects observed in the rats with duodenal infusion of 5% peptone, which has been shown to induce increases in plasma CCK levels. CCK-8 receptor antagonist CR-1409 or perivagal application of capsaicin abolished the effect of CCK on aversive visceral pain memory, which was consistent with the notion that vagal afferent modulates affective aspects of visceral pain. CCK does not change

  9. Cholecystokinin enhances visceral pain-related affective memory via vagal afferent pathway in rats.

    Science.gov (United States)

    Cao, Bing; Zhang, Xu; Yan, Ni; Chen, Shengliang; Li, Ying

    2012-06-09

    Pain contains both sensory and affective dimensions. Using a rodent visceral pain assay that combines the colorectal distension (CRD) model with the conditioned place avoidance (CPA) paradigms, we measured a learned behavior that directly reflects the affective component of visceral pain, and showed that perigenual anterior cingulate cortex (pACC) activation is critical for memory processing involved in long-term visceral affective state and prediction of aversive stimuli by contextual cue. Progress has been made and suggested that activation of vagal afferents plays a role in the behavioral control nociception and memory storage processes.In human patients, electrical vagus nerve stimulation enhanced retention of verbal learning performance. Cholecystokinin-octapeptide (CCK), which is a gastrointestinal hormone released during feeding, has been shown to enhance memory retention. Mice access to food immediately after training session enhanced memory retention. It has been well demonstrated that CCK acting on vagal afferent fibers mediates various physiological functions. We hypothesize that CCK activation of vagal afferent enhances visceral pain-related affective memory. In the presented study, infusion of CCK-8 at physiological concentration combining with conditional training significantly increased the CRD-induced CPA scores, and enhanced the pain affective memory retention. In contrast, CCK had no effect on CPA induced by non-nociceptive aversive stimulus (U69,593). The physiological implications were further strengthened by the similar effects observed in the rats with duodenal infusion of 5% peptone, which has been shown to induce increases in plasma CCK levels. CCK-8 receptor antagonist CR-1409 or perivagal application of capsaicin abolished the effect of CCK on aversive visceral pain memory, which was consistent with the notion that vagal afferent modulates affective aspects of visceral pain. CCK does not change the nociceptive response (visceral pain

  10. Effects of cholecystokinin octapeptide on striatal dopamine metabolism and on apomorphine-induced stereotyped cage-climbing in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kovacs, G L; Szabo, G; Telegdy, G [Institute of Pathophysiology, University Medical School, Szeged, Hungary; Penke, B [Institute of Medical Chemistry, University Medical School, Szeged, Hungary

    1981-01-29

    The effects of sulfated (CCK-8-SE) and non-sulfated (CCK-8-NS) cholecystokinin octapeptide on striatal dopamine (DA) metabolism have been investigated on mice. CCK-8-NS facilitated the disappearance of striatal DA, measured after synthesis inhibition with 350 mg/kg of ..cap alpha..-methyl-p-tyrosine. CCK-8-SE did not affect DA disappearance. In vitro uptake of (/sup 3/H)DA by striatal slices was affected by neither CCK-8-SE, nor CCK-8-NS (10/sup -5/ M). Potassium-induced in vitro release of (/sup 3/H)DA from striatal slices was significantly increased by 10/sup -5/ M CCK-8-NS: however, CCK-8-SE likewise increased DA release in this model system. Apomorphine-induced (1.0 mg/kg) stereotyped cage-climbing behavior was not affected by CCK-8-SE but was enhanced by CCK-8-NS. This effect could be antagonized by haloperidol, but not by naloxone. The data suggest that CCK-8-NS affects striatal DA release, disappearance and receptor sensitivity in the mouse. Dopaminergic mechanisms should therefore be regarded as a possible mode of action of CCK-8-NS on brain functions.

  11. Effects of cholecystokinin octapeptide on striatal dopamine metabolism and on apomorphine-induced stereotyped cage-climbing in mice

    International Nuclear Information System (INIS)

    Kovacs, G.L.; Szabo, G.; Telegdy, G.; Penke, B.

    1981-01-01

    The effects of sulfated (CCK-8-SE) and non-sulfated (CCK-8-NS) cholecystokinin octapeptide on striatal dopamine (DA) metabolism have been investigated on mice. CCK-8-NS facilitated the disappearance of striatal DA, measured after synthesis inhibition with 350 mg/kg of α-methyl-p-tyrosine. CCK-8-SE did not affect DA disappearance. In vitro uptake of [ 3 H]DA by striatal slices was affected by neither CCK-8-SE, nor CCK-8-NS (10 -5 M). Potassium-induced in vitro release of [ 3 H]DA from striatal slices was significantly increased by 10 -5 M CCK-8-NS: however, CCK-8-SE likewise increased DA release in this model system. Apomorphine-induced (1.0 mg/kg) stereotyped cage-climbing behavior was not affected by CCK-8-SE but was enhanced by CCK-8-NS. This effect could be antagonized by haloperidol, but not by naloxone. The data suggest that CCK-8-NS affects striatal DA release, disappearance and receptor sensitivity in the mouse. Dopaminergic mechanisms should therefore be regarded as a possible mode of action of CCK-8-NS on brain functions. (Auth.)

  12. The regulation of aortic endothelial cells by purines and pyrimidines involves co-existing P2y-purinoceptors and nucleotide receptors linked to phospholipase C.

    Science.gov (United States)

    Wilkinson, G F; Purkiss, J R; Boarder, M R

    1993-03-01

    1. We have examined the phospholipase C responses in bovine aortic endothelial cells to purines (ATP, ADP and analogues) and the pyrimidine, uridine triphosphate (UTP). 2. The cells responded to purines in a manner consistent with the presence of P2y purinoceptors; both 2-methylthioadenosine 5'-triphosphate (2MeSATP) and adenosine 5'-0-(2-thiodiphosphate) (ADP beta S) were potent agonists (EC50 0.41 microM and 0.85 microM respectively) while beta, gamma-methylene ATP at 300 microM was not. 3. The cells also responded to UTP. The maximal response to UTP was less than that for either 2MeSATP and ADP beta S while adenosine 5'-0-(3-thiotriphosphate) (ATP gamma S) gave the largest maximal response. 4. The concentration-effect curve to UTP was additive in the presence of either 2MeSATP or ADP beta S. However, the concentration-effect curves to ATP gamma S reached the same maximum in the presence or absence of UTP. 5. Suramin, at concentrations between 10 microM and 100 microM was a competitive antagonist for the response to ADP beta S and 2MeSATP but not the response to UTP. 6. The results show that there are two separate, co-existing, receptor populations: P2y-purinoceptors (responding to purines) and nucleotide receptors (responding to both purines and pyrimidines). We conclude that purines such as ATP/ADP may regulate aortic endothelial cells by interacting with two phospholipase C-linked receptors.

  13. Cholecystokinin inhibits gastrin secretion independently of paracrine somatostatin secretion in the pig

    DEFF Research Database (Denmark)

    Schmidt, P T; Hansen, L; Hilsted, L

    2004-01-01

    BACKGROUND: Cholecystokinin inhibits the secretion of gastrin from antral G cells, an effect that is speculated to be mediated by D cells secreting somatostatin. The aim of the study was to test directly whether cholecystokinin inhibition of antral gastrin secretion is mediated by somatostatin....... METHODS: The effects of CCK on gastrin and somatostatin secretion were studied in isolated vascularly perfused preparations of pig antrum before and after immunoneutralization brought about by infusion of large amounts of a high affinity monoclonal antibody against somatostatin. RESULTS: CCK infusion...... at 10(-9) M and 10(-8) M decreased gastrin output to 70.5% +/- 7.6% (n = 8) and 76.3% +/- 3.6% (n = 7) of basal output, respectively. CCK at 10(-10) M had no effect (n = 6). Somatostatin secretion was dose-dependently increased by CCK infusion and increased to 268 +/- 38.2% (n = 7) of basal secretion...

  14. Reduction of food intake by fenofibrate is associated with cholecystokinin release in long-evanstokushima rats

    Directory of Open Access Journals (Sweden)

    S Yu Vorotnikova

    2012-09-01

    Full Text Available Реферат по статье: Reduction of food intake by fenofibrate is associated with cholecystokinin release in long-evanstokushima rats Park MK, Han Y, Kim MS, Seo E, Kang S, Park SY, Koh H, Kim DK, Lee HJ. Korean J Physiol Pharmacol Vol 16: 181-186, June, 2012

  15. Comparative biodistribution of 12 (1)(1)(1)In-labelled gastrin/CCK2 receptor-targeting peptides

    NARCIS (Netherlands)

    Laverman, P.; Joosten, L.; Eek, A.; Roosenburg, S.; Peitl, P.K.; Maina, T.; Macke, H.; Aloj, L.; Guggenberg, E. von; Sosabowski, J.K.; Jong, M. de; Reubi, J.C.; Oyen, W.J.G.; Boerman, O.C.

    2011-01-01

    PURPOSE: Cholecystokinin 2 (CCK-2) receptor overexpression has been demonstrated in various tumours such as medullary thyroid carcinomas and small-cell lung cancers. Due to this high expression, CCK-2 receptors might be suitable targets for radionuclide imaging and/or radionuclide therapy. Several

  16. Synergistic effect of CART (cocaine- and amphetamine-regulated transcript peptide and cholecystokinin on food intake regulation in lean mice

    Directory of Open Access Journals (Sweden)

    Kiss Alexander

    2008-10-01

    Full Text Available Abstract Background CART (cocaine- and amphetamine-regulated transcript peptide and cholecystokinin (CCK are neuromodulators involved in feeding behavior. This study is based on previously found synergistic effect of leptin and CCK on food intake and our hypothesis on a co-operation of the CART peptide and CCK in food intake regulation and Fos activation in their common targets, the nucleus tractus solitarii of the brainstem (NTS, the paraventricular nucleus (PVN, and the dorsomedial nucleus (DMH of the hypothalamus. Results In fasted C57BL/6 mice, the anorexigenic effect of CART(61-102 in the doses of 0.1 or 0.5 μg/mouse was significantly enhanced by low doses of CCK-8 of 0.4 or 4 μg/kg, while 1 mg/kg dose of CCK-A receptor antagonist devazepide blocked the effect of CART(61-102 on food intake. After simultaneous administration of 0.1 μg/mouse CART(61-102 and of 4 μg/kg of CCK-8, the number of Fos-positive neurons in NTS, PVN, and DMH was significantly higher than after administration of each particular peptide. Besides, CART(61-102 and CCK-8 showed an additive effect on inhibition of the locomotor activity of mice in an open field test. Conclusion The synergistic and long-lasting effect of the CART peptide and CCK on food intake and their additive effect on Fos immunoreactivity in their common targets suggest a co-operative action of CART peptide and CCK which could be related to synergistic effect of leptin on CCK satiety.

  17. Ontogeny of cholecystokinin-like immunoreactivity in the Brazilian opossum brain.

    Science.gov (United States)

    Fox, C A; Jeyapalan, M; Ross, L R; Jacobson, C D

    1991-12-17

    We have studied the anatomical distribution of cholecystokinin-like immunoreactive (CCK-IR) somata and fibers in the brain of the adult and developing Brazilian short-tailed opossum, Monodelphis domestica. Animals ranged in age from the day of birth (1PN) to young adulthood (180PN). A nickel enhanced, avidin-biotin, indirect immunohistochemical technique was used to identify CCK-IR structures. Somata containing CCK immunoreactivity were observed in the cerebral cortex, hippocampus, hypothalamus, thalamus, midbrain, and brainstem in the adult. Cholecystokinin immunoreactive fibers had a wide distribution in the adult Monodelphis brain. The only major region of the brain that did not contain CCK-IR fibers was the cerebellum. The earliest expression of CCK immunoreactivity was found in fibers in the dorsal brainstem of 5-day-old opossum pups. It is possible that the CCK-IR fibers in the brainstem at 5PN are of vagal origin. Cholecystokinin immunoreactive somata were observed in the brainstem on 10PN. The CCK-IR cell bodies observed in the brainstem at 10PN may mark the first expression of CCK-IR elements intrinsic to the brain. A broad spectrum of patterns of onset of CCK expression was observed in the opossum brain. The early occurrence and varied ontogenesis of CCK-IR structures indicates CCK may be involved in the function of a variety of circuits from the brainstem to the cerebral cortex. The early expression of CCK-IR structures in the dorsal brainstem suggests that CCK may modulate feeding behavior in the Monodelphis neonate. Cholecystokinin immunoreactivity in forebrain structures such as the suprachiasmatic nucleus, medial preoptic area, thalamus and cortical structures indicates that CCK may also be involved in circadian rhythmicity, reproductive functions, as well as the state of arousal of the Brazilian opossum. The ontogenic timing of CCK immunoreactivity in specific circuitry also indicates that CCK expression does not occur simultaneously throughout the

  18. In vitro release of cholecystokinin octapeptide-like immunoreactivity from rat brain synaptosomes

    International Nuclear Information System (INIS)

    Klaff, L.J.; Hudson, A.; Sheppard, M.; Tyler, M.

    1981-01-01

    Enriched synaptosome fractions prepared by differential centrifugation and ultracentrifugation of homogenates of rat cortex, striatum, thalamus and hypothalamus contained over 65% of the total immunoreactive cholecystokinin octapeptide (CCK-8) in each area. A calcium dependent release of immunoreactive CCK-8 from these fractions in vitro in response to 2 depolarizing stimuli (60 mM KCl and 75 μM veratrine) has been demonstrated. Released CCK-8 immunoreactivity showed parallelism when serial dilutions were compared with the CCK-8 dose-response curve and eluted similarly to synthetic CCK-8 on Sephadex G-50 superfine chromatography. These results provide further evidence for a neurotransmitter or neuromodulator role for CCK-8 in brain

  19. Expression of receptors for gut peptides in human pancreatic adenocarcinoma and tumour-free pancreas

    NARCIS (Netherlands)

    Tang, C.; Biemond, I.; Offerhaus, G. J.; Verspaget, W.; Lamers, C. B.

    1997-01-01

    Gut hormones that modulate the growth of normal pancreas may also modulate the growth of cancers originating from pancreas. This study visualized and compared the receptors for cholecystokinin (CCK), bombesin (BBS), secretin and vasoactive intestinal peptide (VIP) in tumour-free tissue sections of

  20. Rats with decreased brain cholecystokinin levels show increased responsiveness to peripheral electrical stimulation-induced analgesia.

    Science.gov (United States)

    Zhang, L X; Li, X L; Wang, L; Han, J S

    1997-01-16

    Using the P77PMC strain of rat, which is genetically prone to audiogenic seizures, and also has decreased levels of cholecystokinin (CCK), we examined the analgesic response to peripheral electrical stimulation, which is, in part, opiate-mediated. A number of studies have suggested that CCK may function as an antagonist to endogenous opiate effects. Therefore, we hypothesized that the P77PMC animals would show an enhanced analgesic response based on their decreased CCK levels producing a diminished endogenous opiate antagonism. We found that the analgesic effect on tail flick latency produced by 100 Hz peripheral electrical stimulation was more potent and longer lasting in P77PMC rats than in control rats. Moreover, the potency of the stimulation-produced analgesia correlated with the vulnerability to audiogenic seizures in these rats. We were able to block the peripheral electrical stimulation-induced analgesia (PSIA) using a cholecystokinin octapeptide (CCK-8) administered parenterally. Radioimmunoassay showed that the content of CCK-8 in cerebral cortex, hippocampus and periaqueductal gray was much lower in P77PMC rat than in controls. These results suggest that low CCK-8 content in the central nervous system of the P77PMC rats may be related to the high analgesic response to peripheral electrical stimulation, and further support the notion that CCK may be endogenous opiate antagonist.

  1. Existence of B/E and E receptors on Hep-G2 cells: a study using colloidal gold- and 125I-labeled lipoproteins

    International Nuclear Information System (INIS)

    Hesz, A.; Ingolic, E.; Krempler, F.; Kostner, G.M.

    1987-01-01

    The presence of specific receptors for apolipoprotein B (low-density lipoproteins) and apolipoprotein E (HDL-E) on Hep-G2 cells and human skin fibroblasts was studied by chemical methods and by electron microscopy using a differential gold labeling technique. Fibroblasts bound both types of lipoproteins to one and the same receptor (B/E receptor) as deduced from competition experiments with HDL-E and LDL. Labeled HDL-E, on the other hand, was only partially displaced by cold LDL but was completely displaced by unlabeled HDL-E. Scatchard analysis of lipoprotein binding to Hep-G2 cells revealed an approx 10 times higher binding affinity of apoE-containing lipoproteins as compared to apoB-containing ones. No differences between apoE- or apoB-containing lipoproteins with respect to the morphology of cell binding and intracellular processing were observed. The results are compatible with the concept that Hep-G2 cells possess two kinds of receptors, one specific for apoB- and apoE-containing lipoproteins (B/E receptor) and another specific for apoE only. From these studies we conclude that Hep-G2 cells may serve as a suitable model for studying the lipoprotein metabolism in the liver

  2. Incretin physiology beyond glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide: cholecystokinin and gastrin peptides

    DEFF Research Database (Denmark)

    Rehfeld, J F

    2011-01-01

    Gastrin and cholecystokinin (CCK) are homologous hormone systems known to regulate gastric acid secretion, gallbladder emptying, and cell growth in the pancreas and stomach. They are, however, also involved in the development and secretory functions of pancreatic islet cells. For instance, foetal...

  3. receptores

    Directory of Open Access Journals (Sweden)

    Salete Regina Daronco Benetti

    2006-01-01

    Full Text Available Se trata de un estudio etnográfico, que tuvo lo objetivo de interpretar el sistema de conocimiento y del significado atribuidos a la sangre referente a la transfusión sanguínea por los donadores y receptores de un banco de sangre. Para la colecta de las informaciones se observaron los participantes y la entrevista etnográfica se realizó el análisis de dominio, taxonómicos y temáticos. Los dominios culturales fueron: la sangre es vida: fuente de vida y alimento valioso; creencias religiosas: fuentes simbólicas de apoyos; donación sanguínea: un gesto colaborador que exige cuidarse, gratifica y trae felicidad; donación sanguínea: fuente simbólica de inseguridad; estar enfermo es una condición para realizar transfusión sanguínea; transfusión sanguínea: esperanza de vida; Creencias populares: transfusión sanguínea como riesgo para la salud; donadores de sangre: personas benditas; donar y recibir sangre: como significado de felicidad. Temática: “líquido precioso que origina, sostiene, modifica la vida, provoca miedo e inseguridad”.

  4. Unsulfated cholecystokinin

    DEFF Research Database (Denmark)

    Rehfeld, Jens F; Agersnap, Mikkel

    2012-01-01

    for the cholecystokinetic activity (i.e. gallbladder emptying) of CCK peptides. Accordingly, the purification of CCK as a sulfated peptide was originally monitored by its gallbladder emptying effect. Since then, the dogma has prevailed that CCK peptides are always sulfated. The dogma is correct in a semantic context since...

  5. Cholecystokinin-Assisted Hydrodissection of the Gallbladder Fossa during FDG PET/CT-guided Liver Ablation

    Energy Technology Data Exchange (ETDEWEB)

    Tewari, Sanjit O., E-mail: tewaris@mskcc.org [Memorial Sloan-Kettering Cancer Center, Molecular Imaging and Therapy Service, Department of Radiology (United States); Petre, Elena N., E-mail: petree@mskcc.org [Memorial Sloan-Kettering Cancer Center, Interventional Radiology Service, Department of Radiology (United States); Osborne, Joseph, E-mail: osbornej@mskcc.org [Memorial Sloan-Kettering Cancer Center, Molecular Imaging and Therapy Service, Department of Radiology (United States); Sofocleous, Constantinos T., E-mail: sofoclec@mskcc.org [Memorial Sloan-Kettering Cancer Center, Interventional Radiology Service, Department of Radiology (United States)

    2013-12-15

    A 68-year-old female with colorectal cancer developed a metachronous isolated fluorodeoxyglucose-avid (FDG-avid) segment 5/6 gallbladder fossa hepatic lesion and was referred for percutaneous ablation. Pre-procedure computed tomography (CT) images demonstrated a distended gallbladder abutting the segment 5/6 hepatic metastasis. In order to perform ablation with clear margins and avoid direct puncture and aspiration of the gallbladder, cholecystokinin was administered intravenously to stimulate gallbladder contraction before hydrodissection. Subsequently, the lesion was ablated successfully with sufficient margins, of greater than 1.0 cm, using microwave with ultrasound and FDG PET/CT guidance. The patient tolerated the procedure very well and was discharged home the next day.

  6. Using cholecystokinin to facilitate endoscopic clearance of large common bile duct stones

    Science.gov (United States)

    Tao, Tao; Zhang, Qi-Jie; Zhang, Ming; Zhu, Xiao; Sun, Shu-Xia; Li, Yan-Qing

    2014-01-01

    AIM: To evaluate the effect of cholecystokinin (CCK) during extracorporeal shockwave lithotripsy (ESWL) in the clearance of common bile duct (CBD) stones in endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Between January 2007 and September 2012, patients with large CBD stones who were treated with ESWL and ERCP were identified retrospectively. Patients were randomized in equal numbers to cholecystokinin (CCK) and no CCK groups. For each CCK case, a dose (3 ng/kg per min for 10 min) of sulfated octapeptide of CCK-8 was administered intravenously near the beginning of ESWL. ERCP was performed 4 h after a session of ESWL. The clearance rate of the CBD was assessed between the two groups. RESULTS: A total of 148 consecutive cases (CCK group: 74, no CCK group: 74) were tallied. Overall there were 234 ESWLs and 228 ERCPs in the 148 cases. The use of CCK showed a significantly higher rate of successful stone removal in the first ESWL/ERCP procedure (71.6% vs 55.4%, P = 0.035), but resulted in similar outcomes in the second (42.8% vs 39.4%) and third (41.7% vs 40.0%) sessions, as well as total stone clearance (90.5% vs 83.8%). The use of mechanical lithotripsy was reduced in the CCK group (6.8% vs 17.6%, P = 0.023), and extremely large stone (≥ 30 mm) removal was higher in the CCK group (72.7% vs 41.7%, P = 0.038). CONCLUSION: CCK during ESWL can aid with the clearance of CBD stones in the first ESWL/ERCP session. Mechanical lithotripsy usage was reduced and the extremely large stone (≥ 30 mm) clearance rate can be raised. PMID:25110439

  7. Differential regulation of inositol 1,4,5-trisphosphate by co-existing P2Y-purinoceptors and nucleotide receptors on bovine aortic endothelial cells.

    Science.gov (United States)

    Purkiss, J R; Wilkinson, G F; Boarder, M R

    1994-03-01

    1. We have examined the inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) responses in bovine aortic endothelial (BAE) cells to purines (ATP, ADP and analogues) and the pyrimidine, uridine triphosphate (UTP). 2. Exchange of medium on BAE cells in the absence of agonist was found to be a stimulus for Ins(1,4,5)P3 generation. BAE cells stimulated with 100 microM ATP, 30 microM 2MeSATP (an agonist at P2Y-purinoceptors but not nucleotide receptors) or 100 microM UTP (an agonist at nucleotide receptors but not P2Y-purinoceptors) gave Ins(1,4,5)P3 responses above that caused by exchange of medium. The time course was rapid, with peak response within the first 5 s and levels returning close to basal after 30 s of stimulation. 3. Significant differences in Ins(1,4,5)P3 responses to 100 microM UTP and 30 microM 2MeSATP stimulation were observed. The response to UTP was reproducibly more sustained than that to 2MeSATP. 4. Stimulation of BAE cells with 100 microM UTP plus 30 microM 2MeSATP produced a response statistically indistinguishable from that predicted by addition of the responses to the two agonists in isolation. 5. The Ins(1,4,5)P3 response to UTP was attenuated to 25% of control by pretreatment of BAE cells with pertussis toxin. Responses to 2MeSATP and ADP were essentially unaffected. ATP stimulation was reduced to 65% of control. 6. Activation of protein kinase C with tetradecanoyl phorbol acetate (TPA) profoundly inhibited Ins(1,4,5)P3 responses to 2MeSATP and ADP but had no effect on UTP stimulation. The protein kinase C inhibitor, Ro 31-8220, enhanced responses to 2MeSATP, ADP and ATP but no effect was observed on UTP stimulation. 7. These observations show that nucleotide and P2Y-receptors mobilise the second messenger Ins(1,4,5)P3 by separate routes resulting in different patterns of generation and suggest that while ATP activates both receptors, ADP principally influences these cells by interacting with the P2Y-purinoceptors.

  8. Existence of multiple receptors in single neurons: responses of single bullfrog olfactory neurons to many cAMP-dependent and independent odorants.

    Science.gov (United States)

    Kashiwayanagi, M; Shimano, K; Kurihara, K

    1996-11-04

    The responses of single bullfrog olfactory neurons to various odorants were measured with the whole-cell patch clamp which offers direct information on cellular events and with the ciliary recording technique to obtain stable quantitative data from many neurons. A large portion of single olfactory neurons (about 64% and 79% in the whole-cell recording and in the ciliary recording, respectively) responded to many odorants with quite diverse molecular structures, including both odorants previously indicated to be cAMP-dependent (increasing) and independent odorants. One odorant elicited a response in many cells; e.g. hedione and citralva elicited the response in 100% and 92% of total neurons examined with the ciliary recording technique. To confirm that a single neuron carries different receptors or transduction pathways, the cross-adaptation technique was applied to single neurons. Application of hedione to a single neuron after desensitization of the current in response to lyral or citralva induced an inward current with a similar magnitude to that applied alone. It was suggested that most single olfactory neurons carry multiple receptors and at least dual transduction pathways.

  9. Urotensin II receptor (UTR) exists in hyaline chondrocytes: a study of peripheral distribution of UTR in the African clawed frog, Xenopus laevis.

    Science.gov (United States)

    Konno, Norifumi; Fujii, Yuya; Imae, Haruka; Kaiya, Hiroyuki; Mukuda, Takao; Miyazato, Mikiya; Matsuda, Kouhei; Uchiyama, Minoru

    2013-05-01

    Urotensin II (UII) and UII-related peptide (URP) exhibit diverse physiological actions including vasoconstriction, locomotor activity, osmoregulation, and immune response through UII receptor (UTR), which is expressed in the central nervous system and peripheral tissues of fish and mammals. In amphibians, only UII has been identified. As the first step toward elucidating the actions of UII and URP in amphibians, we cloned and characterized URP and UTR from the African clawed frog Xenopus laevis. Functional analysis showed that treatment of UII or URP with Chinese hamster ovary cells transfected with the cloned receptor increased the intracellular calcium concentration in a concentration-dependent manner, whereas the administration of the UTR antagonist urantide inhibited UII- or URP-induced Ca(2+) mobilization. An immunohistochemical study showed that UTR was expressed in the splenocytes and leukocytes isolated from peripheral blood, suggesting that UII and URP are involved in the regulation of the immune system. UTR was also localized in the apical membrane of the distal tubule of the kidney and in the transitional epithelial cells of the urinary bladder. This result supports the view that the UII/URP-UTR system plays an important role in osmoregulation of amphibians. Interestingly, immunopositive labeling for UTR was first detected in the chondrocytes of various hyaline cartilages (the lung septa, interphalangeal joint and sternum). The expression of UTR was also observed in the costal cartilage, tracheal cartilages, and xiphoid process of the rat. These novel findings probably suggest that UII and URP mediate the formation of the cartilaginous matrix. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Cholecystokinin like immunoreactivity in the brains of young Meishan and Duroc pigs(4).

    Science.gov (United States)

    Elmquist, J K; Ross, L R; Hsu, W; Rothschild, M F; Jacobson, C D

    1993-01-12

    Cholecystokinin (CCK), a peptide found in both the gastrointestinal tract and brain, has been shown to be involved in the control of feed intake in a variety of animals including the pig. Chinese breeds of pigs such as the Meishan are noted for slow growth and heavy adipose deposition. In this study we have described the regional cholecystokinin-like immunoreactivity (CCK-IR) concentrations in the brain of young Duroc and Meishan pigs utilizing radioimmunoassay. Brains of days 1, 10, and 20 postnatal pigs from each breed were examined. The CCK-IR increased with age in all three areas examined (cortex, medulla, and hypothalamus). The cortical concentrations rose significantly from days 1 to 10 and from days 10 to 20. The levels in the hypothalamus and medulla increased significantly between days 1 and 20. There were no statistically significant differences in CCK-IR between the breeds at any of the three ages examined. Our results indicate that a rise in CCK-IR in the regions of the brain involved in the control of feed intake may parallel the ability of the young pigs to assimilate nutrients from a solid diet. ZUSAMMENFASSUNG: Cholecystokinin-ähnliche Immunreaktivität in den Gehirnen junger Meishan- und Durocschweine Das Peptid Cholecystokinin (CCK) wird im Gastrointestinaltrakt und im Gehirn gefunden und beeinflußt Futteraufnahme in einer Reihe von Tieren einschließlich Schwein. Chinesische Rassen wie Meishan sind wegen ihres langsamen Wachstums und der starken Fettablagerung bekannt. In dieser Studie beschreiben wir regionale Cholecystokinin-ähnliche Immunreaktivitäts-(CCK-IR)Konzentrationen im Gehirn junger Duroc- und Meishantiere, mittels Radioimmunassay bestimmt. Gehirne von 1, 10 und 20 Tage alten Ferkeln jeder Rasse wurden untersucht. CCK-IR nahm mit dem Alter in allen drei untersuchten Organen zu (Kortex, Medulla und Hypothalamus). Die kortikalen Spiegel stiegen vom Tag 1 bis 10 und vom Tag 10 bis 20 signifikant, die des Hypothalamus und der Medulla

  11. Role of cholecystokinin in anorexia induction following oral exposure to the 8-ketotrichothecenes deoxynivalenol, 15-acetyldeoxynivalenol, 3-acetyldeoxynivalenol, fusarenon X, and nivalenol.

    Science.gov (United States)

    Wu, Wenda; Zhou, Hui-Ren; He, Kaiyu; Pan, Xiao; Sugita-Konishi, Yoshiko; Watanabe, Maiko; Zhang, Haibin; Pestka, James J

    2014-04-01

    Cereal grain contamination by trichothecene mycotoxins is known to negatively impact human and animal health with adverse effects on food intake and growth being of particular concern. The head blight fungus Fusarium graminearum elaborates five closely related 8-ketotrichothecene congeners: (1) deoxynivalenol (DON), (2) 3-acetyldeoxynivalenol (3-ADON), (3) 15-acetyldeoxynivalenol (15-ADON), (4) fusarenon X (FX), and (5) nivalenol (NIV). While anorexia induction in mice exposed intraperitoneally to DON has been linked to plasma elevation of the satiety hormones cholecystokinin (CCK) and peptide YY₃₋₃₆ (PYY₃₋₃₆), the effects of oral gavage of DON or of other 8-keotrichothecenes on release of these gut peptides have not been established. The purpose of this study was to (1) compare the anorectic responses to the aforementioned 8-ketotrichothecenes following oral gavage at a common dose (2.5 mg/kg bw) and (2) relate these effects to changes plasma CCK and PYY₃₋₃₆ concentrations. Elevation of plasma CCK markedly corresponded to anorexia induction by DON and all other 8-ketotrichothecenes tested. Furthermore, the CCK1 receptor antagonist SR 27897 and the CCK2 receptor antagonist L-365,260 dose-dependently attenuated both CCK- and DON-induced anorexia, which was consistent with this gut satiety hormone being an important mediator of 8-ketotrichothecene-induced food refusal. In contrast to CCK, PYY₃₋₃₆ was moderately elevated by oral gavage with DON and NIV but not by 3-ADON, 15-ADON, or FX. Taken together, the results suggest that CCK plays a major role in anorexia induction following oral exposure to 8-ketotrichothecenes, whereas PYY₃₋₃₆ might play a lesser, congener-dependent role in this response.

  12. Retraction: Borroto-Escuela et al., The existence of FGFR1-5-HT1A receptor heterocomplexes in midbrain 5-HT neurons of the rat: relevance for neuroplasticity.

    Science.gov (United States)

    2013-07-10

    The Journal of Neuroscience has received a report describing an investigation by the Karolinska Institutet, which found substantial data misrepresentation in the article "The Existence of FGFR1-5-HT1A Receptor Heterocomplexes in Midbrain 5-HT Neurons of the Rat: Relevance for Neuroplasticity" by Dasiel O. Borroto-Escuela, Wilber Romero-Fernandez, Mileidys Pérez-Alea, Manuel Narvaez, Alexander O. Tarakanov, Giuseppa Mudó , Luigi F. Agnati, Francisco Ciruela, Natale Belluardo, and Kjell Fuxe, which appeared on pages 6295-6303 of the May 2, 2012 issue. Because the results cannot be considered reliable, the editors of The Journal are retracting the paper.

  13. Modulation of [3H]-dopamine binding by cholecystokinin octapeptide (CCK-8)

    International Nuclear Information System (INIS)

    Murphy, R.B.; Schuster, D.I.

    1982-01-01

    Cholecystokinin-octapeptide (CCK-8) is a putative neurotransmitter which has been demonstrated previously to occur in midbrain dopamine neurones. We observe that CCK-8 causes changes in both the affinity and density of binding sites for [ 3 H]-dopamine in rat striatal homogenates, in vitro, upon incubation with the peptide at a concentration of 1 micromolar. A dose-response study of the competetion of CCK-8 with [ 3 H]-dopamine binding indicates an IC50 for the peptide of 450 nM; desulfated CCK-8 and the related peptide caerulin are at least 4-fold less active than CCK-8. CCK-8 was also administered to rats in a separate study; the binding of [ 3 H]-dopamine was evaluated to homogenates of striata and olfactory tubercles obtained from these animals, which had been treated with systemic injection at a dose of 20 micrograms/kg, daily, for four days. A decrease in the number of striatal binding sites for the radioligand was observed, with a concomitant increase in the number of binding sites in the olfactory tubercle. These data collectively suggest a possible regulatory role for CCK-8 in the ascending dopamine systems

  14. Diet composition alters the satiety effect of cholecystokinin in lean and obese Zucker rats.

    Science.gov (United States)

    Maggio, C A; Haraczkiewicz, E; Vasselli, J R

    1988-01-01

    Although exogenous administration of the peptide cholecystokinin (CCK) has been shown to reduce food intake in a variety of experimental situations, few studies have examined the influence of dietary content upon CCK's effectiveness, particularly in obese states. To evaluate the effectiveness of CCK administration in animals consuming high fat diets, groups of obese and lean Zucker rats were maintained on laboratory chow (CH), a high fat diet isocaloric to chow (IF), or a hypercaloric fat diet (HF). After a 17 hr fast, rats were given intraperitoneal injections of saline or ascending doses of 0.06 to 2.0 micrograms/kg of the synthetic octapeptide of CCK. On all diets, obese rats required higher doses of CCK to significantly reduce feeding and showed smaller intake reductions than lean rats (p less than 0.001). Despite higher baseline caloric intakes (p less than 0.001), rats of both genotypes maintained on HF displayed larger reductions of intake than those fed IF or CH (p less than 0.001). Intake reductions by either genotype maintained on IF or CH were not reliably different. The manner in which the satiety effect of CCK was enhanced in rats consuming the calorically dense, palatable HF diet is unclear but may be related to orosensory and/or postingestive attributes of the diet.

  15. Molecular cloning, characterization, and expression analysis of ghrelin and cholecystokinin in the pigeon (Columba livia).

    Science.gov (United States)

    Xie, P; Wan, X P; Bu, Z; Zou, X T

    2016-11-01

    Ghrelin and cholecystokinin (CCK) are multifunctional peptides. In the current study, complete sequences of ghrelin (800 bp) and CCK (739 bp) were firstly cloned in Columba livia by using rapid amplification of cDNA ends (RACE) method. The open reading frames of ghrelin (351bp) and CCK (393bp) encoded 116 amino acids and 130 amino acids, respectively. Sequence comparison indicated that pigeon ghrelin and CCK shared high identity with those reported in other avian species. Quantitative real-time PCR analysis found that ghrelin and CCK mRNAs expressed in three intestinal segments of pigeon during development. Both ghrelin and CCK showed generally higher expressions at days posthatch than embryonic periods regardless of intestinal segments. In duodenum and ileum, the expressions of ghrelin and CCK mRNA reached the peak values at 8 d posthatch. Jejunum CCK mRNA level increased linearly after hatching, and reached the highest point at posthatch 28 d. Based on documented effects of long chain fatty acids (LCFAs) on pigeon ghrelin and CCK expression were also investigated in vitro. Higher concentrations (50 μM or 250 μM) of linoleic acid, α-linolenic acid or arachidonic acid can significantly increase ghrelin mRNA level in pigeon jejunum. However, for oleic acid, the induction of ghrelin gene expressions needed a lower concentration (5 μM). 5 μM of linoleic acid, α-linolenic acid or arachidonic acid and 250 μM palmitic acid repressed CCK expression significantly. A higher concentration (250 μM) of oleic acid or α-linolenic acid can up-regulate CCK mRNA level significantly. Our results indicated that ghrelin and CCK may act key functions in pigeon intestine development and their expressions could be regulated by LCFAs. © 2016 Poultry Science Association Inc.

  16. Elevated plasma cholecystokinin at high altitude: metabolic implications for the anorexia of acute mountain sickness.

    Science.gov (United States)

    Bailey, D M; Davies, B; Milledge, J S; Richards, M; Williams, S R; Jordinson, M; Calam, J

    2000-01-01

    The aims of the present study were to measure the satiety neuropeptide cholecystokinin (CCK) in humans at terrestrial high altitude to investigate its possible role in the pathophysiology of anorexia, cachexia, and acute mountain sickness (AMS). Nineteen male mountaineers aged 38 +/- 12 years participated in a 20 +/- 5 day trek to Mt. Kanchenjunga basecamp (BC) located at 5,100 m, where they remained for 7 +/- 5 days. Subjects were examined at rest and during a maximal exercise test at sea-level before/after the expedition (SL1/SL2) and during the BC sojourn. There was a mild increase in Lake Louise AMS score from 1.1 +/- 1.2 points at SL1 to 2.3 +/- 2.3 points by the end of the first day at BC (P anorexia on Day 2 compared with those with a normal appetite. While there was no relationship between the increase in CCK and AMS score at BC, a more pronounced increase in resting CCK was observed in subjects with AMS (> or =3 points at the end of Day 1 at BC) compared with those without (+98.9 +/- 1.4 pmol/L(-1) vs. +67.6 +/- 37.2 pmol/L(-1), P < 0.05). Caloric intake remained remarkably low during the stay at BC (8.9 +/- 1.4 MJ.d(-1)) despite a progressive decrease in total body mass (-4.5 +/- 2.1 kg after 31 +/- 13 h at BC, P < 0.05 vs. SL1/SL2), which appeared to be due to a selective loss of torso adipose tissue. These findings suggest that the satiogenic effects of CCK may have contributed to the observed caloric deficit and subsequent cachexia at high altitude despite adequate availability of palatable foods. The metabolic implications of elevated CCK in AMS remain to be elucidated.

  17. Circulating levels of cholecystokinin and gastrin-releasing peptide in rainbow trout fed different diets.

    Science.gov (United States)

    Jönsson, Elisabeth; Forsman, Antti; Einarsdottir, Ingibjörg E; Egnér, Barbro; Ruohonen, Kari; Björnsson, Björn Thrandur

    2006-09-01

    Cholecystokinin (CCK) and gastrin-releasing peptide (GRP) are gastrointestinal peptides thought to be important regulators of intake and digestion of food in vertebrates. In this study, pre- and postprandial plasma levels of CCK and GRP were measured in rainbow trout (Oncorhynchus mykiss) by the establishment of homologous radioimmunoassays, and the hormonal levels assessed in relation to dietary lipid:protein ratio and food intake. Fish were acclimated to either a high protein/low lipid diet (HP/LL diet; 14.1% lipids) or a normal protein/high lipid diet (NP/HL diet; 31.4% lipids). On three consecutive sampling days, radio-dense lead-glass beads were included in the diets for assessment of feed intake. Fish were terminally sampled for blood and stomach contents prior to feeding at time 0, and at 0.3, 1, 2, 4, 6, and 24 h after feeding. There was a postprandial elevation of plasma CCK levels, which was most evident after 4 and 6 h. Fish fed the NP/HL diet had higher plasma CCK levels compared with those fed the HP/LL diet. Plasma CCK levels were not affected by the amount of food ingested. GRP levels in plasma were not influenced by sampling time, diet, or feed intake. The results indicate that the endocrine release of gastrointestinal CCK is increased during feeding and may be further influenced by the dietary lipid:protein ratio in rainbow trout. Plasma GRP levels, on the other hand, appear not to be influenced by feeding or diet composition.

  18. Appetite suppressing effect of Spinacia oleracea in rats: Involvement of the short term satiety signal cholecystokinin.

    Science.gov (United States)

    Panda, Vandana; Shinde, Priyanka

    2017-06-01

    Spinacia oleracea (spinach) is a green leafy vegetable rich in antioxidant phyto-constituents such as flavonoids, polyphenols, carotenoids and vitamins. Fruits and vegetables rich in flavonoids are known to prevent weight gain by inducing satiety. The present study evaluates the appetite suppressing effect of a flavonoid rich extract of the spinach leaf (SOE) in rats. HPTLC of SOE was performed for detecting flavonoids. Rats were administered SOE (200 mg/kg and 400 mg/kg, p. o) and fluoxetine (6 mg/kg i. p) as a pre-meal for 14 days. Food intake and weight gain was observed daily during the treatment period. Serum levels of the short term satiety signals cholecystokinin (CCK) and glucose were measured on the 7th and 14thdays at different time points after start of meal to study the satiety inducing effect of SOE. HPTLC showed the presence of 14 flavonoids in SOE. SOE and fluoxetine treated rats showed a significant reduction in food intake and weight gain when compared with the normal control rats. On the 7th day of treatment, peak CCK levels were reached in 30 min after start of meal in fluoxetine treated rats and in 60 min in the remaining rats. On the 14th day, CCK peaking was observed in 30 min after start of meal in the fluoxetine as well as SOE 400 mg/kg treated rats. Peak glucose levels in all treatment groups were obtained in 60 min after start of feeding on both days of the study. It maybe concluded that SOE exhibited a promising appetite suppressing effect by inducing a quicker than normal release of CCK, thus eliciting an early onset of satiety in rats. This effect may be due to its high flavonoid content. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Diet-induced and monosodium-glutamate obesity in mice: Relationship among neuropeptide Y, CART peptide and cholecystokinin in feeding behavior

    Czech Academy of Sciences Publication Activity Database

    Železná, Blanka; Matyšková, Resha; Maixnerová, Jana; Haugvicová, Renata; Blokešová, Darja; Maletínská, Lenka

    2007-01-01

    Roč. 88, č. 4 (2007), s. 557 ISSN 0006-3525. [American Peptide Society Symposium /20./. 26.06.2007-30.06.2007, Montreal] Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50200510 Keywords : cocaine and amphetamine regulated transcript peptide * cholecystokinin Subject RIV: CE - Biochemistry

  20. Serum gastrin and cholecystokinin are associated with subsequent development of gastric cancer in a prospective cohort of Finnish smokers

    DEFF Research Database (Denmark)

    Murphy, Gwen; Abnet, Christian C; Choo-Wosoba, Hyoyoung

    2017-01-01

    Background: Gastrin, which induces gastric acid secretion, and a structurally similar hormone, cholecystokinin (CCK)-a potent acid inhibitor, may each play a role in gastric cancer. However, few studies have investigated this hypothesis in humans. We therefore investigated whether serum gastrin...... or CCK concentrations at baseline were associated with the incidence of gastric non-cardia adenocarcinomas (GNCA), oesophagogastric junctional adenocarcinomas (EGJA) or gastric carcinoid tumours over 24 years of follow-up in a study nested within the all-male Alpha-Tocopherol, Beta-Carotene Cancer...... suggest that high serum concentrations of gastrin may be associated independently with an increased risk of gastric cancer; the role of CCK in cancer risk is less clear....

  1. Anorexigenic effect of cholecystokinin is lost but that of CART (cocaine and amphetamine regulated transcript) peptide is preserved in monosodium glutamate obese mice

    Czech Academy of Sciences Publication Activity Database

    Železná, Blanka; Maixnerová, Jana; Matyšková, Resha; Haugvicová, Renata; Blokešová, Darja; Maletínská, Lenka

    2009-01-01

    Roč. 58, č. 5 (2009), s. 717-723 ISSN 0862-8408 R&D Projects: GA ČR GA303/05/0614 Grant - others:GA ČR(CZ) GA305/06/0427 Program:GA Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z5020903 Keywords : monosodium glutamate (MSG) obesity * neuropeptide Y (NPY) * cholecystokinin Subject RIV: CC - Organic Chemistry Impact factor: 1.430, year: 2009

  2. Ghrelin suppresses cholecystokinin (CCK), peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) in the intestine, and attenuates the anorectic effects of CCK, PYY and GLP-1 in goldfish (Carassius auratus).

    Science.gov (United States)

    Blanco, Ayelén Melisa; Bertucci, Juan Ignacio; Valenciano, Ana Isabel; Delgado, María Jesús; Unniappan, Suraj

    2017-07-01

    Ghrelin is an important gut-derived hormone with an appetite stimulatory role, while most of the intestinal hormones, including cholecystokinin (CCK), peptide YY (PYY) and glucagon-like peptide-1 (GLP-1), are appetite-inhibitors. Whether these important peptides with opposing roles on food intake interact to regulate energy balance in fish is currently unknown. The aim of this study was to characterize the putative crosstalk between ghrelin and CCK, PYY and GLP-1 in goldfish (Carassius auratus). We first determined the localization of CCK, PYY and GLP-1 in relation to ghrelin and its main receptor GHS-R1a (growth hormone secretagogue 1a) in the goldfish intestine by immunohistochemistry. Colocalization of ghrelin/GHS-R1a and CCK/PYY/GLP-1 was found primarily in the luminal border of the intestinal mucosa. In an intestinal explant culture, a significant decrease in prepro-cck, prepro-pyy and proglucagon transcript levels was observed after 60min of incubation with ghrelin, which was abolished by preincubation with the GHS-R1a ghrelin receptor antagonist [D-Lys3]-GHRP-6 (except for proglucagon). The protein expression of PYY and GLP-1 was also downregulated by ghrelin. Finally, intraperitoneal co-administration of CCK, PYY or GLP-1 with ghrelin results in no modification of food intake in goldfish. Overall, results of the present study show for the first time in fish that ghrelin exerts repressive effects on enteric anorexigens. It is likely that these interactions mediate the stimulatory effects of ghrelin on feeding and metabolism in fish. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. The CCK(-like) receptor in the animal kingdom: functions, evolution and structures.

    Science.gov (United States)

    Staljanssens, Dorien; Azari, Elnaz Karimian; Christiaens, Olivier; Beaufays, Jérôme; Lins, Laurence; Van Camp, John; Smagghe, Guy

    2011-03-01

    In this review, the cholecystokinin (CCK)(-like) receptors throughout the animal kingdom are compared on the level of physiological functions, evolutionary basis and molecular structure. In vertebrates, the CCK receptor is an important member of the G-protein coupled receptors as it is involved in the regulation of many physiological functions like satiety, gastrointestinal motility, gastric acid secretion, gall bladder contraction, pancreatic secretion, panic, anxiety and memory and learning processes. A homolog for this receptor is also found in nematodes and arthropods, called CK receptor and sulfakinin (SK) receptor, respectively. These receptors seem to have evolved from a common ancestor which is probably still closely related to the nematode CK receptor. The SK receptor is more closely related to the CCK receptor and seems to have similar functions. A molecular 3D-model for the CCK receptor type 1 has been built together with the docking of the natural ligands for the CCK and SK receptors in the CCK receptor type 1. These molecular models can help to study ligand-receptor interactions, that can in turn be useful in the development of new CCK(-like) receptor agonists and antagonists with beneficial health effects in humans or potential for pest control. Copyright © 2010 Elsevier Inc. All rights reserved.

  4. Ambulatory blood pressure parameters after canrenone addition to existing treatment regimens with maximum tolerated dose of angiotensin-converting enzyme inhibitors/angiotensin II type 1 receptor blockers plus hydrochlorothiazide in uncontrolled hypertensive patients

    Directory of Open Access Journals (Sweden)

    Guasti L

    2017-08-01

    Full Text Available Luigina Guasti,1,* Giovanni Gaudio,2,* Alessandro Lupi,3 Marinella D’Avino,4 Carla Sala,5,6 Amedeo Mugellini,7 Vito Vulpis,8 Salvatore Felis,9 Riccardo Sarzani,10,11 Massimo Vanasia,12 Pamela Maffioli,7 Giuseppe Derosa7 1Research Center on Dyslipidemia, Internal Medicine 1, University of Insubria, Varese, Italy; 2Internal Medicine Division, Ospedale Angelo Bellini, ASST Valle Olona Somma, Varese, Italy; 3Cardiology Unit, ASL VCO Verbania-Domodossola, Verbania, Italy; 4Unit for the Treatment of Arterial Hypertension, Ospedale Cardarelli, Napoli, Italy; 5Department of Clinical Sciences and Community Health, University of Milan, Milano, Italy; 6Cardiovascular Unit, Fondazione IRCCSS Policlinico, Milano, Italy; 7Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy; 8Unit for the Diagnosis and Treatment of Arterial Hypertension, Department of Internal Medicine, Policlinico di Bari, Bari, Italy; 9Cardiology Unit, Ospedale Garibaldi, Catania, Italy; 10ESH Center of Hypertension, Internal Medicine and Geriatrics, University Politecnica delle Marche, Ancona, Italy; 11IRCCS-INRCA, Ancona, Italy; 12THERABEL GiEnne Pharma, Milano, Italy *These authors contributed equally to this work Background: Blockade of the renin–angiotensin–aldosterone system is a cornerstone in cardiovascular disease prevention and hypertension treatment. The relevance of ambulatory blood pressure monitoring (ABPM has been widely confirmed for both increasing the accuracy of blood pressure (BP measurements, particularly in pharmacological trials, and focusing on 24 h BP prognostic parameters. The aim of this study was to assess the effects of canrenone addition on ambulatory BP in uncontrolled hypertensive patients already treated with the highest tolerated dose of angiotensin-converting enzyme (ACE inhibitors or angiotensin II type 1 receptor (AT1R antagonists plus hydrochlorothiazide (HCT. Methods: ABPM was performed at baseline and after 3

  5. Changes of Serotonin (5-HT), 5-HT2A Receptor, and 5-HT Transporter in the Sprague-Dawley Rats of Depression,Myocardial Infarction and Myocardial Infarction Co-exist with Depression

    Institute of Scientific and Technical Information of China (English)

    Mei-Yan Liu; Yah-Ping Ren; Wan-Lin Wei; Guo-Xiang Tian; Guo Li

    2015-01-01

    Background:To evaluate whether serotonin (5-HT),5-HT2A receptor (5-HT2AR),and 5-HT transporter (serotonin transporter [SERT]) are associated with different disease states of depression,myocardial infarction (MI) and MI co-exist with depression in Sprague-Dawley rats.Methods:After established the animal model of four groups include control,depression,MI and MI with depression,we measured 5-HT,5-HT2AR and SERT from serum and platelet lysate.Results:The serum concentration of 5-HT in depression rats decreased significantly compared with the control group (303.25 ± 9.99 vs.352.98 ± 13.73;P =0.000),while that in MI group increased (381.78 ± 14.17 vs.352.98 ± 13.73;P =0.000).However,the depression + MI group had no change compared with control group (360.62 ± 11.40 vs.352.98 ± 13.73;P =0.036).The changes of the platelet concentration of 5-HT in the depression,MI,and depression + MI group were different from that of serum.The levels of 5-HT in above three groups were lower than that in the control group (380.40 ± 17.90,387.75 ± 22.28,246.40 ± 18.99 vs.500.29 ± 20.91;P =0.000).The platelet lysate concentration of 5-HT2AR increased in depression group,MI group,and depression + MI group compared with the control group (370.75 ± 14.75,393.47 ± 15.73,446.66 ± 18.86 vs.273.66 ± 16.90;P =0.000).The serum and platelet concentration of SERT in the depression group,MI group and depression + MI group were all increased compared with the control group (527.51 ± 28.32,602.02 ± 23.32,734.76 ± 29.59 vs.490.56 ± 16.90;P =0.047,P =0.000,P =0.000 in each and 906.38 ± 51.84,897.33 ± 60.34,1030.17 ± 58.73 vs.708.62 ± 51.15;P =0.000 in each).Conclusions:The concentration of 5-HT2AR in platelet lysate and SERT in serum and platelet may be involved in the pathway of MI with depression.Further studies should examine whether elevated 5-HT2AR and SERT may contribute to the biomarker in MI patients with depression.

  6. Signaling properties and pharmacological analysis of two sulfakinin receptors from the red flour beetle, Tribolium castaneum.

    Directory of Open Access Journals (Sweden)

    Sven Zels

    Full Text Available Sulfakinin is an insect neuropeptide that constitutes an important component of the complex network of hormonal and neural factors that regulate feeding and digestion. The key modulating functions of sulfakinin are mediated by binding and signaling via G-protein coupled receptors. Although a substantial amount of functional data have already been reported on sulfakinins in different insect species, only little information is known regarding the properties of their respective receptors. In this study, we report on the molecular cloning, functional expression and characterization of two sulfakinin receptors in the red flour beetle, Tribolium castaneum. Both receptor open reading frames show extensive sequence similarity with annotated sulfakinin receptors from other insects. Comparison of the sulfakinin receptor sequences with homologous vertebrate cholecystokinin receptors reveals crucial conserved regions for ligand binding and receptor activation. Quantitative reverse transcriptase PCR shows that transcripts of both receptors are primarily expressed in the central nervous system of the beetle. Pharmacological characterization using 29 different peptide ligands clarified the essential requirements for efficient activation of these sulfakinin receptors. Analysis of the signaling pathway in multiple cell lines disclosed that the sulfakinin receptors of T. castaneum can stimulate both the Ca²⁺ and cyclic AMP second messenger pathways. This in depth characterization of two insect sulfakinin receptors may provide useful leads for the further development of receptor ligands with a potential applicability in pest control and crop protection.

  7. Signaling properties and pharmacological analysis of two sulfakinin receptors from the red flour beetle, Tribolium castaneum.

    Science.gov (United States)

    Zels, Sven; Verlinden, Heleen; Dillen, Senne; Vleugels, Rut; Nachman, Ronald J; Vanden Broeck, Jozef

    2014-01-01

    Sulfakinin is an insect neuropeptide that constitutes an important component of the complex network of hormonal and neural factors that regulate feeding and digestion. The key modulating functions of sulfakinin are mediated by binding and signaling via G-protein coupled receptors. Although a substantial amount of functional data have already been reported on sulfakinins in different insect species, only little information is known regarding the properties of their respective receptors. In this study, we report on the molecular cloning, functional expression and characterization of two sulfakinin receptors in the red flour beetle, Tribolium castaneum. Both receptor open reading frames show extensive sequence similarity with annotated sulfakinin receptors from other insects. Comparison of the sulfakinin receptor sequences with homologous vertebrate cholecystokinin receptors reveals crucial conserved regions for ligand binding and receptor activation. Quantitative reverse transcriptase PCR shows that transcripts of both receptors are primarily expressed in the central nervous system of the beetle. Pharmacological characterization using 29 different peptide ligands clarified the essential requirements for efficient activation of these sulfakinin receptors. Analysis of the signaling pathway in multiple cell lines disclosed that the sulfakinin receptors of T. castaneum can stimulate both the Ca²⁺ and cyclic AMP second messenger pathways. This in depth characterization of two insect sulfakinin receptors may provide useful leads for the further development of receptor ligands with a potential applicability in pest control and crop protection.

  8. Requirements for existing buildings

    DEFF Research Database (Denmark)

    Thomsen, Kirsten Engelund; Wittchen, Kim Bjarne

    This report collects energy performance requirements for existing buildings in European member states by June 2012.......This report collects energy performance requirements for existing buildings in European member states by June 2012....

  9. Greening Existing Tribal Buildings

    Science.gov (United States)

    Guidance about improving sustainability in existing tribal casinos and manufactured homes. Many steps can be taken to make existing buildings greener and healthier. They may also reduce utility and medical costs.

  10. Distinct interneuron types express m2 muscarinic receptor immunoreactivity on their dendrites or axon terminals in the hippocampus.

    Science.gov (United States)

    Hájos, N; Papp, E C; Acsády, L; Levey, A I; Freund, T F

    1998-01-01

    In previous studies m2 muscarinic acetylcholine receptor-immunoreactive interneurons and various types of m2-positive axon terminals have been described in the hippocampal formation. The aim of the present study was to identify the types of interneurons expressing m2 receptor and to examine whether the somadendritic and axonal m2 immunostaining labels the same or distinct cell populations. In the CA1 subfield, neurons immunoreactive for m2 have horizontal dendrites, they are located at the stratum oriens/alveus border and have an axon that project to the dendritic region of pyramidal cells. In the CA3 subfield and the hilus, m2-positive neurons are multipolar and are scattered in all layers except stratum lacunosum-moleculare. In stratum pyramidale of the CA1 and CA3 regions, striking axon terminal staining for m2 was observed, surrounding the somata and axon initial segments of pyramidal cells in a basket-like manner. The co-localization of m2 with neurochemical markers and GABA was studied using the "mirror" technique and fluorescent double-immunostaining at the light microscopic level and with double-labelling using colloidal gold-conjugated antisera and immunoperoxidase reaction (diaminobenzidine) at the electron microscopic level. GABA was shown to be present in the somata of most m2-immunoreactive interneurons, as well as in the majority of m2-positive terminals in all layers. The calcium-binding protein parvalbumin was absent from practically all m2-immunoreactive cell bodies and dendrites. In contrast, many of the terminals synapsing on pyramidal cell somata and axon initial segments co-localized parvalbumin and m2, suggesting a differential distribution of m2 receptor immunoreactivity on the axonal and somadendritic membrane of parvalbumin-containing basket and axo-axonic cells. The co-existence of m2 receptors with the calcium-binding protein calbindin and the neuropeptides cholecystokinin and vasoactive intestinal polypeptide was rare throughout the

  11. Effects of a high plant protein diet on the somatotropic system and cholecystokinin in Atlantic salmon (Salmo salar L.).

    Science.gov (United States)

    Hevrøy, Ernst M; El-Mowafi, Adel; Taylor, Richard; Norberg, Birgitta; Espe, Marit

    2008-12-01

    To investigate the endocrine signalling from dietary plant protein on somatotropic system and gastrointestinal hormone cholecystokinin (CCK), two iso-amino acid diets based on either high plant or high fish meal protein were fed to Atlantic salmon. Salmon with an average starting weight of 641+/-23 g (N=180), were fed a fish meal (FM) based diet (containing 40% FM) or diets mainly consisting of blended plant proteins (PP) containing only 13% marine protein, of which only 5% was FM for 3 months. mRNA levels of target genes GH, GH-R, IGF-I, IGF-II, IGFBP-1, IGF-IR in addition to CCK-L, were studied in brain, hepatic tissue and fast muscle, and circulating levels of IGF-I in plasma of Atlantic salmon were measured. We detected reduced feed intake resulting in lower growth, weight gain and muscle protein accretion in salmon fed plant protein compared to a diet based on fish meal. There were no significant effects on the regulation of the target genes in brain or in hepatic tissues, but a trend of down-regulation of IGF-I was detected in fast muscle. Lower feed intake, and therefore lower intake of the indispensable amino acids, may have resulted in lower pituitary GH and lower IGF-I mRNA levels in muscle tissues. This, together with higher protein catabolism, may be the main cause of the reduced growth of salmon fed plant protein diet. There were no signalling effects detected either by the minor differences of the diets on mRNA levels of GH, GH-R, IGF-IR, IGF-II, IGFBP-1, CCK or plasma protein IGF-I.

  12. Characterization of basal hepatic bile flow and the effects of intravenous cholecystokinin on the liver, sphincter, and gallbladder in patients with sphincter of Oddi spasm.

    Science.gov (United States)

    Krishnamurthy, Gerbail T; Krishnamurthy, Shakuntala; Watson, Randy D

    2004-01-01

    The major objectives of this project were to establish the pattern of basal hepatic bile flow and the effects of intravenous administration of cholecystokinin on the liver, sphincter of Oddi, and gallbladder, and to identify reliable parameters for the diagnosis of sphincter of Oddi spasm (SOS). Eight women with clinically suspected sphincter of Oddi spasm (SOS group), ten control subjects (control group), and ten patients who had recently received an opioid (opioid group) were selected for quantitative cholescintigraphy with cholecystokinin. Each patient was studied with 111-185 MBq (3-5 mCi) technetium-99m mebrofenin after 6-8 h of fasting. Hepatic phase images were obtained for 60 min, followed by gallbladder phase images for 30 min. During the gallbladder phase, 10 ng/kg octapeptide of cholecystokinin (CCK-8) was infused over 3 min through an infusion pump. Hepatic extraction fraction, excretion half-time, basal hepatic bile flow into the gallbladder, gallbladder ejection fraction, and post-CCK-8 paradoxical filling (>30% of basal counts) were identified. Seven of the patients with SOS were treated with antispasmodics (calcium channel blockers), and one underwent endoscopic sphincterotomy. Mean (+/-SD) hepatic bile entry into the gallbladder (versus GI tract) was widely variable: it was lower in SOS patients (32%+/-31%) than in controls (61%+/-36%) and the opioid group (61%+/-25%), but the difference was not statistically significant. Hepatic extraction fraction, excretion half-time, and pattern of bile flow through both intrahepatic and extrahepatic ducts were normal in all three groups. Gallbladder mean ejection fraction was 9%+/-4% in the opioid group; this was significantly lower (Pgallbladder refluxed into intrahepatic ducts; it reentered the gallbladder after cessation of CCK-8 infusion (paradoxical gallbladder filling) in all eight patients with SOS, but in none of the patients in the other two groups. Mean paradoxical filling was 204% (+/-193%) in the

  13. Orlistat inhibition of intestinal lipase acutely increases appetite and attenuates postprandial glucagon-like peptide-1-(7-36)-amide-1, cholecystokinin, and peptide YY concentrations

    DEFF Research Database (Denmark)

    Ellrichmann, Mark; Kapelle, Mario; Ritter, Peter R

    2008-01-01

    of Orlistat or placebo. Gastric emptying, gallbladder volume and the plasma levels of CCK, PYY, GLP-1, and ghrelin were determined and appetite sensations were measured using visual analogue scales. RESULTS: Gastric emptying was accelerated by Orlistat administration (P emptying.......0001), whereas appetite and prospective food consumption increased (P gastric and gallbladder emptying and reduces...... whether Orlistat alters the secretion of glucagon-like peptide-1-(7-36)-amide (GLP-1), cholecystokinin (CCK), peptide YY (PYY), and ghrelin as well as postprandial appetite sensations. METHODS: Twenty-five healthy human volunteers were examined with a solid-liquid test meal after the oral administration...

  14. Jejunal feeding is followed by a greater rise in plasma cholecystokinin, peptide YY, glucagon-like peptide 1, and glucagon-like peptide 2 concentrations compared with gastric feeding in vivo in humans

    DEFF Research Database (Denmark)

    Luttikhold, Joanna; van Norren, Klaske; Rijna, Herman

    2016-01-01

    and the associated endocrine response in vivo in humans remains largely unexplored. OBJECTIVE: We compared the impact of administering enteral nutrition as either gastric feeding or jejunal feeding on endocrine responses in vivo in humans. DESIGN: In a randomized, crossover study design, 12 healthy young men (mean...... and a greater postprandial incremental AUC for GLP-1 and cholecystokinin (all P young men results in similar postprandial plasma amino acid and glucose concentrations....... However, the endocrine response differs substantially, with higher peak plasma cholecystokinin, PYY, GLP-1, and GLP-2 concentrations being attained after jejunal feeding. This effect may result in an improved anabolic response, greater insulin sensitivity, and an improved intestinotropic effect...

  15. Receptors for sensory neuropeptides in human inflammatory diseases: Implications for the effector role of sensory neurons

    International Nuclear Information System (INIS)

    Mantyh, P.W.; Catton, M.D.; Boehmer, C.G.; Welton, M.L.; Passaro, E.P. Jr.; Maggio, J.E.; Vigna, S.R.

    1989-01-01

    Glutamate and several neuropeptides are synthesized and released by subpopulations of primary afferent neurons. These sensory neurons play a role in regulating the inflammatory and immune responses in peripheral tissues. Using quantitative receptor autoradiography we have explored what changes occur in the location and concentration of receptor binding sites for sensory neurotransmitters in the colon in two human inflammatory diseases, ulcerative colitis and Crohn's disease. The sensory neurotransmitter receptors examined included bombesin, calcitonin gene related peptide-alpha, cholecystokinin, galanin, glutamate, somatostatin, neurokinin A (substance K), substance P, and vasoactive intestinal polypeptide. Of the nine receptor binding sites examined only substance P binding sites associated with arterioles, venules and lymph nodules were dramatically up-regulated in the inflamed tissue. These data suggest that substance P is involved in regulating the inflammatory and immune responses in human inflammatory diseases and indicate a specificity of efferent action for each sensory neurotransmitter in peripheral tissues

  16. Electroacupuncture modulation of reflex hypertension in rats: role of cholecystokinin octapeptide

    Science.gov (United States)

    Tjen-A-Looi, Stephanie C.; Guo, Zhi-Ling; Longhurst, John C.

    2013-01-01

    Acupuncture or electroacupuncture (EA) potentially offers a nonpharmacological approach to reduce high blood pressure (BP). However, ∼70% of the patients and animal subjects respond to EA, while 30% do not. EA acts, in part, through an opioid mechanism in the rostral ventrolateral medulla (rVLM) to inhibit sympathoexcitatory reflexes induced by gastric distention. CCK-8 opposes the action of opioids during analgesia. Therefore, we hypothesized that CCK-8 in the rVLM antagonizes EA modulation of sympathoexcitatory cardiovascular reflex responses. Male rats anesthetized with ketamine and α-chloralose subjected to repeated gastric distension every 10 min were examined for their responsiveness to EA (2 Hz, 0.5 ms, 1–4 mA) at P5-P6 acupoints overlying median nerve. Repeated gastric distension every 10 min evoked consistent sympathoexcitatory responses. EA at P5-P6 modulated gastric distension-induced responses. Microinjection of CCK-8 in the rVLM reversed the EA effect in seven responders. The CCK1 receptor antagonist devazepide microinjected into the rVLM converted six nonresponders to responders by lowering the reflex response from 21 ± 2.2 to 10 ± 2.9 mmHg (first vs. second application of EA). The EA modulatory action in rats converted to responders with devazepide was reversed with rVLM microinjection of naloxone (n = 6). Microinjection of devazepide in the absence of a second application of EA did not influence the primary pressor reflexes of nonresponders. These data suggest that CCK-8 antagonizes EA modulation of sympathoexcitatory cardiovascular responses through an opioid mechanism and that inhibition of CCK-8 can convert animals that initially are unresponsive to EA to become responsive. PMID:23785073

  17. Effects of +G_z exposure on gallbladder emptying function,cholecystokinin,and somatostatin in rabbits with high cholesterol diets

    Directory of Open Access Journals (Sweden)

    Guo-feng XIAO

    2011-12-01

    Full Text Available Objective The present study explores the effects of +Gz exposure on the gallbladder emptying function,cholecystokinin(CCK,and somatostatin(SS in rabbits with high cholesterol diets and investigates its mechanism in the occurrence of cholecystolithiasis.Methods Twenty-four male New Zealand rabbits were randomly divided into the high cholesterol diet(control group,n=8 and high cholesterol diet plus +Gz exposure groups.The latter was divided into the four-and six-week +Gz exposure groups(n=8 based on the exposure time.Radioimmunoassay was used to determine the CCK and SS contents of the gallbladder at the end of the experiment in the fourth and sixth weeks and to calculate the gallbladder volume and maximum emptying ratio.A microcomputer biodynamic pressure monitor was used to record the hydrostatic pressure in the gallbladder to measure its capacity.Moreover,the bile properties and formation of concretion were observed with the naked eye,and polarized light microscopy was used to observe cholesterin crystallization on the gallbladder wall.Results The gallbladder capacity increased upon +Gz exposure for four and six weeks,indicating that the maximum emptying ratio(E% decreased,the empty and residual volumes improved,and the pressure increased(P < 0.05.After +Gz exposure for four and six weeks,the CCK contents in the experimental groups were evidently lower than that in the control group and gradually decreased(P < 0.05 as the +Gz exposure time increased.On the other hand,after +Gz exposure for four and six weeks,the SS contents in the experimental groups were higher than that in the control group and gradually improved(P < 0.05 as the +Gz exposure time increased.After +Gz exposure for four and six weeks,bile was turbid and sticky with cholesterol crystals and without visible concretion.Conclusions Therefore,+Gz exposure may cause abnormal gallbladder emptying functions,decrease CCK content,increase SS content,and thus cause bile stasis

  18. Effect of anorexinergic peptides, cholecystokinin (CCK) and cocaine and amphetamine regulated transcript (CART) peptide, on the activity of neurons in hypothalamic structures of C57Bl/6 mice involved in the food intake regulation

    Czech Academy of Sciences Publication Activity Database

    Pirnik, Z.; Maixnerová, Jana; Matyšková, Resha; Koutová, Darja; Železná, Blanka; Maletínská, Lenka; Kiss, A.

    2010-01-01

    Roč. 31, č. 1 (2010), s. 139-144 ISSN 0196-9781 R&D Projects: GA ČR GA303/05/0614 Institutional research plan: CEZ:AV0Z40550506 Keywords : cholecystokinin * CART * hypocretin * Fos peptide Subject RIV: CE - Biochemistry Impact factor: 2.654, year: 2010

  19. Effect of exogenous cholecystokinin (CCK)-8 on food intake and plasma CCK, leptin, and insulin concentrations in older and young adults: evidence for increased CCK activity as a cause of the anorexia of aging.

    NARCIS (Netherlands)

    MacIntosh, C.G.; Morley, J.E.; Wishart, J.M.; Morris, H.A.; Jansen, J.B.M.J.; Horowitz, M.M.; Chapman, I.M.

    2001-01-01

    Healthy aging is associated with reductions in appetite and food intake--the so-called anorexia of aging, which may predispose to protein-energy malnutrition. One possible cause of the anorexia of aging is an increased satiating effect of cholecystokinin (CCK). To investigate the impact of aging on

  20. The cell-specific pattern of cholecystokinin peptides in endocrine cells versus neurons is governed by the expression of prohormone convertases 1/3, 2, and 5/6

    DEFF Research Database (Denmark)

    Bundgaard, J.R.; Hannibal, J.; Zhu, X.

    2008-01-01

    Most peptide hormone genes are, in addition to endocrine cells, also expressed in neurons. The peptide hormone cholecystokinin (CCK) is expressed in different molecular forms in cerebral neurons and intestinal endocrine cells. To understand this difference, we examined the roles of the neuroendoc...

  1. Cholecystokinin regulates satiation idependently of the abdominal vagal nerve in a pig model of total subdiaphragmatic vagotomy

    NARCIS (Netherlands)

    Ripken, D.; Wielen, van der N.; Meulen, van der J.; Schuurman, T.; Witkamp, R.F.; Hendriks, H.F.J.; Koopmans, S.J.

    2015-01-01

    The vagal nerve and gut hormones CCK and GLP-1 play important roles in the control of food intake. However, it is not clear to what extent CCK and GLP-1 increase satiation by stimulating receptors located on abdominal vagal nerve endings or via receptors located elsewhere. This study aimed to

  2. Cholecystokinin regulates satiation independently of the abdominal vagal nerve in a pig model of total subdiaphragmatic vagotomy

    NARCIS (Netherlands)

    Ripken, D.; Wielen, N. van der; Meulen, J. van der; Schuurman, T.; Witkamp, R.F.; Hendriks, H.F.J.; Koopmans, S.J.

    2015-01-01

    The vagal nerve and gut hormones CCK and GLP-1 play important roles in the control of food intake. However, it is not clear to what extent CCK and GLP-1 increase satiation by stimulating receptors located on abdominal vagal nerve endings or via receptors located elsewhere. This study aimed to

  3. Carbachol does not down-regulate substance P receptors in pancreatic acini.

    Science.gov (United States)

    Patto, R J; Vinayek, R; Jensen, R T; Gardner, J D

    1992-01-01

    In a previous study, we found that first incubating guinea pig pancreatic acini with carbachol caused desensitization of the enzyme secretory response to cholecystokinin-octapeptide (CCK-8), bombesin, and carbachol but not that to substance P. This carbachol-induced desensitization could be accounted for by carbachol-induced down-regulation of receptors for CCK-8, bombesin, and carbachol. Although carbachol did not desensitize the enzyme secretory response to substance P, an effect of carbachol on substance P receptors was not examined. In the present study, in dispersed acini from guinea pig pancreas, substance P caused a twofold increase in amylase secretion. Stimulation was half-maximal at 0.7 nM and was maximal at 10 nM. Analysis of the ability of substance P to inhibit binding of 125I-substance P to substance P receptors indicated that acini possess a single class of receptors for substance P (Kd = 0.8 +/- 0.1 nM; Bmax = 1,037 +/- 145 fmol/mg of DNA). There was a close correlation between the relative potency with which substance P stimulated amylase secretion (0.7 nM) and the potency for inhibiting binding of 125I-substance P (Kd = 0.8 nM). First incubating pancreatic acini with carbachol did not alter either substance P-stimulated enzyme secretion or binding of 125I-substance P to substance P receptors, whereas in the same experiments, carbachol reduced binding of 125I-CCK-8 to cholecystokinin receptors by 50% and decreased in CCK-8-stimulated enzyme secretion by 50%.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Why preeclampsia still exists?

    Science.gov (United States)

    Chelbi, Sonia T; Veitia, Reiner A; Vaiman, Daniel

    2013-08-01

    Preeclampsia (PE) is a deadly gestational disease affecting up to 10% of women and specific of the human species. Preeclampsia is clearly multifactorial, but the existence of a genetic basis for this disease is now clearly established by the existence of familial cases, epidemiological studies and known predisposing gene polymorphisms. PE is very common despite the fact that Darwinian pressure should have rapidly eliminated or strongly minimized the frequency of predisposing alleles. Consecutive pregnancies with the same partner decrease the risk and severity of PE. Here, we show that, due to this peculiar feature, preeclampsia predisposing-alleles can be differentially maintained according to the familial structure. Thus, we suggest that an optimal frequency of PE-predisposing alleles in human populations can be achieved as a result of a trade-off between benefits of exogamy, importance for maintaining genetic diversity and increase of the fitness owing to a stable paternal investment. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Existence of Projective Planes

    OpenAIRE

    Perrott, Xander

    2016-01-01

    This report gives an overview of the history of finite projective planes and their properties before going on to outline the proof that no projective plane of order 10 exists. The report also investigates the search carried out by MacWilliams, Sloane and Thompson in 1970 [12] and confirms their result by providing independent verification that there is no vector of weight 15 in the code generated by the projective plane of order 10.

  6. Does bioethics exist?

    Science.gov (United States)

    Turner, L

    2009-12-01

    Bioethicists disagree over methods, theories, decision-making guides, case analyses and public policies. Thirty years ago, the thinking of many scholars coalesced around a principlist approach to bioethics. That mid-level mode of moral reasoning is now one of many approaches to moral deliberation. Significant variation in contemporary approaches to the study of ethical issues related to medicine, biotechnology and health care raises the question of whether bioethics exists as widely shared method, theory, normative framework or mode of moral reasoning.

  7. Insulin receptors

    International Nuclear Information System (INIS)

    Kahn, C.R.; Harrison, L.C.

    1988-01-01

    This book contains the proceedings on insulin receptors. Part A: Methods for the study of structure and function. Topics covered include: Method for purification and labeling of insulin receptors, the insulin receptor kinase, and insulin receptors on special tissues

  8. Measurement of nonsulfated cholecystokinins

    DEFF Research Database (Denmark)

    Agersnap, Mikkel; Rehfeld, Jens F

    2014-01-01

    Most proteins undergo posttranslational modifications that govern the function of the protein. In synchrony, correspondingly unmodified proteins that are functionally silent or act differently may also be synthesized. The gut hormone precursor, procholecystokinin (proCCK) is an example of a protein...... such as the recently described CCKomas and medullary thyroid C-cell carcinomas....

  9. Infusion of exogenous cholecystokinin-8, gastrin releasing peptide-29 and their combination reduce body weight in diet-induced obese male rats.

    Science.gov (United States)

    Mhalhal, Thaer R; Washington, Martha C; Newman, Kayla; Heath, John C; Sayegh, Ayman I

    2017-02-01

    We hypothesized that exogenous gastrin releasing peptide-29 (GRP-29), cholecystokinin-8 (CCK-8) and their combination reduce body weight (BW). To test this hypothesis, BW was measured in four groups of diet-induced obese (DIO) male rats infused in the aorta (close to the junctions of the celiac and cranial mesenteric arteries) with saline, CCK-8 (0.5 nmol/kg), GRP-29 (0.5 nmol/kg) and CCK-8+GRP-29 (0.5 nmol/kg each) once daily for a total of 23 days. We found that CCK-8, GRP-29 and CCK-8+GRP-29 reduce BW relative to saline control. In conclusion, CCK-8, GRP-29 and their combination reduce BW in the DIO rat model. If infused near their gastrointestinal sites of action CCK-8, GRP-29 and their combination may have a role in regulating BW. Published by Elsevier Ltd.

  10. Characterization of basal hepatic bile flow and the effects of intravenous cholecystokinin on the liver, sphincter, and gallbladder in patients with sphincter of Oddi spasm

    International Nuclear Information System (INIS)

    Krishnamurthy, Gerbail T.; Krishnamurthy, Shakuntala; Watson, Randy D.

    2004-01-01

    The major objectives of this project were to establish the pattern of basal hepatic bile flow and the effects of intravenous administration of cholecystokinin on the liver, sphincter of Oddi, and gallbladder, and to identify reliable parameters for the diagnosis of sphincter of Oddi spasm (SOS). Eight women with clinically suspected sphincter of Oddi spasm (SOS group), ten control subjects (control group), and ten patients who had recently received an opioid (opioid group) were selected for quantitative cholescintigraphy with cholecystokinin. Each patient was studied with 111-185 MBq (3-5 mCi) technetium-99m mebrofenin after 6-8 h of fasting. Hepatic phase images were obtained for 60 min, followed by gallbladder phase images for 30 min. During the gallbladder phase, 10 ng/kg octapeptide of cholecystokinin (CCK-8) was infused over 3 min through an infusion pump. Hepatic extraction fraction, excretion half-time, basal hepatic bile flow into the gallbladder, gallbladder ejection fraction, and post-CCK-8 paradoxical filling (>30% of basal counts) were identified. Seven of the patients with SOS were treated with antispasmodics (calcium channel blockers), and one underwent endoscopic sphincterotomy. Mean (±SD) hepatic bile entry into the gallbladder (versus GI tract) was widely variable: it was lower in SOS patients (32%±31%) than in controls (61%±36%) and the opioid group (61%±25%), but the difference was not statistically significant. Hepatic extraction fraction, excretion half-time, and pattern of bile flow through both intrahepatic and extrahepatic ducts were normal in all three groups. Gallbladder mean ejection fraction was 9%±4% in the opioid group; this was significantly lower (P<0.0001) than the values in the control group (54%±18%) and the SOS group (48%±29%). Almost all of the bile emptied from the gallbladder refluxed into intrahepatic ducts; it reentered the gallbladder after cessation of CCK-8 infusion (paradoxical gallbladder filling) in all eight

  11. Characterization of basal hepatic bile flow and the effects of intravenous cholecystokinin on the liver, sphincter, and gallbladder in patients with sphincter of Oddi spasm

    Energy Technology Data Exchange (ETDEWEB)

    Krishnamurthy, Gerbail T.; Krishnamurthy, Shakuntala [Department of Nuclear Medicine, Tuality Community Hospital, 335 SE 8th Avenue, OR 97123, Hillsboro (United States); Watson, Randy D. [Department of Gastroenterology, Tuality Community Hospital, Hillsboro, OR (United States)

    2004-01-01

    The major objectives of this project were to establish the pattern of basal hepatic bile flow and the effects of intravenous administration of cholecystokinin on the liver, sphincter of Oddi, and gallbladder, and to identify reliable parameters for the diagnosis of sphincter of Oddi spasm (SOS). Eight women with clinically suspected sphincter of Oddi spasm (SOS group), ten control subjects (control group), and ten patients who had recently received an opioid (opioid group) were selected for quantitative cholescintigraphy with cholecystokinin. Each patient was studied with 111-185 MBq (3-5 mCi) technetium-99m mebrofenin after 6-8 h of fasting. Hepatic phase images were obtained for 60 min, followed by gallbladder phase images for 30 min. During the gallbladder phase, 10 ng/kg octapeptide of cholecystokinin (CCK-8) was infused over 3 min through an infusion pump. Hepatic extraction fraction, excretion half-time, basal hepatic bile flow into the gallbladder, gallbladder ejection fraction, and post-CCK-8 paradoxical filling (>30% of basal counts) were identified. Seven of the patients with SOS were treated with antispasmodics (calcium channel blockers), and one underwent endoscopic sphincterotomy. Mean ({+-}SD) hepatic bile entry into the gallbladder (versus GI tract) was widely variable: it was lower in SOS patients (32%{+-}31%) than in controls (61%{+-}36%) and the opioid group (61%{+-}25%), but the difference was not statistically significant. Hepatic extraction fraction, excretion half-time, and pattern of bile flow through both intrahepatic and extrahepatic ducts were normal in all three groups. Gallbladder mean ejection fraction was 9%{+-}4% in the opioid group; this was significantly lower (P<0.0001) than the values in the control group (54%{+-}18%) and the SOS group (48%{+-}29%). Almost all of the bile emptied from the gallbladder refluxed into intrahepatic ducts; it reentered the gallbladder after cessation of CCK-8 infusion (paradoxical gallbladder filling

  12. O Ponto G Existe?

    Directory of Open Access Journals (Sweden)

    Carlos Alexandre Molina Noccioli

    2016-07-01

    Full Text Available Este trabalho busca analisar o tratamento linguístico-discursivo das informações acerca de um tópicotemático tradicionalmente visto como tabu, relacionado a questões sexuais, na notícia O ponto G existe?, publicada em 2008, na revista brasileira Superinteressante, destacando-se como o conhecimento em questão é representado socialmente ao se considerar a linha editorial da revista. A notícia caracteriza-se como um campo fértil para a análise das estratégias divulgativas, já que atrai, inclusive pelas escolhas temáticas, a curiosidade dos leitores. Imbuído de um tema excêntrico, o texto consegue angariar um público jovem interessado em discussões polêmicas relacionadas ao seu universo.

  13. Lebesgue Sets Immeasurable Existence

    Directory of Open Access Journals (Sweden)

    Diana Marginean Petrovai

    2012-12-01

    Full Text Available It is well known that the notion of measure and integral were released early enough in close connection with practical problems of measuring of geometric figures. Notion of measure was outlined in the early 20th century through H. Lebesgue’s research, founder of the modern theory of measure and integral. It was developed concurrently a technique of integration of functions. Gradually it was formed a specific area todaycalled the measure and integral theory. Essential contributions to building this theory was made by a large number of mathematicians: C. Carathodory, J. Radon, O. Nikodym, S. Bochner, J. Pettis, P. Halmos and many others. In the following we present several abstract sets, classes of sets. There exists the sets which are not Lebesgue measurable and the sets which are Lebesgue measurable but are not Borel measurable. Hence B ⊂ L ⊂ P(X.

  14. EXIST Perspective for SFXTs

    Science.gov (United States)

    Ubertini, Pietro; Sidoli, L.; Sguera, V.; Bazzano, A.

    2009-12-01

    Supergiant Fast X-ray Transients (SFXTs) are one of the most interesting (and unexpected) results of the INTEGRAL mission. They are a new class of HMXBs displaying short hard X-ray outbursts (duration less tha a day) characterized by fast flares (few hours timescale) and large dinamic range (10E3-10E4). The physical mechanism driving their peculiar behaviour is still unclear and highly debated: some models involve the structure of the supergiant companion donor wind (likely clumpy, in a spherical or non spherical geometry) and the orbital properties (wide separation with eccentric or circular orbit), while others involve the properties of the neutron star compact object and invoke very low magnetic field values (B 1E14 G, magnetars). The picture is still highly unclear from the observational point of view as well: no cyclotron lines have been detected in the spectra, thus the strength of the neutron star magnetic field is unknown. Orbital periods have been measured in only 4 systems, spanning from 3.3 days to 165 days. Even the duty cycle seems to be quite different from source to source. The Energetic X-ray Imaging Survey Telescope (EXIST), with its hard X-ray all-sky survey and large improved limiting sensitivity, will allow us to get a clearer picture of SFXTs. A complete census of their number is essential to enlarge the sample. A long term and continuous as possible X-ray monitoring is crucial to -(1) obtain the duty cycle, -(2 )investigate their unknown orbital properties (separation, orbital period, eccentricity),- (3) to completely cover the whole outburst activity, (4)-to search for cyclotron lines in the high energy spectra. EXIST observations will provide crucial informations to test the different models and shed light on the peculiar behaviour of SFXTs.

  15. Neuronal Fibers and Neurotransmitter Receptor Expression in the Human Endolymphatic Sac

    DEFF Research Database (Denmark)

    Møller, Martin Nue; Kirkeby, Svend; Vikeså, Jonas

    2017-01-01

    in intracranial pressure homeostasis. The anatomical location towards the sigmoid sinus would suggest a possible endo- and/or paracrine signaling. However, neuronal connections may also apply, but it remains very scarcely explored in the human ES. STUDY DESIGN: DNA micro-arrays and immunohistochemistry were used...... of genes specific for neuronal signaling was determined and results for selected key molecules verified by immunohistochemistry. Transmission electron microscopy was used for ultrastructural analysis. RESULTS: For the transmission electron microscopy analysis, a direct innervation of the ES was observed...... with unmyelinated fibers imbedded in the ES epithelial lining. The microarrays confirmed, that several molecules involved in neuronal signaling were found expressed significantly in the ES DNA profile, such as the Cholecystokinin peptide and related receptors, Dopamine receptors 2 and 5, vesicular monoamine...

  16. A new, highly selective CCK-B receptor radioligand ([3H][N-methyl-Nle28,31]CCK26-33): Evidence for CCK-B receptor heterogeneity

    International Nuclear Information System (INIS)

    Knapp, R.J.; Vaughn, L.K.; Fang, S.N.; Bogert, C.L.; Yamamura, M.S.; Hruby, V.J.; Yamamura, H.I.

    1990-01-01

    [N-methyl-Nle28,31]CCK26-33 (SNF 8702) is a nonsulfated cholecystokinin octapeptide analog that is highly selective for cholecystokinin-B (CCK-B) receptors. Inhibition studies using [125I] Bolton-Hunter-labeled CCK-8 show that SNF 8702 has over 4,000-fold greater affinity for CCK receptors in guinea pig cortex relative to those in guinea pig pancreas. SNF 8702 was tritium-labeled to a specific activity of 23.7 Ci/mmol and its binding properties characterized for guinea pig brain membrane preparations. [3H]SNF 8702 binds to a single site with high affinity (Kd = 0.69-0.90 nM) in guinea pig cortex, cerebellum, hippocampus and pons-medulla. Of these four tissues, the highest receptor density was measured in the cortex (86 fmol/mg of protein) and the lowest in the pons-medulla (22 fmol/mg of protein). In contrast to findings of single-site binding in some brain regions, evidence for CCK-B receptor heterogeneity is observed under other conditions. [3H]SNF 8702 binding to membranes prepared from whole guinea pig brain shows biphasic association kinetics at a concentration of 2.0 nM consistent with the presence of binding site heterogeneity. Binding site heterogeneity is consistently observed for [3H]SNF 8702 binding to guinea pig whole brain membranes in saturation studies where a high-affinity site (Kd = 0.31 nM) is distinguished from a low-affinity site (Kd = 3.3 nM). Binding site heterogeneity is also observed for the midbrain-thalamic region. CCK-B receptor heterogeneity is suggested by the effect of the guanyl nucleotide analogue, guanylyl-imidodiphosphate (Gpp(NH)p), on [3H]SNF 8702 binding to CCK-B receptors in the cerebellum

  17. The role of CCK2 receptors in energy homeostasis: insights from the CCK2 receptor-deficient mouse.

    Science.gov (United States)

    Weiland, Tracey J; Voudouris, Nicholas J; Kent, Stephen

    2004-09-15

    The present study explored the contribution of type 2 cholecystokinin (CCK) receptors in energy regulation. A total of 78 CCK2 receptor-deficient mice and 80 wild-type controls were acclimated to a 12:12 light-dark cycle at 30 +/- 1 degrees C. Using a computer-monitored biotelemetry system, circadian patterns of body temperature, food intake, and activity were monitored for 4 days. Body weight and water consumption were manually recorded during this period. Results indicate that CCK2 receptor invalidation produces elevated body temperature during both the photophase and scotophase (by 0.38 and 0.12 degrees C, respectively), increased body weight (29.3 +/- 0.2 vs. 26.8 +/- 0.2 g) and water consumption (4.1 +/- 0.1 vs. 3.2 +/- 0.1 ml), and decreased scotophase locomotor activity (WT: 7.0 +/- 0.2 vs. KO: 6.1 +/- 0.2 counts/min). These findings suggest an important role for CCK2 receptors in processes underlying energy regulation during basal and possibly pathological states.

  18. Receptor-receptor interactions within receptor mosaics. Impact on neuropsychopharmacology.

    Science.gov (United States)

    Fuxe, K; Marcellino, D; Rivera, A; Diaz-Cabiale, Z; Filip, M; Gago, B; Roberts, D C S; Langel, U; Genedani, S; Ferraro, L; de la Calle, A; Narvaez, J; Tanganelli, S; Woods, A; Agnati, L F

    2008-08-01

    Future therapies for diseases associated with altered dopaminergic signaling, including Parkinson's disease, schizophrenia and drug addiction or drug dependence may substantially build on the existence of intramembrane receptor-receptor interactions within dopamine receptor containing receptor mosaics (RM; dimeric or high-order receptor oligomers) where it is believed that the dopamine D(2) receptor may operate as the 'hub receptor' within these complexes. The constitutive adenosine A(2A)/dopamine D(2) RM, located in the dorsal striato-pallidal GABA neurons, are of particular interest in view of the demonstrated antagonistic A(2A)/D(2) interaction within these heteromers; an interaction that led to the suggestion and later demonstration that A(2A) antagonists could be used as novel anti-Parkinsonian drugs. Based on the likely existence of A(2A)/D(2)/mGluR5 RM located both extrasynaptically on striato-pallidal GABA neurons and on cortico-striatal glutamate terminals, multiple receptor-receptor interactions within this RM involving synergism between A(2A)/mGluR5 to counteract D(2) signaling, has led to the proposal of using combined mGluR5 and A(2A) antagonists as a future anti-Parkinsonian treatment. Based on the same RM in the ventral striato-pallidal GABA pathways, novel strategies for the treatment of schizophrenia, building on the idea that A(2A) agonists and/or mGluR5 agonists will help reduce the increased dopaminergic signaling associated with this disease, have been suggested. Such treatment may ensure the proper glutamatergic drive from the mediodorsal thalamic nucleus to the prefrontal cortex, one which is believed to be reduced in schizophrenia due to a dominance of D(2)-like signaling in the ventral striatum. Recently, A(2A) receptors also have been shown to counteract the locomotor and sensitizing actions of cocaine and increases in A(2A) receptors have also been observed in the nucleus accumbens after extended cocaine self-administration, probably

  19. Incretin physiology beyond glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide: cholecystokinin and gastrin peptides

    DEFF Research Database (Denmark)

    Rehfeld, J F

    2011-01-01

    and neonatal islets express significant amounts of gastrin, and human as well as porcine islet cells express the gastrin/CCK-B receptor abundantly. Therefore, exogenous gastrin and CCK peptides stimulate insulin and glucagon secretion in man. Accordingly, endogenous hypergastrinaemia is accompanied by islet...... cell hyperplasia and increased insulin secretion. Conventionally, the effect of gastrointestinal hormones on insulin secretion (the incretin effect) has been defined and quantified in relation to oral versus intravenous glucose loadings. Under these unphysiological conditions, the release of gastrin...

  20. Possible Relevance of Receptor-Receptor Interactions between Viral- and Host-Coded Receptors for Viral-Induced Disease

    Directory of Open Access Journals (Sweden)

    Luigi F. Agnati

    2007-01-01

    Full Text Available It has been demonstrated that some viruses, such as the cytomegalovirus, code for G-protein coupled receptors not only to elude the immune system, but also to redirect cellular signaling in the receptor networks of the host cells. In view of the existence of receptor-receptor interactions, the hypothesis is introduced that these viral-coded receptors not only operate as constitutively active monomers, but also can affect other receptor function by interacting with receptors of the host cell. Furthermore, it is suggested that viruses could also insert not single receptors (monomers, but clusters of receptors (receptor mosaics, altering the cell metabolism in a profound way. The prevention of viral receptor-induced changes in host receptor networks may give rise to novel antiviral drugs that counteract viral-induced disease.

  1. Somatostatin receptors

    DEFF Research Database (Denmark)

    Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette

    2003-01-01

    functional units, receptors co-operate. The total receptor apparatus of individual cell types is composed of different-ligand receptors (e.g. SRIF and non-SRIF receptors) and co-expressed receptor subtypes (e.g. sst(2) and sst(5) receptors) in characteristic proportions. In other words, levels of individual......-peptides, receptor agonists and antagonists. Relatively long half lives, as compared to those of the endogenous ligands, have been paramount from the outset. Motivated by theoretical puzzles or the shortcomings of present-day diagnostics and therapy, investigators have also aimed to produce subtype...

  2. Exogenous glucagon-like peptide-1 reduces body weight and cholecystokinin-8 enhances this reduction in diet-induced obese male rats.

    Science.gov (United States)

    Mhalhal, Thaer R; Washington, Martha C; Newman, Kayla; Heath, John C; Sayegh, Ayman I

    2017-10-01

    The sites of action regulating meal size (MS) and intermeal interval (IMI) length by glucagon like peptide-1 (7-36) (GLP-1 (7-36)) and cholecystokinin-8 (CCK-8) reside in the areas supplied by the two major branches of the abdominal aorta, celiac and cranial mesenteric arteries. We hypothesized that infusing GLP-1 near those sites reduces body weight (BW) and adding CCK-8 to this infusion enhances the reduction. Here, we measured BW in diet-induced obese (DIO) male rats maintained and tested on normal rat chow and infused with saline, GLP-1 (0.5nmol/kg) and GLP-1+CCK-8 (0.5nmol/kg each) in the aorta once daily for 21days. We found that GLP-1 and GLP-1+CCK-8 decrease BW relative to saline vehicle and GLP-1+CCK-8 reduced it more than GLP-1 alone. Reduction of BW by GLP-1 alone was accompanied by decreased 24-h food intake, first MS, duration of first meal and number of meals, and an increase in latency to first meal. Reduction of BW by the combination of the peptides was accompanied by decrease 24-h food intake, first MS, duration of first meal and number of meals, and increase in the IMI length, satiety ratio and latency to first meal. In conclusion, GLP-1 reduces BW and CCK-8 enhances this reduction if the peptides are given near their sites of action. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Bovine pancreatic polypeptide as an antagonist of muscarinic cholinergic receptors

    International Nuclear Information System (INIS)

    Pan, G.Z.; Lu, L.; Qian, J.; Xue, B.G.

    1987-01-01

    In dispersed acini from rat pancreas, it was found that bovine pancreatic polypeptide (BPP) and its C-fragment hexapeptide amide (PP-6), at concentrations of 0.1 and 30 μM, respectively, could significantly inhibit amylase secretion stimulated by carbachol, and this inhibition by BPP was dose dependent. 45 Ca outflux induced by carbachol was also inhibited by BPP or PP-6, but they had no effect on cholecystokinin octapeptide- (CCK-8) or A23187-stimulated 45 Ca outflux. BPP was also capable of displacing the specific binding of [ 3 H]-quinuclidinyl benzilate to its receptors, and it possessed a higher affinity (K/sub i/35nM) than carbachol (K/sub i/ 1.8 μM) in binding with M-receptors. It is concluded from this study that BPP acts as an antagonist of muscarinic cholinergic receptors in rat pancreatic acini. In addition, BPP inhibited the potentiation of amylase secretion caused by the combination of carbachol plus secretin or vasoactive intestinal peptide. This may be a possible explanation of the inhibitory effect of BPP on secretin-induced pancreatic enzyme secretion shown in vivo, since pancreatic enzyme secretion stimulated by secretin under experimental conditions may be the result of potentiation of enzyme release produced by the peptide in combination with a cholinergic stimulant

  4. Expression of CCK Receptors in Carcinoma Gallbladder and Cholelithiasis: A Pilot Study.

    Science.gov (United States)

    Faridi, Mohammad Shazib; Jaiswal, Mahabir Saran Das; Goel, Sudhir K

    2015-07-01

    Gastrin and cholecystokinin (CCK) receptors are trophic for various gastrointestinal malignancies. Their role in gallbladder cancer has not been widely studied. To identify expression of CCK-A and CCK-B receptors in the tissue and blood of patients suffering from carcinoma (CA) gallbladder and gallstone disease and to compare expression of CCK A and B receptors in the gall bladder tissue and blood of healthy individuals and patients of CA gallbladder, and gallstone diseases. Forty nine subjects of both genders were recruited, comprising of 22 patients of CA gall bladder, 19 cases of cholelithiasis and, 8 normal gallbladders obtained from patients operated for trauma of the biliary system or Whipple's procedure. RNA extraction and cDNA formation for CCK-A and CCK-B receptors were carried out. Real Time PCR was performed on cDNA and threshold cycle (Ct) value of each sample was obtained and ΔCt was calculated. Chi-square test for comparing two groups and ANOVA test for comparing multiple groups were applied and if pgallbladder and there was no difference among them (p>0.05). This preliminary study showed higher expression of CCK-A receptors in patients of cholelithiasis and decreased expression of CCK-A receptors in patients of CA gallbladder as compared to normal gallbladder although it did not rise to statistical significance.

  5. Gut satiety hormones cholecystokinin and glucagon-like Peptide-17-36 amide mediate anorexia induction by trichothecenes T-2 toxin, HT-2 toxin, diacetoxyscirpenol and neosolaniol.

    Science.gov (United States)

    Zhang, Jie; Liu, Shengli; Zhang, Hua; Li, Yuanyuan; Wu, Wenda; Zhang, Haibin

    2017-11-15

    The food-borne trichothecene mycotoxins have been documented to cause human and animal food poisoning. Anorexia is a hallmark of the trichothecene mycotoxins-induced adverse effects. Type B trichothecenes have been previously demonstrated to elicit robust anorectic responses, and this response has been directly linked to secretion of the gut satiety hormones cholecystokinin (CCK) and glucagon-like peptide-1 7-36 amide (GLP-1). However, less is known about the anorectic effects and underlying mechanisms of the type A trichothecenes, including T-2 toxin (T-2), HT-2 toxin (HT-2), diacetoxyscirpenol (DAS), neosolaniol (NEO). The purpose of this study was to relate type A trichothecenes T-2, HT-2, DAS and NEO-induced anorectic response to changes plasma concentrations of CCK and GLP-1. Following both oral gavage and intraperitoneal (IP) administration of 1mg/kg bw T-2, HT-2, DAS and NEO evoked robust anorectic response and secretion of CCK and GLP-1. Elevations of plasma CCK markedly corresponded to anorexia induction by T-2, HT-2, DAS and NEO. Following oral exposure, plasma CCK was peaked at 6h, 6h, 2h, 2h and lasted up to 24h, 24h, > 6h, > 6h for T-2, HT-2, DAS and NEO, respectively. IP exposed to four toxins all induced elevation of CCK with peak point and duration at 6h and >24h, respectively. In contrast to CCK, GLP-1 was moderately elevated by these toxins. Following both oral and IP exposure, T-2 and HT-2 evoked plasma GLP-1 elevation with peak point and duration at 2h and 6h, respectively. Plasma GLP-1 was peaked at 2h and still increased at 6h for IP and oral administration with DAS and NEO, respectively. In conclusion, CCK plays a contributory role in anorexia induction but GLP-1 might play a lesser role in this response. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Management of gallbladder dyskinesia: patient outcomes following positive 99mtechnetium (Tc)-labelled hepatic iminodiacetic acid (HIDA) scintigraphy with cholecystokinin (CCK) provocation and laparoscopic cholecystectomy

    International Nuclear Information System (INIS)

    Dave, R.V.; Pathak, S.; Cockbain, A.J.; Lodge, J.P.; Smith, A.M.; Chowdhury, F.U.; Toogood, G.J.

    2015-01-01

    Aims: To evaluate clinical outcomes in patients with typical biliary pain, normal ultrasonic findings, and a positive 99m technetium (Tc)-labelled hepatic iminodiacetic acid analogue (HIDA) scintigraphy with cholecystokinin (CCK) provocation indicating gallbladder dyskinesia, as per Rome III criteria, undergoing laparoscopic cholecystectomy (LC). Methods and materials: Consecutive patients undergoing LC for gallbladder dyskinesia were identified retrospectively. They were followed up by telephone interview and review of the electronic case records to assess symptom resolution. Results: One hundred consecutive patients (median age 44; 80% female) with abnormal gallbladder ejection fraction (GB-EF <35%) were followed up for a median of 12 months (range 2–80 months). Following LC, 84% reported symptomatic improvement and 52% had no residual pain. Twelve percent had persisting preoperative-type pain of either unchanged or worsening severity. Neither pathological features of chronic cholecystitis (87% of 92 incidences when histology available) nor reproduction of pain on CCK injection were significantly predictive of symptom outcome or pain relief post-LC. Conclusion: In one of the largest outcome series of gallbladder dyskinesia patients in the UK with a positive provocation HIDA scintigraphy examination and LC, the present study shows that the test is a useful functional diagnostic tool in the management of patients with typical biliary pain and normal ultrasound, with favourable outcomes following surgery. - Highlights: • Gallbladder dyskinesia (GD) is a challenging condition to diagnose and treat. • This study evaluated clinical outcomes following laparoscopic cholecystectomy (LC). • There was sustained symptomatic benefit in >80% following surgery. • Pre-operative counselling before LC is important

  7. Ontological Proofs of Existence and Non-Existence

    Czech Academy of Sciences Publication Activity Database

    Hájek, Petr

    2008-01-01

    Roč. 90, č. 2 (2008), s. 257-262 ISSN 0039-3215 R&D Projects: GA AV ČR IAA100300503 Institutional research plan: CEZ:AV0Z10300504 Keywords : ontological proofs * existence * non-existence * Gödel * Caramuel Subject RIV: BA - General Mathematics

  8. Association of ghrelin receptor gene polymorphism with bulimia nervosa in a Japanese population.

    Science.gov (United States)

    Miyasaka, K; Hosoya, H; Sekime, A; Ohta, M; Amono, H; Matsushita, S; Suzuki, K; Higuchi, S; Funakoshi, A

    2006-09-01

    Eating disorders (EDs) have a highly heterogeneous etiology and multiple genetic factors might contribute to their pathogenesis. Ghrelin, a novel growth hormone-releasing peptide, enhances appetite and increases food intake, and human ghrelin plasma levels are inversely correlated with body mass index. In the present study, we examined the 171T/C polymorphism of the ghrelin receptor (growth hormone secretagogue receptor, GHSR) gene in patients diagnosed with EDs, because the subjects having ghrelin gene polymorphism (Leu72Met) was not detected in a Japanese population, previously. In addition, beta3 adrenergic receptor gene polymorphism (Try64Arg) and cholecystokinin (CCK)-A receptor (R) gene polymorphism (-81A/G, -128G/T), which are both associated with obesity, were investigated. The subjects consisted of 228 Japanese patients with EDs [96 anorexia nervosa (AN), 116 bulimia nervosa (BN) and 16 not otherwise specified (NOS)]. The age- and gender-matched control group consisted of 284 unrelated Japanese subjects. The frequency of the CC type of the GHSR gene was significantly higher in BN subjects than in control subjects (chi(2) = 4.47, p = 0.035, odds ratio = 2.05, Bonferroni correction: p = 0.070), while the frequency in AN subjects was not different from that in controls. The distribution of neither beta3 adrenergic receptor gene nor CCK-AR polymorphism differed between EDs and control subjects. Therefore, the CC type of GHSR gene polymorphism (171T/C) is a risk factor for BN, but not for AN.

  9. Existence theory in optimal control

    International Nuclear Information System (INIS)

    Olech, C.

    1976-01-01

    This paper treats the existence problem in two main cases. One case is that of linear systems when existence is based on closedness or compactness of the reachable set and the other, non-linear case refers to a situation where for the existence of optimal solutions closedness of the set of admissible solutions is needed. Some results from convex analysis are included in the paper. (author)

  10. Receptor assay

    Energy Technology Data Exchange (ETDEWEB)

    Kato, K; Ibayashi, H [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1975-05-01

    This paper summarized present status and problems of analysis of hormone receptor and a few considerations on clinical significance of receptor abnormalities. It was pointed that in future clinical field quantitative and qualitative analysis of receptor did not remain only in the etiological discussion, but that it was an epoch-making field of investigation which contained the possiblity of artificial change of sensitivity of living body on drugs and the development connected directly with treatment of various diseases.

  11. Multiple sources of 1,2-diacylglycerol in isolated rat pancreatic acini stimulated by cholecystokinin. Involvement of phosphatidylinositol bisphosphate and phosphatidylcholine hydrolysis

    International Nuclear Information System (INIS)

    Matozaki, T.; Williams, J.A.

    1989-01-01

    Changes in the cellular content of 1,2-diacylglycerol (DAG) in isolated rat pancreatic acini in response to agonist stimulation were studied using a sensitive mass assay. When acini were stimulated by 10 nM COOH-terminal cholecystokinin-octapeptide (CCK8), the increase in DAG was biphasic, consisting of an early peak at 5 s and a second, larger, gradual increase that was maximal by 15 min. The basal level of DAG in acini was 1.04 nmol/mg of protein, which was increased to 1.24 nmol/mg of protein at 5 s and 2.76 nmol/mg of protein at 30 min. In comparison, the increase in DAG stimulated by 30 pM CCK8, a submaximal concentration for amylase release, was monophasic, increasing without an early peak but sustained to 60 min. Other Ca2+-mobilizing secretagogues such as carbamylcholine and bombesin increased DAG in acini, whereas vasoactive intestinal peptide, which acts to increase cAMP, had no effect. Phorbol ester and Ca2+ ionophore also stimulated DAG production. Analysis of the mass level of inositol 1,4,5-trisphosphate (1,4,5-IP3) showed that the generation of 1,4,5-IP3 stimulated by 10 nM CCK8 peaked at 5 s, a finding consistent with the early peak of DAG. The basal level was 4.7 pmol/mg of protein, which was increased to 144.6 pmol/mg of protein at 5 s by 10 nM CCK8. The levels of 1,4,5-IP3 then returned toward basal in contrast to the gradual and sustained increase of DAG. The dose dependencies of 1,4,5-IP3 and DAG formation at 5 s with respect to CCK8 were almost identical. This suggests that phosphatidylinositol 4,5-bisphosphate hydrolysis is a major source of the early increase in DAG but not of the sustained increase in DAG. Therefore, a possible contribution of phosphatidylcholine hydrolysis to DAG formation was examined utilizing acini prelabeled with [3H]choline. CCK8 (1 nM) maximally increased [3H]choline metabolite release by 133% of control at 30 min

  12. Common Hepatic Branch of Vagus Nerve-Dependent Expression of Immediate Early Genes in the Mouse Brain by Intraportal L-Arginine: Comparison with Cholecystokinin-8

    Directory of Open Access Journals (Sweden)

    Daisuke Yamada

    2017-06-01

    Full Text Available Information from the peripheral organs is thought to be transmitted to the brain by humoral factors and neurons such as afferent vagal or spinal nerves. The common hepatic branch of the vagus (CHBV is one of the main vagus nerve branches, and consists of heterogeneous neuronal fibers that innervate multiple peripheral organs such as the bile duct, portal vein, paraganglia, and gastroduodenal tract. Although, previous studies suggested that the CHBV has a pivotal role in transmitting information on the status of the liver to the brain, the details of its central projections remain unknown. The purpose of the present study was to investigate the brain regions activated by the CHBV. For this purpose, we injected L-arginine or anorexia-associated peptide cholecystokinin-8 (CCK, which are known to increase CHBV electrical activity, into the portal vein of transgenic Arc-dVenus mice expressing the fluorescent protein Venus under control of the activity-regulated cytoskeleton-associated protein (Arc promotor. The brain slices were prepared from these mice and the number of Venus positive cells in the slices was counted. After that, c-Fos expression in these slices was analyzed by immunohistochemistry using the avidin-biotin-peroxidase complex method. Intraportal administration of L-arginine increased the number of Venus positive or c-Fos positive cells in the insular cortex. This action of L-arginine was not observed in CHBV-vagotomized Arc-dVenus mice. In contrast, intraportal administration of CCK did not increase the number of c-Fos positive or Venus positive cells in the insular cortex. Intraportal CCK induced c-Fos expression in the dorsomedial hypothalamus, while intraportal L-arginine did not. This action of CCK was abolished by CHBV vagotomy. Intraportal L-arginine reduced, while intraportal CCK increased, the number of c-Fos positive cells in the nucleus tractus solitarii in a CHBV-dependent manner. The present results suggest that the CHBV

  13. Pancreatic acini possess endothelin receptors whose internalization is regulated by PLC-activating agents.

    Science.gov (United States)

    Hildebrand, P; Mrozinski, J E; Mantey, S A; Patto, R J; Jensen, R T

    1993-05-01

    Endothelin-1 (ET-1) and ET-3 mRNA have been found in the pancreas. We investigated the ability of ET-1, ET-2, and ET-3 to interact with and alter dispersed rat pancreatic acinar cell function. Radiolabeled ETs bound in a time- and temperature-dependent fashion, which was specific and saturable. Analysis demonstrated two classes of receptors, one class (ETA receptor) had a high affinity for ET-1 but a low affinity for ET-3, and the other class (ETB receptor) had equally high affinities for ET-1 and ET-3. No specific receptor for ET-2 was identified. Pancreatic secretagogues that activate phospholipase C (PLC) inhibited binding of 125I-labeled ET-1 (125I-ET-1) or 125I-ET-3, whereas agents that act through adenosine 3',5'-cyclic monophosphate (cAMP) did not. A23187 had no effect on 125I-ET-1 or 125I-ET-3 binding, whereas the phorbol ester 12-O-tetradecanoylphorbol 13-acetate reduced binding. The effect of cholecystokinin octapeptide (CCK-8) was mediated through its own receptor. Stripping of surface bound ligand studies demonstrated that both 125I-labeled ET-1 and 125I-labeled ET-3 were rapidly internalized. CCK-8 decreased the internalization but did not change the amount of surface bound ligand. Endothelins neither stimulate nor alter changes in enzyme secretion, intracellular calcium, cAMP, or [3H]inositol trisphosphate (IP3). This study demonstrates the presence of ETA and ETB receptors on rat pancreatic acini; occupation of both receptors resulted in rapid internalization, which is regulated by PLC-activating secretagogues. Occupation of either ET receptor did not alter intracellular calcium, cAMP, IP3, or stimulate amylase release.

  14. Existing Steel Railway Bridges Evaluation

    Science.gov (United States)

    Vičan, Josef; Gocál, Jozef; Odrobiňák, Jaroslav; Koteš, Peter

    2016-12-01

    The article describes general principles and basis of evaluation of existing railway bridges based on the concept of load-carrying capacity determination. Compared to the design of a new bridge, the modified reliability level for existing bridges evaluation should be considered due to implementation of the additional data related to bridge condition and behaviour obtained from regular inspections. Based on those data respecting the bridge remaining lifetime, a modification of partial safety factors for actions and materials could be respected in the bridge evaluation process. A great attention is also paid to the specific problems of determination of load-caring capacity of steel railway bridges in service. Recommendation for global analysis and methodology for existing steel bridge superstructure load-carrying capacity determination are described too.

  15. Existing Steel Railway Bridges Evaluation

    Directory of Open Access Journals (Sweden)

    Vičan Josef

    2016-12-01

    Full Text Available The article describes general principles and basis of evaluation of existing railway bridges based on the concept of load-carrying capacity determination. Compared to the design of a new bridge, the modified reliability level for existing bridges evaluation should be considered due to implementation of the additional data related to bridge condition and behaviour obtained from regular inspections. Based on those data respecting the bridge remaining lifetime, a modification of partial safety factors for actions and materials could be respected in the bridge evaluation process. A great attention is also paid to the specific problems of determination of load-caring capacity of steel railway bridges in service. Recommendation for global analysis and methodology for existing steel bridge superstructure load-carrying capacity determination are described too.

  16. Limitations of existing web services

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Limitations of existing web services. Uploading or downloading large data. Serving too many user from single source. Difficult to provide computer intensive job. Depend on internet and its bandwidth. Security of data in transition. Maintain confidentiality of data ...

  17. Performance of Existing Hydrogen Stations

    Energy Technology Data Exchange (ETDEWEB)

    Sprik, Samuel [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Kurtz, Jennifer M [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Ainscough, Christopher D [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Saur, Genevieve [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Peters, Michael C [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-12-01

    In this presentation, the National Renewable Energy Laboratory presented aggregated analysis results on the performance of existing hydrogen stations, including performance, operation, utilization, maintenance, safety, hydrogen quality, and cost. The U.S. Department of Energy funds technology validation work at NREL through its National Fuel Cell Technology Evaluation Center (NFCTEC).

  18. The EXIST Mission Concept Study

    Science.gov (United States)

    Fishman, Gerald J.; Grindlay, J.; Hong, J.

    2008-01-01

    EXIST is a mission designed to find and study black holes (BHs) over a wide range of environments and masses, including: 1) BHs accreting from binary companions or dense molecular clouds throughout our Galaxy and the Local Group, 2) supermassive black holes (SMBHs) lying dormant in galaxies that reveal their existence by disrupting passing stars, and 3) SMBHs that are hidden from our view at lower energies due to obscuration by the gas that they accrete. 4) the birth of stellar mass BHs which is accompanied by long cosmic gamma-ray bursts (GRBs) which are seen several times a day and may be associated with the earliest stars to form in the Universe. EXIST will provide an order of magnitude increase in sensitivity and angular resolution as well as greater spectral resolution and bandwidth compared with earlier hard X-ray survey telescopes. With an onboard optical-infra red (IR) telescope, EXIST will measure the spectra and redshifts of GRBs and their utility as cosmological probes of the highest z universe and epoch of reionization. The mission would retain its primary goal of being the Black Hole Finder Probe in the Beyond Einstein Program. However, the new design for EXIST proposed to be studied here represents a significant advance from its previous incarnation as presented to BEPAC. The mission is now less than half the total mass, would be launched on the smallest EELV available (Atlas V-401) for a Medium Class mission, and most importantly includes a two-telescope complement that is ideally suited for the study of both obscured and very distant BHs. EXIST retains its very wide field hard X-ray imaging High Energy Telescope (HET) as the primary instrument, now with improved angular and spectral resolution, and in a more compact payload that allows occasional rapid slews for immediate optical/IR imaging and spectra of GRBs and AGN as well as enhanced hard X-ray spectra and timing with pointed observations. The mission would conduct a 2 year full sky survey in

  19. The Greenhouse Effect Does Exist!

    OpenAIRE

    Ebel, Jochen

    2009-01-01

    In particular, without the greenhouse effect, essential features of the atmospheric temperature profile as a function of height cannot be described, i.e., the existence of the tropopause above which we see an almost isothermal temperature curve, whereas beneath it the temperature curve is nearly adiabatic. The relationship between the greenhouse effect and observed temperature curve is explained and the paper by Gerlich and Tscheuschner [arXiv:0707.1161] critically analyzed. Gerlich and Tsche...

  20. Europe - space for transcultural existence?

    OpenAIRE

    Tamcke, Martin; Janny, de Jong; Klein, Lars; Waal, Margriet

    2013-01-01

    Europe - Space for Transcultural Existence? is the first volume of the new series, Studies in Euroculture, published by Göttingen University Press. The series derives its name from the Erasmus Mundus Master of Excellence Euroculture: Europe in the Wider World, a two year programme offered by a consortium of eight European universities in collaboration with four partner universities outside Europe. This master highlights regional, national and supranational dimensions of the European democrati...

  1. Existence of undiscovered Uranian satellites

    International Nuclear Information System (INIS)

    Boice, D.C.

    1986-04-01

    Structure in the Uranian ring system as observed in recent occultations may contain indirect evidence for the existence of undiscovered satellites. Using the Alfven and Arrhenius (1975, 1976) scenario for the formation of planetary systems, the orbital radii of up to nine hypothetical satellites interior to Miranda are computed. These calculations should provide interesting comparisons when the results from the Voyager 2 encounter with Uranus are made public. 15 refs., 1 fig., 1 tab

  2. UNCITRAL: Changes to existing law

    OpenAIRE

    Andersson, Joakim

    2008-01-01

    The UNCITRAL Convention on Contracts for the International Carriage of Goods [wholly or partly] by Sea has an ambition of replacing current maritime regimes and expands the application of the Convention to include also multimodal transport. This thesis questions what changes to existing law, in certain areas, the new Convention will bring compared to the current regimes. In the initial part, the thesis provides for a brief background and history of international maritime regulations and focus...

  3. Existence Results for Incompressible Magnetoelasticity

    Czech Academy of Sciences Publication Activity Database

    Kružík, Martin; Stefanelli, U.; Zeman, J.

    2015-01-01

    Roč. 35, č. 6 (2015), s. 2615-2623 ISSN 1078-0947 R&D Projects: GA ČR GA13-18652S Institutional support: RVO:67985556 Keywords : magnetoelasticity * magnetostrictive solids * incompressibility * existence of minimizers * quasistatic evolution * energetic solution Subject RIV: BA - General Mathematics Impact factor: 1.127, year: 2015 http://library.utia.cas.cz/separaty/2015/MTR/kruzik-0443017.pdf

  4. The two-state dimer receptor model: a general model for receptor dimers.

    Science.gov (United States)

    Franco, Rafael; Casadó, Vicent; Mallol, Josefa; Ferrada, Carla; Ferré, Sergi; Fuxe, Kjell; Cortés, Antoni; Ciruela, Francisco; Lluis, Carmen; Canela, Enric I

    2006-06-01

    Nonlinear Scatchard plots are often found for agonist binding to G-protein-coupled receptors. Because there is clear evidence of receptor dimerization, these nonlinear Scatchard plots can reflect cooperativity on agonist binding to the two binding sites in the dimer. According to this, the "two-state dimer receptor model" has been recently derived. In this article, the performance of the model has been analyzed in fitting data of agonist binding to A(1) adenosine receptors, which are an example of receptor displaying concave downward Scatchard plots. Analysis of agonist/antagonist competition data for dopamine D(1) receptors using the two-state dimer receptor model has also been performed. Although fitting to the two-state dimer receptor model was similar to the fitting to the "two-independent-site receptor model", the former is simpler, and a discrimination test selects the two-state dimer receptor model as the best. This model was also very robust in fitting data of estrogen binding to the estrogen receptor, for which Scatchard plots are concave upward. On the one hand, the model would predict the already demonstrated existence of estrogen receptor dimers. On the other hand, the model would predict that concave upward Scatchard plots reflect positive cooperativity, which can be neither predicted nor explained by assuming the existence of two different affinity states. In summary, the two-state dimer receptor model is good for fitting data of binding to dimeric receptors displaying either linear, concave upward, or concave downward Scatchard plots.

  5. Quantum logics with existence property

    International Nuclear Information System (INIS)

    Schindler, C.

    1991-01-01

    A quantum logic (σ-orthocomplete orthomodular poset L with a convex, unital, and separating set Δ of states) is said to have the existence property if the expectation functionals on lin(Δ) associated with the bounded observables of L form a vector space. Classical quantum logics as well as the Hilbert space logics of traditional quantum mechanics have this property. The author shows that, if a quantum logic satisfies certain conditions in addition to having property E, then the number of its blocks (maximal classical subsystems) must either be one (classical logics) or uncountable (as in Hilbert space logics)

  6. Nonsulfated cholecystokinins in cerebral neurons

    DEFF Research Database (Denmark)

    Agersnap, Mikkel; Zhang, Ming-Dong; Harkany, Tibor

    2016-01-01

    ) and rats (n=6) contained nonsulfated CCK. The highest concentrations were measured in the neocortex; 4.7±0.25pmol/g (7.4%) in the rat and 4.3±1.88pmol/g (2.3%) in the pig. Chromatography of porcine cortical extracts revealed that 96.4% of the CCK was O-sulfated CCK-8. A higher fraction of the larger...

  7. Plasma cholecystokinin in obese patients before and after jejunoileal bypass with 3:1 or 1:3 jejunoileal ratio--no role in the increased risk of gallstone formation

    DEFF Research Database (Denmark)

    Sørensen, T I; Toftdahl, D B; Højgaard, L

    1994-01-01

    BACKGROUND AND AIM: Jejunoileal bypass surgery for obesity increases the risk of gallstone formation, and, contrary to expectations, the incidence is greater in patients with a long as compared to a short ileum left in continuity. Impaired gallbladder motility due to reduced cholecystokinin (CCK...... bypass surgery with either a 1:3 jejunoileal ratio (n = 14) or a 3:1 ratio (n = 15), and in unoperated obese patients (n = 7). Plasma CCK levels were determined during fasting and during 150 min following ingestion of a liquid test meal. RESULTS: There were no significant changes over time following......) stimulation could be an explanation. The aim of this study was to investigate the CCK levels in such patients. SETTING: The randomized trial of bypass surgery named The Danish Obesity Project. DESIGN AND METHODS: We compared plasma levels of CCK in obese patients at three, nine or 15 months after jejunoileal...

  8. Neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART) and cholecystokinin (CCK) in winter skate (Raja ocellata): cDNA cloning, tissue distribution and mRNA expression responses to fasting.

    Science.gov (United States)

    MacDonald, Erin; Volkoff, Hélène

    2009-04-01

    cDNAs encoding for neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART) and cholecystokinin (CCK) were cloned in an elasmobranch fish, the winter skate. mRNA tissue distribution was examined for the three peptides as well as the effects of two weeks of fasting on their expression. Skate NPY, CART and CCK sequences display similarities with sequences for teleost fish but in general the degree of identity is relatively low (50%). All three peptides are present in brain and in several peripheral tissues, including gut and gonads. Within the brain, the three peptides are expressed in the hypothalamus, telencephalon, optic tectum and cerebellum. Two weeks of fasting induced an increase in telencephalon NPY and an increase in CCK in the gut but had no effects on hypothalamic NPY, CART and CCK, or on telencephalon CART. Our results provide basis for further investigation into the regulation of feeding in winter skate.

  9. Does cold nuclear fusion exist?

    International Nuclear Information System (INIS)

    Brudanin, V.B.; Bystritskij, V.M.; Egorov, V.G.; Shamsutdinov, S.G.; Shyshkin, A.L.; Stolupin, V.A.; Yutlandov, I.A.

    1989-01-01

    The results of investigation of cold nuclear fusion on palladium are given both for electrolysis of heavy water D 2 O and mixture D 2 O + H 2 O) (1:1) and for palladium saturation with gaseous deuterium. The possibility of existance of this phenomenon was examined by detection of neutrons and gamma quanta from reactions: d + d → 3 He + n + 3.27 MeV, p + d → 3 He + γ + 5.5 MeV. Besides these reactions were identified by measuring the characteristic X radiation of palladium due to effect of charged products 3 He, p, t. The upper limits of the intensities of hypothetical sources of neutrons and gamma quanta at the 95% confidence level were obtained to be Q n ≤ 2x10 -2 n/sxcm 3 Pd, Q γ ≤ 2x10 -3 γ/sxcm 3 Pd. 2 refs.; 4 figs.; 2 tabs

  10. Straightening: existence, uniqueness and stability

    Science.gov (United States)

    Destrade, M.; Ogden, R. W.; Sgura, I.; Vergori, L.

    2014-01-01

    One of the least studied universal deformations of incompressible nonlinear elasticity, namely the straightening of a sector of a circular cylinder into a rectangular block, is revisited here and, in particular, issues of existence and stability are addressed. Particular attention is paid to the system of forces required to sustain the large static deformation, including by the application of end couples. The influence of geometric parameters and constitutive models on the appearance of wrinkles on the compressed face of the block is also studied. Different numerical methods for solving the incremental stability problem are compared and it is found that the impedance matrix method, based on the resolution of a matrix Riccati differential equation, is the more precise. PMID:24711723

  11. Why do interstellar grains exist

    International Nuclear Information System (INIS)

    Seab, C.G.; Hollenbach, D.J.; Mckee, C.F.; Tielens, A.G.G.M.

    1986-01-01

    There exists a discrepancy between calculated destruction rates of grains in the interstellar medium and postulated sources of new grains. This problem was examined by modelling the global life cycle of grains in the galaxy. The model includes: grain destruction due to supernovae shock waves; grain injection from cool stars, planetary nebulae, star formation, novae, and supernovae; grain growth by accretion in dark clouds; and a mixing scheme between phases of the interstellar medium. Grain growth in molecular clouds is considered as a mechanism or increasing the formation rate. To decrease the shock destruction rate, several new physical processes, such as partial vaporization effects in grain-grain collisions, breakdown of the small Larmor radius approximation for betatron acceleration, and relaxation of the steady-state shock assumption are included

  12. Distribution of melatonin receptor in human fetal brain

    Institute of Scientific and Technical Information of China (English)

    WANG Guo-quan; SHAO Fu-yuan; ZHAO Ying; LIU Zhi-min

    2001-01-01

    Objective: To study the distribution of 2 kinds of melatonin receptor subtypes (mtl and MT2) in human fetal brain. Methods: The fetal brain tissues were sliced and the distribution ofmelatonin receptors in human fetal brain were detected using immunohistochemistry and in situ hybridization. Results: Melatonin receptor mtl existed in the cerebellun and hypothalamus, melatonin receptor MT2 exists in hypothalamus, occipital and medulla. Conclusion: Two kinds of melatonin receptors, mtl and MT2 exist in the membrane and cytosol of brain cells, indicating that human fetal brain is a target organ of melatonin.

  13. Existe sujeito em Michel Maffesoli?

    Directory of Open Access Journals (Sweden)

    Marli Appel da Silva

    2010-06-01

    Full Text Available Este ensaio discute a concepção de sujeito na abordagem teórica de Michel Maffesoli. As ideias desse autor estão em voga em alguns meios acadêmicos no Brasil e são difundidas por algumas mídias de grande circulação nacional. Entretanto, ao longo de suas obras, os pressupostos que definem quem é o sujeito maffesoliano se encontram pouco clarificados. Portanto, para alcançar o objetivo a que se propõe, este ensaio desenvolve uma análise da epistemologia e da ontologia maffesoliana com a finalidade de compreender as origens dos pressupostos desse autor, ou seja, as teorias e os autores em que Maffesoli se baseou para desenvolver uma visão de sujeito. Com essa compreensão, pretende-se responder à questão: existe sujeito na abordagem teórica de Maffesoli.

  14. Summary of existing uncertainty methods

    International Nuclear Information System (INIS)

    Glaeser, Horst

    2013-01-01

    A summary of existing and most used uncertainty methods is presented, and the main features are compared. One of these methods is the order statistics method based on Wilks' formula. It is applied in safety research as well as in licensing. This method has been first proposed by GRS for use in deterministic safety analysis, and is now used by many organisations world-wide. Its advantage is that the number of potential uncertain input and output parameters is not limited to a small number. Such a limitation was necessary for the first demonstration of the Code Scaling Applicability Uncertainty Method (CSAU) by the United States Regulatory Commission (USNRC). They did not apply Wilks' formula in their statistical method propagating input uncertainties to obtain the uncertainty of a single output variable, like peak cladding temperature. A Phenomena Identification and Ranking Table (PIRT) was set up in order to limit the number of uncertain input parameters, and consequently, the number of calculations to be performed. Another purpose of such a PIRT process is to identify the most important physical phenomena which a computer code should be suitable to calculate. The validation of the code should be focused on the identified phenomena. Response surfaces are used in some applications replacing the computer code for performing a high number of calculations. The second well known uncertainty method is the Uncertainty Methodology Based on Accuracy Extrapolation (UMAE) and the follow-up method 'Code with the Capability of Internal Assessment of Uncertainty (CIAU)' developed by the University Pisa. Unlike the statistical approaches, the CIAU does compare experimental data with calculation results. It does not consider uncertain input parameters. Therefore, the CIAU is highly dependent on the experimental database. The accuracy gained from the comparison between experimental data and calculated results are extrapolated to obtain the uncertainty of the system code predictions

  15. Quantitative receptor radioautography in the study of receptor-receptor interactions in the nucleus tractus solitarii

    Directory of Open Access Journals (Sweden)

    Fior-Chadi D.R.

    1998-01-01

    Full Text Available The nucleus tractus solitarii (NTS in the dorsomedial medulla comprises a wide range of neuropeptides and biogenic amines. Several of them are related to mechanisms of central blood pressure control. Angiotensin II (Ang II, neuropeptide Y (NPY and noradrenaline (NA are found in the NTS cells, as well as their receptors. Based on this observation we have evaluated the modulatory effect of these peptide receptors on a2-adrenoceptors in the NTS. Using quantitative receptor radioautography, we observed that NPY and Ang II receptors decreased the affinity of a2-adrenoceptors for their agonists in the NTS of the rat. Cardiovascular experiments agreed with the in vitro data. Coinjection of a threshold dose of Ang II or of the NPY agonists together with an ED50 dose of adrenergic agonists such as NA, adrenaline and clonidine counteracted the depressor effect produced by the a2-agonist in the NTS. The results provide evidence for the existence of an antagonistic interaction between Ang II at1 receptors and NPY receptor subtypes with the a2-adrenoceptors in the NTS. This receptor interaction may reduce the transduction over the a2-adrenoceptors which can be important in central cardiovascular regulation and in the development of hypertension

  16. Phencyclidine-induced social withdrawal results from deficient stimulation of cannabinoid CB₁ receptors: implications for schizophrenia.

    Science.gov (United States)

    Seillier, Alexandre; Martinez, Alex A; Giuffrida, Andrea

    2013-08-01

    The neuronal mechanisms underlying social withdrawal, one of the core negative symptoms of schizophrenia, are not well understood. Recent studies suggest an involvement of the endocannabinoid system in the pathophysiology of schizophrenia and, in particular, of negative symptoms. We used biochemical, pharmacological, and behavioral approaches to investigate the role played by the endocannabinoid system in social withdrawal induced by sub-chronic administration of phencyclidine (PCP). Pharmacological enhancement of endocannabinoid levels via systemic administration of URB597, an inhibitor of endocannabinoid degradation, reversed social withdrawal in PCP-treated rats via stimulation of CB1 receptors, but reduced social interaction in control animals through activation of a cannabinoid/vanilloid-sensitive receptor. In addition, the potent CB agonist CP55,940 reversed PCP-induced social withdrawal in a CB₁-dependent manner, whereas pharmacological blockade of CB₁ receptors by either AM251 or SR141716 reduced the time spent in social interaction in control animals. PCP-induced social withdrawal was accompanied by a decrease of anandamide (AEA) levels in the amygdala and prefrontal cortex, and these deficits were reversed by URB597. As CB₁ receptors are predominantly expressed on GABAergic interneurons containing the anxiogenic peptide cholecystokinin (CCK), we also examined whether the PCP-induced social withdrawal resulted from deficient CB₁-mediated modulation of CCK transmission. The selective CCK2 antagonist LY225910 blocked both PCP- and AM251-induced social withdrawal, but not URB597 effect in control rats. Taken together, these findings indicate that AEA-mediated activation of CB₁ receptors is crucial for social interaction, and that PCP-induced social withdrawal results from deficient endocannabinoid transmission.

  17. The daidzein- and estradiol- induced anorectic action in CCK or leptin receptor deficiency rats.

    Science.gov (United States)

    Fujitani, Mina; Mizushige, Takafumi; Bhattarai, Keshab; Iwahara, Asami; Aida, Ryojiro; Kishida, Taro

    2015-01-01

    We investigated the effect of daidzein feeding and estradiol treatment on food intake in cholecystokinin-1 receptor (CCK1R) deficiency, leptin receptor (ObRb) deficiency rats and their wild-type rats. These rats underwent an ovariectomy or a sham operation. For the 5 week experiment, each rat was divided in three groups: control, daidzein (150 mg/kg diet), and estradiol (4.2 μg/rat/day) groups. In both CCK1R+ and CCK1R- rats, daidzein feeding and estradiol treatment significantly decreased food intake. Daidzein feeding significantly reduced food intake in ovariectomized ObRb- rats, although not in ObRb+ rats. Estradiol treatment significantly lowered food intake in ovariectomized ObRb+ and ObRb- rats. In the ovariectomized rats, estradiol treatment significantly increases uterine weight, while daidzein feeding did not change it, suggesting that daidzein might have no or weak estrogenic effect in our experiment. These results suggest that CCK1R and ObRb signalings were not essential for the daidzein- and estradiol-induced anorectic action.

  18. 10 CFR 4.127 - Existing facilities.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Existing facilities. 4.127 Section 4.127 Energy NUCLEAR... 1973, as Amended Discriminatory Practices § 4.127 Existing facilities. (a) Accessibility. A recipient... make each of its existing facilities or every part of an existing facility accessible to and usable by...

  19. Qualitative variation of photolabelled benzodiazepine receptors in different species.

    Science.gov (United States)

    Hebebrand, J; Friedl, W; Lentes, K U; Propping, P

    1986-01-01

    In order to examine whether species differences of benzodiazepine receptor subunits exist, we compared the fluorographic pattern of photoaffinity labelled subunits after SDS-PAGE in five species: fish, frog, chicken, mouse and calf. Each species showed a distinct pattern of specifically labelled proteins. We conclude that species variation of benzodiazepine receptor does indeed exist.

  20. Do Elementary Particles Have an Objective Existence?

    OpenAIRE

    Nissenson, Bilha

    2007-01-01

    The formulation of quantum theory does not comply with the notion of objective existence of elementary particles. Objective existence independent of observation implies the distinguishability of elementary particles. In other words: If elementary particles have an objective existence independent of observations, then they are distinguishable. Or if elementary particles are indistinguishable then matter cannot have existence independent of our observation. This paper presents a simple deductio...

  1. 34 CFR 104.22 - Existing facilities.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Existing facilities. 104.22 Section 104.22 Education... Accessibility § 104.22 Existing facilities. (a) Accessibility. A recipient shall operate its program or activity.... This paragraph does not require a recipient to make each of its existing facilities or every part of a...

  2. 45 CFR 1170.32 - Existing facilities.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Existing facilities. 1170.32 Section 1170.32... ASSISTED PROGRAMS OR ACTIVITIES Accessibility § 1170.32 Existing facilities. (a) Accessibility. A recipient... require a recipient to make each of its existing facilities or every part of a facility accessible to and...

  3. 45 CFR 605.22 - Existing facilities.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Existing facilities. 605.22 Section 605.22 Public... Accessibility § 605.22 Existing facilities. (a) Accessibility. A recipient shall operate each program or... existing facilities or every part of a facility accessible to and usable by qualified handicapped persons...

  4. 14 CFR 1251.301 - Existing facilities.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Existing facilities. 1251.301 Section 1251... HANDICAP Accessibility § 1251.301 Existing facilities. (a) Accessibility. A recipient shall operate each... existing facilities or every part of a facility accessible to and usable by handicapped persons. (b...

  5. 45 CFR 1151.22 - Existing facilities.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Existing facilities. 1151.22 Section 1151.22... Prohibited Accessibility § 1151.22 Existing facilities. (a) A recipient shall operate each program or... make each of its existing facilities or every part of a facility accessible to and usable by...

  6. 10 CFR 611.206 - Existing facilities.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Existing facilities. 611.206 Section 611.206 Energy... PROGRAM Facility/Funding Awards § 611.206 Existing facilities. The Secretary shall, in making awards to those manufacturers that have existing facilities, give priority to those facilities that are oldest or...

  7. The LDL receptor.

    Science.gov (United States)

    Goldstein, Joseph L; Brown, Michael S

    2009-04-01

    In this article, the history of the LDL receptor is recounted by its codiscoverers. Their early work on the LDL receptor explained a genetic cause of heart attacks and led to new ways of thinking about cholesterol metabolism. The LDL receptor discovery also introduced three general concepts to cell biology: receptor-mediated endocytosis, receptor recycling, and feedback regulation of receptors. The latter concept provides the mechanism by which statins selectively lower plasma LDL, reducing heart attacks and prolonging life.

  8. Phencyclidine-Induced Social Withdrawal Results from Deficient Stimulation of Cannabinoid CB1 Receptors: Implications for Schizophrenia

    Science.gov (United States)

    Seillier, Alexandre; Martinez, Alex A; Giuffrida, Andrea

    2013-01-01

    The neuronal mechanisms underlying social withdrawal, one of the core negative symptoms of schizophrenia, are not well understood. Recent studies suggest an involvement of the endocannabinoid system in the pathophysiology of schizophrenia and, in particular, of negative symptoms. We used biochemical, pharmacological, and behavioral approaches to investigate the role played by the endocannabinoid system in social withdrawal induced by sub-chronic administration of phencyclidine (PCP). Pharmacological enhancement of endocannabinoid levels via systemic administration of URB597, an inhibitor of endocannabinoid degradation, reversed social withdrawal in PCP-treated rats via stimulation of CB1 receptors, but reduced social interaction in control animals through activation of a cannabinoid/vanilloid-sensitive receptor. In addition, the potent CB agonist CP55,940 reversed PCP-induced social withdrawal in a CB1-dependent manner, whereas pharmacological blockade of CB1 receptors by either AM251 or SR141716 reduced the time spent in social interaction in control animals. PCP-induced social withdrawal was accompanied by a decrease of anandamide (AEA) levels in the amygdala and prefrontal cortex, and these deficits were reversed by URB597. As CB1 receptors are predominantly expressed on GABAergic interneurons containing the anxiogenic peptide cholecystokinin (CCK), we also examined whether the PCP-induced social withdrawal resulted from deficient CB1-mediated modulation of CCK transmission. The selective CCK2 antagonist LY225910 blocked both PCP- and AM251-induced social withdrawal, but not URB597 effect in control rats. Taken together, these findings indicate that AEA-mediated activation of CB1 receptors is crucial for social interaction, and that PCP-induced social withdrawal results from deficient endocannabinoid transmission. PMID:23563893

  9. The AT2 Receptor and Inflammation

    DEFF Research Database (Denmark)

    Esquitino, Veronica Valero; Danyel, Leon Alexander; Steckelings, Ulrike M.

    2015-01-01

    This chapter summarizes current knowledge about the role of the angiotensin type 2 (AT2) receptor in inflammation. The first section provides an overview about molecular mechanisms underlying the anti-inflammatory action of the AT2 receptor. This section is followed...... by a review of the existing literature addressing the role of the AT2 receptor in a wide range of disorders, in which acute or chronic inflammation is an essential contributor to the pathology. These disorders comprise cardiovascular, cerebrovascular, renal, and autoimmune diseases.Taken as a whole......, the vast majority of data support an anti-inflammatory and immunomodulatory role of the AT2 receptor. In light of the current development of AT2 receptor agonists as future drugs for clinical use, diseases with a marked inflammatory component may become a major area of therapeutic use...

  10. Multiple Receptor Subtypes for the CGRP Super-Family

    Directory of Open Access Journals (Sweden)

    R. Quirion

    2001-01-01

    Full Text Available Molecular evidence for the existence of multiple receptors for CGRP has been rather difficult to obtain. Over 10 years after suggesting the existence of at least two classes (CGRP1 and CGRP2 of CGRP receptors on the basis of pharmacological data[1], molecular data on the CGRP2 receptor subtype are still lacking as well as potent and selective antagonists. The situation is somewhat different for the functional CGRP1 subtype which is likely composed of diverse subunits CRLR, RAMP1 and possibly RCP[2]. Moreover, BIBN 4096BS was recently reported as the first nonpeptide highly potent CGRP1 receptor antagonist[3]. However, in situ hybridization and receptor autoradiographic data have clearly shown the existence of major mismatches (e.g., cerebellum between the discrete localization of CRLR, RAMP1, and specific CGRP binding sites supporting the existence of CGRP receptor subtypes. Functional studies have also provided evidence in that regard (for a recent review: [4]. Accordingly, additional studies aiming at cloning additional CGRP receptors are certainly warranted. Similarly, recent evidence from various laboratories including ours suggests the existence of more than one class (CRLR and RAMP2 of adrenomedullin receptors at least in the rat brain. In contrast, most evidence suggests the existence of a single class of amylin receptors. In brief, it appears that multiple receptors or receptor complexes do exist for CGRP and related peptides but their composition is apparently unique among the GPCR super-family and additional data are needed to fully establish the molecular organization of each subtype. Supported by CIHR of Canada.

  11. Existence of equilibria in articulated bearings

    Science.gov (United States)

    Buscaglia, G.; Ciuperca, I.; Hafidi, I.; Jai, M.

    2007-04-01

    The existence of equilibrium solutions for a lubricated system consisting of an articulated body sliding over a flat plate is considered. Though this configuration is very common (it corresponds to the popular tilting-pad thrust bearings), the existence problem has only been addressed in extremely simplified cases, such as planar sliders of infinite width. Our results show the existence of at least one equilibrium for a quite general class of (nonplanar) slider shapes. We also extend previous results concerning planar sliders.

  12. CCK1-Receptor Stimulation Protects Against Gut Mediator-Induced Lung Damage During Endotoxemia

    Directory of Open Access Journals (Sweden)

    Friederike Eisner

    2013-12-01

    Full Text Available Background/Aims: Cholecystokinin 1-receptor (CCK1-R activation by long chain fatty acid (LCFA absorption stimulates vago-vagal reflex pathways in the brain stem. The present study determines whether this reflex also activates the cholinergic anti-inflammatory pathway, a pathway known to modulate cytokine release during endotoxemia. Methods:Mesenteric lymph was obtained from wild type (WT and CCK1-R knockout (CCK1-R-/- mice intraperitoneally challenged with Lipopolysaccharid (LPS (endotoxemic lymph, EL and intestinally infused with vehicle or LCFA-enriched solution. The lymph was analyzed for TNFα, IL-6 and IL-10 concentration and administered to healthy recipient mice via jugular infusion. Alveolar wall thickness, myeloperoxidase (MPO and TUNEL positive cells were determined in lung tissue of recipient mice. Results: LCFA infusion in WT mice reduced TNFα concentration in EL by 49% compared to vehicle infusion, but had no effect in CCK1-R-/- mice. EL significantly increased the alveolar wall thickness, the number of MPO-positive and TUNEL-positive cells compared to control lymph administration. LCFA infusion in WT, but not in CCK1R-/- mice, significantly reduced these pathological effects of EL. Conclusion: During endotoxemia enteral LCFA absorption reduces TNFα release into mesenteric lymph and attenuates histomorphologic parameters of lung dysfunction. Failure to elicit this effect in CCK1R-/- mice demonstrates that anti-inflammatory properties of LCFAs are mediated through CCK1-Rs.

  13. 47 CFR 17.17 - Existing structures.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Existing structures. 17.17 Section 17.17... STRUCTURES Federal Aviation Administration Notification Criteria § 17.17 Existing structures. (a) The requirements found in § 17.23 relating to painting and lighting of antenna structures shall not apply to those...

  14. 10 CFR 1040.72 - Existing facilities.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Existing facilities. 1040.72 Section 1040.72 Energy... § 1040.72 Existing facilities. (a) Accessibility. A recipient shall operate any program or activity to... facilities or every part of a facility accessible to and useable by handicapped persons. (b) Methods. A...

  15. 45 CFR 84.22 - Existing facilities.

    Science.gov (United States)

    2010-10-01

    ... HANDICAP IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Accessibility § 84.22 Existing facilities. (a) Accessibility. A recipient shall operate its program or activity so that when each part is..., welfare, or other social services at alternate accessible sites, alteration of existing facilities and...

  16. Financial gap calculations for existing cogeneration 2008

    International Nuclear Information System (INIS)

    Hers, S.J.; Wetzels, W.; Seebregts, A.J.; Van der Welle, A.J.

    2008-05-01

    The Dutch SDE (abbreviation for the renewable energy incentive) subsidy scheme promotes the reduction of CO2 emissions which results from the use of Combined Heat and Power (CHP) plants. This report calculates the profitability of operation of existing CHP plants. This information can be used for decision making on the SDE subsidy for existing CHP plants in 2008 [nl

  17. On the existence of consistent price systems

    DEFF Research Database (Denmark)

    Bayraktar, Erhan; Pakkanen, Mikko S.; Sayit, Hasanjan

    2014-01-01

    We formulate a sufficient condition for the existence of a consistent price system (CPS), which is weaker than the conditional full support condition (CFS). We use the new condition to show the existence of CPSs for certain processes that fail to have the CFS property. In particular this condition...

  18. The macrophage scavenger receptor CD163

    DEFF Research Database (Denmark)

    Nielsen, Marianne Jensby; Madsen, Mette; Møller, Holger J

    2006-01-01

    CD163 is the monocyte/macrophage-specific receptor for haptoglobin-hemoglobin (Hp-Hb) complexes. The cytoplasmic tail of human CD163 exists as a short tail variant and two long tail variants. Reverse transcriptase-polymerase chain reaction analysis indicated that all three CD163 variants are subs......CD163 is the monocyte/macrophage-specific receptor for haptoglobin-hemoglobin (Hp-Hb) complexes. The cytoplasmic tail of human CD163 exists as a short tail variant and two long tail variants. Reverse transcriptase-polymerase chain reaction analysis indicated that all three CD163 variants...

  19. The existence of trajectories joining critical points

    International Nuclear Information System (INIS)

    Yu Shuxiang.

    1985-01-01

    In this paper, using the notion of an isolating block and the concept of canonical regions, three existence criteria of trajectories connecting a pair of critical points of planar differential equations are given. (author)

  20. Pre-Existing Condition Insurance Plan Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Affordable Care Act created the new Pre-Existing Condition Insurance Plan (PCIP) program to make health insurance available to Americans denied coverage by...

  1. Seismic assessment of existing nuclear chemical plants

    International Nuclear Information System (INIS)

    Merriman, P.A.

    1997-01-01

    This paper outlines the generic approach to the seismic assessment of existing structures. It describes the role of the safety case in determining the studies carried out by the functional departments on individual projects. There is an emphasis on the role of existing information and material tests to provide realistic properties for analysis to account for possible degradation effects. Finally, a case study of a concrete containment cell is shown to illustrate the approach. (author)

  2. Solar Panel Installations on Existing Structures

    OpenAIRE

    Tim D. Sass; Pe; Leed

    2013-01-01

    The rising price of fossil fuels, government incentives and growing public aware-ness for the need to implement sustainable energy supplies has resulted in a large in-crease in solar panel installations across the country. For many sites the most eco-nomical solar panel installation uses existing, southerly facing rooftops. Adding solar panels to an existing roof typically means increased loads that must be borne by the building-s structural elements. The structural desig...

  3. The global existence problem in general relativity

    CERN Document Server

    Andersson, L

    2000-01-01

    We survey some known facts and open questions concerning the global properties of 3+1 dimensional space--times containing a compact Cauchy surface. We consider space--times with an $\\ell$--dimensional Lie algebra of space--like Killing fields. For each $\\ell \\leq 3$, we give some basic results and conjectures on global existence and cosmic censorship. For the case of the 3+1 dimensional Einstein equations without symmetries, a new small data global existence result is announced.

  4. Expression of feeding-related peptide receptors mRNA in GT1-7 cell line and roles of leptin and orexins in control of GnRH secretion.

    Science.gov (United States)

    Yang, Ying; Zhou, Li-bin; Liu, Shang-quan; Tang, Jing-feng; Li, Feng-yin; Li, Rong-ying; Song, Huai-dong; Chen, Ming-dao

    2005-08-01

    To investigate the expression of feeding-related peptide receptors mRNA in GT1-7 cell line and roles of leptin and orexins in the control of GnRH secretion. Receptors of bombesin3, cholecystokinin (CCK)-A, CCK-B, glucagon-like peptide (GLP)1, melanin-concentrating hormone (MCH)1, orexin1, orexin2, neuromedin-B, neuropeptide Y (NPY)1 and NPY5, neurotensin (NT)1, NT2, NT3, and leptin receptor long form mRNA in GT1-7 cells were detected by reversed transcriptase-polymerase chain reaction. GT1-7 cells were treated with leptin, orexin A and orexin B at a cohort of concentrations for different lengths of time, and GnRH in medium was determined by radioimmunoassay (RIA). Receptors of bombesin 3, CCK-B, GLP1, MCH1, orexin1, neuromedin-B, NPY1, NPY5, NT1, NT3, and leptin receptor long form mRNA were expressed in GT1-7 cells, of which, receptors of GLP1, neuromedin-B, NPY1, and NT3 were highly expressed. No amplified fragments of orexin2, NT2, and CCK-A receptor cDNA were generated with GT1-7 RNA, indicating that the GT1-7 cells did not express mRNA of them. Leptin induced a significant stimulation of GnRH release, the results being most significant at 0.1 nmol/L for 15 min. In contrast to other studies in hypothalamic explants, neither orexin A nor orexin B affected basal GnRH secretion over a wide range of concentrations ranging from 1 nmol/L to 500 nmol/Lat 15, 30, and 60 min. Feeding and reproductive function are closely linked. Many orexigenic and anorexigenic signals may control feeding behavior as well as alter GnRH secretion through their receptors on GnRH neurons.

  5. Macrocyclic chelator-coupled gastrin-based radiopharmaceuticals for targeting of gastrin receptor-expressing tumours

    International Nuclear Information System (INIS)

    Good, Stephan; Wang, Xuejuan; Maecke, Helmut R.; Walter, Martin A.; Mueller-Brand, Jan; Waser, Beatrice; Reubi, Jean-Claude; Behe, Martin P.

    2008-01-01

    Diethylenetriamine-pentaacetic acid (DTPA)-coupled minigastrins are unsuitable for therapeutic application with the available β-emitting radiometals due to low complex stability. Low tumour-to-kidney ratio of the known radiopharmaceuticals is further limiting their potency. We used macrocyclic chelators for coupling to increase complex stability, modified the peptide sequence to enhance radiolytic stability and studied tumour-to-kidney ratio and metabolic stability using 111 In-labelled derivatives. Gastrin derivatives with decreasing numbers of glutamic acids were synthesised using 111 In as surrogate for therapeutic radiometals for in vitro and in vivo studies. Gastrin receptor affinities of the nat In-metallated compounds were determined by receptor autoradiography using 125 I-CCK as radioligand. Internalisation was evaluated in AR4-2J cells. Enzymatic stability was determined by incubating the 111 In-labelled peptides in human serum. Biodistribution was performed in AR4-2J-bearing Lewis rats. IC 50 values of the nat In-metallated gastrin derivatives vary between 1.2 and 4.8 nmol/L for all methionine-containing derivatives. Replacement of methionine by norleucine, isoleucine, methionine-sulfoxide and methionine-sulfone resulted in significant decrease of receptor affinity (IC 50 between 9.9 and 1,195 nmol/L). All cholecystokinin receptor affinities were >100 nmol/L. All 111 In-labelled radiopeptides showed receptor-specific internalisation. Serum mean-life times varied between 2.0 and 72.6 h, positively correlating with the number of Glu residues. All 111 In-labelled macrocyclic chelator conjugates showed higher tumour-to-kidney ratios after 24 h (0.37-0.99) compared to 111 In-DTPA-minigastrin 0(0.05). Tumour wash out between 4 and 24 h was low. Imaging studies confirmed receptor-specific blocking of the tumour uptake. Reducing the number of glutamates increased tumour-to-kidney ratio but resulted in lower metabolic stability. The properties of the macrocyclic

  6. Macrocyclic chelator-coupled gastrin-based radiopharmaceuticals for targeting of gastrin receptor-expressing tumours

    Energy Technology Data Exchange (ETDEWEB)

    Good, Stephan; Wang, Xuejuan; Maecke, Helmut R. [University Hospital Basel, Division of Radiological Chemistry, Basel (Switzerland); Walter, Martin A.; Mueller-Brand, Jan [University Hospital, Institute of Nuclear Medicine, Basel (Switzerland); Waser, Beatrice; Reubi, Jean-Claude [University of Berne, Department of Pathology, Bern (Switzerland); Behe, Martin P. [Philipps-University of Marburg, Department of Nuclear Medicine, Marburg (Germany)

    2008-10-15

    Diethylenetriamine-pentaacetic acid (DTPA)-coupled minigastrins are unsuitable for therapeutic application with the available {beta}-emitting radiometals due to low complex stability. Low tumour-to-kidney ratio of the known radiopharmaceuticals is further limiting their potency. We used macrocyclic chelators for coupling to increase complex stability, modified the peptide sequence to enhance radiolytic stability and studied tumour-to-kidney ratio and metabolic stability using {sup 111}In-labelled derivatives. Gastrin derivatives with decreasing numbers of glutamic acids were synthesised using {sup 111}In as surrogate for therapeutic radiometals for in vitro and in vivo studies. Gastrin receptor affinities of the {sup nat}In-metallated compounds were determined by receptor autoradiography using {sup 125}I-CCK as radioligand. Internalisation was evaluated in AR4-2J cells. Enzymatic stability was determined by incubating the {sup 111}In-labelled peptides in human serum. Biodistribution was performed in AR4-2J-bearing Lewis rats. IC{sub 50} values of the {sup nat}In-metallated gastrin derivatives vary between 1.2 and 4.8 nmol/L for all methionine-containing derivatives. Replacement of methionine by norleucine, isoleucine, methionine-sulfoxide and methionine-sulfone resulted in significant decrease of receptor affinity (IC{sub 50} between 9.9 and 1,195 nmol/L). All cholecystokinin receptor affinities were >100 nmol/L. All {sup 111}In-labelled radiopeptides showed receptor-specific internalisation. Serum mean-life times varied between 2.0 and 72.6 h, positively correlating with the number of Glu residues. All {sup 111}In-labelled macrocyclic chelator conjugates showed higher tumour-to-kidney ratios after 24 h (0.37-0.99) compared to {sup 111}In-DTPA-minigastrin 0(0.05). Tumour wash out between 4 and 24 h was low. Imaging studies confirmed receptor-specific blocking of the tumour uptake. Reducing the number of glutamates increased tumour-to-kidney ratio but resulted in

  7. Acetylcholine receptor antibody

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003576.htm Acetylcholine receptor antibody To use the sharing features on this page, please enable JavaScript. Acetylcholine receptor antibody is a protein found in the blood of ...

  8. Existence test for asynchronous interval iterations

    DEFF Research Database (Denmark)

    Madsen, Kaj; Caprani, O.; Stauning, Ole

    1997-01-01

    In the search for regions that contain fixed points ofa real function of several variables, tests based on interval calculationscan be used to establish existence ornon-existence of fixed points in regions that are examined in the course ofthe search. The search can e.g. be performed...... as a synchronous (sequential) interval iteration:In each iteration step all components of the iterate are calculatedbased on the previous iterate. In this case it is straight forward to base simple interval existence and non-existencetests on the calculations done in each step of the iteration. The search can also...... on thecomponentwise calculations done in the course of the iteration. These componentwisetests are useful for parallel implementation of the search, sincethe tests can then be performed local to each processor and only when a test issuccessful do a processor communicate this result to other processors....

  9. Seismic reevaluation of existing nuclear power plants

    International Nuclear Information System (INIS)

    Hennart, J.C.

    1978-01-01

    The codes and regulations governing Nuclear Power Plant seismic analysis are continuously becoming more stringent. In addition, design ground accelerations of existing plants must sometimes be increased as a result of discovery of faulting zones or recording of recent earthquakes near the plant location after plant design. These new factors can result in augmented seismic design criteria. Seismic reanalysius of the existing Nuclear Power Plant structures and equipments is necessary to prevent the consequences of newly postulated accidents that could cause undue risk to the health or safety of the public. This paper reviews the developments of seismic analysis as applied to Nuclear Power Plants and the methods used by Westinghouse to requalify existing plants to the most recent safety requirements. (author)

  10. The Existence of Public Protection Unit

    Directory of Open Access Journals (Sweden)

    Moh. Ilham A. Hamudy

    2014-12-01

    Full Text Available This article is about the Public Protection Unit (Satlinmas formerly known as civil defence (Hansip. This article is a summary of the results of the desk study and fieldwork conducted in October-November 2013 in the town of Magelang and Surabaya. This study used descriptive qualitative approach to explore the combined role and existence Satlinmas. The results of the study showed, the existence of the problem Satlinmas still leave many, including, first, the legal basis for the establishment of Satlinmas. Until now, there has been no new regulations governing Satlinmas. Existing regulations are too weak and cannot capture the times. Second, the formulation of concepts and basic tasks and functions Satlinmas overlap with other institutions. Third, Satlinmas image in society tend to fade and abused. Fourth, Satlinmas incorporation into the Municipal Police deemed not appropriate, because different philosophy.

  11. Radiation protection programme for existing exposure situation

    International Nuclear Information System (INIS)

    Ramadhani, Hilali Hussein

    2016-04-01

    This study was conducted to develop the Radiation protection Programme (RPP) to ensure that measures are in place for protection of individuals from the existing source of exposure. The study established a number of protective and remedial actions to be considered by the responsible regulatory Authority, licensee for existing exposure in workplace and dwellings. Tanzania is endowed with a number NORMs processing industries with an experience of uncontrolled exploration and extraction of minerals and the use of unsafe mining methods leading to severe environmental damage and appalling living conditions in the mining communities. Some of NORMs industries have been abandoned due to lack of an effect management infrastructure. The residual radioactive materials have been found to be the most import source of existing exposure resulted from NORMs industries. The Radon gas and its progeny have also been found to be a source of existing exposure from natural source as well as the major source of risk and health effects associated with existing exposure situation. The following measures have been discovered to play a pivotal role in avoiding or reducing the source of exposure to individuals such as restriction of the use of the construction materials, restriction on the consumption of foodstuffs and restriction on the access to the land and buildings, the removal of the magnitude of the source in terms of activity concentration as well as improvement of ventilation in dwellings. Therefore, the regulatory body (Tanzania Atomic Energy Commission) should examine the major areas outlined in the established RRP for existing exposure situation resulted from the NORMs industries and natural sources so as to develop strategies that will ensure the adequate protection of members of the public and the environment as well as guiding operating organizations to develop radiation protection and safety measures for workers. (au)

  12. Cooperative ethylene receptor signaling

    OpenAIRE

    Liu, Qian; Wen, Chi-Kuang

    2012-01-01

    The gaseous plant hormone ethylene is perceived by a family of five ethylene receptor members in the dicotyledonous model plant Arabidopsis. Genetic and biochemical studies suggest that the ethylene response is suppressed by ethylene receptor complexes, but the biochemical nature of the receptor signal is unknown. Without appropriate biochemical measures to trace the ethylene receptor signal and quantify the signal strength, the biological significance of the modulation of ethylene responses ...

  13. Pre-existing high glucocorticoid receptor number predicting development of posttraumatic stress symptoms after military deployment

    NARCIS (Netherlands)

    van Zuiden, Mirjam; Geuze, Elbert; Willemen, Hanneke L. D. M.; Vermetten, Eric; Maas, Mirjam; Heijnen, Cobi J.; Kavelaars, Annemieke

    2011-01-01

    The development of posttraumatic stress disorder (PTSD) is influenced by preexisting vulnerability factors. The authors aimed at identifying a preexisting biomarker representing a vulnerability factor for the development of PTSD. To that end, they determined whether the dexamethasone binding

  14. Comparative biodistribution of 12 {sup 111}In-labelled gastrin/CCK2 receptor-targeting peptides

    Energy Technology Data Exchange (ETDEWEB)

    Laverman, Peter; Joosten, Lieke; Eek, Annemarie; Roosenburg, Susan; Oyen, Wim J.G.; Boerman, Otto C. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands); Peitl, Petra Kolenc [University Medical Centre Ljubljana, Department of Nuclear Medicine, Ljubljana (Slovenia); Maina, Theodosia [National Center for Scientific Research Demokritos, Molecular Radiopharmacy, Institute of Radioisotopes-Radiodiagnostic Products, Athens (Greece); Maecke, Helmut [University Hospital Freiburg, Department of Nuclear Medicine, Freiburg (Germany); Aloj, Luigi [Fondazione ' ' G. Pascale' ' , Department of Nuclear Medicine, Istituto Nazionale Tumouri, Naples (Italy); Guggenberg, Elisabeth von [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria); Sosabowski, Jane K. [Queen Mary, University of London, Centre for Molecular Oncology and Imaging, Institute of Cancer, Barts and The London School of Medicine and Dentistry, London (United Kingdom); Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Reubi, Jean-Claude [University of Berne, Institute of Pathology, Berne (Switzerland)

    2011-08-15

    Cholecystokinin 2 (CCK-2) receptor overexpression has been demonstrated in various tumours such as medullary thyroid carcinomas and small-cell lung cancers. Due to this high expression, CCK-2 receptors might be suitable targets for radionuclide imaging and/or radionuclide therapy. Several CCK-2 receptor-binding radiopeptides have been developed and some have been tested in patients. Here we aimed to compare the in vivo tumour targeting properties of 12 {sup 111}In-labelled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-conjugated gastrin/CCK2 receptor-binding peptides. Two CCK8-based peptides and ten gastrin-based peptide analogues were tested. All peptides were conjugated with DOTA and labelled with {sup 111}In. Biodistribution studies were performed in mice with subcutaneous CCK2/gastrin receptor-expressing tumours and with receptor-negative tumours contralaterally. Biodistribution was studied by counting dissected tissues at 1 and 4 h after injection. Both the CCK analogues displayed relatively low tumour uptake (approximately 2.5%ID/g) as compared to minigastrin analogues. Two linear minigastrin peptides (MG0 and sargastrin) displayed moderate tumour uptake at both 1 and 4 h after injection, but also very high kidney uptake (both higher than 48%ID/g). The linear MG11, lacking the penta-Glu sequence, showed lower tumour uptake and also low kidney uptake. Varying the N-terminal Glu residues in the minigastrin analogues led to improved tumour targeting properties, with PP-F11 displaying the optimal biodistribution. Besides the monomeric linear peptides, a cyclized peptide and a divalent peptide were tested. Based on these studies, optimal peptides for peptide receptor radionuclide targeting of CCK2/gastrin receptor-expressing tumours were the linear minigastrin analogue with six D-Glu residues (PP-F11), the divalent analogue MGD5 and the cyclic peptide cyclo-MG1. These peptides combined high tumour uptake with low kidney retention, and may

  15. Foucault, Counselling and the Aesthetics of Existence

    Science.gov (United States)

    Peters, Michael A.

    2005-01-01

    Michel Foucault was drawn late in life to study the "arts of the self" in Greco-Roman culture as a basis, following Nietzsche, for what he called an "aesthetics of existence." By this, he meant a set of creative and experimental processes and techniques by which an individual turns him- or herself into a work of art. For Nietzsche, it was above…

  16. How to prove the existence of metabolons?

    DEFF Research Database (Denmark)

    Bassard, Jean-Étienne André; Halkier, Barbara Ann

    2017-01-01

    Sequential enzymes in biosynthetic pathways are organized in metabolons. It is challenging to provide experimental evidence for the existence of metabolons as biosynthetic pathways are composed of highly dynamic protein–protein interactions. Many different methods are being applied, each with str...

  17. Conditions for the Existence of Market Equilibrium.

    Science.gov (United States)

    Bryant, William D. A.

    1997-01-01

    Maintains that most graduate-level economics textbooks rarely mention the need for consumers to be above their minimum wealth position as a condition for market equilibrium. Argues that this omission leaves students with a mistaken sense about the range of circumstances under which market equilibria can exist. (MJP)

  18. 22 CFR 142.16 - Existing facilities.

    Science.gov (United States)

    2010-04-01

    ... OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Accessibility § 142.16 Existing facilities. (a) Accessibility. A recipient shall operate each program or activity to which this part applies so that when each...., telecommunication device for the deaf) redesign of equipment, reassignment of classes or other services to...

  19. Transportation capabilities of the existing cask fleet

    International Nuclear Information System (INIS)

    Johnson, P.E.; Joy, D.S.; Wankerl, M.W.

    1991-01-01

    This paper describes a number of scenarios estimating the amount of spent nuclear fuel that could be transported to a Monitored Retrievable Storage (MRS) Facility by various combinations of existing cask fleets. To develop the scenarios, the data provided by the Transportation System Data Base (TSDB) were modified to reflect the additional time for cask turnaround resulting from various startup and transportation issues. With these more realistic speed and cask-handling assumptions, the annual transportation capability of a fleet consisting of all of the existing casks is approximately 46 metric tons of uranium (MTU). The most likely fleet of existing casks that would be made available to the Department of Energy (DOE) consists of two rail, three overweight truck, and six legal weight truck casks. Under the same transportation assumptions, this cask fleet is capable of approximately transporting 270 MTU/year. These ranges of capability is a result of the assumptions pertaining to the number of casks assumed to be available. It should be noted that this assessment assumes additional casks based on existing certifications are not fabricated. 5 refs., 4 tabs

  20. Conservation and Development Options existing on Uluguru ...

    African Journals Online (AJOL)

    Effective management of projects on Uluguru Mountains requires that both development and conservation options are weighed and that opportunities and challenges are considered. This study identified various conservation and development options existing on Uluguru Mountains and assessed the perceptions of the local ...

  1. Transportation capabilities of the existing cask fleet

    International Nuclear Information System (INIS)

    Johnson, P.E.; Wankerl, M.W.; Joy, D.S.

    1991-01-01

    This paper describes a number of scenarios estimating the amount of spent nuclear fuel that could be transported to a Monitored Retrievable Storage (MRS) Facility by various combinations of existing cask fleets. To develop the scenarios, the data provided by the Transportation System Data Base (TSDB) were modified to reflect the additional time for cask turnaround resulting from various startup and transportation issues. With these more realistic speed and cask-handling assumptions, the annual transportation capability of a fleet consisting of all of the existing casks is approximately 465 metric tons of uranium (MTU). The most likely fleet of existing casks that would be made available to the DOE consists of two rail, three overweight truck, and six legal weight truck casks. Under the same transportation assumptions, this cask fleet is capable of approximately transporting 270 MTU/year. These ranges of capability is a result of the assumptions pertaining to the number of casks assumed to be available. It should be noted that this assessment assumes additional casks based on existing certifications are not fabricated

  2. Does the Kuleshov Effect really Exist?

    DEFF Research Database (Denmark)

    Barratt, Daniel; Cabak Rédei, Anna

    2013-01-01

    with a doll, a dead woman in a coffin, and a bowl of soup; the viewers of the three sequences were reported to have perceived Mozhukin’s face as expressing happiness, sadness, and hunger/thoughtfulness respectively. It is not clear, however, whether or not the socalled “Kuleshov effect” really exists...

  3. COMPARATIVE ANALYSIS OF SOME EXISTING KINETIC MODELS ...

    African Journals Online (AJOL)

    The biosorption of three heavy metal ions namely; Zn2+, Cu2+ and Mn2+ using five microorganisms namely; Bacillus circulans, Pseudomonas aeruginosa, Staphylococcus xylosus, Streptomyces rimosus and Yeast (Saccharomyces sp.) were studied. In this paper, the effectiveness of six existing and two proposed kinetic ...

  4. Do ‘African’ universities exist?

    DEFF Research Database (Denmark)

    Jensen, Stig; Adriansen, Hanne Kirstine; Madsen, Lene Møller

    2015-01-01

    This chapter provides a background for understanding the book. We outline some of the debates in which the individual chapters are situated and thereby show how the book contributes to and fills gaps in existing research. After providing a short history of African universities, the chapter subseq...

  5. Do Biopositive Effects of Ionizing Radiations Exist

    International Nuclear Information System (INIS)

    Broda, E.

    1983-01-01

    The claim that radiations, e.g, in spas, can have biopositive actions on humans is unproven and unplausible. It also conflicts with the contents of the standard handbooks and with national legislation everywhere. Further, stimulation of plants by radiation is badly reproducible. But even if existing it need not be beneficial to the plant itself ("selfpositive"). (author)

  6. Repurposing Existing Material for Performance Support.

    Science.gov (United States)

    Harvey, Francis A.; Nelson, Adam

    1995-01-01

    Presents an overview of performance support systems (PSS), describes their role in promoting productivity in agile organizations, and discusses issues related to developing effective performance support using existing orientation, training, or procedural manuals. Topics include strategic principles of agility, and adding value when incorporating…

  7. Global existence proof for relativistic Boltzmann equation

    International Nuclear Information System (INIS)

    Dudynski, M.; Ekiel-Jezewska, M.L.

    1992-01-01

    The existence and causality of solutions to the relativistic Boltzmann equation in L 1 and in L loc 1 are proved. The solutions are shown to satisfy physically natural a priori bounds, time-independent in L 1 . The results rely upon new techniques developed for the nonrelativistic Boltzmann equation by DiPerna and Lions

  8. 38 CFR 18.422 - Existing facilities.

    Science.gov (United States)

    2010-07-01

    ... THE CIVIL RIGHTS ACT OF 1964 Nondiscrimination on the Basis of Handicap Accessibility § 18.422 Existing facilities. (a) Accessibility. A recipient shall operate each program or activity to which this... visits, delivery of health, or other social services at alternate accessible sites, alteration of...

  9. Developing an Actuarial Track Utilizing Existing Resources

    Science.gov (United States)

    Rodgers, Kathy V.; Sarol, Yalçin

    2014-01-01

    Students earning a degree in mathematics often seek information on how to apply their mathematical knowledge. One option is to follow a curriculum with an actuarial emphasis designed to prepare students as an applied mathematician in the actuarial field. By developing only two new courses and utilizing existing courses for Validation by…

  10. 7 CFR 1718.52 - Existing mortgages.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Existing mortgages. 1718.52 Section 1718.52 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE LOAN SECURITY DOCUMENTS FOR ELECTRIC BORROWERS Mortgage for Distribution Borrowers § 1718.52...

  11. Transforming existing content into reusable Learning Objects

    NARCIS (Netherlands)

    Doorten, Monique; Giesbers, Bas; Janssen, José; Daniels, Jan; Koper, Rob

    2003-01-01

    Please cite as: Doorten, M., Giesbers, B., Janssen, J., Daniëls, J, & Koper, E.J.R., (2004). Transforming existing content into reusable learning objects. In R. McGreal, Online Education using Learning Objects (pp. 116-127). London: RoutledgeFalmer.

  12. Psychology's struggle for existence: Second edition, 1913.

    Science.gov (United States)

    Wundt, Wilhelm; Lamiell, James T

    2013-08-01

    Presents an English translation of Wilhelm Wundt's Psychology's struggle for existence: Second edition, 1913, by James T. Lamiell in August, 2012. In his essay, Wundt advised against the impending divorce of psychology from philosophy. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

  13. Altering existing buildings in the UK

    International Nuclear Information System (INIS)

    Roberts, Simon

    2008-01-01

    The profiles of both existing housing and existing public and commercial buildings show that many have very poor thermal efficiency. The UK housing stock is replaced at a low rate of about 1% a year, so to cut energy use it is essential to address the challenges of existing buildings. This will involve reducing energy demand through passive measures such as retrofitted insulation, replacement of windows and proper airtightness, while ensuring adequate ventilation. Active measures include upgrading improved boilers and adding locally produced energy from wind, biomass, solar power and other sources. The introduction of Display Energy Certificates will increase energy awareness but there will also need to be a programme of increased demolition for the worst-performing homes. In addition, buildings will need to be adapted to cope with worse weather, higher temperatures and increased flood risk as climate change takes effect. Overheating, rather than excessive cold, is set to become a growing problem for householders and employees in existing UK buildings

  14. Adding Semantic Support to Existing UDDI Infrastructure

    National Research Council Canada - National Science Library

    Luo, Jim; Montrose, Bruce; Kang, Myong

    2005-01-01

    .... The advantage is that it is completely backward compatible. The add-on modules only need to be installed on the clients of users who wish to take advantage of semantic markups. They can be integrated seamlessly into existing systems and operations without any modification of the infrastructure.

  15. Essence and Existence in Avicenna and Averroes

    Directory of Open Access Journals (Sweden)

    Belo, Catarina

    2009-12-01

    Full Text Available This article explores the views on existence of medieval Muslim philosophers Avicenna (d. 1037 and Averroes (d. 1198, whose works followed closely the philosophy of Aristotle. In addition to the Aristotelian influence, which permeated all medieval Islamic philosophy, Avicenna and Averroes were also inspired by Islamic theology, known in Arabic as kalām. The distinction between essence and existence is one of the most central and controversial aspects of Avicenna’s philosophy, together with his claim that existence is an accident. Averroes in turn has a radically different conception of existence, identifying it with existing beings rather than considering it as something in itself. With the Latin translation of Avicenna’s metaphysical works in the 12th century, the Avicennian distinction went on to shape much of the debate on existence in medieval Scholastic philosophy and beyond. This article assesses the meaning of the distinction in Avicenna as well as Averroes’ criticism. In explicating their radically different views on existence, it also touches on later discussions concerning existence, for example the issue whether existence is a predicate, in the Modern Age.

    El presente artículo explora las percepciones sobre la existencia de los filósofos medievales musulmanes Avicena (m. 1037 y Averroes (m. 1198, cuyas obras se encuentran muy próximas a la filosofía de Aristóteles. Además de la influencia aristotélica, que caló en toda la filosofía islámica medieval, Avicena y Averroes estuvieron inspirados por la teología islámica, conocida en árabe como Kalām. La distinción entre esencia y existencia es uno de los más fundamentales y controvertidos aspectos de la filosofía de Avicena junto a su aseveración de que la existencia es un accidente. Averroes, en cambio, concibe de forma radicalmente diferente la existencia, identificándola con los seres existentes más que considerarla como algo en

  16. Constitutive dimerization of the G-protein coupled receptor, neurotensin receptor 1, reconstituted into phospholipid bilayers.

    Science.gov (United States)

    Harding, Peter J; Attrill, Helen; Boehringer, Jonas; Ross, Simon; Wadhams, George H; Smith, Eleanor; Armitage, Judith P; Watts, Anthony

    2009-02-01

    Neurotensin receptor 1 (NTS1), a Family A G-protein coupled receptor (GPCR), was expressed in Escherichia coli as a fusion with the fluorescent proteins eCFP or eYFP. A fluorophore-tagged receptor was used to study the multimerization of NTS1 in detergent solution and in brain polar lipid bilayers, using fluorescence resonance energy transfer (FRET). A detergent-solubilized receptor was unable to form FRET-competent complexes at concentrations of up to 200 nM, suggesting that the receptor is monomeric in this environment. When reconstituted into a model membrane system at low receptor density, the observed FRET was independent of agonist binding, suggesting constitutive multimer formation. In competition studies, decreased FRET in the presence of untagged NTS1 excludes the possibility of fluorescent protein-induced interactions. A simulation of the experimental data indicates that NTS1 exists predominantly as a homodimer, rather than as higher-order multimers. These observations suggest that, in common with several other Family A GPCRs, NTS1 forms a constitutive dimer in lipid bilayers, stabilized through receptor-receptor interactions in the absence of other cellular signaling components. Therefore, this work demonstrates that well-characterized model membrane systems are useful tools for the study of GPCR multimerization, allowing fine control over system composition and complexity, provided that rigorous control experiments are performed.

  17. Design, synthesis, and testing of multivalent compounds targeted to melanocortin receptors

    Science.gov (United States)

    Dehigaspitiya, Dilani Chathurika

    Our focus is on developing non-invasive molecular imaging reagents, which target human cancers that presently are difficult to detect, such as melanoma. We wish to apply the multivalency concept to differentiate between healthy cells and melanoma cells. Melanoma cells are known to over-express alpha melanocyte stimulating hormone receptors. A successful multivalent construct should show greater avidity towards melanoma cells than healthy cells due to the synergistic effects arising from multivalency. Both oligomeric and shorter linear constructs bearing the minimum active sequence of melanocyte stimulating hormone, His-DPhe-Arg-Trp-NH2(MSH4), which binds with low micromolar affinity to alpha melanocyte stimulating hormone receptors, were synthesized. Binding affinities of these constructs were evaluated in a competitive binding assay by competing with labeled ligands, Eu-DTPA-PEGO-MSH7 and/or Eu-DTPA-PEGO-NDP-alpha-MSH on the engineered cell line HEK293 CCK2R/hMC4R, which is genetically modified to over-express both the cholecystokinin 2 receptor (CCK2R) and human melanocortin 4 receptor (hMC4R). The oligomers were rapidly assembled using microwave-assisted copper catalyzed azide-alkyne cycloaddition between a dialkyne derivative of MSH4 and a diazide derivative of (Pro-Gly)3 as co-monomers. Three oligomer mixtures were further analyzed based on their degree of oligomerization and the route by which the MSH4 monomers were oligomerized, protected vs deprotected. Completive binding assay against Eu-DTPA-PEGO-MSH7 showed only a statistical enhancement of binding when calculated based on the total MSH4 concentration. However, when the calculation of avidity is based on an estimation of the particles numbers, there was a seven times enhancement of binding compared to a monovalent MSH4 control. The shorter linear multivalent MSH4 constructs were synthesized using ethylene glycol, glycerol, and mannitol as core scaffolds with maximum inter-ligand distances ranging from 27

  18. Overview of Existing Wind Energy Ordinances

    Energy Technology Data Exchange (ETDEWEB)

    Oteri, F.

    2008-12-01

    Due to increased energy demand in the United States, rural communities with limited or no experience with wind energy now have the opportunity to become involved in this industry. Communities with good wind resources may be approached by entities with plans to develop the resource. Although these opportunities can create new revenue in the form of construction jobs and land lease payments, they also create a new responsibility on the part of local governments to ensure that ordinances will be established to aid the development of safe facilities that will be embraced by the community. The purpose of this report is to educate and engage state and local governments, as well as policymakers, about existing large wind energy ordinances. These groups will have a collection of examples to utilize when they attempt to draft a new large wind energy ordinance in a town or county without existing ordinances.

  19. Co-existence in multispecies biofilm communities

    DEFF Research Database (Denmark)

    Røder, Henriette Lyng

    of these emergent properties which are relevant to as diverse areas as clinical settings and natural systems. In this thesis, I have attempted to contribute to our knowledge on the multispecies interactions with a special focus on biofilm communities. I was especially interested in how co-existing species affect...... each other and in understanding the key mechanisms and interactions involved. In the introduction of this thesis the most important concepts of multi-species interactions and biofilm development are explained. After this the topic changes to the various ways of examining community interactions...... and production. The analysis was further extended in manuscript 3, in which the effect of social interac-tions on biofilm formation in multispecies co-cultures isolated from a diverse range of environments was examined. The question raised was whether the interspecific interactions of co-existing bacteria...

  20. Partial Cooperative Equilibria: Existence and Characterization

    Directory of Open Access Journals (Sweden)

    Amandine Ghintran

    2010-09-01

    Full Text Available We study the solution concepts of partial cooperative Cournot-Nash equilibria and partial cooperative Stackelberg equilibria. The partial cooperative Cournot-Nash equilibrium is axiomatically characterized by using notions of rationality, consistency and converse consistency with regard to reduced games. We also establish sufficient conditions for which partial cooperative Cournot-Nash equilibria and partial cooperative Stackelberg equilibria exist in supermodular games. Finally, we provide an application to strategic network formation where such solution concepts may be useful.

  1. Does evaporation paradox exist in China?

    Directory of Open Access Journals (Sweden)

    Z. T. Cong

    2009-03-01

    Full Text Available One expected consequence of global warming is the increase in evaporation. However, lots of observations show that the rate of evaporation from open pans of water has been steadily decreasing all over the world in the past 50 years. The contrast between expectation and observation is called "evaporation paradox". Based on data from 317 weather stations in China from 1956 to 2005, the trends of pan evaporation and air temperature were obtained and evaporation paradox was analyzed. The conclusions include: (1 From 1956 to 2005, pan evaporation paradox existed in China as a whole while pan evaporation kept decreasing and air temperature became warmer and warmer, but it does not apply to Northeast and Southeast China; (2 From 1956 to 1985, pan evaporation paradox existed narrowly as a whole with unobvious climate warming trend, but it does not apply to Northeast China; (3 From 1986 to 2005, in the past 20 years, pan evaporation paradox did not exist for the whole period while pan evaporation kept increasing, although it existed in South China. Furthermore, the trend of other weather factors including sunshine duration, windspeed, humidity and vapor pressure deficit, and their relations with pan evaporation are discussed. As a result, it can be concluded that pan evaporation decreasing is caused by the decreasing in radiation and wind speed before 1985 and pan evaporation increasing is caused by the decreasing in vapor pressure deficit due to strong warming after 1986. With the Budyko curve, it can be concluded that the actual evaporation decreased in the former 30 years and increased in the latter 20 year for the whole China.

  2. Existence and Comparability of data sources

    OpenAIRE

    KUHNIMHOF, T; ARMOOGUM, J

    2007-01-01

    The deliverable at hand comprises a comprehensive overview over existing data sources which can be used for analysis of long distance travel demand. This encompasses both national and international data sources with a focus on household travel surveys. Three types of relevant surveys were identified: - National travel surveys with focus on daily mobility - Travel survey elements dedicated to long distance mobility - Long distance travel surveys. RAPPORT DE CONTRAT

  3. Transgender Parenting: A Review of Existing Research

    OpenAIRE

    Stotzer, Rebecca L; Herman, Jody L; Hasenbush, Amira

    2014-01-01

    The authors of this report reviewed 51 studies that analyze data about transgender parents. This report reviews the existing research on the prevalence and characteristics of transgender people who are parents, the quality of relationships between transgender parents and their children, outcomes for children with a transgender parent, and the reported needs of transgender parents. Overall, the authors found that substantial numbers of transgender people are parents, though at rates below the ...

  4. Streamlining Research by Using Existing Tools

    OpenAIRE

    Greene, Sarah M.; Baldwin, Laura-Mae; Dolor, Rowena J.; Thompson, Ella; Neale, Anne Victoria

    2011-01-01

    Over the past two decades, the health research enterprise has matured rapidly, and many recognize an urgent need to translate pertinent research results into practice, to help improve the quality, accessibility, and affordability of U.S. health care. Streamlining research operations would speed translation, particularly for multi-site collaborations. However, the culture of research discourages reusing or adapting existing resources or study materials. Too often, researchers start studies and...

  5. Seismic evaluation of existing nuclear power plants

    International Nuclear Information System (INIS)

    2003-01-01

    The IAEA nuclear safety standards publications address the site evaluation and the design of new nuclear power plants (NPPs), including seismic hazard assessment and safe seismic design, at the level of the Safety Requirements as well as at the level of dedicated Safety Guides. It rapidly became apparent that the existing nuclear safety standards documents were not adequate for handling specific issues in the seismic evaluation of existing NPPs, and that a dedicated document was necessary. This is the purpose of this Safety Report, which is written in the spirit of the nuclear safety standards and can be regarded as guidance for the interpretation of their intent. Worldwide experience shows that an assessment of the seismic capacity of an existing operating facility can be prompted for the following: (a) Evidence of a greater seismic hazard at the site than expected before, owing to new or additional data and/or to new methods; (b) Regulatory requirements, such as periodic safety reviews, to ensure that the plant has adequate margins for seismic loads; (c) Lack of anti-seismic design or poor anti-seismic design; (d) New technical finding such as vulnerability of some structures (masonry walls) or equipment (relays), other feedback and new experience from real earthquakes. Post-construction evaluation programmes evaluate the current capability of the plant to withstand the seismic concern and identify any necessary upgrades or changes in operating procedures. Seismic qualification is distinguished from seismic evaluation primarily in that seismic qualification is intended to be performed at the design stage of a plant, whereas seismic evaluation is intended to be applied after a plant has been constructed. Although some guidelines do exist for the evaluation of existing NPPs, these are not established at the level of a regulatory guide or its equivalent. Nevertheless, a number of existing NPPs throughout the world have been and are being subjected to review of their

  6. Development of gene diagnosis for diabetes and cholecystitis based on gene analysis of CCK-A receptor

    International Nuclear Information System (INIS)

    Kono, Akira

    1999-01-01

    Base sequence analysis of CCKAR gene (a gene of A-type receptor for cholecystokinin) from OLETF rat, a model rat for insulin-independent diabetes was made based on the base sequence of wild CCKAR gene, which had been clarified in the previous year. From the pancreas of OLETF rat, DNA was extracted and transduced into λphage after fragmentation to construct the gene library of OLETF. Then, λphage DNA clone bound with labelled cDNA of CCKAR gene was analyzed and the gene structure was compared with that of the wild gene. It was demonstrated that CCKAR gene of OLETF had a deletion (6800 b.p.) ranging from the promoter region to the Exon 2, suggesting that CCKAR gene is not functional in OLETF rat. The whole sequence of this mutant gene was registered into Japan DNA Bank (D 50610). Then, F 2 offspring rats were obtained through crossing OLETF (female) and F344 (male) and the time course-changes in the blood glucose level after glucose loading were compared among them. The blood glucose level after glucose loading was significantly higher in the homo-mutant F 2 (CCKAR,-/-) as well as the parent OLETF rat than hetero-mutant F 2 (CCKARm-/+) or the wild rat (CCKAR,+/+). This suggests that CCKAR gene might be involved in the control of blood glucose level and an alteration of the expression level or the functions of CCKAR gene might affect the blood glucose level. (M.N.)

  7. GABA receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Doo [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA{sub A}-receptor that allows chloride to pass through a ligand gated ion channel and GABA{sub B}-receptor that uses G-proteins for signaling. The GABA{sub A}-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA{sub A}-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with {sup 11}C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, {sup 18}F-fluoroflumazenil (FFMZ) has been developed to overcome {sup 11}C's short half-life. {sup 18}F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1{sup 1}C-FMZ PET instead of {sup 18}F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA{sub A} receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

  8. GABA receptor imaging

    International Nuclear Information System (INIS)

    Lee, Jong Doo

    2007-01-01

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA A -receptor that allows chloride to pass through a ligand gated ion channel and GABA B -receptor that uses G-proteins for signaling. The GABA A -receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA A -receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with 11 C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, 18 F-fluoroflumazenil (FFMZ) has been developed to overcome 11 C's short half-life. 18 F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1 1 C-FMZ PET instead of 18 F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA A receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas

  9. Existing and new techniques in uranium exploration

    International Nuclear Information System (INIS)

    Bowie, S.H.U.; Cameron, J.

    1976-01-01

    The demands on uranium exploration over the next 25 years will be very great indeed and will call for every possible means of improvement in exploration capability. The first essential is to increase geological knowledge of the mode of occurrence of uranium ore deposits. The second is to improve existing exploration techniques and instrumentation while, at the same time, promoting research and development on new methods to discover uranium ore bodies on the earth's surface and at depth. The present symposium is an effort to increase co-operation and the exchange of information in the critical field of uranium exploration techniques and instrumentation. As an introduction to the symposium a brief review is presented, firstly of what can be considered as existing techniques and, secondly, of techniques which have not yet been used on an appreciable scale. Some fourteen techniques used over the last 30 years are identified and their appropriate application, advantages and limitations are briefly summarized and the possibilities of their further development considered. The aim of future research on new techniques, in addition to finding new ways and means of identifying surface deposits, should be mainly directed to devising methods and instrumentation capable of detecting buried ore bodies that do not give a gamma signal at the surface. To achieve this aim, two contributory factors are essential: adequate financial support for research and development and increased specialized training in uranium exploration and instrumentation design. The papers in this symposium describe developments in the existing techniques, proposals for future research and development and case histories of exploration programmes

  10. Does the Kuleshov Effect Really Exist?

    DEFF Research Database (Denmark)

    Barratt, Daniel; Rédei, Anna Cabak; Innes-Ker, Åse

    2016-01-01

    to replicate Kuleshov’s original experiment using an improved experimental design. In a behavioral and eye tracking study, 36 participants were each presented with 24 film sequences of neutral faces across six emotional conditions. For each film sequence, the participants were asked to evaluate the emotion...... of the target person in terms of valence, arousal, and category. The participants’ eye movements were recorded throughout. The results suggest that some sort of Kuleshov effect does in fact exist. For each emotional condition, the participants tended to choose the appropriate category more frequently than...... between the emotional conditions....

  11. Energy Savings Measure Packages. Existing Homes

    Energy Technology Data Exchange (ETDEWEB)

    Casey, Sean [National Renewable Energy Lab. (NREL), Golden, CO (United States); Booten, Chuck [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2011-11-01

    This document presents the most cost effective Energy Savings Measure Packages (ESMP) for existing mixed-fuel and all electric homes to achieve 15% and 30% savings for each BetterBuildings grantee location across the United States. These packages are optimized for minimum cost to homeowners for source energy savings given the local climate and prevalent building characteristics (i.e. foundation types). Maximum cost savings are typically found between 30% and 50% energy savings over the reference home; this typically amounts to $300 - $700/year.

  12. Analysis of field errors in existing undulators

    International Nuclear Information System (INIS)

    Kincaid, B.M.

    1990-01-01

    The Advanced Light Source (ALS) and other third generation synchrotron light sources have been designed for optimum performance with undulator insertion devices. The performance requirements for these new undulators are explored, with emphasis on the effects of errors on source spectral brightness. Analysis of magnetic field data for several existing hybrid undulators is presented, decomposing errors into systematic and random components. An attempts is made to identify the sources of these errors, and recommendations are made for designing future insertion devices. 12 refs., 16 figs

  13. Melatonin membrane receptors in peripheral tissues: Distribution and functions

    Science.gov (United States)

    Slominski, Radomir M.; Reiter, Russel J.; Schlabritz-Loutsevitch, Natalia; Ostrom, Rennolds S.; Slominski, Andrzej T.

    2012-01-01

    Many of melatonin’s actions are mediated through interaction with the G-protein coupled membrane bound melatonin receptors type 1 and type 2 (MT1 and MT2, respectively) or, indirectly with nuclear orphan receptors from the RORα/RZR family. Melatonin also binds to the quinone reductase II enzyme, previously defined the MT3 receptor. Melatonin receptors are widely distributed in the body; herein we summarize their expression and actions in non-neural tissues. Several controversies still exist regarding, for example, whether melatonin binds the RORα/RZR family. Studies of the peripheral distribution of melatonin receptors are important since they are attractive targets for immunomodulation, regulation of endocrine, reproductive and cardiovascular functions, modulation of skin pigmentation, hair growth, cancerogenesis, and aging. Melatonin receptor agonists and antagonists have an exciting future since they could define multiple mechanisms by which melatonin modulates the complexity of such a wide variety of physiological and pathological processes. PMID:22245784

  14. Existence families, functional calculi and evolution equations

    CERN Document Server

    deLaubenfels, Ralph

    1994-01-01

    This book presents an operator-theoretic approach to ill-posed evolution equations. It presents the basic theory, and the more surprising examples, of generalizations of strongly continuous semigroups known as 'existent families' and 'regularized semigroups'. These families of operators may be used either to produce all initial data for which a solution in the original space exists, or to construct a maximal subspace on which the problem is well-posed. Regularized semigroups are also used to construct functional, or operational, calculi for unbounded operators. The book takes an intuitive and constructive approach by emphasizing the interaction between functional calculus constructions and evolution equations. One thinks of a semigroup generated by A as etA and thinks of a regularized semigroup generated by A as etA g(A), producing solutions of the abstract Cauchy problem for initial data in the image of g(A). Material that is scattered throughout numerous papers is brought together and presented in a fresh, ...

  15. LDEF data: Comparisons with existing models

    Science.gov (United States)

    Coombs, Cassandra R.; Watts, Alan J.; Wagner, John D.; Atkinson, Dale R.

    1993-04-01

    The relationship between the observed cratering impact damage on the Long Duration Exposure Facility (LDEF) versus the existing models for both the natural environment of micrometeoroids and the man-made debris was investigated. Experimental data was provided by several LDEF Principal Investigators, Meteoroid and Debris Special Investigation Group (M&D SIG) members, and by the Kennedy Space Center Analysis Team (KSC A-Team) members. These data were collected from various aluminum materials around the LDEF satellite. A PC (personal computer) computer program, SPENV, was written which incorporates the existing models of the Low Earth Orbit (LEO) environment. This program calculates the expected number of impacts per unit area as functions of altitude, orbital inclination, time in orbit, and direction of the spacecraft surface relative to the velocity vector, for both micrometeoroids and man-made debris. Since both particle models are couched in terms of impact fluxes versus impactor particle size, and much of the LDEF data is in the form of crater production rates, scaling laws have been used to relate the two. Also many hydrodynamic impact computer simulations were conducted, using CTH, of various impact events, that identified certain modes of response, including simple metallic target cratering, perforations and delamination effects of coatings.

  16. Eternally existing self-reproducing inflationary universe

    International Nuclear Information System (INIS)

    Linde, A.D.

    1986-05-01

    It is shown that the large-scale quantum fluctuations of the scalar field φ generated in the chaotic inflation scenario lead to an infinite process of self-reproduction of inflationary mini-universes. A model of eternally existing chaotic inflationary universe is suggested. It is pointed out that whereas the universe locally is very homogeneous as a result of inflation, which occurs at the classical level, the global structure of the universe is determined by quantum effects and is highly non-trivial. The universe consists of exponentially large number of different mini-universes, inside which all possible (metastable) vacuum states and all possible types of compactification are realized. The picture differs crucially from the standard picture of a one-domain universe in a ''true'' vacuum state. Our results may serve as a justification of the anthropic principle in the inflationary cosmology. These results may have important implications for the elementary particle theory as well. Namely, since all possible types of mini-universes, in which inflation may occur, should exist in our universe, there is no need to insist (as it is usually done) that in realistic theories the vacuum state of our type should be the only possible one or the best one. (author)

  17. Glucocorticoid receptor modulators.

    Science.gov (United States)

    Meijer, Onno C; Koorneef, Lisa L; Kroon, Jan

    2018-06-01

    The glucocorticoid hormone cortisol acts throughout the body to support circadian processes and adaptation to stress. The glucocorticoid receptor is the target of cortisol and of synthetic glucocorticoids, which are used widely in the clinic. Both agonism and antagonism of the glucocorticoid receptor may be beneficial in disease, but given the wide expression of the receptor and involvement in various processes, beneficial effects are often accompanied by unwanted side effects. Selective glucocorticoid receptor modulators are ligands that induce a receptor conformation that allows activation of only a subset of downstream signaling pathways. Such molecules thereby combine agonistic and antagonistic properties. Here we discuss the mechanisms underlying selective receptor modulation and their promise in treating diseases in several organ systems where cortisol signaling plays a role. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  18. Dengue virus receptor

    OpenAIRE

    Hidari, Kazuya I.P.J.; Suzuki, Takashi

    2011-01-01

    Dengue virus is an arthropod-borne virus transmitted by Aedes mosquitoes. Dengue virus causes fever and hemorrhagic disorders in humans and non-human primates. Direct interaction of the virus introduced by a mosquito bite with host receptor molecule(s) is crucial for virus propagation and the pathological progression of dengue diseases. Therefore, elucidation of the molecular mechanisms underlying the interaction between dengue virus and its receptor(s) in both humans and mosquitoes is essent...

  19. Oral insulin delivery: existing barriers and current counter-strategies.

    Science.gov (United States)

    Gedawy, Ahmed; Martinez, Jorge; Al-Salami, Hani; Dass, Crispin R

    2018-02-01

    The chronic and progressive nature of diabetes is usually associated with micro- and macrovascular complications where failure of pancreatic β-cell function and a general condition of hyperglycaemia is created. One possible factor is failure of the patient to comply with and adhere to the prescribed insulin due to the inconvenient administration route. This review summarizes the rationale for oral insulin administration, existing barriers and some counter-strategies trialled. Oral insulin mimics the physiology of endogenous insulin secreted by pancreas. Following the intestinal absorption of oral insulin, it reaches the liver at high concentration via the portal vein. Oral insulin on the other hand has the potential to protect pancreatic β-cells from autoimmune destruction. Structural modification, targeting a particular tissue/receptor, and the use of innovative pharmaceutical formulations such as nanoparticles represent strategies introduced to improve oral insulin bioavailability. They showed promising results in overcoming the hurdles facing oral insulin delivery, although delivery is far from ideal. The use of advanced pharmaceutical technologies and further research in particulate carrier system delivery predominantly nanoparticle utilization would offer useful tools in delivering insulin via the oral route which in turn would potentially improve diabetic patient compliance to insulin and the overall management of diabetes. © 2017 Royal Pharmaceutical Society.

  20. Existing ingestion guidance: Problems and recommendations

    Energy Technology Data Exchange (ETDEWEB)

    Mooney, Robert R; Ziegler, Gordon L; Peterson, Donald S [Environmental Radiation Section, Division of Radiation Protection, WA (United States)

    1989-09-01

    Washington State has been developing plans and procedures for responding to nuclear accidents since the early 1970s. A key part of this process has been formulating a method for calculating ingestion pathway concentration guides (CGs). Such a method must be both technically sound and easy to use. This process has been slow and frustrating. However, much technical headway has been made in recent years, and hopefully the experience of the State of Washington will provide useful insight to problems with the existing guidance. Several recommendations are offered on ways to deal with these problems. In January 1986, the state held an ingestion pathway exercise which required the determination of allowed concentrations of isotopes for various foods, based upon reactor source term and field data. Objectives of the exercise were not met because of the complexity of the necessary calculations. A major problem was that the allowed concentrations had to be computed for each isotope and each food group, given assumptions on the average diet. To solve problems identified during that exercise, Washington developed, by March 1986, partitioned CGs. These CGs apportioned doses from each food group for an assumed mix of radionuclides expected to result from a reactor accident. This effort was therefore in place just in time for actual use during the Chernobyl fallout episode in May 1986. This technique was refined and described in a later report and presented at the 1987 annual meeting of the Health Physics Society. Realizing the technical weaknesses which still existed and a need to simplify the numbers for decision makers, Washington State has been developing computer methods to quickly calculate, from an accident specific relative mix of isotopes, CGs which allow a single radionuclide concentration for all food groups. This latest approach allows constant CGs for different periods of time following the accident, instead of peak CGs, which are good only for a short time after the

  1. Existing ingestion guidance: Problems and recommendations

    International Nuclear Information System (INIS)

    Mooney, Robert R.; Ziegler, Gordon L.; Peterson, Donald S.

    1989-01-01

    Washington State has been developing plans and procedures for responding to nuclear accidents since the early 1970s. A key part of this process has been formulating a method for calculating ingestion pathway concentration guides (CGs). Such a method must be both technically sound and easy to use. This process has been slow and frustrating. However, much technical headway has been made in recent years, and hopefully the experience of the State of Washington will provide useful insight to problems with the existing guidance. Several recommendations are offered on ways to deal with these problems. In January 1986, the state held an ingestion pathway exercise which required the determination of allowed concentrations of isotopes for various foods, based upon reactor source term and field data. Objectives of the exercise were not met because of the complexity of the necessary calculations. A major problem was that the allowed concentrations had to be computed for each isotope and each food group, given assumptions on the average diet. To solve problems identified during that exercise, Washington developed, by March 1986, partitioned CGs. These CGs apportioned doses from each food group for an assumed mix of radionuclides expected to result from a reactor accident. This effort was therefore in place just in time for actual use during the Chernobyl fallout episode in May 1986. This technique was refined and described in a later report and presented at the 1987 annual meeting of the Health Physics Society. Realizing the technical weaknesses which still existed and a need to simplify the numbers for decision makers, Washington State has been developing computer methods to quickly calculate, from an accident specific relative mix of isotopes, CGs which allow a single radionuclide concentration for all food groups. This latest approach allows constant CGs for different periods of time following the accident, instead of peak CGs, which are good only for a short time after the

  2. Do Bare Rocks Exist on the Moon?

    Science.gov (United States)

    Allen, Carlton; Bandfield, Joshua; Greenhagen, Benjamin; Hayne, Paul; Leader, Frank; Paige, David

    2017-01-01

    Astronaut surface observations and close-up images at the Apollo and Chang'e 1 landing sites confirm that at least some lunar rocks have no discernable dust cover. However, ALSEP (Apollo Lunar Surface Experiments Package) measurements as well as astronaut and LADEE (Lunar Atmosphere and Dust Environment Explorer) orbital observations and laboratory experiments possibly suggest that a fine fraction of dust is levitated and moves across and above the lunar surface. Over millions of years such dust might be expected to coat all exposed rock surfaces. This study uses thermal modeling, combined with Diviner (a Lunar Reconnaissance Orbiter experiment) orbital lunar eclipse temperature data, to further document the existence of bare rocks on the lunar surface.

  3. Integrating existing software toolkits into VO system

    Science.gov (United States)

    Cui, Chenzhou; Zhao, Yong-Heng; Wang, Xiaoqian; Sang, Jian; Luo, Ze

    2004-09-01

    Virtual Observatory (VO) is a collection of interoperating data archives and software tools. Taking advantages of the latest information technologies, it aims to provide a data-intensively online research environment for astronomers all around the world. A large number of high-qualified astronomical software packages and libraries are powerful and easy of use, and have been widely used by astronomers for many years. Integrating those toolkits into the VO system is a necessary and important task for the VO developers. VO architecture greatly depends on Grid and Web services, consequently the general VO integration route is "Java Ready - Grid Ready - VO Ready". In the paper, we discuss the importance of VO integration for existing toolkits and discuss the possible solutions. We introduce two efforts in the field from China-VO project, "gImageMagick" and "Galactic abundance gradients statistical research under grid environment". We also discuss what additional work should be done to convert Grid service to VO service.

  4. Seismic review of existing nuclear power plants

    International Nuclear Information System (INIS)

    Yanev, P.I.; Mayes, R.L.; Jones, L.R.

    1975-01-01

    Because of developments in the fields of earthquake and structural engineering over the last two decades, the codes, standards and design criteria for Nuclear Power Plants and other critical structures have changed substantially. As a result, plants designed only a few years ago do not satisfy the requirements for new plants. Accordingly, the Regulatory Agencies are requiring owners of older Nuclear Power Plants to re-qualify the plants seismically, using codes, standards, analytical techniques and knowledge developed in recent years. Seismic review consists of three major phases: establishing the design and performance criteria, re-qualifying the structures, and re-qualifying the equipment. The authors of the paper have been recently involved in the seismic review of existing nuclear power plants in the United States. This paper is a brief summary of their experiences

  5. Welfare Economics: A Story of Existence

    Directory of Open Access Journals (Sweden)

    Khalid Iqbal

    2017-06-01

    Full Text Available The purpose of this study is to explore that, despite severe challenges, welfare economics still exists. This descriptive study is conducted through some specific time line developments in this field. Economists are divided over the veracity and survival of the welfare economics. Welfare economics emphasizes on the optimum resource and goods allocation with the objective of better living standard, materialistic gains, social welfare and ethical decisions. It origins back to the political economics and utilitarianism. Adam Smith, Irving Fisher and Pareto contributed significantly towards it. During 1930 to 1940, American and British approaches were developed. Many economists tried to explore the relationship between level of income and happiness. Amartya Sen gave the comparative approach and Tinbergen pioneered the theory of equity. Contemporarily the futuristic restoration of welfare economics is on trial and hopes are alive. This study may be useful to understand the transitional and survival process of welfare economics.

  6. Testing Metadata Existence of Web Map Services

    Directory of Open Access Journals (Sweden)

    Jan Růžička

    2011-05-01

    Full Text Available For a general user is quite common to use data sources available on WWW. Almost all GIS software allow to use data sources available via Web Map Service (ISO/OGC standard interface. The opportunity to use different sources and combine them brings a lot of problems that were discussed many times on conferences or journal papers. One of the problem is based on non existence of metadata for published sources. The question was: were the discussions effective? The article is partly based on comparison of situation for metadata between years 2007 and 2010. Second part of the article is focused only on 2010 year situation. The paper is created in a context of research of intelligent map systems, that can be used for an automatic or a semi-automatic map creation or a map evaluation.

  7. On the existence of hot positronium reactions

    International Nuclear Information System (INIS)

    Lazzarini, E.

    1984-01-01

    The existence of hot Ps reactions is nowadays questioned; the controversy arises from the two models (the Ore gap and the spur theories) advanced in order to explain the mechanism of the positronium formation and of its inhibition in liquids by dissolution of certain compounds. The hypothesis of the hot Ps reactions was initially advanced as an additional statement for explaining the inhibition phenomenon within the framework of the Ore gap theory, but it is not considered necessary for the spur theory. The present paper is chiefly intended as a presentation of this particular aspect of Ps chemistry to hot atom chemists unspecialized in the field. The reader is assumed to be familiar with the basic physics and experimental methods used in positronium chemistry. Contents: positrons and positronium formation; inhibition and enhancement of Ps formation in solutions; positronium reactions in gases. (Auth.)

  8. Sustainability in the existing building stock

    DEFF Research Database (Denmark)

    Elle, Morten; Nielsen, Susanne Balslev; Hoffmann, Birgitte

    2005-01-01

    , QRWfacilities management’s most important contribution to sustainable development in the built environment. Space management is an essential tool in facilities management – and it could be considered a powerful tool in sustainable development; remembering that the building not being built is perhaps the most......This paper explores the role of Facilities Management in the relation to sustainable development in the existing building stock. Facilities management is a concept still developing as the management of buildings are becoming more and more professional. Many recognize today that facilities...... management is a concept relevant to others than large companies. Managing the flows of energy and other resources is a part of facilities management, and an increased professionalism could lead to the reduction of the use of energy and water and the generation of waste and wastewater. This is, however...

  9. Compilation of Existing Neutron Screen Technology

    Directory of Open Access Journals (Sweden)

    N. Chrysanthopoulou

    2014-01-01

    Full Text Available The presence of fast neutron spectra in new reactors is expected to induce a strong impact on the contained materials, including structural materials, nuclear fuels, neutron reflecting materials, and tritium breeding materials. Therefore, introduction of these reactors into operation will require extensive testing of their components, which must be performed under neutronic conditions representative of those expected to prevail inside the reactor cores when in operation. Due to limited availability of fast reactors, testing of future reactor materials will mostly take place in water cooled material test reactors (MTRs by tailoring the neutron spectrum via neutron screens. The latter rely on the utilization of materials capable of absorbing neutrons at specific energy. A large but fragmented experience is available on that topic. In this work a comprehensive compilation of the existing neutron screen technology is attempted, focusing on neutron screens developed in order to locally enhance the fast over thermal neutron flux ratio in a reactor core.

  10. [The depression epidemic does not exist].

    Science.gov (United States)

    van der Feltz-Cornelis, Christina M

    2009-01-01

    There has been much discussion in the media about the question of the existence of a depression epidemic. This leads on to the questions of whether the social and economic approaches are adequate, and what the alternatives are. The concept of the disease 'depression' can be defined using a medical model, or from a patient's or a societal perspective. From a medical perspective, indeed a depression epidemic has ensued from the increased prosperity and the associated decompression of the mortality rate. Society responded with preventative measures and policies aimed at improving functioning in the workplace. However, patients with a major depressive disorder (MDD) who are eligible for treatment are often not motivated to take it up, or are undertreated. Research is necessary in order to explore what patients think about the identification and treatment of depression. The confusion regarding the concept of depression found in the media, needs to be cleared.

  11. On the existence of Levi Foliations

    Directory of Open Access Journals (Sweden)

    RENATA N. OSTWALD

    2001-03-01

    Full Text Available Let L be a real 3 dimensional analytic variety. For each regular point p L there exists a unique complex line l p on the space tangent to L at p. When the field of complex line p l p is completely integrable, we say that L is Levi variety. More generally; let L M be a real subvariety in an holomorphic complex variety M. If there exists a real 2 dimensional integrable distribution on L which is invariant by the holomorphic structure J induced by M, we say that L is a Levi variety. We shall prove: Theorem. Let be a Levi foliation and let be the induced holomorphic foliation. Then, admits a Liouvillian first integral. In other words, if is a 3 dimensional analytic foliation such that the induced complex distribution defines an holomorphic foliation ; that is, if is a Levi foliation; then admits a Liouvillian first integral--a function which can be constructed by the composition of rational functions, exponentiation, integration, and algebraic functions (Singer 1992. For example, if f is an holomorphic function and if theta is real a 1-form on ; then the pull-back of theta by f defines a Levi foliation : f*theta = 0 which is tangent to the holomorphic foliation : df = 0. This problem was proposed by D. Cerveau in a meeting (see Fernandez 1997.Seja L Ì uma variedade real de dimensão 3. Para todo ponto regular p Î L existe uma única reta complexa l p no espaço tangente à L em p. Quando o campo de linhas complexas p l p é completamente integrável, dizemos que L é uma variedade de Levi. Mais geralmente, seja L Ì M uma subvariedade real em uma variedade analítica complexa. Se existe uma distribuição real integrável de dimensão 2 em L que é invariante pela estrutura holomorfa J induzida pela variedade complexa M, dizemos que L é uma variedade de Levi. Vamos provar: Teorema. Seja uma folheação de Levi e seja a folheação holomorfa induzida. Então tem integral primeira Liouvilliana. Em outras palavras, se é uma folheação real de

  12. How many N = 4 strings exist?

    International Nuclear Information System (INIS)

    Ketov, S.V.

    1994-09-01

    Possible ways of constructing extended fermionic strings with N=4 world-sheet supersymmetry are reviewed. String theory constraints form, in general, a non-linear quasi(super)conformal algebra, and can have conformal dimensions ≥1. When N=4, the most general N=4 quasi-superconformal algebra to consider for string theory building is D(1, 2; α), whose linearisation is the so-called ''large'' N=4 superconformal algebra. The D(1, 2; α) algebra has su(2)sub(κ + )+su(2)sub(κ - )+u(1) Kac-Moody component, and α=κ - /κ + . We check the Jacobi identities and construct a BRST charge for the D(1, 2; α) algebra. The quantum BRST operator can be made nilpotent only when κ + =κ - =-2. The D(1, 2; 1) algebra is actually isomorphic to the SO(4)-based Bershadsky-Knizhnik non-linear quasi-superconformal algebra. We argue about the existence of a string theory associated with the latter, and propose the (non-covariant) hamiltonian action for this new N=4 string theory. Our results imply the existence of two different N=4 fermionic string theories: the old one based on the ''small'' linear N=4 superconformal algebra and having the total ghost central charge c gh =+12, and the new one with non-linearly realised N=4 supersymmetry, based on the SO(4) quasi-superconformal algebra and having c gh =+6. Both critical string theories have negative ''critical dimensions'' and do not admit unitary matter representations. (orig.)

  13. Anatomical and histological profiling of orphan G-protein-coupled receptor expression in gastrointestinal tract of C57BL/6J mice.

    Science.gov (United States)

    Ito, Junko; Ito, Masahiko; Nambu, Hirohide; Fujikawa, Toru; Tanaka, Kenichi; Iwaasa, Hisashi; Tokita, Shigeru

    2009-11-01

    G-protein-coupled receptors (GPCRs) constitute the largest family of transmembrane receptors and regulate a variety of physiological and disease processes. Although the roles of many non-odorant GPCRs have been identified in vivo, several GPCRs remain orphans (oGPCRs). The gastrointestinal (GI) tract is the largest endocrine organ and is a promising target for drug discovery. Given their close link to physiological function, the anatomical and histological expression profiles of benchmark GI-related GPCRs, such as the cholecystokinin-1 receptor and GPR120, and 106 oGPCRs were investigated in the mucosal and muscle-myenteric nerve layers in the GI tract of C57BL/6J mice by quantitative real-time polymerase chain reaction. The mRNA expression patterns of these benchmark molecules were consistent with previous in situ hybridization and immunohistochemical studies, validating the experimental protocols in this study. Of 96 oGPCRs with significant mRNA expression in the GI tract, several oGPCRs showed unique expression patterns. GPR85, GPR37, GPR37L1, brain-specific angiogenesis inhibitor (BAI) 1, BAI2, BAI3, and GPRC5B mRNAs were preferentially expressed in the muscle-myenteric nerve layer, similar to GPCRs that are expressed in both the central and enteric nerve systems and that play multiple regulatory roles throughout the gut-brain axis. In contrast, GPR112, trace amine-associated receptor (TAAR) 1, TAAR2, and GPRC5A mRNAs were preferentially expressed in the mucosal layer, suggesting their potential roles in the regulation of secretion, immunity, and epithelial homeostasis. These anatomical and histological mRNA expression profiles of oGPCRs provide useful clues about the physiological roles of oGPCRs in the GI tract.

  14. Energy consumptions in existing buildings; Les consommations d'energie des batiments existants

    Energy Technology Data Exchange (ETDEWEB)

    Nuss, St. [Ecole Nationale Superieure des Arts et Industries de Strasbourg, 78 - Saint-Remy-Les-Chevreuse (France)]|[Costic, 78 - Sainte Remy les Chevreuses (France)

    2002-05-01

    This document presents a sectoral analysis of the energy consumptions in existing French buildings: 1) - residential sector: social buildings, private dwellings; 2) - tertiary sector: office buildings, hotels, commercial buildings, school buildings, hospitals; 3) - industry; 4) - general status. (J.S.)

  15. Effectiveness of Existing International Nuclear Liability Regime

    International Nuclear Information System (INIS)

    Al-Doais, Salwa; Kessel, Daivd

    2015-01-01

    The first convention was the Paris Convention on Third Party Liability in the Field of Nuclear Energy (the Paris Convention) had been adopted on 29 July 1960 under the auspices of the OECD, and entered into force on 1 April 1968. In 1963,the Brussels Convention - supplementary to the Paris Convention- was adopted in to provide additional funds to compensate damage as a result of a nuclear incident where Paris Convention funds proved to be insufficient. The IAEA's first convention was the Vienna Convention on Civil Liability for Nuclear Damage (the Vienna Convention) which adopted on 21 May 1963,and entered into force in 1977. Both the Paris Convention and the Vienna Convention laid down very similar nuclear liability rules based on the same general principles. The broad principles in these conventions can be summarized as follows: 1- The no-fault liability principle (strict liability) 2- Liability is channeled exclusively to the operator of the nuclear installation (legal channeling) 3- Only courts of the state in which the nuclear accident occurs would have jurisdiction (exclusive jurisdiction) 4- Limitation of the amount of liability and the time frame for claiming damages (limited liability) 5- The operator is required to have adequate insurance or financial guarantees to the extent of its liability amount (liability must be financially secured). 6- Liability is limited in time. Compensation rights are extinguished after specific time. 7- Non-discrimination of victims on the grounds of nationality, domicile or residence. Nuclear liability conventions objective is to provide adequate compensation payments to victims of a nuclear accident. Procedures for receiving these compensation are controlled by some rules such as exclusive jurisdiction, that rule need a further amendment to ensure the effectiveness of the exiting nuclear liability regime . Membership of the Conventions is a critical issue, because the existence of the conventions without being party to

  16. Existing facilities and past practices: Lessons learned

    International Nuclear Information System (INIS)

    Huizenga, D.; Tonkay, D.W.; Owens, K.

    2000-01-01

    Article 12 of the Joint Convention on the Safety of Spent Fuel Management and on the Safety of Radioactive Waste Management (Joint Convention) requires parties to the Joint Convention to review the safety of existing radioactive waste management facilities 'to ensure that, if necessary, all reasonably practicable improvements are made to upgrade the safety of such a facility'. Also required is a review of the results of past practices to determine 'whether any intervention is needed for reasons of radiation protection' and to consider whether the benefits of the intervention or remediation are sufficient, with regard to the costs and the impact on workers, the public and the environment. This paper discusses the experience of the United States Department of Energy in terms of the lessons learned from operating radioactive waste management facilities and from undertaking intervention or remedial action, and from decision making in an international context. Overarching safety principles are discussed, including integrating safety into all work practices and minimizing the generation of waste. Safety review lessons learned with existing facilities are discussed with respect to: applying new requirements to old facilities, taking a life-cycle perspective of waste management, improving high level waste facility management, and blending current and past practices with respect to the process used to arrive at decisions for intervention. Special emphasis is placed on the need to provide for early and substantive input from the involved regulatory agencies, Native American tribes, and those citizens and groups with an interest in the decisions. Examples of intervention decisions are discussed, including examples taken from uranium mill tailings operations, from cleanup of a former uranium processing plant site, from evaluation of pre-1970 buried 'transuranic waste' sites, and from decommissioning or closure of high level waste storage tanks. The paper concludes that on the

  17. Measuring Input Thresholds on an Existing Board

    Science.gov (United States)

    Kuperman, Igor; Gutrich, Daniel G.; Berkun, Andrew C.

    2011-01-01

    A critical PECL (positive emitter-coupled logic) interface to Xilinx interface needed to be changed on an existing flight board. The new Xilinx input interface used a CMOS (complementary metal-oxide semiconductor) type of input, and the driver could meet its thresholds typically, but not in worst-case, according to the data sheet. The previous interface had been based on comparison with an external reference, but the CMOS input is based on comparison with an internal divider from the power supply. A way to measure what the exact input threshold was for this device for 64 inputs on a flight board was needed. The measurement technique allowed an accurate measurement of the voltage required to switch a Xilinx input from high to low for each of the 64 lines, while only probing two of them. Directly driving an external voltage was considered too risky, and tests done on any other unit could not be used to qualify the flight board. The two lines directly probed gave an absolute voltage threshold calibration, while data collected on the remaining 62 lines without probing gave relative measurements that could be used to identify any outliers. The PECL interface was forced to a long-period square wave by driving a saturated square wave into the ADC (analog to digital converter). The active pull-down circuit was turned off, causing each line to rise rapidly and fall slowly according to the input s weak pull-down circuitry. The fall time shows up as a change in the pulse width of the signal ready by the Xilinx. This change in pulse width is a function of capacitance, pulldown current, and input threshold. Capacitance was known from the different trace lengths, plus a gate input capacitance, which is the same for all inputs. The pull-down current is the same for all inputs including the two that are probed directly. The data was combined, and the Excel solver tool was used to find input thresholds for the 62 lines. This was repeated over different supply voltages and

  18. Effectiveness of Existing International Nuclear Liability Regime

    Energy Technology Data Exchange (ETDEWEB)

    Al-Doais, Salwa; Kessel, Daivd [KEPCO International Nuclear Graduate School, Daejeon (Korea, Republic of)

    2015-10-15

    The first convention was the Paris Convention on Third Party Liability in the Field of Nuclear Energy (the Paris Convention) had been adopted on 29 July 1960 under the auspices of the OECD, and entered into force on 1 April 1968. In 1963,the Brussels Convention - supplementary to the Paris Convention- was adopted in to provide additional funds to compensate damage as a result of a nuclear incident where Paris Convention funds proved to be insufficient. The IAEA's first convention was the Vienna Convention on Civil Liability for Nuclear Damage (the Vienna Convention) which adopted on 21 May 1963,and entered into force in 1977. Both the Paris Convention and the Vienna Convention laid down very similar nuclear liability rules based on the same general principles. The broad principles in these conventions can be summarized as follows: 1- The no-fault liability principle (strict liability) 2- Liability is channeled exclusively to the operator of the nuclear installation (legal channeling) 3- Only courts of the state in which the nuclear accident occurs would have jurisdiction (exclusive jurisdiction) 4- Limitation of the amount of liability and the time frame for claiming damages (limited liability) 5- The operator is required to have adequate insurance or financial guarantees to the extent of its liability amount (liability must be financially secured). 6- Liability is limited in time. Compensation rights are extinguished after specific time. 7- Non-discrimination of victims on the grounds of nationality, domicile or residence. Nuclear liability conventions objective is to provide adequate compensation payments to victims of a nuclear accident. Procedures for receiving these compensation are controlled by some rules such as exclusive jurisdiction, that rule need a further amendment to ensure the effectiveness of the exiting nuclear liability regime . Membership of the Conventions is a critical issue, because the existence of the conventions without being party to

  19. Angiotensin type 2 receptors

    DEFF Research Database (Denmark)

    Sumners, Colin; de Kloet, Annette D; Krause, Eric G

    2015-01-01

    In most situations, the angiotensin AT2-receptor (AT2R) mediates physiological actions opposing those mediated by the AT1-receptor (AT1R), including a vasorelaxant effect. Nevertheless, experimental evidence vastly supports that systemic application of AT2R-agonists is blood pressure neutral...

  20. Existing reflection seismic data re-processing

    International Nuclear Information System (INIS)

    Higashinaka, Motonori; Sano, Yukiko; Kozawa, Takeshi

    2005-08-01

    This document is to report the results of existing seismic data re-processing around Horonobe town, Hokkaido, Japan, which is a part of the Horonobe Underground Research Project. The main purpose of this re-processing is to recognize the subsurface structure of Omagari Fault and fold system around Omagari Fault. The seismic lines for re-processing are TYHR-A3 line and SHRB-2 line, which JAPEX surveyed in 1975. Applying weathering static correction using refraction analysis and noise suppression procedure, we have much enhanced seismic profile. Following information was obtained from seismic re-processing results. TYHR-A3 line: There are strong reflections, dipping to the west. These reflections are corresponding western limb of anticline to the west side of Omagari Fault. SHRB-2 line: There are strong reflections, dipping to the west, at CDP 60-140, while there are reflections, dipping to the east, to the east side of CDP 140. These reflections correspond to the western limb and the eastern limb of the anticline, which is parallel to Omagari FAULT. This seismic re-processing provides some useful information to know the geological structure around Omagari Fault. (author)

  1. On the Existence of Evolutionary Learning Equilibriums

    Directory of Open Access Journals (Sweden)

    Masudul Alam Choudhury

    2011-12-01

    Full Text Available The usual kinds of Fixed-Point Theorems formalized on the existence of competitive equilibrium that explain much of economic theory at the core of economics can operate only on bounded and closed sets with convex mappings. But these conditions are hardly true of the real world of economic and financial complexities and perturbations. The category of learning sets explained by continuous fields of interactive, integrative and evolutionary behaviour caused by dynamic preferences at the individual and institutional and social levels cannot maintain the assumption of closed, bounded and convex sets. Thus learning sets and multi-system inter-temporal relations explained by pervasive complementarities and  participation between variables and entities, and evolution by learning, have evolutionary equilibriums. Such a study requires a new methodological approach. This paper formalizes such a methodology for evolutionary equilibriums in learning spaces. It briefly points out the universality of learning equilibriums in all mathematical structures. For a particular case though, the inter-systemic interdependence between sustainable development and ethics and economics in the specific understanding of learning domain is pointed out.

  2. Does the chromatic Mach bands effect exist?

    Science.gov (United States)

    Tsofe, Avital; Spitzer, Hedva; Einav, Shmuel

    2009-06-30

    The achromatic Mach bands effect is a well-known visual illusion, discovered over a hundred years ago. This effect has been investigated thoroughly, mainly for its brightness aspect. The existence of Chromatic Mach bands, however, has been disputed. In recent years it has been reported that Chromatic Mach bands are not perceived under controlled iso-luminance conditions. However, here we show that a variety of Chromatic Mach bands, consisting of chromatic and achromatic regions, separated by a saturation ramp, can be clearly perceived under iso-luminance and iso-brightness conditions. In this study, observers' eye movements were recorded under iso-brightness conditions. Several observers were tested for their ability to perceive the Chromatic Mach bands effect and its magnitude, across different cardinal and non-cardinal Chromatic Mach bands stimuli. A computational model of color adaptation, which predicted color induction and color constancy, successfully predicts this variation of Chromatic Mach bands. This has been tested by measuring the distance of the data points from the "achromatic point" and by calculating the shift of the data points from predicted complementary lines. The results suggest that the Chromatic Mach bands effect is a specific chromatic induction effect.

  3. Evaluation and modification of existing CETP.

    Science.gov (United States)

    Sharma, Bhavisha; Shah, A R

    2013-07-01

    For the development of small and medium scale industries in various Gujarat industrial development corporation (GIDC) areas and in clusters of industrial areas, the common effluent treatment plant (CETP) has always been found advantageous in view of cost of treatment, operation and maintenance and disposal of residues being produced. In small scale industrial units due to market requirement, product changes and quantity enhancement are taking place. Due to such changes, the effluent characteristics are continuously changing which affects performance of CETP. Hence it has been found necessary to study continuously the performance, evaluation and modification in the working of the CETP. This paper contains a case study of one of the existing CETP near Baroda which is facing the problem of disposal of treated effluent in which the important parameters like COD, BOD, Suspended Solid, NH3-N and oil and grease were analyzed. Based on the characterization of wastewater, the various treatability studies were carried out on CETP wastewater. To comply with disposal standard prescribed by Effluent Channel Project Ltd.(ECPL)* and Gujarat Pollution Control Board (GPCB) for discharge of industrial effluent into channel, various treatments in form of ammonia stripping, coagulation and flocculation, biological treatment, filtration and chlorination are suggested.

  4. On the existence of tropical anvil clouds

    Science.gov (United States)

    Seeley, J.; Jeevanjee, N.; Langhans, W.; Romps, D.

    2017-12-01

    In the deep tropics, extensive anvil clouds produce a peak in cloud cover below the tropopause. The dominant paradigm for cloud cover attributes this anvil peak to a layer of enhanced mass convergence in the clear-sky upper-troposphere, which is presumed to force frequent detrainment of convective anvils. However, cloud cover also depends on the lifetime of cloudy air after it detrains, which raises the possibility that anvil clouds may be the signature of slow cloud decay rather than enhanced detrainment. Here we measure the cloud decay timescale in cloud-resolving simulations, and find that cloudy updrafts that detrain in the upper troposphere take much longer to dissipate than their shallower counterparts. We show that cloud lifetimes are long in the upper troposphere because the saturation specific humidity becomes orders of magnitude smaller than the typical condensed water loading of cloudy updrafts. This causes evaporative cloud decay to act extremely slowly, thereby prolonging cloud lifetimes in the upper troposphere. As a consequence, extensive anvil clouds still occur in a convecting atmosphere that is forced to have no preferential clear-sky convergence layer. On the other hand, when cloud lifetimes are fixed at a characteristic lower-tropospheric value, extensive anvil clouds do not form. Our results support a revised understanding of tropical anvil clouds, which attributes their existence to the microphysics of slow cloud decay rather than a peak in clear-sky convergence.

  5. Bibliography - Existing Guidance for External Hazard Modelling

    International Nuclear Information System (INIS)

    Decker, Kurt

    2015-01-01

    The bibliography of deliverable D21.1 includes existing international and national guidance documents and standards on external hazard assessment together with a selection of recent scientific papers, which are regarded to provide useful information on the state of the art of external event modelling. The literature database is subdivided into International Standards, National Standards, and Science Papers. The deliverable is treated as a 'living document' which is regularly updated as necessary during the lifetime of ASAMPSA-E. The current content of the database is about 140 papers. Most of the articles are available as full-text versions in PDF format. The deliverable is available as an EndNote X4 database and as text files. The database includes the following information: Reference, Key words, Abstract (if available), PDF file of the original paper (if available), Notes (comments by the ASAMPSA-E consortium if available) The database is stored at the ASAMPSA-E FTP server hosted by IRSN. PDF files of original papers are accessible through the EndNote software

  6. Glutamate receptor agonists

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart

    2011-01-01

    The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally a-amino acids with one or more...... stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

  7. AMPA receptor ligands

    DEFF Research Database (Denmark)

    Strømgaard, Kristian; Mellor, Ian

    2004-01-01

    Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player in the f......Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player...... in the formation of memory. Hence, ligands affecting AMPARs are highly important for the study of the structure and function of this receptor, and in this regard polyamine-based ligands, particularly polyamine toxins, are unique as they selectively block Ca2+ -permeable AMPARs. Indeed, endogenous intracellular...

  8. The importance of the adenosine A(2A) receptor-dopamine D(2) receptor interaction in drug addiction.

    Science.gov (United States)

    Filip, M; Zaniewska, M; Frankowska, M; Wydra, K; Fuxe, K

    2012-01-01

    Drug addiction is a serious brain disorder with somatic, psychological, psychiatric, socio-economic and legal implications in the developed world. Illegal (e.g., psychostimulants, opioids, cannabinoids) and legal (alcohol, nicotine) drugs of abuse create a complex behavioral pattern composed of drug intake, withdrawal, seeking and relapse. One of the hallmarks of drugs that are abused by humans is that they have different mechanisms of action to increase dopamine (DA) neurotransmission within the mesolimbic circuitry of the brain and indirectly activate DA receptors. Among the DA receptors, D(2) receptors are linked to drug abuse and addiction because their function has been proven to be correlated with drug reinforcement and relapses. The recognition that D(2) receptors exist not only as homomers but also can form heteromers, such as with the adenosine (A)(2A) receptor, that are pharmacologically and functionally distinct from their constituent receptors, has significantly expanded the range of potential drug targets and provided new avenues for drug design in the search for novel drug addiction therapies. The aim of this review is to bring current focus on A(2A) receptors, their physiology and pharmacology in the central nervous system, and to discuss the therapeutic relevance of these receptors to drug addiction. We concentrate on the contribution of A(2A) receptors to the effects of different classes of drugs of abuse examined in preclinical behavioral experiments carried out with pharmacological and genetic tools. The consequences of chronic drug treatment on A(2A) receptor-assigned functions in preclinical studies are also presented. Finally, the neurochemical mechanism of the interaction between A(2A) receptors and drugs of abuse in the context of the heteromeric A(2A)-D(2) receptor complex is discussed. Taken together, a significant amount of experimental analyses provide evidence that targeting A(2A) receptors may offer innovative translational strategies

  9. Interim Storage of Plutonium in Existing Facilities

    International Nuclear Information System (INIS)

    Woodsmall, T.D.

    1999-01-01

    'In this era of nuclear weapons disarmament and nonproliferation treaties, among many problems being faced by the Department of Energy is the safe disposal of plutonium. There is a large stockpile of plutonium at the Rocky Flats Environmental Technology Center and it remains politically and environmentally strategic to relocate the inventory closer to a processing facility. Savannah River Site has been chosen as the final storage location, and the Actinide Packaging and Storage Facility (APSF) is currently under construction for this purpose. With the ability of APSF to receive Rocky Flats material an estimated ten years away, DOE has decided to use the existing reactor building in K-Area of SRS as temporary storage to accelerate the removal of plutonium from Rocky Flats. There are enormous cost savings to the government that serve as incentive to start this removal as soon as possible, and the KAMS project is scheduled to receive the first shipment of plutonium in January 2000. The reactor building in K-Area was chosen for its hardened structure and upgraded seismic qualification, both resulting from an effort to restart the reactor in 1991. The KAMS project has faced unique challenges from Authorization Basis and Safety Analysis perspectives. Although modifying a reactor building from a production facility to a storage shelter is not technically difficult, the nature of plutonium has caused design and safety analysis engineers to make certain that the design of systems, structures and components included will protect the public, SRS workers, and the environment. A basic overview of the KAMS project follows. Plutonium will be measured and loaded into DOT Type-B shipping packages at Rocky Flats. The packages are 35-gallon stainless steel drums with multiple internal containment boundaries. DOE transportation vehicles will be used to ship the drums to the KAMS facility at SRS. They will then be unloaded, stacked and stored in specific locations throughout the

  10. Sharing information among existing data sources

    Science.gov (United States)

    Ashley, W. R., III

    1999-01-01

    The sharing of information between law enforcement agencies is a premise for the success of all jurisdictions. A wealth of information resides in both the databases and infrastructures of local, state, and regional agencies. However, this information is often not available to the law enforcement professionals who require it. When the information is, available, individual investigators must not only know that it exists, but where it resides, and how to retrieve it. In many cases, these types of cross-jurisdictional communications are limited to personal relationships that result from telephone calls, faxes, and in some cases, e-mail. As criminal elements become more sophisticated and distributed, law enforcement agencies must begin to develop infrastructures and common sharing mechanisms that address a constantly evolving criminal threat. Historically, criminals have taken advantage of the lack of communication between law enforcement agencies. Examples of this are evident in the search for stolen property and monetary dealings. Pawned property, cash transactions, and failure to supply child support are three common cross- jurisdictional crimes that could be better enforced by strengthening the lines of communication. Criminal behavior demonstrates that it is easier to profit from their actions by dealing in separate jurisdictions. For example, stolen property is sold outside of the jurisdiction of its origin. In most cases, simply traveling a short distance to the adjoining county or municipality is sufficient to ensure that apprehension of the criminal or seizure of the stolen property is highly unlikely. In addition to the traditional burglar, fugitives often sell or pawn property to finance their continued evasion from the law. Sharing of information in a rapid manner would increase the ability of law enforcement personnel to track and capture fugitives, as well as criminals. In an example to combat this threat, the State of Florida recently acted on the need to

  11. Seismic evaluation of existing nuclear facilities. Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-07-01

    Programmes for re-evaluation and upgrading of safety of existing nuclear facilities are presently under way in a number of countries around the world. An important component of these programmes is the re-evaluation of the seismic safety through definition of new seismic parameters at the site and evaluation of seismic capacity of structures, equipment and distribution systems following updated information and criteria. The Seminar is intended to provide a forum for the exchange of information and discussion of the state-of-the-art on seismic safety of nuclear facilities in operation or under construction. Both analytical and experimental techniques for the evaluation of seismic capacity of structures, equipment and distribution systems are discussed. Full scale and field tests of structures and components using shaking tables, mechanical exciters, explosive and shock tests, and ambient vibrations are included in the seminar programme with emphasis on recent case histories. Presentations at the Seminar also include analytical techniques for the determination of dynamic properties of soil-structure systems from experiments as well as calibration of numerical models. Methods and criteria for seismic margin assessment based on experience data obtained from the behaviour of structures and components in real earthquakes are discussed. Guidelines for defining technical requirements for capacity re-evaluation (i.e. acceptable behaviour limits and design and implementation of structure and components upgrades are also presented and discussed. The following topics were covered during 7 sessions: earthquake experience and seismic re-evaluation; country experience in seismic re-evaluation programme; generic WWER studies; analytical methods for seismic capacity re-evaluation; experimental methods for seismic capacity re-evaluation; case studies.

  12. Does Glocal Political Power Already Exist?

    Directory of Open Access Journals (Sweden)

    Lorenzo Ornaghi

    2017-05-01

    Full Text Available Large periods of history are usually characterized by equally important moments of change in scientific knowledge and, in particular, in the understanding of political power. We still need to study in depth whether the former provokes (almost of out necessity the latter, or whether they are “great” because they are favored by the innovation of the paradigms of knowledge. The passage from medieval universalism to the particularism of the modern age represents an extremely interesting analogy when compared to the transformations that are now underway. The example of John of Salisbury’s Policratus, the starting point of this article, is illuminating in our comprehension of the relevance of the interweaving between the persistence of the ancient forms of recognition of power and the search for new forms. The existence of glocal realities is already a fact. Even if it is relatively easy to recognize these realities (a business, a university, a humanitarian association, not a few of the same “parts” which constitute the traditional organization of the State, it is more difficult to define the specific characteristics of the power at their disposal. Moving from the widening gap between “actual” power and “potential” power, the article examines the motives for which the classical definitions of power are always becoming more insufficient in understanding the role now emerging from glocal realities. And, in particular, by looking at how the “command-obedience” relationship is changing also as a consequence of communication networks and information technology, the article analyzes that specific “contamination” within global elements and local elements, which seems to be the main base of glocal political power.

  13. David Barker: the revolution that anticipates existence

    Directory of Open Access Journals (Sweden)

    Italo Farnetani

    2014-01-01

    Full Text Available David Barker is the man who “anticipated" the existence of babies by focusing attention on the importance of the fetus and what takes place during intrauterine life. Barker was one of the physicians who in the last decades brought about the greatest changes in medicine, changes so important as to represent a veritable revolution in medical thought. According to Barker's studies, the embryo obviously has a genetic complement coming from the mother and father, but from the very first stages of development it begins to undergo the influence of the outside environment, just as occurs for adults whose biological, psychological and pathological aspects are influenced by the environment to a not well-established percentage between genetic complement and epigenetics. Much of our future lives as adults is decided in our mothers' wombs. If Barker's discovery was revolutionary from the cultural standpoint, it was even more so from the strictly medical one. Barker's research method was rigid from the methodological standpoint, but innovative and speculative in its working hypotheses, with a humanistic slant. Barker's idea has another practical corollary: it is evident that the role of obstetricians, perinatologists and neonatologists is more and more relevant in medicine and future prevention. Unquestionably, besides the enormous merits of his clinical research, among the benefits that Barker has contributed there is that of having helped us to see things from new points of view. Not only is the neonate (and even more so the fetus not an adult of reduced proportions, but perhaps the neonate is the "father" of the adult person.

  14. Virtual existence in contemporary Serbian novel

    Directory of Open Access Journals (Sweden)

    Gordić-Petković Vladislava S.

    2017-01-01

    Full Text Available The paper sets out to explore the perspectives and strategies of virtual existence in contemporary Serbian novel in order to illustrate radical changes in the concept of reality and writers' concern with the fidelity to experience. A new surge of the so-called digital realism emerges simultaneously with the increase of awareness that the line between our digital selves and our real-world selves has become blurred and difficult to explain, while new technologies are required to go beyond what our human senses can encompass and deliver. The fictional realism of the digital age will also commit itself to young or middle-aged individuals that passionately attempt to define their aims and objectives so that they could fit into a newly constructed and acquired concept of reality. This is the case with the protagonists in the novels by Ivančica Đerić, Tamara Jecić and Aleksandar Ilić, all of them questioning both their offline and online identities. Their everyday life in a postmillennial world includes many intersecting empirical and virtual realities: love, career and sex take place in a dimension which ignores geography and physical distance and ultimately alters the concepts of time and space, as well the concepts of privacy and intimacy. The paper intends to examine the ways new digital technologies contribute to representations of reality in the novels of both accomplished and aspiring authors whose novels deal with ways of life amid social networks. The novels we analyzed show that the distinction between the virtual and the real world narrows, as the narratives range from intimate confession in letters and journals to tweets, notes and statuses, introducing verbal and structural experimental practices which involve shifting points of view.

  15. Thallium exists in opioid poisoned patients.

    Science.gov (United States)

    Ghaderi, Amir; Vahdati-Mashhadian, Naser; Oghabian, Zohreh; Moradi, Valiallah; Afshari, Reza; Mehrpour, Omid

    2015-08-01

    Thallium (Tl) is a toxic heavy metal that exists in nature. Tl poisoning (thallotoxicosis) may occur in opioid addicts. This study was designed to evaluate the frequency and level of urinary Tl in opioid abusers. In addition, clinical findings were evaluated. A total of 150 subjects were examined. Cases with a history of at least 3 years of abuse were admitted in the Imam Reza Hospital as the case group; 50 non-opioid abusers from the target population were included as the control group. Twenty-four hour urinary qualitative and quantitative Tl analyses were performed on both groups. Out of the 150 subjects, 128 (85 %) were negative for qualitative urinary Tl, followed by 5 % (trace), 7 % (1+), 2 % (2+), and 1 % (3+). Mean (standard error (SE), Min-Max) quantitative urinary Tl level was 14 μg/L (3.5 μg/L, 0-346 μg/L). Mean urinary Tl level in the case group was 21 μg/L (5 μg/L, 0-346 μg/L) and that in the controls was 1 μg/L (0.14 μg/L, 0-26 μg/L), which were significantly different (P = 0.001). The most frequent clinical findings were ataxia (86 %), sweating (81 %), and constipation (54 %). In all cases (n = 150), the mean (SE) value for cases with positive qualitative urinary Tl was 26.8 μg/L (0.9 μg/L) and that in the negative cases was 2.3 μg/L (0.2 μg/L), which were significantly different (P = 0.002). This study showed that long-term opioid abuse may lead to Tl exposure. In opioid abusers with the clinical manifestation of thallotoxicosis, urinary Tl should be determined.

  16. Seismic evaluation of existing nuclear facilities. Proceedings

    International Nuclear Information System (INIS)

    1995-01-01

    Programmes for re-evaluation and upgrading of safety of existing nuclear facilities are presently under way in a number of countries around the world. An important component of these programmes is the re-evaluation of the seismic safety through definition of new seismic parameters at the site and evaluation of seismic capacity of structures, equipment and distribution systems following updated information and criteria. The Seminar is intended to provide a forum for the exchange of information and discussion of the state-of-the-art on seismic safety of nuclear facilities in operation or under construction. Both analytical and experimental techniques for the evaluation of seismic capacity of structures, equipment and distribution systems are discussed. Full scale and field tests of structures and components using shaking tables, mechanical exciters, explosive and shock tests, and ambient vibrations are included in the seminar programme with emphasis on recent case histories. Presentations at the Seminar also include analytical techniques for the determination of dynamic properties of soil-structure systems from experiments as well as calibration of numerical models. Methods and criteria for seismic margin assessment based on experience data obtained from the behaviour of structures and components in real earthquakes are discussed. Guidelines for defining technical requirements for capacity re-evaluation (i.e. acceptable behaviour limits and design and implementation of structure and components upgrades are also presented and discussed. The following topics were covered during 7 sessions: earthquake experience and seismic re-evaluation; country experience in seismic re-evaluation programme; generic WWER studies; analytical methods for seismic capacity re-evaluation; experimental methods for seismic capacity re-evaluation; case studies

  17. Lipophorin Receptor: The Insect Lipoprotein Receptor

    Indian Academy of Sciences (India)

    IAS Admin

    Director of ... function of the Lp is to deliver lipids throughout the insect body for metabolism ... Lipid is used as a major energy source for development as well as other metabolic .... LpR4 receptor variant was expressed exclusively in the brain and.

  18. Does GaH5 exist?

    Science.gov (United States)

    Speakman, Lucas D.; Turney, Justin M.; Schaefer, Henry F.

    2005-11-01

    The existence or nonexistence of GaH5 has been widely discussed [N. M. Mitzel, Angew. Chem. Int. Ed. 42, 3856 (2003)]. Seven possible structures for gallium pentahydride have been systematically investigated using ab initio electronic structure theory. Structures and vibrational frequencies have been determined employing self-consistent field, coupled cluster including all single and double excitations (CCSD), and CCSD with perturbative triples levels of theory, with at least three correlation-consistent polarized-valence-(cc-pVXZ and aug-cc-pVXZ) type basis sets. The X˜A'1 state for GaH5 is predicted to be weakly bound complex 1 between gallane and molecular hydrogen, with Cs symmetry. The dissociation energy corresponding to GaH5→GaH3+H2 is predicted to be De=2.05kcalmol-1. The H-H stretching fundamental is predicted to be v =4060cm-1, compared to the tentatively assigned experimental feature of Wang and Andrews [J. Phys. Chem. A 107, 11371 (2003)] at 4087cm-1. A second Cs structure 2 with nearly equal energy is predicted to be a transition state, corresponding to a 90° rotation of the H2 bond. Thus the rotation of the hydrogen molecule is essentially free. However, hydrogen scrambling through the C2v structure 3 seems unlikely, as the activation barrier for scrambling is at least 30kcalmol-1 higher in energy than that for the dissociation of GaH5 to GaH3 and H2. Two additional structures consisting of GaH3 with a dihydrogen bond perpendicular to gallane (C3v structure 4) and an in-plane dihydrogen bond [Cs(III) structure 5] were also examined. A C3v symmetry second-order saddle point has nearly the same energy as the GaH3+H2 dissociation limit, while the Cs(III) structure 5 is a transition structure to the C3v structure. The C4v structure 6 and the D3h structure 7 are much higher in energy than GaH3+H2 by 88 and 103kcalmol-1, respectively.

  19. PASSCLAIM - Synthesis and review of existing processes.

    Science.gov (United States)

    Richardson, David P; Affertsholt, Tage; Asp, Nils-Georg; Bruce, Ake; Grossklaus, Rolf; Howlett, John; Pannemans, Daphne; Ross, Richard; Verhagen, Hans; Viechtbauer, Volker

    2003-03-01

    Several approaches to the use of health claims on foods have been made around the world, and the common theme is that any health claim will require scientific validation and substantiation. There is also broad consensus that any regulatory framework should protect the consumer, promote fair trade and encourage innovation in the food industry.This paper is based on a critical evaluation of existing international approaches to the scientific substantiation of health claims, with a view to identifying common new ideas, definitions, best practice and a methodology to underpin current and future developments. There is a clear need to have uniform understanding, terminology and description of types of nutrition and health claims. Two broad categories were defined: Nutrition Claims, i. e. what the product contains, and Health Claims, i. e. relating to health, well-being and/or performance, including well-established nutrient function claims, enhanced function claims and disease risk reduction claims. Such health claims relate to what the food or food components does or do. The categories of health claims are closely and progressively related and are, in practice, part of a continuum. Provision is also made for "generic" or well-established, generally accepted claims and for "innovative" or "product-specific" claims. Special attention was paid to reflect the health-promoting properties of a food or food component in such a way as to facilitate the making of risk reduction claims outside the medical scope of the term prevention. The paper sets out basic principles and guidelines for communication of health claims and principles of nutritional safety. The main body of the work examines the process for the assessment of scientific support for health claims on food and emphasises an evidence-based approach consisting of: Identification of all relevant studies exploring the collection of evidence, data searches, the nature of the scientific evidence, sources of scientific data

  20. Vascular endothelium receptors and transduction mechanisms

    CERN Document Server

    Gillis, C; Ryan, Una; Proceedings of the Advanced Studies Institute on "Vascular Endothelium: Receptors and Transduction Mechanisms"

    1989-01-01

    Beyond their obvious role of a barrier between blood and tissue, vascular endothelial cells are now firmly established as active and essential participants in a host of crucial physiological and pathophysiological functions. Probably the two most important factors responsible for promoting the current knowledge of endothelial functions are 1) observations in the late sixties-early seventies that many non-ventilatory properties of the lung could be attributed to the pulmonary endothelium and 2) the establishment, in the early and mid-seventies of procedures for routine culture of vascular endothelial cells. Many of these endothelial functions require the presence of receptors on the surface of the plasma membrane. There is now evidence for the existence among others of muscarinic, a-and /3-adrenergic, purine, insulin, histamine, bradykinin, lipoprotein, thrombin, paf, fibronectin, vitronectin, interleukin and albumin receptors. For some of these ligands, there is evidence only for the existence of endothelial ...

  1. Utilization of the Tango beta-arrestin recruitment technology for cell-based EDG receptor assay development and interrogation.

    Science.gov (United States)

    Wetter, Justin A; Revankar, Chetana; Hanson, Bonnie J

    2009-10-01

    Cellular assay development for the endothelial differentiation gene (EDG) family of G-protein-coupled receptors (GPCRs) and related lysophospholipid (LP) receptors is complicated by endogenous receptor expression and divergent receptor signaling. Endogenously expressed LP receptors exist in most tissue culture cell lines. These LP receptors, along with other endogenously expressed GPCRs, contribute to off-target signaling that can complicate interpretation of second-messenger-based cellular assay results. These receptors also activate a diverse and divergent set of cellular signaling pathways, necessitating the use of a variety of assay formats with mismatched procedures and functional readouts. This complicates examination and comparison of these receptors across the entire family. The Tango technology uses the conserved beta-arrestin-dependent receptor deactivation process to allow interrogation of the EDG and related receptors with a single functional assay. This method also isolates the target receptor signal, allowing the use of tissue culture cell lines regardless of their endogenous receptor expression. The authors describe the use of this technique to build cell-based receptor-specific assays for all 8 members of the EDG receptor family as well as the related LPA receptors GPR23, GPR92, and GPR87. In addition, they demonstrate the value of this technology for identification and investigation of functionally selective receptor compounds as demonstrated by the immunosuppressive compound FtY720-P and its action at the EDG(1) and EDG(3) receptors.

  2. A precariedade humana e a existência estilizada Human precariousness and stylized existence

    Directory of Open Access Journals (Sweden)

    Rita Paiva

    2013-04-01

    Full Text Available Este artigo tematiza o desamparo vivenciado pela consciência ante a ausência de bases sólidas para seus anseios de felicidade e para suas representações simbólicas. Com esse propósito, toma como objeto de reflexão um dos ensaios filosóficos de Albert Camus, O mito de Sísifo, equacionando a possibilidade de uma ética que estilize a vida, sem que se minimize a dolorosa precariedade da existência humana. Posteriormente, em diálogo com alguns textos de M. Foucault, a reflexão procura estabelecer os vínculos possíveis entre a ética camusiana e a ética como uma estética da existência, tal como pensada entre os gregos antigos.This article discusses the helplessness experienced by the consciousness vis-à-vis the absence of solid bases for its longings for happiness and for its symbolic representations. For this purpose, the object of reflection of the article is one of Albert Camus' philosophical essays, The Myth of Sisyphus, and we inquire into the possibility of an ethics that stylizes life without minimizing the painful precariousness of human existence. Making reference to certain texts by Foucault, we attempt to establish possible connections between Camus' ethics and an ethics of the aesthetics of existence as found in the thinkers of ancient Greece.

  3. Existence and non-existence of solutions for a singular problem with variable potentials

    Directory of Open Access Journals (Sweden)

    Kamel Saoudi

    2017-11-01

    Full Text Available The purpose of this article is to prove some existence and nonexistence theorems for the inhomogeneous singular Dirichlet problem $$ - \\Delta_p u = \\frac{\\lambda k(x}{u^\\delta}\\pm h(x u^q. $$ For proving our results we use the sub and super solution method, and monotonicity arguments.

  4. Serotonin Receptors in Hippocampus

    Science.gov (United States)

    Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

    2012-01-01

    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system. PMID:22629209

  5. Ophthalmic antihistamines and H1-H4 receptors.

    Science.gov (United States)

    Wade, Laurie; Bielory, Leonard; Rudner, Shara

    2012-10-01

    Antihistamines exert pharmacologic effects by binding to four histamine receptors (H1-H4) at different affinities, producing variable effects depending on the receptor they predominantly bind to. This review's purpose is to determine the relative potency of antihistamines by comparing their binding affinities to these receptors. Studies on binding affinities of antihistamines to histamine receptors were reviewed and the dissociation constant for inhibitor binding (Ki) analyzed to determine the most and least potent antihistamine for each receptor. We retrieved the binding affinities for nineteen antihistamines. For H1 receptors, pyrilamine exhibited the highest affinity (Ki = 0.8 nM), and thioperamide the lowest (Ki = 280, 000 nM). For H2 receptors, ranitidine exhibited the highest affinity (Ki = 187 nM), and olopatadine the lowest (Ki = 100 ,000 nM). For the recently discovered H3 and H4 receptors, thioperamide exhibited the highest affinity (Ki = 1.1 nM), and olopatadine exhibited the lowest (Ki = 79 ,400 nM), to H3. Data on binding affinities to the H4 receptor exist for: ketotifen, pheniramine, ranitidine, cimetidine and thioperamide. Of these, thioperamide exhibited the highest affinity (Ki = 27 nM), whereas cimetidine and ranitidine exhibited the lowest affinity (Ki = >10, 000 nM) for H4 receptors. This review summarizes the relative potency of antihistamines based on their binding affinities to the four histamine receptors. Although data on binding affinities of antihistamines to the H4 receptor are sparse, it is apparent that further research on these histamine subtypes may open new venues for more direct treatment with a higher therapeutic efficacy on allergic disorders including those affecting the ocular surface.

  6. Dimer-based model for heptaspanning membrane receptors.

    Science.gov (United States)

    Franco, Rafael; Casadó, Vicent; Mallol, Josefa; Ferré, Sergi; Fuxe, Kjell; Cortés, Antonio; Ciruela, Francisco; Lluis, Carmen; Canela, Enric I

    2005-07-01

    The existence of intramembrane receptor-receptor interactions for heptaspanning membrane receptors is now fully accepted, but a model considering dimers as the basic unit that binds to two ligand molecules is lacking. Here, we propose a two-state-dimer model in which the ligand-induced conformational changes from one component of the dimer are communicated to the other. Our model predicts cooperativity in binding, which is relevant because the other current models fail to address this phenomenon satisfactorily. Our two-state-dimer model also predicts the variety of responses elicited by full or partial agonists, neutral antagonists and inverse agonists. This model can aid our understanding of the operation of heptaspanning receptors and receptor channels, and, potentially, be important for improving the treatment of cardiovascular, neurological and neuropsychyatric diseases.

  7. Black Hole Caught Zapping Galaxy into Existence?

    Science.gov (United States)

    2009-11-01

    , construction and operation of powerful ground-based observing facilities enabling astronomers to make important scientific discoveries. ESO also plays a leading role in promoting and organising cooperation in astronomical research. ESO operates three unique world-class observing sites in Chile: La Silla, Paranal and Chajnantor. At Paranal, ESO operates the Very Large Telescope, the world's most advanced visible-light astronomical observatory. ESO is the European partner of a revolutionary astronomical telescope ALMA, the largest astronomical project in existence. ESO is currently planning a 42-metre European Extremely Large optical/near-infrared Telescope, the E-ELT, which will become "the world's biggest eye on the sky".

  8. Sex Hormone Receptor Expression in the Human Vocal Fold Subunits.

    Science.gov (United States)

    Kirgezen, Tolga; Sunter, Ahmet Volkan; Yigit, Ozgur; Huq, Gulben Erdem

    2017-07-01

    The study aimed to evaluate the existence of sex hormone receptors in the subunits of vocal fold. This is a cadaver study. The androgen, estrogen, and progesterone receptors were examined in the epithelium (EP), superficial layer of the lamina propria (SLP), vocal ligament (VL), and macula flava (MF) of the vocal folds from 42 human cadavers (21 male, 21 female) by immunohistochemical methods. Their staining ratios were scored and statistically compared. The androgen receptor score was significantly higher for the MF than for the EP and SLP (P vocal fold, mostly in the MF and VLs. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  9. Existence and non-existence of solutions for a p(x-biharmonic problem

    Directory of Open Access Journals (Sweden)

    Ghasem A. Afrouzi

    2015-06-01

    Full Text Available In this article, we study the following problem with Navier boundary conditions $$\\displaylines{ \\Delta (|\\Delta u|^{p(x-2}\\Delta u+|u|^{p(x-2}u =\\lambda |u|^{q(x-2}u +\\mu|u|^{\\gamma(x-2}u\\quad \\text{in } \\Omega,\\cr u=\\Delta u=0 \\quad \\text{on } \\partial\\Omega. }$$ where $\\Omega$ is a bounded domain in $\\mathbb{R}^{N}$ with smooth boundary $\\partial \\Omega$, $N\\geq1$. $p(x,q(x$ and $\\gamma(x$ are continuous functions on $\\overline{\\Omega}$, $\\lambda$ and $\\mu$ are parameters. Using variational methods, we establish some existence and non-existence results of solutions for this problem.

  10. 40 CFR 427.34 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ...) EFFLUENT GUIDELINES AND STANDARDS ASBESTOS MANUFACTURING POINT SOURCE CATEGORY Asbestos Paper (Starch Binder) Subcategory § 427.34 Pretreatment standards for existing sources. Any existing source subject to...

  11. 40 CFR 427.44 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ...) EFFLUENT GUIDELINES AND STANDARDS ASBESTOS MANUFACTURING POINT SOURCE CATEGORY Asbestos Paper (Elastomeric Binder) Subcategory § 427.44 Pretreatment standards for existing sources. Any existing source subject to...

  12. 40 CFR 417.84 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ...) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Manufacture of Liquid Soaps Subcategory § 417.84 Pretreatment standards for existing sources. Any existing source...

  13. Sulpiride and the role of dopaminergic receptor blockade in the antipsychotic activity of neuroleptics

    Energy Technology Data Exchange (ETDEWEB)

    Memo, M; Battaini, F; Spano, P F; Trabucchi, M [University of Brescia, (Italy). Dept. of Pharmacology

    1981-01-01

    It is now generally recognized that dopamine receptors excist in the CNS as different subtypes: D/sub 1/ receptors, associated with adenylyl cyclase activity, and D/sub 2/ receptor, uncoupled to a cyclic AMP generating system. In order to understand the role of D/sub 1/ and D/sub 2/ receptors in the antipsychotic action of neuroleptics, we have performed subchronic treatment with haloperidol, a drug which acts on D/sub 1/ receptors, and sulpiride, a selective antagonist to D/sub 2/ receptors. Long-term treatment with haloperidol does not induce significant supersensitivity of the D/sub 2/ receptors. In fact under these conditions /sup 3/H-(-)-sulpiride binding, which is a marker of D/sub 2/ receptor function, does not increase in rat striatum, while the long-term administration of sulpiride, itself produces supersensitivity of D/sub 2/ receptors. Moreover, sulpiride does not induce supersensitivity of the D/sub 1/ receptors, characterized by /sup 3/H-spiroperidol binding. These data suggest that both types of dopamine receptors may be involved in the clinical antipsychotic effects of neuroleptics. Unilateral leison of the nigrostriatal dopaminergic pathway produces an increase of striatal dopaminergic receptors, measured either by /sup 3/H-spiroperidol and /sup 3/H-(-)-sulpiride binding. These findings suggest that D/sub 1/ and D/sub 2/ receptors are present in postsynaptic membranes while it is still not known whether they exist in the same cellular elements.

  14. Sulpiride and the role of dopaminergic receptor blockade in the antipsychotic activity of neuroleptics

    International Nuclear Information System (INIS)

    Memo, M.; Battaini, F.; Spano, P.F.; Trabucchi, M.

    1981-01-01

    It is now generally recognized that dopamine receptors excist in the CNS as different subtypes: D 1 receptors, associated with adenylyl cyclase activity, and D 2 receptor, uncoupled to a cyclic APM generating system. In order to understand the role of D 1 and D 2 receptors in the antipsychotic action of neuroleptics, we have performed subchronic treatment with haloperidol, a drug which acts on D 1 receptors, and sulpiride, a selective antagonist to D 2 receptors. Long-term treatment with haloperidol does not induce significant supersensitivity of the D 2 receptors. In fact under these conditions 3 H-(-)-sulpiride binding, which is a marker of D 2 receptor function, does not increase in rat striatum, while the long-term administration of sulpiride, itself produces supersensitivity of D 2 receptors. Moreover, sulpiride does not induce supersensitivity of the D 1 receptors, characterized by 3 H-spiroperidol binding. These data suggest that both types of dopamine receptors may be involved in the clinical antipsychotic effects of neuroleptics. Unilateral leison of the nigrostriatal dopaminergic pathway produces an increase of striatal dopaminergic receptors, measured either by 3 H-spiroperidol and 3 H-(-)-sulpiride binding. These findings suggest that D 1 and D 2 receptors are present in postsynaptic membranes while it is still not known whether they exist in the same cellular elements. (author)

  15. Epilepsy, E/I balance and GABAA receptor plasticity

    Directory of Open Access Journals (Sweden)

    Jean-Marc Fritschy

    2008-03-01

    Full Text Available GABAA receptors mediate most of the fast inhibitory transmission in the CNS. They form heteromeric complexes assembled from a large family of subunit genes. The existence of multiple GABAA receptor subtypes differing in subunit composition, localization and functional properties underlies their role for fi ne-tuning of neuronal circuits and genesis of network oscillations. The differential regulation of GABAA receptor subtypes represents a major facet of homeostatic synaptic plasticity and contributes to the excitation/inhibition (E/I balance under physiological conditions and upon pathological challenges. The purpose of this review is to discuss recent fi ndings highlighting the signifi cance of GABAA receptor heterogeneity for the concept of E/I balance and its relevance for epilepsy. Specifi cally, we address the following issues: (1 role for tonic inhibition, mediated by extrasynaptic GABAA receptors, for controlling neuronal excitability; (2 signifi cance of chloride ion transport for maintenance of the E/I balance in adult brain; and (3 molecular mechanisms underlying GABAA receptor regulation (traffi cking, posttranslational modifi cation, gene transcription that are important for homoeostatic plasticity. Finally, the relevance of these fi ndings is discussed in light of the involvement of GABAA receptors in epileptic disorders, based on recent experimental studies of temporal lobe epilepsy (TLE and absence seizures and on the identifi cation of mutations in GABAA receptor subunit genes underlying familial forms of epilepsy.

  16. Amyotrophic Lateral Sclerosis (ALS and Adenosine Receptors

    Directory of Open Access Journals (Sweden)

    Ana M. Sebastião

    2018-04-01

    Full Text Available In the present review we discuss the potential involvement of adenosinergic signaling, in particular the role of adenosine receptors, in amyotrophic lateral sclerosis (ALS. Though the literature on this topic is not abundant, the information so far available on adenosine receptors in animal models of ALS highlights the interest to continue to explore the role of these receptors in this neurodegenerative disease. Indeed, all motor neurons affected in ALS are responsive to adenosine receptor ligands but interestingly, there are alterations in pre-symptomatic or early symptomatic stages that mirror those in advanced disease stages. Information starts to emerge pointing toward a beneficial role of A2A receptors (A2AR, most probably at early disease states, and a detrimental role of caffeine, in clear contrast with what occurs in other neurodegenerative diseases. However, some evidence also exists on a beneficial action of A2AR antagonists. It may happen that there are time windows where A2AR prove beneficial and others where their blockade is required. Furthermore, the same changes may not occur simultaneously at the different synapses. In line with this, it is not fully understood if ALS is a dying back disease or if it propagates in a centrifugal way. It thus seems crucial to understand how motor neuron dysfunction occurs, how adenosine receptors are involved in those dysfunctions and whether the early changes in purinergic signaling are compensatory or triggers for the disease. Getting this information is crucial before starting the design of purinergic based strategies to halt or delay disease progression.

  17. Modelling the interdependence between the stoichiometry of receptor oligomerization and ligand binding for a coexisting dimer/tetramer receptor system.

    Science.gov (United States)

    Rovira, X; Vivó, M; Serra, J; Roche, D; Strange, P G; Giraldo, J

    2009-01-01

    Many G protein-coupled receptors have been shown to exist as oligomers, but the oligomerization state and the effects of this on receptor function are unclear. For some G protein-coupled receptors, in ligand binding assays, different radioligands provide different maximal binding capacities. Here we have developed mathematical models for co-expressed dimeric and tetrameric species of receptors. We have considered models where the dimers and tetramers are in equilibrium and where they do not interconvert and we have also considered the potential influence of the ligands on the degree of oligomerization. By analogy with agonist efficacy, we have considered ligands that promote, inhibit or have no effect on oligomerization. Cell surface receptor expression and the intrinsic capacity of receptors to oligomerize are quantitative parameters of the equations. The models can account for differences in the maximal binding capacities of radioligands in different preparations of receptors and provide a conceptual framework for simulation and data fitting in complex oligomeric receptor situations.

  18. Rat hepatic β2-adrenergic receptor: structural similarities to the rat fat cell β1-adrenergic receptor

    International Nuclear Information System (INIS)

    Graziano, M.P.

    1984-01-01

    The mammalian β 2 -adrenergic receptor from rat liver has been purified by sequential cycles of affinity chromatography followed by steric-exclusion high performance liquid chromatography. Electrophoresis of highly purified receptor preparations on polyacrylamide gels in the presence of sodium dodecyl sulfate under reducing conditions reveals a single peptide M/sub r/ = 67,000, as judged by silver staining. Purified β 2 -adrenergic receptor migrates on steric-exclusion high performance liquid chromatography in two peaks, with M/sub r/ = 140,000 and 67,000. Specific binding of the high affinity, β-adrenergic receptor antagonists (-)[ 3 H]dihydroalprenolol and (-)[ 125 I]iodocyanopindolol to purified rat liver β-adrenergic receptor preparations displays stereoselectivity for (-)isomers of agonists and a rank order of potencies for agonists characteristics of a β 2 -adrenergic receptor. Radioiodinated, β 1 -adrenergic receptors from rat fat cells and β 2 -adrenergic receptors from rat liver purified in the presence of protease inhibitors comigrate in electrophoretic separations on polyacrylamide gels in the presence of sodium dodecyl sulfate as 67,000-M/sub r/ peptides. Autoradiograms of two dimensional partial proteolytic digests of the purified, radioiodinated rat liver β 2 -adrenergic receptor, generated with α-chymotrypsin, S. aureus V8 protease and elastase reveal a pattern of peptide fragments essentially identical to those generated by partial proteolytic digests of the purified, radioiodinated β 1 -adrenergic receptor from rat fat cells, by these same proteases. These data indicate that a high degree of homology exists between these two pharmacologically distinct mammalian β-adrenergic receptor proteins

  19. Ionotropic crustacean olfactory receptors.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Corey

    Full Text Available The nature of the olfactory receptor in crustaceans, a major group of arthropods, has remained elusive. We report that spiny lobsters, Panulirus argus, express ionotropic receptors (IRs, the insect chemosensory variants of ionotropic glutamate receptors. Unlike insects IRs, which are expressed in a specific subset of olfactory cells, two lobster IR subunits are expressed in most, if not all, lobster olfactory receptor neurons (ORNs, as confirmed by antibody labeling and in situ hybridization. Ligand-specific ORN responses visualized by calcium imaging are consistent with a restricted expression pattern found for other potential subunits, suggesting that cell-specific expression of uncommon IR subunits determines the ligand sensitivity of individual cells. IRs are the only type of olfactory receptor that we have detected in spiny lobster olfactory tissue, suggesting that they likely mediate olfactory signaling. Given long-standing evidence for G protein-mediated signaling in activation of lobster ORNs, this finding raises the interesting specter that IRs act in concert with second messenger-mediated signaling.

  20. Degradation rate of acetylcholine receptors inserted into denervated vertebrate neuromuscular junctions

    International Nuclear Information System (INIS)

    Shyng, S.L.; Salpeter, M.M.

    1989-01-01

    Many studies exist on the effect of denervation on the degradation of acetylcholine receptors (AChRs) at the vertebrate neuromuscular junction (nmj). These studies have described the behavior of either the total population of junctional receptors at different times after denervation, or of the receptors present at the time of denervation. No experimental studies yet exist on the degradation rate of the receptors newly inserted into denervated junctions. In the previous studies, the original receptors of mouse sternomastoid muscles were found to retain the slow degradation (t 1/2) of approximately 8-10 d of innervated junctional receptors for up to 10 d after denervation before accelerating to a t 1/2 of approximately 3 d. The total junctional receptors, on the other hand, showed a progressive increase in degradation rate from a t 1/2 of 8-10 d to a t 1/2 of 1 d. To reconcile these earlier observations, the present study examines the degradation of new receptors inserted into the nmj after denervation. To avoid possible contamination of the data with postdenervation extrajunctional receptors, we used transmission electron microscope autoradiography to study only receptors located at the postjunctional fold of the nmj. We established that the new receptors inserted into denervated junctions have a t 1/2 of approximately 1 d, considerably faster than that of the original receptors and equivalent to that of postdenervation extrajunctional receptors. Both original and new receptors are interspersed at the top of the junctional folds. Thus, until all the original receptors are degraded, the postjunctional membrane contains two populations of AChRs that maintain a total steady-state site density but degrade at different rates

  1. Synthesis and characterization of time-resolved fluorescence probes for evaluation of competitive binding to melanocortin receptors.

    Science.gov (United States)

    Alleti, Ramesh; Vagner, Josef; Dehigaspitiya, Dilani Chathurika; Moberg, Valerie E; Elshan, N G R D; Tafreshi, Narges K; Brabez, Nabila; Weber, Craig S; Lynch, Ronald M; Hruby, Victor J; Gillies, Robert J; Morse, David L; Mash, Eugene A

    2013-09-01

    Probes for use in time-resolved fluorescence competitive binding assays at melanocortin receptors based on the parental ligands MSH(4), MSH(7), and NDP-α-MSH were prepared by solid phase synthesis methods, purified, and characterized. The saturation binding of these probes was studied using HEK-293 cells engineered to overexpress the human melanocortin 4 receptor (hMC4R) as well as the human cholecystokinin 2 receptor (hCCK2R). The ratios of non-specific binding to total binding approached unity at high concentrations for each probe. At low probe concentrations, receptor-mediated binding and uptake was discernable, and so probe concentrations were kept as low as possible in determining Kd values. The Eu-DTPA-PEGO-MSH(4) probe exhibited low specific binding relative to non-specific binding, even at low nanomolar concentrations, and was deemed unsuitable for use in competition binding assays. The Eu-DTPA-PEGO probes based on MSH(7) and NDP-α-MSH exhibited Kd values of 27±3.9nM and 4.2±0.48nM, respectively, for binding with hMC4R. These probes were employed in competitive binding assays to characterize the interactions of hMC4R with monovalent and divalent MSH(4), MSH(7), and NDP-α-MSH constructs derived from squalene. Results from assays with both probes reflected only statistical enhancements, suggesting improper ligand spacing on the squalene scaffold for the divalent constructs. The Ki values from competitive binding assays that employed the MSH(7)-based probe were generally lower than the Ki values obtained when the probe based on NDP-α-MSH was employed, which is consistent with the greater potency of the latter probe. The probe based on MSH(7) was also competed with monovalent, divalent, and trivalent MSH(4) constructs that previously demonstrated multivalent binding in competitive binding assays against a variant of the probe based on NDP-α-MSH. Results from these assays confirm multivalent binding, but suggest a more modest increase in avidity for these

  2. Functional Validation of Heteromeric Kainate Receptor Models.

    Science.gov (United States)

    Paramo, Teresa; Brown, Patricia M G E; Musgaard, Maria; Bowie, Derek; Biggin, Philip C

    2017-11-21

    Kainate receptors require the presence of external ions for gating. Most work thus far has been performed on homomeric GluK2 but, in vivo, kainate receptors are likely heterotetramers. Agonists bind to the ligand-binding domain (LBD) which is arranged as a dimer of dimers as exemplified in homomeric structures, but no high-resolution structure currently exists of heteromeric kainate receptors. In a full-length heterotetramer, the LBDs could potentially be arranged either as a GluK2 homomer alongside a GluK5 homomer or as two GluK2/K5 heterodimers. We have constructed models of the LBD dimers based on the GluK2 LBD crystal structures and investigated their stability with molecular dynamics simulations. We have then used the models to make predictions about the functional behavior of the full-length GluK2/K5 receptor, which we confirmed via electrophysiological recordings. A key prediction and observation is that lithium ions bind to the dimer interface of GluK2/K5 heteromers and slow their desensitization. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  3. Assays for calcitonin receptors

    International Nuclear Information System (INIS)

    Teitelbaum, A.P.; Nissenson, R.A.; Arnaud, C.D.

    1985-01-01

    The assays for calcitonin receptors described focus on their use in the study of the well-established target organs for calcitonin, bone and kidney. The radioligand used in virtually all calcitonin binding studies is 125 I-labelled salmon calcitonin. The lack of methionine residues in this peptide permits the use of chloramine-T for the iodination reaction. Binding assays are described for intact bone, skeletal plasma membranes, renal plasma membranes, and primary kidney cell cultures of rats. Studies on calcitonin metabolism in laboratory animals and regulation of calcitonin receptors are reviewed

  4. Synergistic Action of Presynaptic Muscarinic Acetylcholine Receptors and Adenosine Receptors in Developmental Axonal Competition at the Neuromuscular Junction.

    Science.gov (United States)

    Nadal, Laura; Garcia, Neus; Hurtado, Erica; Simó, Anna; Tomàs, Marta; Lanuza, Maria Angel; Cilleros, Victor; Tomàs, Josep Maria

    2016-01-01

    The development of the nervous system involves the initial overproduction of synapses, which promotes connectivity. Hebbian competition between axons with different activities leads to the loss of roughly half of the overproduced elements and this refines connectivity. We used quantitative immunohistochemistry to investigate, in the postnatal day 7 (P7) to P9 neuromuscular junctions, the involvement of muscarinic receptors (muscarinic acetylcholine autoreceptors and the M1, M2, and M4 subtypes) and adenosine receptors (A1 and A2A subtypes) in the control of axonal elimination after the mouse levator auris longus muscle had been exposed to selective antagonists in vivo. In a previous study we analyzed the role of each of the individual receptors. Here we investigate the additive or occlusive effects of their inhibitors and thus the existence of synergistic activity between the receptors. The main results show that the A2A, M1, M4, and A1 receptors (in this order of ability) delayed axonal elimination at P7. M4 produces some occlusion of the M1 pathway and some addition to the A1 pathway, which suggests that they cooperate. M2 receptors may modulate (by allowing a permissive action) the other receptors, mainly M4 and A1. The continued action of these receptors (now including M2 but not M4) finally promotes axonal loss at P9. All 4 receptors (M2, M1, A1, and A2A, in this order of ability) are necessary. The M4 receptor (which in itself does not affect axon loss) seems to modulate the other receptors. We found a synergistic action between the M1, A1, and A2A receptors, which show an additive effect, whereas the potent M2 effect is largely independent of the other receptors (though can be modulated by M4). At P9, there is a full mutual dependence between the A1 and A2A receptors in regulating axon loss. In summary, postnatal axonal elimination is a regulated multireceptor mechanism that involves the cooperation of several muscarinic and adenosine receptor subtypes.

  5. AMP is an adenosine A1 receptor agonist.

    Science.gov (United States)

    Rittiner, Joseph E; Korboukh, Ilia; Hull-Ryde, Emily A; Jin, Jian; Janzen, William P; Frye, Stephen V; Zylka, Mark J

    2012-02-17

    Numerous receptors for ATP, ADP, and adenosine exist; however, it is currently unknown whether a receptor for the related nucleotide adenosine 5'-monophosphate (AMP) exists. Using a novel cell-based assay to visualize adenosine receptor activation in real time, we found that AMP and a non-hydrolyzable AMP analog (deoxyadenosine 5'-monophosphonate, ACP) directly activated the adenosine A(1) receptor (A(1)R). In contrast, AMP only activated the adenosine A(2B) receptor (A(2B)R) after hydrolysis to adenosine by ecto-5'-nucleotidase (NT5E, CD73) or prostatic acid phosphatase (PAP, ACPP). Adenosine and AMP were equipotent human A(1)R agonists in our real-time assay and in a cAMP accumulation assay. ACP also depressed cAMP levels in mouse cortical neurons through activation of endogenous A(1)R. Non-selective purinergic receptor antagonists (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid and suramin) did not block adenosine- or AMP-evoked activation. Moreover, mutation of His-251 in the human A(1)R ligand binding pocket reduced AMP potency without affecting adenosine potency. In contrast, mutation of a different binding pocket residue (His-278) eliminated responses to AMP and to adenosine. Taken together, our study indicates that the physiologically relevant nucleotide AMP is a full agonist of A(1)R. In addition, our study suggests that some of the physiological effects of AMP may be direct, and not indirect through ectonucleotidases that hydrolyze this nucleotide to adenosine.

  6. Angiotensin type 2 receptor (AT2R) and receptor Mas

    DEFF Research Database (Denmark)

    Villela, Daniel; Leonhardt, Julia; Patel, Neal

    2015-01-01

    The angiotensin type 2 receptor (AT2R) and the receptor Mas are components of the protective arms of the renin-angiotensin system (RAS), i.e. they both mediate tissue protective and regenerative actions. The spectrum of actions of these two receptors and their signalling mechanisms display striki...

  7. Unraveling the high- and low-sensitivity agonist responses of nicotinic acetylcholine receptors

    DEFF Research Database (Denmark)

    Harpsøe, Kasper; Ahring, Philip K; Christensen, Jeppe K

    2011-01-01

    The neuronal a4ß2 nicotinic acetylcholine receptors exist as two distinct subtypes, (a4)(2)(ß2)(3) and (a4)(3)(ß2)(2), and biphasic responses to acetylcholine and other agonists have been ascribed previously to coexistence of these two receptor subtypes. We offer a novel and radical explanation...

  8. Evidence for the involvement of MC4 receptors in the central mechanisms of opioid antinociception

    NARCIS (Netherlands)

    Starowicz, Katarzyna

    2005-01-01

    The data described in this thesis extend general knowledge of the involvement of the MC4 receptor in mechanisms of analgesia. The following aspects outlined below constitute novel information. Firstly, the MC4R localization in the DRG is demonstrated. The MC4 receptor was assumed to exist

  9. How Far Does a Receptor Influence Vibrational Properties of an Odorant?

    DEFF Research Database (Denmark)

    Reese, Anna; List, Nanna Holmgaard; Kongsted, Jacob

    2016-01-01

    -assisted electron transfer. Through molecular dynamics simulations we elucidate the binding specificity of a receptor towards acetophenone odorant. The vibrational properties of acetophenone inside the receptor are then studied by the polarizable embedding density functional theory approach, allowing to quantify...... protein-odorant interactions. Finally, we judge whether the effects of the protein provide any indications towards the existing theories of olfaction....

  10. Expression and role of gonadotropin-releasing hormone 2 and its receptor in mammals

    Science.gov (United States)

    Gonadotropin-releasing hormone (GnRH1) and its receptor (GnRHR1) drive mammalian reproduction via regulation of the gonadotropins. Yet, a second form of GnRH (GnRH2) and its receptor (GnRHR2) also exist in some mammals. GnRH2 has been completely conserved throughout 500 million years of evolution, s...

  11. TLX: An elusive receptor.

    Science.gov (United States)

    Benod, Cindy; Villagomez, Rosa; Webb, Paul

    2016-03-01

    TLX (tailless receptor) is a member of the nuclear receptor superfamily and belongs to a class of nuclear receptors for which no endogenous or synthetic ligands have yet been identified. TLX is a promising therapeutic target in neurological disorders and brain tumors. Thus, regulatory ligands for TLX need to be identified to complete the validation of TLX as a useful target and would serve as chemical probes to pursue the study of this receptor in disease models. It has recently been proved that TLX is druggable. However, to identify potent and specific TLX ligands with desirable biological activity, a deeper understanding of where ligands bind, how they alter TLX conformation and of the mechanism by which TLX mediates the transcription of its target genes is needed. While TLX is in the process of escaping from orphanhood, future ligand design needs to progress in parallel with improved understanding of (i) the binding cavity or surfaces to target with small molecules on the TLX ligand binding domain and (ii) the nature of the TLX coregulators in particular cell and disease contexts. Both of these topics are discussed in this review. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Glutamate receptor ligands

    DEFF Research Database (Denmark)

    Guldbrandt, Mette; Johansen, Tommy N; Frydenvang, Karla Andrea

    2002-01-01

    Homologation and substitution on the carbon backbone of (S)-glutamic acid [(S)-Glu, 1], as well as absolute stereochemistry, are structural parameters of key importance for the pharmacological profile of (S)-Glu receptor ligands. We describe a series of methyl-substituted 2-aminoadipic acid (AA...

  13. Ginkgolides and glycine receptors

    DEFF Research Database (Denmark)

    Jaracz, Stanislav; Nakanishi, Koji; Jensen, Anders A.

    2004-01-01

    Ginkgolides from the Ginkgo biloba tree are diterpenes with a cage structure consisting of six five-membered rings and a unique tBu group. They exert a variety of biological properties. In addition to being antagonists of the platelet activating factor receptor (PAFR), it has recently been shown ...

  14. adrenergic receptor with preeclampsia

    African Journals Online (AJOL)

    User

    2011-05-09

    May 9, 2011 ... due to a post- receptor defect (Karadas et al., 2007). Several polymorphisms have ... the detection of the Arg16Gly polymorphism, overnight digestion at. 37°C with 10 U ..... DW, Wood AJ, Stein CM (2004). Beta2-adrenoceptor ...

  15. Metformin and insulin receptors

    International Nuclear Information System (INIS)

    Vigneri, R.; Gullo, D.; Pezzino, V.

    1984-01-01

    The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific 125 I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific 125 I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded

  16. Performance assessment for proposed disposal of NORM at an existing landfill in New South Wales, Australia

    Energy Technology Data Exchange (ETDEWEB)

    Fountain, S., E-mail: sfountain@geosyntec.com [Geosyntec Consultants, Inc., Kennesaw, Georgia (United States); Jones, J., E-mail: john.jones@sita.com.au [SITA Australia, Chullora, New South Wales (Australia); Christopherson, J.; Drummond, C., E-mail: jchristopherson@geosyntec.com, E-mail: cdrummond@geosyntec.com [Geosyntec Consultants, Inc., Orlando, FL (United States); Bruce, R.; Duffy, D., E-mail: rbruce@geosyntec.com, E-mail: dduffy@geosyntec.com [Geosyntec Consultants, Sdn. Bhd., Kuala Lumpur (Malaysia); Beech, J., E-mail: jbeech@geosyntec.com [Geosyntec Consultants, Inc., Kennesaw, Georgia (United States)

    2014-07-01

    Approximately 5,000 tonnes of soil containing naturally occurring radioactive materials (NORM), primarily consisting of the uranium and thorium series, were proposed to be removed from properties undergoing remedial action in New South Wales (NSW), Australia. These 'NORM soils' were proposed to be excavated and transported for disposal at an existing landfill facility in NSW. Once at the landfill facility and confirmed to meet appropriate acceptance criteria, the NORM soils were proposed to be disposed of in an encapsulated waste cell (EWC) within a previously permitted and constructed restricted solid waste (RSW) cell at the landfill. The characteristics of the NORM soils require that they be disposed of and managed in an appropriate manner, both near-term as well as beyond the time when the EWC liner system can be assumed to have degraded. A Performance Assessment (PA) was conducted to help assess the potential long-term incremental dose received by a target receptor group related to the disposal of the NORM soils at the landfill facility. The PA consisted of computing the doses to a designated receptor group associated with the planned disposal of the soils within the licensed RSW cell at the landfill facility. Primary tasks performed for this PA included conceptual site model (CSM) development, infiltration (Hydrologic Evaluation of Landfill Performance [HELP]) modeling, and radionuclide fate and transport and dose (RESidual RADioactivity-OFFSITE [RESRAD-OFFSITE]) modeling. The results of the PA indicated that the computed doses to the receptors associated with the disposal of NORM soils in the EWC within the RSW at the landfill facility was in compliance with both the current NSW Radiation Control Regulation 2013 and International Commission on Radiological Protection (ICRP) dose limits for the designated potential receptor group. (author)

  17. Assembly and activation of neurotrophic factor receptor complexes.

    Science.gov (United States)

    Simi, Anastasia; Ibáñez, Carlos F

    2010-04-01

    Neurotrophic factors play important roles in the development and function of both neuronal and glial elements of the central and peripheral nervous systems. Their functional diversity is in part based on their ability to interact with alternative complexes of receptor molecules. This review focuses on our current understanding of the mechanisms that govern the assembly and activation of neurotrophic factor receptor complexes. The realization that many, if not the majority, of these complexes exist in a preassembled form at the plasma membrane has forced the revision of classical ligand-mediated oligomerization models, and led to the discovery of novel mechanisms of receptor activation and generation of signaling diversity which are likely to be shared by many different classes of receptors.

  18. 75 FR 45013 - Pre-Existing Condition Insurance Plan Program

    Science.gov (United States)

    2010-07-30

    ... Department of Homeland Security's U.S. Citizenship and Immigration Services (USCIS) Systematic Alien... pre-existing condition based on evidence of the existence or history of certain medical or health...

  19. EXISTENCE OF POSITIVE SOLUTIONS FOR AN ELASTIC CURVED BEAM EQUATION

    Directory of Open Access Journals (Sweden)

    Béla Kovacs

    2017-06-01

    Full Text Available This paper investigates the existence of positive solutions for a sixth-order differential equations. By using the Leggett-Williams fixed point theorem we give some new existence results.

  20. Imaging opiate receptors with positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Frost, J.J.; Dannals, R.F.; Ravert, H.T.; Wilson, A.A.; Wong, D.F.; Links, J.M.; Burns, H.D.; Kuhar, M.J.; Snyder, S.H.; Wagner, H.N. Jr.

    1984-01-01

    Opiate receptors exist in the mammalian brain and are thought to meditate the diverse pharmacological actions of the opiates, such as analgesia, euphoria, and sedation. The 4-carbomethoxyl derivatives of fentanyl, such as lofentanil and R31833 (4-carbomethoxyfentanyl) bind to the opiate receptor with high affinity. C-11 R31833 was synthesized by reacting C-11 methyl iodide with the appropriate carboxylate. Male ICR mice were injected intravenously with C-11 R31833 (5..mu..g/kg), killed 30 minutes later, and the brains rapidly dissected. The thalami, striata, and cerebral cortex are rich in opiate receptors, but the cerebellum contains a very low concentration of opiate receptors. The thalamus/cerebellum and striatum/cerebellum activity ratios, calculated per mg of wet tissue, were 4.1 and 5.2 respectively. Coinjection of 5mg/kg naloxone reduced the ratios to 1.1, which indicates that the preferential localization of C-11 R31833 in the thalami and striata is due to binding to opiate is due to binding to opiate receptors. A 22 kg anesthetized male baboon was imaged using the NeuroECAT after injection of 18.9 mCi of C-11 R13833 (0.50 ..mu..g/kg, specific activity 616 Ci/mmole at time of injection). From 15-70 minutes after injection preferential accumulation of activity could be seen in the thalami, caudate nuclei, and cerebral cortex and, conversely, low activity was demonstrated in the cerebellum. At one hour postinjection the maximum measured caudate/cerebellum activity ratio per pixel was 2.9. For the NeuroECAT the recovery coefficient for the baboon caudate is ca. 0.2-0.3, and therefore the actual caudate/cerebellum ratio is ca. 10-15.

  1. Imaging opiate receptors with positron emission tomography

    International Nuclear Information System (INIS)

    Frost, J.J.; Dannals, R.F.; Ravert, H.T.

    1984-01-01

    Opiate receptors exist in the mammalian brain and are thought to meditate the diverse pharmacological actions of the opiates, such as analgesia, euphoria, and sedation. The 4-carbomethoxyl derivatives of fentanyl, such as lofentanil and R31833 (4-carbomethoxyfentanyl) bind to the opiate receptor with high affinity. C-11 R31833 was synthesized by reacting C-11 methyl iodide with the appropriate carboxylate. Male ICR mice were injected intravenously with C-11 R31833 (5μg/kg), killed 30 minutes later, and the brains rapidly dissected. The thalami, striata, and cerebral cortex are rich in opiate receptors, but the cerebellum contains a very low concentration of opiate receptors. The thalamus/cerebellum and striatum/cerebellum activity ratios, calculated per mg of wet tissue, were 4.1 and 5.2 respectively. Coinjection of 5mg/kg naloxone reduced the ratios to 1.1, which indicates that the preferential localization of C-11 R31833 in the thalami and striata is due to binding to opiate is due to binding to opiate receptors. A 22 kg anesthetized male baboon was imaged using the NeuroECAT after injection of 18.9 mCi of C-11 R13833 (0.50 μg/kg, specific activity 616 Ci/mmole at time of injection). From 15-70 minutes after injection preferential accumulation of activity could be seen in the thalami, caudate nuclei, and cerebral cortex and, conversely, low activity was demonstrated in the cerebellum. At one hour postinjection the maximum measured caudate/cerebellum activity ratio per pixel was 2.9. For the NeuroECAT the recovery coefficient for the baboon caudate is ca. 0.2-0.3, and therefore the actual caudate/cerebellum ratio is ca. 10-15

  2. 40 CFR 406.34 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for existing sources. 406.34 Section 406.34 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... § 406.34 Pretreatment standards for existing sources. Any existing source subject to this subpart that...

  3. 40 CFR 406.44 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for existing sources. 406.44 Section 406.44 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... § 406.44 Pretreatment standards for existing sources. Any existing source subject to this subpart that...

  4. Existence of pareto equilibria for multiobjective games without compactness

    OpenAIRE

    Shiraishi, Yuya; Kuroiwa, Daishi

    2013-01-01

    In this paper, we investigate the existence of Pareto and weak Pareto equilibria for multiobjective games without compactness. By employing an existence theorem of Pareto equilibria due to Yu and Yuan([10]), several existence theorems of Pareto and weak Pareto equilibria for the multiobjective games are established in a similar way to Flores-B´azan.

  5. Olfactory Receptor Database: a sensory chemoreceptor resource

    OpenAIRE

    Skoufos, Emmanouil; Marenco, Luis; Nadkarni, Prakash M.; Miller, Perry L.; Shepherd, Gordon M.

    2000-01-01

    The Olfactory Receptor Database (ORDB) is a WWW-accessible database that has been expanded from an olfactory receptor resource to a chemoreceptor resource. It stores data on six classes of G-protein-coupled sensory chemoreceptors: (i) olfactory receptor-like proteins, (ii) vomeronasal receptors, (iii) insect olfactory receptors, (iv) worm chemoreceptors, (v) taste papilla receptors and (vi) fungal pheromone receptors. A complementary database of the ligands of these receptors (OdorDB) has bee...

  6. Characterization of 5-hydroxytryptamine receptors in the cardiovascular system

    NARCIS (Netherlands)

    A.H.A. Bom (Anton)

    1990-01-01

    textabstractUntil recently, mainly rats, guinea pigs, rabbits, cats and dogs were used to study the cardiovascular effects of 5-HT. From these studies it was clear that for some effects of 5-HT (e.g. 5-HT-induced tachycardia) there exists a large heterogeneity with respect to receptor subtype(s)

  7. Comparison of biological stability and metabolism of CCK2 receptor targeting peptides, a collaborative project under COST BM0607

    Energy Technology Data Exchange (ETDEWEB)

    Ocak, Meltem [Innsbruck Medical University, Clinical Department of Nuclear Medicine, Innsbruck (Austria); Istanbul University, Department of Pharmaceutical Technology, Pharmacy Faculty, Istanbul (Turkey); Helbok, Anna; Rangger, Christine; Decristoforo, Clemens [Innsbruck Medical University, Clinical Department of Nuclear Medicine, Innsbruck (Austria); Peitl, Petra Kolenc [University Medical Centre Ljubljana, Department for Nuclear Medicine, Ljubljana (Slovenia); Nock, Berthold A. [National Center for Scientific Research Demokritos, Molecular Radiopharmacy, Institute of Radioisotopes-Radiodiagnostic Products, Athens (Greece); Morelli, Giancarlo [University of Naples ' ' Federico II' ' and IBB-CN, Department of Biological Sciences, CIRPeB, Naples (Italy); Eek, Annemarie [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands); Sosabowski, Jane K. [Institute of Cancer, Barts and the London Queen Mary' s School of Medicine and Dentistry, Centre for Molecular Oncology and Imaging, London (United Kingdom); Breeman, W.A.P. [Erasmus MC Rotterdam, Department of Nuclear Medicine, Rotterdam (Netherlands); Reubi, Jean Claude [University of Berne, Division of Cell Biology and Experimental Cancer Research Institute of Pathology, Berne (Switzerland)

    2011-08-15

    Stability of radiolabelled cholecystokinin 2 (CCK2) receptor targeting peptides has been a major limitation in the use of such radiopharmaceuticals especially for targeted radionuclide therapy applications, e.g. for treatment of medullary thyroid carcinoma (MTC). The purpose of this study was to compare the in vitro stability of a series of peptides binding to the CCK2 receptor [selected as part of the COST Action on Targeted Radionuclide Therapy (BM0607)] and to identify major cleavage sites. Twelve different 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-minigastrin/CCK conjugates were provided within an European COST Action (BM0607) by different laboratories and radiolabelled with {sup 177}Lu. Their in vitro stabilities were tested in fresh human serum. Radiochemical yields (RCY) and intact radioligands for half-life calculations were determined by radio-HPLC. Matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) analysis of metabolites was performed to identify cleavage products using conjugates labelled with excess stable {sup nat}Lu, incubated in serum at 37 C. Urine metabolite analysis after injection in normal mice was performed by radio-HPLC analysis. Variable stability in human serum was found for the different peptides with calculated half-lives between 4.5 {+-} 0.1 h and 198 {+-} 0.1 h (n = 2). In urine of normal mice only metabolised peptide fragments were detected even at short times after injection for all peptides. MALDI-TOF MS revealed a major cleavage site of all minigastrin derivatives between Asp and Phe-NH{sub 2} at the C-terminal end. Development of CCK2 receptor ligands especially for therapeutic purposes in patients with MTC or small cell lung cancer (SCLC) is still ongoing in different laboratories. This comparative study provided valuable insight into the importance of biological stability especially in the context of other results of this comparative

  8. Prostaglandin Receptor Signaling in Disease

    Directory of Open Access Journals (Sweden)

    Toshiyuki Matsuoka

    2007-01-01

    Full Text Available Prostanoids, consisting of the prostaglandins (PGs and the thromboxanes (TXs, are a group of lipid mediators formed in response to various stimuli. They include PGD2, PGE2, PGF2α, PGI2, and TXA2. They are released outside of the cells immediately after synthesis, and exert their actions by binding to a G-protein coupled rhodopsin-type receptor on the surface of target cells. There are eight types of the prostanoid receptors conserved in mammals from mouse to human. They are the PGD receptor (DP, four subtypes of the PGE receptor (EP1, EP2, EP3, and EP4, the PGF receptor (FP, PGI receptor (IP, and TXA receptor (TP. Recently, mice deficient in each of these prostanoid receptors were generated and subjected to various experimental models of disease. These studies have revealed the roles of PG receptor signaling in various pathological conditions, and suggest that selective manipulation of the prostanoid receptors may be beneficial in treatment of the pathological conditions. Here we review these recent findings of roles of prostanoid receptor signaling and their therapeutic implications.

  9. Phenotypic T cell exhaustion in a murine model of bacterial infection in the setting of pre-existing malignancy.

    Directory of Open Access Journals (Sweden)

    Rohit Mittal

    Full Text Available While much of cancer immunology research has focused on anti-tumor immunity both systemically and within the tumor microenvironment, little is known about the impact of pre-existing malignancy on pathogen-specific immune responses. Here, we sought to characterize the antigen-specific CD8+ T cell response following a bacterial infection in the setting of pre-existing pancreatic adenocarcinoma. Mice with established subcutaneous pancreatic adenocarcinomas were infected with Listeria monocytogenes, and antigen-specific CD8+ T cell responses were compared to those in control mice without cancer. While the kinetics and magnitude of antigen-specific CD8+ T cell expansion and accumulation was comparable between the cancer and non-cancer groups, bacterial antigen-specific CD8+ T cells and total CD4+ and CD8+ T cells in cancer mice exhibited increased expression of the coinhibitory receptors BTLA, PD-1, and 2B4. Furthermore, increased inhibitory receptor expression was associated with reduced IFN-γ and increased IL-2 production by bacterial antigen-specific CD8+ T cells in the cancer group. Taken together, these data suggest that cancer's immune suppressive effects are not limited to the tumor microenvironment, but that pre-existing malignancy induces phenotypic exhaustion in T cells by increasing expression of coinhibitory receptors and may impair pathogen-specific CD8+ T cell functionality and differentiation.

  10. Mammalian β1- and β2-adrenergic receptors: immunological and structural comparison

    International Nuclear Information System (INIS)

    Moxham, C.P.; George, S.T.; Graziano, M.P.; Brandwein, H.J.; Malbon, C.C.

    1986-01-01

    β 1 - and β 2 -adrenergic receptors, pharmacologically distinct proteins, have been reported to be structurally dissimilar. In the present study three techniques were employed to compare the nature of mammalian β 1 - and β 2 -adrenergic receptors. Antibodies against each of the receptor subtypes were raised separately. Polyclonal antisera against β 1 -receptors of rat fat cells were raised in mice, and antisera against β 2 -receptors of guinea pig lung were raised in rabbits. Receptors purified from rat fat cells (β 1 -), S49 mouse lymphoma cells (β 2 -), and rat liver (β 2 -) were probed with these antisera. Each anti-receptor antisera demonstrated the ability to immunoprecipitate purified receptors of both β 1 - and β 2 -subtypes. The mobility of β-receptors subjected to polyacrylamide gel electrophoresis was probed using antireceptor antibodies and nitrocellulose blots of the gels. Fat cell β 1 -adrenergic receptors display M/sub r/ = 67,000 under reducing conditions and M/sub r/ = 54,000 under nonreducing conditions, as previously reported. Both β 1 - and β 2 -receptors displayed this same shift in electrophoretic mobility observed in the presence as compared to the absence of disulfide bridge-reducing agents, as detected both by autoradiography of the radiolabeled receptors and by immunoblotting of native receptors. Finally, isoelectric focusing of purified radioiodinated β 1 - and β 2 -adrenergic receptors revealed identical isoelectric points. These data are the first to provide analyses of immunological, structural, and biochemical features of β 1 - and β 2 -subtypes in tandem and underscore the structural similarities that exist between these pharmacologically distinct receptors

  11. Functional Analyses of Bitter Taste Receptors in Domestic Cats (Felis catus.

    Directory of Open Access Journals (Sweden)

    Weiwei Lei

    Full Text Available Cats are obligate carnivores and under most circumstances eat only animal products. Owing to the pseudogenization of one of two subunits of the sweet receptor gene, they are indifferent to sweeteners, presumably having no need to detect plant-based sugars in their diet. Following this reasoning and a recent report of a positive correlation between the proportion of dietary plants and the number of Tas2r (bitter receptor genes in vertebrate species, we tested the hypothesis that if bitter perception exists primarily to protect animals from poisonous plant compounds, the genome of the domestic cat (Felis catus should have lost functional bitter receptors and they should also have reduced bitter receptor function. To test functionality of cat bitter receptors, we expressed cat Tas2R receptors in cell-based assays. We found that they have at least 7 functional receptors with distinct receptive ranges, showing many similarities, along with some differences, with human bitter receptors. To provide a comparative perspective, we compared the cat repertoire of intact receptors with those of a restricted number of members of the order Carnivora, with a range of dietary habits as reported in the literature. The numbers of functional bitter receptors in the terrestrial Carnivora we examined, including omnivorous and herbivorous species, were roughly comparable to that of cats thereby providing no strong support for the hypothesis that a strict meat diet influences bitter receptor number or function. Maintenance of bitter receptor function in terrestrial obligate carnivores may be due to the presence of bitter compounds in vertebrate and invertebrate prey, to the necessary role these receptors play in non-oral perception, or to other unknown factors. We also found that the two aquatic Carnivora species examined had fewer intact bitter receptors. Further comparative studies of factors driving numbers and functions of bitter taste receptors will aid in

  12. Functional Analyses of Bitter Taste Receptors in Domestic Cats (Felis catus).

    Science.gov (United States)

    Lei, Weiwei; Ravoninjohary, Aurore; Li, Xia; Margolskee, Robert F; Reed, Danielle R; Beauchamp, Gary K; Jiang, Peihua

    2015-01-01

    Cats are obligate carnivores and under most circumstances eat only animal products. Owing to the pseudogenization of one of two subunits of the sweet receptor gene, they are indifferent to sweeteners, presumably having no need to detect plant-based sugars in their diet. Following this reasoning and a recent report of a positive correlation between the proportion of dietary plants and the number of Tas2r (bitter receptor) genes in vertebrate species, we tested the hypothesis that if bitter perception exists primarily to protect animals from poisonous plant compounds, the genome of the domestic cat (Felis catus) should have lost functional bitter receptors and they should also have reduced bitter receptor function. To test functionality of cat bitter receptors, we expressed cat Tas2R receptors in cell-based assays. We found that they have at least 7 functional receptors with distinct receptive ranges, showing many similarities, along with some differences, with human bitter receptors. To provide a comparative perspective, we compared the cat repertoire of intact receptors with those of a restricted number of members of the order Carnivora, with a range of dietary habits as reported in the literature. The numbers of functional bitter receptors in the terrestrial Carnivora we examined, including omnivorous and herbivorous species, were roughly comparable to that of cats thereby providing no strong support for the hypothesis that a strict meat diet influences bitter receptor number or function. Maintenance of bitter receptor function in terrestrial obligate carnivores may be due to the presence of bitter compounds in vertebrate and invertebrate prey, to the necessary role these receptors play in non-oral perception, or to other unknown factors. We also found that the two aquatic Carnivora species examined had fewer intact bitter receptors. Further comparative studies of factors driving numbers and functions of bitter taste receptors will aid in understanding the forces

  13. The interleukin-4 receptor: signal transduction by a hematopoietin receptor.

    Science.gov (United States)

    Keegan, A D; Pierce, J H

    1994-02-01

    Over the last several years, the receptors for numerous cytokines have been molecularly characterized. Analysis of their amino acid sequences shows that some of these receptors bear certain motifs in their extracellular domains that define a family of receptors called the Hematopoietin receptor superfamily. Significant advances in characterizing the structure, function, and mechanisms of signal transduction have been made for several members of this family. The purpose of this review is to discuss the recent advances made for one of the family members, the interleukin (IL) 4 receptor. Other receptor systems have recently been reviewed elsewhere. The IL-4 receptor consists of, at the minimum, the cloned 140 kDa IL-4-binding chain with the potential for associating with other chains. The IL-4 receptor transduces its signal by activating a tyrosine kinase that phosphorylates cellular substrates, including the receptor itself, and the 170 kDa substrate called 4PS. Phosphorylated 4PS interacts with the SH2 domain of the enzyme PI-3'-kinase and increases its enzymatic activity. These early events in the IL-4 receptor initiated signaling pathway may trigger a series of signals that will ultimately lead to an IL-4 specific biologic outcome.

  14. Meeting report: nuclear receptors

    DEFF Research Database (Denmark)

    Tuckermann, Jan; Bourguet, William; Mandrup, Susanne

    2010-01-01

    The biannual European Molecular Biology Organization (EMBO) conference on nuclear receptors was organized by Beatrice Desvergne and Laszlo Nagy and took place in Cavtat near Dubrovnik on the Adriatic coast of Croatia September 25-29, 2009. The meeting brought together researchers from all over...... the world covering a wide spectrum from fundamental mechanistic studies to metabolism, clinical studies, and drug development. In this report, we summarize the recent and exciting findings presented by the speakers at the meeting....

  15. Neurotransmitter receptor imaging

    International Nuclear Information System (INIS)

    Cordes, M.; Hierholzer, J.; Nikolai-Beyer, K.

    1993-01-01

    The importance of neuroreceptor imaging in vivo using single photon emission tomography (SPECT) and positron emission tomography (PET) has increased enormously. The principal neurotransmitters, such as dopamine, GABA/benzodiazepine, acetylcholine, and serotonin, are presented with reference to anatomical, biochemical, and physiological features. The main radioligands for SPECT and PET are introduced, and methodological characteristics of both PET and SPECT presented. Finally, the results of neurotransmitter receptor imaging obtained so far will be discussed. (orig.) [de

  16. Thyroid Stimulating Hormone Receptor

    Directory of Open Access Journals (Sweden)

    Murat Tuncel

    2017-02-01

    Full Text Available Thyroid stimulating hormone receptor (TSHR plays a pivotal role in thyroid hormone metabolism. It is a major controller of thyroid cell function and growth. Mutations in TSHR may lead to several thyroid diseases, most commonly hyperthyroidism. Although its genetic and epigenetic alterations do not directly lead to carcinogenesis, it has a crucial role in tumor growth, which is initiated by several oncogenes. This article will provide a brief review of TSHR and related diseases.

  17. Teleost Chemokines and Their Receptors

    Directory of Open Access Journals (Sweden)

    Steve Bird

    2015-11-01

    Full Text Available Chemokines are a superfamily of cytokines that appeared about 650 million years ago, at the emergence of vertebrates, and are responsible for regulating cell migration under both inflammatory and physiological conditions. The first teleost chemokine gene was reported in rainbow trout in 1998. Since then, numerous chemokine genes have been identified in diverse fish species evidencing the great differences that exist among fish and mammalian chemokines, and within the different fish species, as a consequence of extensive intrachromosomal gene duplications and different infectious experiences. Subsequently, it has only been possible to establish clear homologies with mammalian chemokines in the case of some chemokines with well-conserved homeostatic roles, whereas the functionality of other chemokine genes will have to be independently addressed in each species. Despite this, functional studies have only been undertaken for a few of these chemokine genes. In this review, we describe the current state of knowledge of chemokine biology in teleost fish. We have mainly focused on those species for which more research efforts have been made in this subject, specially zebrafish (Danio rerio, rainbow trout (Oncorhynchus mykiss and catfish (Ictalurus punctatus, outlining which genes have been identified thus far, highlighting the most important aspects of their expression regulation and addressing any known aspects of their biological role in immunity. Finally, we summarise what is known about the chemokine receptors in teleosts and provide some analysis using recently available data to help characterise them more clearly.

  18. Dithiothreitol activation of the insulin receptor/kinase does not involve subunit dissociation of the native α2β2 insulin receptor subunit complex

    International Nuclear Information System (INIS)

    Sweet, L.J.; Wilden, P.A.; Pessin, J.E.

    1986-01-01

    The subunit composition of the dithiothreitol- (DTT) activated insulin receptor/kinase was examined by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and gel filtration chromatography under denaturing or nondenaturing conditions. Pretreatment of 32 P-labeled insulin receptors with 50 mM DTT followed by gel filtration chromatography in 0.1% SDS demonstrated the dissociation of the α 2 β 2 insulin receptor complex (M/sub r/ 400,000) into the monomeric 95,000 β subunit. In contrast, pretreatment of the insulin receptors with 1-50 mM DTT followed by gel filtration chromatography in 0.1% Triton X-100 resulted in no apparent alteration in mobility compared to the untreated insulin receptors. Resolution of this complex by nonreducing SDS-polyacrylamide gel electrophoresis and autoradiography demonstrated the existence of the α 2 β 2 heterotetrameric complex with essentially no αβ heterodimeric or free monomeric β subunit species present. This suggests that the insulin receptor can reoxidize into the M/sub r/ 400,000 complex after the removal of DTT by gel filtration chromatography. To prevent reoxidation, the insulin receptors were pretreated with 50 mM DTT. Under the conditions the insulin receptors migrated as the M/sub r/ 400,000 α 2 β 2 complex. These results demonstrate that treatment of the insulin receptors with high concentrations of DTT, followed by removal of DTT by gel filtration, results in reoxidation of the reduced α 2 β 2 insulin receptor complex. Further, these results document that although the DTT stimulation of the insulin receptor/kinase does involve reduction of the insulin receptor subunits, it does not result in dissociation of the native α 2 β 2 insulin receptor subunit complex

  19. Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors

    International Nuclear Information System (INIS)

    Pazos, A.; Palacios, M.

    1985-01-01

    The distribution of serotonin-1 (5-HT 1 ) receptors in the rat brain was studied by light microscopic quantitative autoradiography. Receptors were labeled with [ 3 H]serotonin (5-[ 3 H]HT), 8-hydroxy-2-[N-dipropylamino- 3 H]tetralin (8-OH-[ 3 H]DPAT), [ 3 H]LSD and [ 3 H]mesulergine, and the densities quantified by microdensitometry with the aid of a computer-assisted image-analysis system. Competition experiments for 5-[ 3 H]HT binding by several serotonin-1 agonists led to the identification of brain areas enriched in each one of the three subtypes of 5-HT 1 recognition sites already described. The existence of these 'selective' areas allowed a detailed pharmacological characterization of these sites to be made in a more precise manner than has been attained in membrane-binding studies. Very high concentrations of 5-HT 1 receptors were localized in the choroid plexus, lateroseptal nucleus, globus pallidus and ventral pallidum, dentate gyrus, dorsal subiculum, olivary pretectal nucleus, substantia nigra, reticular and external layer of the entorhinal cortex. The distribution of 5-HT 1 receptors reported here is discussed in correlation with the distribution of serotoninergic neurons and fibers, the related anatomical pathways and the effects which appear to be mediated by these sites. (Auth.)

  20. NCS-1 associates with adenosine A2A receptors and modulates receptor function

    Directory of Open Access Journals (Sweden)

    Gemma eNavarro

    2012-04-01

    Full Text Available Modulation of G protein-coupled receptor (GPCR signalling by local changes in intracellular calcium concentration is an established function of Calmodulin which is known to interact with many GPCRs. Less is known about the functional role of the closely related neuronal EF-hand Ca2+-sensor proteins that frequently associate with calmodulin targets with different functional outcome. In the present study we aimed to investigate if a target of calmodulin – the A2A adenosine receptor, is able to associate with two other neuronal calcium binding proteins, namely NCS-1 and caldendrin. Using bioluminescence resonance energy transfer and co-immunoprecipitation experiments we show the existence of A2A - NCS-1 complexes in living cells whereas caldendrin did not associate with A2A receptors under the conditions tested. Interestingly, NCS-1 binding modulated downstream A2A receptor intracellular signalling in a Ca2+-dependent manner. Taken together this study provides further evidence that neuronal Ca2+-sensor proteins play an important role in modulation of GPCR signalling.

  1. Method and refrigerants for replacing existing refrigerants in centrifugal compressors

    International Nuclear Information System (INIS)

    Kopko, W.L.

    1991-01-01

    This patent describes a method for replacing an existing refrigerant in a centrifugal compressor. It comprises selecting a desired impeller Mach number for the centrifugal compressor; selecting a base refrigerant constituent; combining at least one additive refrigerant constituent with the base refrigerant constituent to form a replacement refrigerant having at least one physical or chemical property different from the existing refrigerant and substantially providing the desired impeller Mach number in the centrifugal compressor; and replacing the existing refrigerant with the replacement refrigerant

  2. Magnetic nesting and co-existence of ferromagnetism and superconductivity

    International Nuclear Information System (INIS)

    Elesin, V.F.; Kapaev, V.V.; Kopaev, Yu.V.

    2004-01-01

    In the case of providing for the magnetic nesting conditions of the electron spin dispersion law the co-existence of ferromagnetism and superconductivity is possible by any high magnetization. The co-existence of ferromagnetism and superconductivity in the layered cuprate compounds of the RuSr 2 GdCu 2 O 8 -type is explained on this basis, wherein due to the nonstrict provision of the magnetic nesting condition there exists the finite but sufficiently high critical magnetization [ru

  3. The global existence problem and cosmic censorship in general relativity

    International Nuclear Information System (INIS)

    Moncrief, V.; Eardley, D.M.

    1981-01-01

    Two global existence conjectures for the Einstein equations are formulated and their relevance to the cosmic censorship conjecture discussed. It is argued that the reformulation of the cosmic censorship conjecture as a global existence problem renders it more amenable to direct analytical attack. To demonstrate the facility of this approach the cosmological version of the global existence conjecture is proved for the Gowdy spacetimes on T 3 X R. (author)

  4. Melatonin Receptor Genes in Vertebrates

    Directory of Open Access Journals (Sweden)

    Hua Dong Yin

    2013-05-01

    Full Text Available Melatonin receptors are members of the G protein-coupled receptor (GPCR family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A and MT2 (or Mel1b or MTNR1B receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C, has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor.

  5. 40 CFR 407.74 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ...) EFFLUENT GUIDELINES AND STANDARDS CANNED AND PRESERVED FRUITS AND VEGETABLES PROCESSING POINT SOURCE CATEGORY Canned and Preserved Vegetables Subcategory § 407.74 Pretreatment standards for existing sources...

  6. INFORMATION SECURITY RISK ASSESSMENT USING EXISTING LEGAL AND METHODOLOGICAL BASE

    Directory of Open Access Journals (Sweden)

    A. I. Trubei

    2015-01-01

    Full Text Available The article provides a survey of the existing regulatory framework for information security riskmanagement. Practical methods for information security risk and vulnerability assessment are proposed.

  7. Expandable External Payload Carrier for Existing Launch Vehicles, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Numerous existing launch vehicles have excess performance that is not being optimized. By taking advantage of excess, unused, performance, additional NASA...

  8. Acetylcholine receptors and cholinergic ligands: biochemical and genetic aspects in Torpedo californica and Drosophila melanogaster

    International Nuclear Information System (INIS)

    Rosenthal, L.S.

    1987-01-01

    This study evaluates the biochemical and genetic aspects of the acetylcholine receptor proteins and cholinergic ligands in Drosophila melanogaster and Torpedo californica. Included are (1) a comparative study of nicotinic ligand-induced cation release from acetylcholine receptors isolated from Torpedo californica and from Drosophila melanogaster, (2) solution studies of the cholinergic ligands, nikethamide and ethamivan, aimed at measuring internal molecular rotational barriers in solvents of different polarity; and (3) the isolation and characterization of the gene(s) for the acetylcholine receptor in Drosophila melasogaster. Acetylcholine receptor proteins isolated from Drosphila melanogaster heads were found to behave kinetically similar (with regards to cholinergic ligand-induced 155 Eu: 3+ displacement from prelabeled proteins) to receptor proteins isolated from Torpedo californica electric tissue, providing additional biochemical evidence for the existence of a Drosophila acetylcholine receptor

  9. Functional relevance of neurotransmitter receptor heteromers in the central nervous system.

    Science.gov (United States)

    Ferré, Sergi; Ciruela, Francisco; Woods, Amina S; Lluis, Carme; Franco, Rafael

    2007-09-01

    The existence of neurotransmitter receptor heteromers is becoming broadly accepted and their functional significance is being revealed. Heteromerization of neurotransmitter receptors produces functional entities that possess different biochemical characteristics with respect to the individual components of the heteromer. Neurotransmitter receptor heteromers can function as processors of computations that modulate cell signaling. Thus, the quantitative or qualitative aspects of the signaling generated by stimulation of any of the individual receptor units in the heteromer are different from those obtained during coactivation. Furthermore, recent studies demonstrate that some neurotransmitter receptor heteromers can exert an effect as processors of computations that directly modulate both pre- and postsynaptic neurotransmission. This is illustrated by the analysis of striatal receptor heteromers that control striatal glutamatergic neurotransmission.

  10. Flavivirus Entry Receptors: An Update

    Directory of Open Access Journals (Sweden)

    Manuel Perera-Lecoin

    2013-12-01

    Full Text Available Flaviviruses enter host cells by endocytosis initiated when the virus particles interact with cell surface receptors. The current model suggests that flaviviruses use at least two different sets of molecules for infectious entry: attachment factors that concentrate and/or recruit viruses on the cell surface and primary receptor(s that bind to virions and direct them to the endocytic pathway. Here, we present the currently available knowledge regarding the flavivirus receptors described so far with specific attention to C-type lectin receptors and the phosphatidylserine receptors, T-cell immunoglobulin and mucin domain (TIM and TYRO3, AXL and MER (TAM. Their role in flavivirus attachment and entry as well as their implication in the virus biology will be discussed in depth.

  11. ''Spare'' alpha 1-adrenergic receptors and the potency of agonists in rat vas deferens

    International Nuclear Information System (INIS)

    Minneman, K.P.; Abel, P.W.

    1984-01-01

    The existence of ''spare'' alpha 1-adrenergic receptors in rat vas deferens was examined directly using radioligand binding assays and contractility measurements. Alpha 1-adrenergic receptors in homogenates of rat vas deferens were labeled with [ 125 I]BE 2254 ( 125 IBE). Norepinephrine and other full alpha 1-adrenergic receptor agonists were much less potent in inhibiting 125 IBE binding than in contracting the vas deferens in vitro. Treatment with 300 nM phenoxybenzamine for 10 min to irreversibly inactivate alpha 1-adrenergic receptors caused a large decrease in the potency of full agonists in causing contraction of this tissue and a 23-48% decrease in the maximal contraction observed. Using those data, equilibrium constants for activation (Kact values) of the receptors by agonists were calculated. These Kact values agreed well with the equilibrium binding constants (KD values) determined from displacement of 125 IBE binding. The reduction in alpha 1-adrenergic receptor density following phenoxybenzamine treatment was determined by Scatchard analysis of specific 125 IBE binding sites and compared with the expected reduction (q values) calculated from the agonist dose-response curves before and after phenoxybenzamine treatment. This suggests that phenoxybenzamine functionally inactivates alpha 1-adrenergic receptors at or near the receptor binding site. These experiments suggest that the potencies of agonists in activating alpha 1-adrenergic receptors in rat vas deferens agree well with their potencies in binding to the receptors. The greater potency of agonists in causing contraction may be due to spare receptors in this tissue. The data also demonstrate that phenoxybenzamine irreversibly inactivates alpha 1-adrenergic receptors in rat vas deferens, but that the decrease in receptor density is much smaller than that predicted from receptor theory

  12. Tachyons imply the existence of a privileged frame

    Energy Technology Data Exchange (ETDEWEB)

    Sjoedin, T.; Heylighen, F.

    1985-12-16

    It is shown that the existence of faster-than-light signals (tachyons) would imply the existence (and detectability) of a privileged inertial frame and that one can avoid all problems with reversed-time order only by using absolute synchronization instead of the standard one. The connection between these results and the EPR-paradox is discussed.

  13. Safety assessment of existing highway bridges and viaducts

    NARCIS (Netherlands)

    Maljaars, J.; Steenbergen, R.; Abspoel, L.; Kolstein, M.H.

    2012-01-01

    The assessment of the structural safety of existing br idges and viaducts becomes increasingly important in many countries owing to an increase in traffic loads. Most existing standards, however, are developed for the design of new structures. For this reason, an assessment method for determining

  14. Neural Network for Optimization of Existing Control Systems

    DEFF Research Database (Denmark)

    Madsen, Per Printz

    1995-01-01

    The purpose of this paper is to develop methods to use Neural Network based Controllers (NNC) as an optimization tool for existing control systems.......The purpose of this paper is to develop methods to use Neural Network based Controllers (NNC) as an optimization tool for existing control systems....

  15. The Relationship among Localization Skill, Existence Constancy and Object Permanence.

    Science.gov (United States)

    Townes-Rosenwein, Linda

    Two component skills of object permanence were studied: existence constancy -- the infants' ability to expect that an object continues to exist after it is hidden, and localization skill -- infants' ability to search in the correct place for a hidden object. Contradictions within the literature may occur because of task lability caused by failure…

  16. 40 CFR 63.312 - Existing regulations and requirements.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Existing regulations and requirements. 63.312 Section 63.312 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... National Emission Standards for Coke Oven Batteries § 63.312 Existing regulations and requirements. (a) The...

  17. Existence of solutions of nonlinear integrodifferential equations of ...

    Indian Academy of Sciences (India)

    The results are obtained by using semigroup theory and the Schauder fixed point ... The problem of existence of solutions of evolution equations with nonlocal ... we assume that there exists an operator E on DЕEЖИX given by the formula.

  18. The solution of location problems with certain existing facility structures

    DEFF Research Database (Denmark)

    Juel, Henrik; Love, Robert F.

    1983-01-01

    It is known that in the Euclidean distance case, the optimal minisum location of a new facility in relation to four existing facilities is at the intersection of the two lines joining two pairs of the facilities. The authors extend this concept to minisum problems having any even number of existing...... facilities and characterized by generalized distance norms...

  19. Existence of the Stark-Wannier quantum resonances

    Energy Technology Data Exchange (ETDEWEB)

    Sacchetti, Andrea, E-mail: andrea.sacchetti@unimore.it [Department of Physics, Computer Sciences and Mathematics, University of Modena e Reggio Emilia, Modena (Italy)

    2014-12-15

    In this paper, we prove the existence of the Stark-Wannier quantum resonances for one-dimensional Schrödinger operators with smooth periodic potential and small external homogeneous electric field. Such a result extends the existence result previously obtained in the case of periodic potentials with a finite number of open gaps.

  20. Does Absolute Synonymy exist in Owere-Igbo? | Omego | AFRREV ...

    African Journals Online (AJOL)

    Among Igbo linguistic researchers, determining whether absolute synonymy exists in Owere–Igbo, a dialect of the Igbo language predominantly spoken by the people of Owerri, Imo State, Nigeria, has become a thorny issue. While some linguistic scholars strive to establish that absolute synonymy exists in the lexical ...

  1. Existence and attractors of solutions for nonlinear parabolic systems

    Directory of Open Access Journals (Sweden)

    Hamid El Ouardi

    2001-01-01

    Full Text Available We prove existence and asymptotic behaviour results for weak solutions of a mixed problem (S. We also obtain the existence of the global attractor and the regularity for this attractor in $\\left[H^{2}(\\Omega \\right] ^{2}$ and we derive estimates of its Haussdorf and fractal dimensions.

  2. Remarks on the existence of non equilibrium dynamics

    International Nuclear Information System (INIS)

    Marchioro, C.; Pellegrinotti, A.; Pulvirenti, M.

    1981-01-01

    The authors give an existence theorem for the dynamics of an infinite system of anharmonic oscillators. They obtain another proof of the existence of the dynamics in the case of one-dimensional system of infinitely many particles interacting via a bounded potential. The case of very singular potential is also solved. (Auth.)

  3. Global existence of small solutions to semilinear Schroedinger equations

    International Nuclear Information System (INIS)

    Chihara, Hiroyuki

    1996-01-01

    We present global existence theorem for semilinear Schrodinger equations. In general, Schrodinger-type equations do not admit the classical energy estimates. To avoid this difficulty, we use S. Doi's method for linear Schrodinger-type equations. Combining his method and L p -L q estimates, we prove the global existence of solutions with small initial data

  4. 49 CFR 223.15 - Requirements for existing passenger cars.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Requirements for existing passenger cars. 223.15... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION SAFETY GLAZING STANDARDS-LOCOMOTIVES, PASSENGER CARS AND CABOOSES Specific Requirements § 223.15 Requirements for existing passenger cars. (a) Passenger cars built or...

  5. Existing knowledge related to mainstreaming IKS into Educational ...

    African Journals Online (AJOL)

    The study aimed at determining existing knowledge related to mainstreaming of IKS into education system. The qualitative research methodology was appropriate for this study to explore and describe the mainstreaming of IKS into the existing education system. The study included 10 school teachers (5male and 5 females) ...

  6. An existence result of energy minimizer maps between Riemannian polyhedra

    International Nuclear Information System (INIS)

    Bouziane, T.

    2004-06-01

    In this paper, we prove the existence of energy minimizers in each free homotopy class of maps between polyhedra with target space without focal points. Our proof involves a careful study of some geometric properties of Riemannian polyhedra without focal points. Among other things, we show that on the relevant polyhedra, there exists a convex supporting function. (author)

  7. 30 CFR 784.12 - Operation plan: Existing structures.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Operation plan: Existing structures. 784.12... PLAN § 784.12 Operation plan: Existing structures. (a) Each application shall contain a description of... and reclamation operation. The description shall include: (1) Location; (2) Plans of the structure...

  8. 30 CFR 780.12 - Operation plan: Existing structures.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Operation plan: Existing structures. 780.12... PLAN § 780.12 Operation plan: Existing structures. (a) Each application shall contain a description of... and reclamation operation. The description shall include— (1) Location; (2) Plans of the structure...

  9. Chromosomal organization of adrenergic receptor genes

    International Nuclear Information System (INIS)

    Yang-Feng, T.L.; Xue, Feiyu; Zhong, Wuwei; Cotecchia, S.; Frielle, T.; Caron, M.G.; Lefkowitz, R.J.; Francke, U.

    1990-01-01

    The adrenergic receptors (ARs) (subtypes α 1 , α 2 , β 1 , and β 2 ) are a prototypic family of guanine nucleotide binding regulatory protein-coupled receptors that mediate the physiological effects of the hormone epinephrine and the neurotransmitter norepinephrine. The authors have previously assigned the genes for β 2 -and α 2 -AR to human chromosomes 5 and 10, respectively. By Southern analysis of somatic cell hybrids and in situ chromosomal hybridization, they have now mapped the α 1 -AR gene to chromosome 5q32→q34, the same position as β 2 -AR, and the β 1 -AR gene to chromosome 10q24→q26, the region where α 2 -AR, is located. In mouse, both α 2 -and β 1 -AR genes were assigned to chromosome 19, and the α 1 -AR locus was localized to chromosome 11. Pulsed field gel electrophoresis has shown that the α 1 -and β 2 -AR genes in humans are within 300 kilobases (kb) and the distance between the α 2 - and β 1 -AR genes is <225 kb. The proximity of these two pairs of AR genes and the sequence similarity that exists among all the ARs strongly suggest that they are evolutionarily related. Moreover, they likely arose from a common ancestral receptor gene and subsequently diverged through gene duplication and chromosomal duplication to perform their distinctive roles in mediation the physiological effects of catecholamines. The AR genes thus provide a paradigm for understanding the evolution of such structurally conserved yet functionally divergent families off receptor molecules

  10. Cysteinyl-Leukotriene Receptors and Cellular Signals

    Directory of Open Access Journals (Sweden)

    G. Enrico Rovati

    2007-01-01

    Full Text Available Cysteinyl-leukotrienes (cysteinyl-LTs exert a range of proinflammatory effects, such as constriction of airways and vascular smooth muscle, increase of endothelial cell permeability leading to plasma exudation and edema, and enhanced mucus secretion. They have proved to be important mediators in asthma, allergic rhinitis, and other inflammatory conditions, including cardiovascular diseases, cancer, atopic dermatitis, and urticaria. The classification into subtypes of the cysteinyl-LT receptors (CysLTRs was based initially on binding and functional data, obtained using the natural agonists and a wide range of antagonists. CysLTRs have proved remarkably resistant to cloning. However, in 1999 and 2000, the CysLT1R and CysLT2R were successfully cloned and both shown to be members of the G-protein coupled receptors (GPCRs superfamily. Molecular cloning has confirmed most of the previous pharmacological characterization and identified distinct expression patterns only partially overlapping. Recombinant CysLTRs couple to the Gq/11 pathway that modulates inositol phospholipids hydrolysis and calcium mobilization, whereas in native systems, they often activate a pertussis toxin-insensitive Gi/o-protein, or are coupled promiscuously to both G-proteins. Interestingly, recent data provide evidence for the existence of an additional receptor subtype that seems to respond to both cysteinyl-LTs and uracil nucleosides, and of an intracellular pool of CysLTRs that may have roles different from those of plasma membrane receptors. Finally, a cross-talk between the cysteinyl-LT and the purine systems is being delineated. This review will summarize recent data derived from studies on the molecular and cellular pharmacology of CysLTRs.

  11. Characterization of the interleukin 3 receptor

    International Nuclear Information System (INIS)

    Murthy, S.C.; Mui, A.L.; Krystal, G.

    1990-01-01

    A variety of homobifunctional crosslinking agents have been used to gain insight into the nature of the murine interleukin 3 (mIL-3) receptor. When [125I]mIL-3 was cross-linked to receptor sites on the surfaces of intact B6SUtA1 cells with disuccinimidyl suberate (DSS), sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) revealed the existence of two radiolabeled species with molecular weights of 140 (p140) and 70 (p70) kd (after subtraction of [125I]mIL-3). The relative intensities of the two bands did not change when the [125I]mIL-3 concentration was varied, confirming Scatchard results which suggested only one affinity class. However, when [125I]mIL-3 was crosslinked to intact cells and then incubated at 37 degrees C, the intensity of p140 decreased relative to p70, suggesting a conversion of p140 to p70. This conversion could be inhibited by sodium azide, methylamine, and bacitracin and could also be prevented by first boiling for 1 min in 2% SDS and 5% 2-mercaptoethanol. The putative protease that carried out this apparent conversion appeared to be associated both with plasma membranes prepared from these cells and also with solubilized receptors. Moreover, when p140, crosslinked with both dithiobis succinimidylpropionate and glutaraldehyde, was purified and reelectrophoresed under reducing conditions, p70 could be generated. N-glycanase digestion of p140 and p70 revealed a similar level of N-linked carbohydrate, which upon closer study appeared to consist of two chains, a 3-kd and an 8-kd moiety. Consistent with this data, we propose that the receptor is a 140-kd glycoprotein that is cleaved to a 70-kd surface protein upon mIL-3 binding and chemical crosslinking

  12. IGF-Binding Proteins: Why Do They Exist and Why Are There So Many?

    Directory of Open Access Journals (Sweden)

    John B. Allard

    2018-04-01

    Full Text Available Insulin-like growth factors (IGFs are key growth-promoting peptides that act as both endocrine hormones and autocrine/paracrine growth factors. In the bloodstream and in local tissues, most IGF molecules are bound by one of the members of the IGF-binding protein (IGFBP family, of which six distinct types exist. These proteins bind to IGF with an equal or greater affinity than the IGF1 receptor and are thus in a key position to regulate IGF signaling globally and locally. Binding to an IGFBP increases the half-life of IGF in the circulation and blocks its potential binding to the insulin receptor. In addition to these classical roles, IGFBPs have been shown to modulate IGF signaling locally under various conditions. Although members of the IGFBP family share significant sequence homology, they each have unique structural features and play distinct roles. These IGFBP genes also have different modes of regulation and distinct expression patterns. Some IGFBPs have been found to bind to their own receptors or to translocate into the interior compartments of cells where they may execute IGF-independent actions. In spite of this functional and regulatory diversity, it has been puzzling that loss-of-function studies have yielded relatively little information about the physiological functions of IGFBPs. In this review, we suggest that evolution has tended to retain an array of IGFBPs in order to facilitate fine-tuning of IGF signaling. We explore the emerging explanation that many IGFBP functions have evolved to allow the targeted adjustment of IGF signaling under stressful or irregular conditions, which would likely not be revealed in a standard laboratory setting.

  13. Kierkegaard e a existência possível

    Directory of Open Access Journals (Sweden)

    Roberto S. Kahlmeyer-Mertens

    2013-05-01

    Full Text Available Resumo: A relação entre a existência e a possibilidade, objeto deste artigo, merece especial atenção quando se trata de Kierkegaard. Isso porque, estes dois conceitos ocupam papéis primordiais na filosofia do autor, constituindo, justamente, o ponto a partir do qual o pensador se distancia criticamente da tradição filosófica. Caracterizar sumariamente os conceitos de existência e possibilidade na filosofia de Kierkegaard, bem como ambientar o filósofo em sua época como um pensador da existência, para além do rótulo de “existencialista”, são nossos presentes objetivos.   Palavras-chave: Kierkegaard, filosofia da existência, existência, possibilidade

  14. Interactions between estrogen receptors and metabotropic glutamate receptors and their impact on drug addiction in females.

    Science.gov (United States)

    Tonn Eisinger, Katherine R; Gross, Kellie S; Head, Brian P; Mermelstein, Paul G

    2018-03-10

    Estrogen receptors α and β (ERα and ERβ) have a unique relationship with metabotropic glutamate receptors (mGluRs) in the female rodent brain such that estradiol is able to recruit intracellular G-protein signaling cascades to influence neuronal physiology, structure, and ultimately behavior. While this association between ERs and mGluRs exists in many cell types and brain regions, its effects are perhaps most striking in the nucleus accumbens (NAc). This review will discuss the original characterization of ER/mGluR signaling and how estradiol activity in the NAc confers increased sensitivity to drugs of abuse in females through this mechanism. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Adenosine Receptors and Wound Healing

    Directory of Open Access Journals (Sweden)

    Bruce N. Cronstein

    2004-01-01

    Full Text Available Recent studies have demonstrated that application of topical adenosine A2A receptor agonists promotes more rapid wound closure and clinical studies are currently underway to determine the utility of topical A2A adenosine receptor agonists in the therapy of diabetic foot ulcers. The effects of adenosine A2A receptors on the cells and tissues of healing wounds have only recently been explored. We review here the known effects of adenosine A2A receptor occupancy on the cells involved in wound healing.

  16. Virally encoded 7TM receptors

    DEFF Research Database (Denmark)

    Rosenkilde, M M; Waldhoer, M; Lüttichau, H R

    2001-01-01

    expression of this single gene in certain lymphocyte cell lineages leads to the development of lesions which are remarkably similar to Kaposi's sarcoma, a human herpesvirus 8 associated disease. Thus, this and other virally encoded 7TM receptors appear to be attractive future drug targets.......A number of herpes- and poxviruses encode 7TM G-protein coupled receptors most of which clearly are derived from their host chemokine system as well as induce high expression of certain 7TM receptors in the infected cells. The receptors appear to be exploited by the virus for either immune evasion...

  17. Adenosine receptor desensitization and trafficking.

    Science.gov (United States)

    Mundell, Stuart; Kelly, Eamonn

    2011-05-01

    As with the majority of G-protein-coupled receptors, all four of the adenosine receptor subtypes are known to undergo agonist-induced regulation in the form of desensitization and trafficking. These processes can limit the ability of adenosine receptors to couple to intracellular signalling pathways and thus reduce the ability of adenosine receptor agonists as well as endogenous adenosine to produce cellular responses. In addition, since adenosine receptors couple to multiple signalling pathways, these pathways may desensitize differentially, while the desensitization of one pathway could even trigger signalling via another. Thus, the overall picture of adenosine receptor regulation can be complex. For all adenosine receptor subtypes, there is evidence to implicate arrestins in agonist-induced desensitization and trafficking, but there is also evidence for other possible forms of regulation, including second messenger-dependent kinase regulation, heterologous effects involving G proteins, and the involvement of non-clathrin trafficking pathways such as caveolae. In this review, the evidence implicating these mechanisms is summarized for each adenosine receptor subtype, and we also discuss those issues of adenosine receptor regulation that remain to be resolved as well as likely directions for future research in this field. Copyright © 2010 Elsevier B.V. All rights reserved.

  18. Conformational transitions and interactions underlying the function of membrane embedded receptor protein kinases.

    Science.gov (United States)

    Bocharov, Eduard V; Sharonov, Georgy V; Bocharova, Olga V; Pavlov, Konstantin V

    2017-09-01

    Among membrane receptors, the single-span receptor protein kinases occupy a broad but specific functional niche determined by distinctive features of the underlying transmembrane signaling mechanisms that are briefly overviewed on the basis of some of the most representative examples, followed by a more detailed discussion of several hierarchical levels of organization and interactions involved. All these levels, including single-molecule interactions (e.g., dimerization, liganding, chemical modifications), local processes (e.g. lipid membrane perturbations, cytoskeletal interactions), and larger scale phenomena (e.g., effects of membrane surface shape or electrochemical potential gradients) appear to be closely integrated to achieve the observed diversity of the receptor functioning. Different species of receptor protein kinases meet their specific functional demands through different structural features defining their responses to stimulation, but certain common patterns exist. Signaling by receptor protein kinases is typically associated with the receptor dimerization and clustering, ligand-induced rearrangements of receptor domains through allosteric conformational transitions with involvement of lipids, release of the sequestered lipids, restriction of receptor diffusion, cytoskeleton and membrane shape remodeling. Understanding of complexity and continuity of the signaling processes can help identifying currently neglected opportunities for influencing the receptor signaling with potential therapeutic implications. This article is part of a Special Issue entitled: Interactions between membrane receptors in cellular membranes edited by Kalina Hristova. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. An unusual protein kinase phosphorylates the chemotactic receptor of Dictystelium discoideum

    International Nuclear Information System (INIS)

    Meier, K.; Klein, C.

    1988-01-01

    The authors report the cAMP-dependent phosphorylation of the chemotactic receptor of Dictyostelium discoideum in partially purified plasma membranes. The protein kinase responsible for receptor phosphorylation is associated with this fraction and preferentially phosphorylates the ligand-occupied form of the receptor. 8-Azido[ 32 P]cAMP labeling of the cell surface has shown that the cAMP receptor exists in two forms. A 45-kDa protein is predominant on unstimulated cells. cAMP stimulation results in an increased receptor phosphorylation such that the receptor migrates on NaDodSO 4 /PAGE as a 47-kDa protein. Phosphorylation of the chemotactic receptor is not detected in membrane preparations unless cAMP is added to the incubation mixture. Only under those conditions is the phosphorylated 47-kDa form observed. The requirement for cAMP reflects the fact that the kinase involved preferentially uses the ligand-occupied receptor as a substrate. In vitro phosphorylation of the receptor does not involve tyrosine residues. The enzyme does not appear to be a cAMP- or cGMP-dependent protein kinase nor is it sensitive to guanine nucleotides, Ca 2+ /calmodulin, Ca 2+ /phospholipid, or EGTA. Similarities with the β-adrenergic receptor protein kinase are discussed

  20. Obesity and Cancer: Existing and New Hypotheses for a Causal Connection

    Directory of Open Access Journals (Sweden)

    Trevor W. Stone

    2018-04-01

    Full Text Available Existing explanations of obesity-associated cancer emphasise direct mutagenic effects of dietary components or hormonal imbalance. Some of these hypotheses are reviewed briefly, but recent evidence suggests a major role for chronic inflammation in cancer risk, possibly involving dietary content. These ideas include the inflammation-induced activation of the kynurenine pathway and its role in feeding and metabolism by activation of the aryl hydrocarbon receptor (AHR and by modulating synaptic transmission in the brain. Evidence for a role of the kynurenine pathway in carcinogenesis then provides a potentially major link between obesity and cancer. A second new hypothesis is based on evidence that serine proteases can deplete cells of the tumour suppressors Deleted in Colorectal Cancer (DCC and neogenin. These enzymes include mammalian chymotryptic proteases released by pro-inflammatory neutrophils and macrophages. Blood levels of chymotrypsin itself increase in parallel with food intake. The mechanistically similar bacterial enzyme subtilisin is widespread in the environment, animal probiotics, meat processing and cleaning products. Simple public health schemes in these areas, with selective serine protease inhibitors and AHR antagonists and could prevent a range of intestinal and other cancers. Keywords: Obesity, Serine proteases, Chymotrypsin, Subtilisin, Dependence receptors, DCC, Kynurenine

  1. Polymorphisms in drug-metabolizing enzymes: What is their clinical relevance and why do they exist?

    Energy Technology Data Exchange (ETDEWEB)

    Nebert, D.W. [Univ. of Cincinnati Medical Center, OH (United States)

    1997-02-01

    The beautiful report by Sachse in this issue of the journal represents the culmination of 2 decades of increasingly exciting work on the {open_quotes}debrisoquine oxidation polymorphism,{close_quotes} one of dozens of pharmacogenetic or ecogenetic polymorphisms that have been shown to have an important impact on innumerable clinical diseases. Pharmacogenetics is the study of the hereditary basis of the differences in responses to drugs. Ecogenetics is the broader field of interindividual differences in response to all environmental chemical and physical agents (e.g., heavy metals, insecticides, compounds formed during combustion, and UV radiation). It is now clear that each of us has his or her own {open_quotes}individual fingerprint{close_quotes} of unique alleles encoding the so-called drug-metabolizing enzymes (DMEs) and the receptors that regulate these enzymes. In this invited editorial, I first introduce the current thinking in the field of DME (and DME-receptor) research and how DMEs have evolved from animal-plant interactions. I then describe the debrisoquine oxidation polymorphism, as well as two other relevant DME polymorphisms; show the relationship between these polymorphisms and human disease; provide examples of synergistic effects caused by the combination of two DME polymorphisms; and discuss the ethical considerations of such research. Last, I speculate on why these allelic frequencies of the DME genes might exist in human populations in the first place. 35 refs.

  2. Toxicological implications of polymorphisms in receptors for xenobiotic chemicals: The case of the aryl hydrocarbon receptor

    International Nuclear Information System (INIS)

    Okey, Allan B.; Franc, Monique A.; Moffat, Ivy D.; Tijet, Nathalie; Boutros, Paul C.; Korkalainen, Merja; Tuomisto, Jouko; Pohjanvirta, Raimo

    2005-01-01

    Mechanistic toxicology has predominantly been focused on adverse effects that are caused by reactive metabolites or by reactive oxygen species. However, many important xenobiotics exert their toxicity, not by generating reactive products, but rather by altering expression of specific genes. In particular, some environmental contaminants target nuclear receptors that function as regulators of transcription. For example, binding of xenobiotic chemicals to steroid receptors is a principle mechanism of endocrine disruption. The aryl hydrocarbon receptor (AHR) mediates toxicity of dioxin-like compounds. In mice, a polymorphism in the AHR ligand-binding domain reduces binding affinity by about 10-fold in the DBA/2 strain compared with the C57BL/6 strain; consequently, dose-response curves for numerous biochemical and toxic effects are shifted about one log to the right in DBA/2 mice. In the Han/Wistar (Kuopio) (H/W) rat strain, a polymorphism causes a deletion of 38 or 43 amino acids from the AHR transactivation domain. This deletion is associated with a greater than 1000-fold resistance to lethality from 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Genes in the conventional AH gene battery (e.g. CYP1A1, CYP1A2, CYP1B1, ALDH3A1, NQO1 and UGT1A1) remain responsive to TCDD in H/W rats despite the large deletion. However, the deletion may selectively alter the receptor's ability to dysregulate specific genes that are key to dioxin toxicity. We are identifying these genes using an expression array approach in dioxin-sensitive vs. dioxin-resistant rat strains and lines. Polymorphisms exist in the human AH receptor, but thus far they have not been shown to have any substantial effect on human responses to AHR-ligands

  3. Axonal GABAA receptors.

    Science.gov (United States)

    Trigo, Federico F; Marty, Alain; Stell, Brandon M

    2008-09-01

    Type A GABA receptors (GABA(A)Rs) are well established as the main inhibitory receptors in the mature mammalian forebrain. In recent years, evidence has accumulated showing that GABA(A)Rs are prevalent not only in the somatodendritic compartment of CNS neurons, but also in their axonal compartment. Evidence for axonal GABA(A)Rs includes new immunohistochemical and immunogold data: direct recording from single axonal terminals; and effects of local applications of GABA(A)R modulators on action potential generation, on axonal calcium signalling, and on neurotransmitter release. Strikingly, whereas presynaptic GABA(A)Rs have long been considered inhibitory, the new studies in the mammalian brain mostly indicate an excitatory action. Depending on the neuron that is under study, axonal GABA(A)Rs can be activated by ambient GABA, by GABA spillover, or by an autocrine action, to increase either action potential firing and/or transmitter release. In certain neurons, the excitatory effects of axonal GABA(A)Rs persist into adulthood. Altogether, axonal GABA(A)Rs appear as potent neuronal modulators of the mammalian CNS.

  4. A coupled chemotaxis-fluid model: Global existence

    KAUST Repository

    Liu, Jian-Guo; Lorz, Alexander

    2011-01-01

    We consider a model arising from biology, consisting of chemotaxis equations coupled to viscous incompressible fluid equations through transport and external forcing. Global existence of solutions to the Cauchy problem is investigated under certain conditions. Precisely, for the chemotaxis-Navier- Stokes system in two space dimensions, we obtain global existence for large data. In three space dimensions, we prove global existence of weak solutions for the chemotaxis-Stokes system with nonlinear diffusion for the cell density.© 2011 Elsevier Masson SAS. All rights reserved.

  5. A coupled chemotaxis-fluid model: Global existence

    KAUST Repository

    Liu, Jian-Guo

    2011-09-01

    We consider a model arising from biology, consisting of chemotaxis equations coupled to viscous incompressible fluid equations through transport and external forcing. Global existence of solutions to the Cauchy problem is investigated under certain conditions. Precisely, for the chemotaxis-Navier- Stokes system in two space dimensions, we obtain global existence for large data. In three space dimensions, we prove global existence of weak solutions for the chemotaxis-Stokes system with nonlinear diffusion for the cell density.© 2011 Elsevier Masson SAS. All rights reserved.

  6. Receptor studies in biological psychiatry

    International Nuclear Information System (INIS)

    Fujiwara, Yutaka

    1992-01-01

    Recent advances in the pharmacological treatment of endogenous psychosis have led to the development of biological studies in psychiatry. Studies on neurotransmitter receptors were reviewed in order to apply positron-emission tomograph (PET) for biological psychiatry. The dopamine (DA) hypothesis for schizophrenia was advanced on the basis of the observed effects of neuroleptics and methamphetamine, and DA(D 2 ) receptor supersensitivity measured by PET and receptor binding in the schizophrenic brain. The clinical potencies of neuroleptics for schizophrenia were correlated with their abilities to inhibit the D 2 receptor, and not other receptors. The σ receptor was expected to be a site of antipsychotic action. However, the potency of drugs action on it was not correlated with clinical efficacy. Haloperidol binds with high affinity to the σ receptor, which may mediate acute dystonia, an extrapyramidal side effect of neuroleptics. Behavioral and neurochemical changes induced by methamphetamine treatment were studied as an animal model of schizophrenia, and both a decrease of D 2 receptor density and an increase of DA release were detected. The monoamine hypothesis for manic-depressive psychosis was advanced on the basis of the effect of reserpine, monoamine oxidase inhibitor and antidepressants. 3 H-clonidine binding sites were increased in platelet membranes of depressive patients, 3 H-imipramine binding sites were decreased. The GABA A receptor is the target site for the action of anxiolytics and antiepileptics such as benzodiazepines and barbiturates. Recent developments in molecular biology techniques have revealed the structure of receptor proteins, which are classified into two receptor families, the G-protein coupled type (D 2 ) and the ion-channel type (GABA A ). (J.P.N.)

  7. Absence of down-regulation of the insulin receptor by insulin. A possible mechanism of insulin resistance in the rat.

    OpenAIRE

    Walker, A P; Flint, D J

    1983-01-01

    Insulin resistance occurs in rat adipocytes during pregnancy and lactation despite increased or normal insulin binding respectively; this suggests that a post-receptor defect exists. The possibility has been examined that, although insulin binding occurs normally, internalization of insulin or its receptor may be impaired in these states. Insulin produced a dose-dependent reduction in the number of insulin receptors on adipocytes from virgin rats maintained in culture medium, probably due to ...

  8. Comparison of the binding and internalization properties of 12 DOTA-coupled and {sup 111}In-labelled CCK2/gastrin receptor binding peptides: a collaborative project under COST Action BM0607

    Energy Technology Data Exchange (ETDEWEB)

    Aloj, Luigi; Aurilio, Michela; Rinaldi, Valentina; D' Ambrosio, Laura [Istituto Nazionale Tumori, Fondazione ' ' G. Pascale' ' , AF Medicina Nucleare, Naples (Italy); Tesauro, Diego [Universita ' ' Federico II' ' , CIRPeB, Naples (Italy); Peitl, Petra Kolenc [University Medical Centre Ljubljana, Department of Nuclear Medicine, Ljubljana (Slovenia); Maina, Theodosia [National Center for Scientific Research Demokritos, Molecular Radiopharmacy, Institute of Radioisotopes-Radiodiagnostic Products, Athens (Greece); Mansi, Rosalba [University Hospital Freiburg, Department of Nuclear Medicine, Freiburg (Germany); Guggenberg, Elisabeth von [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria); Joosten, Lieke [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands); Sosabowski, Jane K. [Institute of Cancer, Barts and the London Queen Mary' s School of Medicine and Dentistry, Centre for Molecular Oncology and Imaging, London (United Kingdom); Breeman, W.A.P.; Blois, Erik de; Koelewijn, Stuart; Melis, Marleen; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Waser, Beatrice; Beetschen, Karin; Reubi, Jean Claude [University of Berne, Berne (Switzerland)

    2011-08-15

    Specific overexpression of cholecystokinin 2 (CCK2)/gastrin receptors has been demonstrated in several tumours of neuroendocrine origin. In some of these cancer types, such as medullary thyroid cancer (MTC), a sensitive diagnostic modality is still unavailable and therapeutic options for inoperable lesions are needed. Peptide receptor radionuclide therapy (PRRT) may be a viable therapeutic strategy in the management of these patients. Several CCK2R-targeted radiopharmaceuticals have been described in recent years. As part of the European Union COST Action BM0607 we studied the in vitro and in vivo characteristics of 12 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-conjugated CCK2R binding peptides. In the present study, we analysed binding and internalization characteristics. Stability, biodistribution and imaging studies have been performed in parallel by other centres involved in the project. Determination of IC{sub 50} values was performed using autoradiography, with DOTA-peptides displacing {sup 125}I-CCK from receptors on tissue sections from human tumours. Saturation binding and internalization experiments were performed using {sup 111}In-labelled peptides. The rat AR42J cell line and the human A431-CCK2R transfected cell line were utilized for in vitro experiments; dissociation constants (K{sub d}) and apparent number of binding sites (B{sub max}) were determined. Internalization was determined in receptor-expressing cells by incubating with tracer amounts of peptide at 37 and 4 C for different times up to 120 min. Surface-bound peptide was then stripped either by acid wash or subsequent incubation with 1 {mu}M unlabelled peptide at 4 C. All peptides showed high receptor affinity with IC{sub 50} values ranging from 0.2 to 3.4 nM. Saturation experiments also showed high affinity with K{sub d} values in the 10{sup -9}-10{sup -8} M range. B{sub max} values estimated in A431-CCK2R cells ranged from 0.6 to 2.2 x 10{sup 6} per cell. All peptides

  9. 40 CFR 407.64 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ...) EFFLUENT GUIDELINES AND STANDARDS CANNED AND PRESERVED FRUITS AND VEGETABLES PROCESSING POINT SOURCE CATEGORY Canned and Preserved Fruits Subcategory § 407.64 Pretreatment standards for existing sources. Any...

  10. Branding in children: a barbaric practice still exists in India.

    Science.gov (United States)

    Patra, Pratap Kumar

    2016-01-01

    Branding is an inhuman traditional practice most commonly employed to treat various disorders in neonates and children in certain community in India. Though stringent law exists to prevent such harmful practices, cases of branding is not uncommon in current era.

  11. Non-existence of limit cycles for planar vector fields

    Directory of Open Access Journals (Sweden)

    Jaume Gine

    2014-03-01

    Full Text Available This article presents sufficient conditions for the non-existence of limit cycles for planar vector fields. Classical methods for the nonexistence of limit cycles are connected with the theory developed here.

  12. 31 CFR 370.26 - What limitations exist on liability?

    Science.gov (United States)

    2010-07-01

    ... TRANSFERS RELATING TO UNITED STATES SECURITIES Debit Entries § 370.26 What limitations exist on liability? If we sustain a loss because a financial institution fails to handle an entry in accordance with this...

  13. Protection of continued economic existence and major changes. 1. paper

    International Nuclear Information System (INIS)

    Backherms, J.

    1980-01-01

    On the issue of protecting continued economic existence according to Sect. 18 of the Atomic Energy Law, a difference is made between changes occurring in the environment of the plant, in the existing knowledge in science and technology, and changes occurring in the safety philosophy held by the authorities. In case of conditions being subsequently imposed because of a change in the existing knowledge in science and technology, the liability of the authorities to pay compensation is ruled out according to Sect. 18, para. 2 No. 3 of the Atomic Energy Law. The difference made between a change in the safety philosophy held by the authorities and a change in the existing knowledge in science and technology seems to be obvious. In the first case it is a matter of changing the legal evaluation of unchanged technological findings, in the legal evaluation, however, the licence granted has to have a lasting effect on principle. (HP) [de

  14. Existence results for anisotropic discrete boundary value problems

    Directory of Open Access Journals (Sweden)

    Avci Avci

    2016-06-01

    Full Text Available In this article, we prove the existence of nontrivial weak solutions for a class of discrete boundary value problems. The main tools used here are the variational principle and critical point theory.

  15. Possible existence of wormholes in the central regions of halos

    Energy Technology Data Exchange (ETDEWEB)

    Rahaman, Farook, E-mail: rahaman@iucaa.ernet.in [Department of Mathematics, Jadavpur University, Kolkata 700032, West Bengal (India); Salucci, P., E-mail: salucci@sissa.it [SISSA, International School for Advanced Studies, Via Bonomea 265, 34136, Trieste (Italy); INFN, Sezione di Trieste, Via Valerio 2, 34127, Trieste (Italy); Kuhfittig, P.K.F., E-mail: kuhfitti@msoe.edu [Department of Mathematics, Milwaukee School of Engineering, Milwaukee, WI 53202-3109 (United States); Ray, Saibal, E-mail: saibal@iucaa.ernet.in [Department of Physics, Government College of Engineering and Ceramic Technology, Kolkata 700010, West Bengal (India); Rahaman, Mosiur, E-mail: mosiurju@gmail.com [Department of Mathematics, Meghnad Saha Institute of Technology, Kolkata 700150 (India)

    2014-11-15

    An earlier study (Rahaman, et al., 2014 and Kuhfittig, 2014) has demonstrated the possible existence of wormholes in the outer regions of the galactic halo, based on the Navarro–Frenk–White (NFW) density profile. This paper uses the Universal Rotation Curve (URC) dark matter model to obtain analogous results for the central parts of the halo. This result is an important compliment to the earlier result, thereby confirming the possible existence of wormholes in most of the spiral galaxies. - Highlights: • Earlier we showed possible existence of wormholes in the outer regions of halo. • We obtain here analogous results for the central parts of the galactic halo. • Our result is an important compliment to the earlier result. • This confirms possible existence of wormholes in most of the spiral galaxies.

  16. DOES ABSOLUTE SYNONYMY EXIST IN OWERE-IGBO?

    African Journals Online (AJOL)

    USER

    The researcher also interviewed native speakers of the dialect. The study ... The word 'synonymy' means sameness of meaning, i.e., a relationship in which more ... whether absolute synonymy exists in Owere–Igbo or not. ..... 'close this book'.

  17. Existence of Solutions of Nonlinear Integrodifferential Equations of ...

    Indian Academy of Sciences (India)

    Abstract. In this paper we prove the existence of mild and strong solutions of a nonlinear integrodifferential equation of Sobolev type with nonlocal condition. The results are obtained by using semigroup theory and the Schauder fixed point theorem.

  18. Problem of mathematical deduction of the existence of black holes

    Directory of Open Access Journals (Sweden)

    Yuan-Shun Chin

    1990-01-01

    Full Text Available The mathematical proof of existence of Black Hole is based on the assumption of mass being independent of speed. Considering the effect of special relativity of the dependence of mass with speed there is no Black hole.

  19. On the existence and dynamics of braneworld black holes

    International Nuclear Information System (INIS)

    Fitzpatrick, Andrew Liam; Randall, Lisa; Wiseman, Toby

    2006-01-01

    Based on holographic arguments Tanaka and Emparan et al have claimed that large localized static black holes do not exist in the one-brane Randall-Sundrum model. If such black holes are time-dependent as they propose, there are potentially significant phenomenological and theoretical consequences. We revisit the issue, arguing that their reasoning does not take into account the strongly coupled nature of the holographic theory. We claim that static black holes with smooth metrics should indeed exist in these theories, and give a simple example. However, although the existence of such solutions is relevant to exact and numerical solution searches, such static solutions might be dynamically unstable, again leading to time dependence with phenomenological consequences. We explore a plausible instability, suggested by Tanaka, analogous to that of Gregory and Laflamme, but argue that there is no reliable reason at this point to assume it must exist

  20. A corrosion monitoring system for existing reinforced concrete structures.

    Science.gov (United States)

    2015-05-01

    This study evaluated a multi-parameter corrosion monitoring system for existing reinforced concrete structures in chloride-laden service environments. The system was fabricated based on a prototype concrete corrosion measurement system that : had bee...

  1. Report on the Pre-existing Condition Insurance Plan Program

    Data.gov (United States)

    U.S. Department of Health & Human Services — Before the Affordable Care Act, Americans with pre-existing conditions who did not receive health coverage through their employers had few affordable options to get...

  2. Existence for a class of discrete hyperbolic problems

    Directory of Open Access Journals (Sweden)

    Luca Rodica

    2006-01-01

    Full Text Available We investigate the existence and uniqueness of solutions to a class of discrete hyperbolic systems with some nonlinear extreme conditions and initial data, in a real Hilbert space.

  3. Existence of Weak Solutions for a Nonlinear Elliptic System

    Directory of Open Access Journals (Sweden)

    Gilbert RobertP

    2009-01-01

    Full Text Available We investigate the existence of weak solutions to the following Dirichlet boundary value problem, which occurs when modeling an injection molding process with a partial slip condition on the boundary. We have in ; in ; , and on .

  4. Existence of Positive Solutions for Nonlinear Eigenvalue Problems

    Directory of Open Access Journals (Sweden)

    Wong Fu-Hsiang

    2010-01-01

    Full Text Available We use a fixed point theorem in a cone to obtain the existence of positive solutions of the differential equation, , , with some suitable boundary conditions, where is a parameter.

  5. comparative performance evaluation of an existing and modified

    African Journals Online (AJOL)

    PROF. BARTH EKWEME

    and fan speeds of 2800 rpm as against the existing cylinder and fan speeds of 934 rpm. The performance evaluation for ... KEYWORDS: Acha, fonio, dehuller, performance evaluation, ... centrifugal force as a result of the rotation of the cylinder.

  6. The Histamine H4 Receptor: From Orphan to the Clinic

    Directory of Open Access Journals (Sweden)

    Robin L. Thurmond

    2015-03-01

    Full Text Available The histamine H4 receptor (H4R was first noted as a sequence in genomic databases that had features of a G-protein coupled receptor. This putative receptor was found to bind histamine consistent with its homology to other histamine receptors and thus became the fourth member of the histamine receptor family. Due to the previous success of drugs that target the H1 and H2 receptors, an effort was made to understand the function of this receptor and determine if it represented a drug target. Taking advantage of the vast literature on histamine, a search for histamine activity that did not appear to be mediated by the other three histamine receptors was undertaken. From this asthma and pruritus emerged as areas of particular interest. Histamine has long been suspected to play a role in the pathogenesis of asthma, but antihistamines that target the H1 and H2 receptors have not been shown to be effective for this condition. The use of selective ligands in animal models of asthma has now potentially filled this gap by showing a role for the H4R in mediating lung function and inflammation. A similar story exists for chronic pruritus associated with conditions such as atopic dermatitis. Antihistamines that target the H1 receptor are effective in reducing acute pruritus, but are ineffective in pruritus experienced by patients with atopic dermatitis. As for asthma, animal models have now suggested a role for the H4R in mediating pruritic responses, with antagonists to the H4R reducing pruritus in a number of different conditions. The anti-pruritic effect of H4R antagonists has recently been shown in human clinical studies, validating the preclinical findings in the animal models. A selective H4R antagonist inhibited histamine-induced pruritus in health volunteers and reduced pruritus in patients with atopic dermatitis. The history to date of the H4R provides an excellent example of the deorphanization of a novel receptor and the translation of this into

  7. Newspaper and internet display advertising: Co-existence or substitution?

    OpenAIRE

    Lindstädt, Nadine; Budzinski, Oliver

    2012-01-01

    Newspapers have been experiencing declining circulation figures and diminishing advertising revenues for several years – both effects might pose a threat to the continuing existence of (print) newspapers. In an earlier paper, Lindstädt & Budzinski (2011) argued from a theoretical viewpoint that industry-specific patterns exist that determine substitution or complementation effects between internet and newspaper advertising. It was argued that retail advertising, in particular, may offer a nic...

  8. Evaluation of the integrity of existing NFS waste tanks

    International Nuclear Information System (INIS)

    1977-12-01

    Various means of investigating the integrity of the existing NFS waste tanks are presented, including: visual inspection, ultrasonic testing, acoustic-emission monitoring, radiography, and forced-vibration testing. The experience that exists in performing such investigations of high-level radioactive waste tanks is documented, including: visual inspections, photography, wall-thickness measurements, and forced-vibration testing. An evaluation is made on the relative merits of the presented inspection and testing alternatives

  9. Non-existence criteria for Laurent polynomial first integrals

    Directory of Open Access Journals (Sweden)

    Shaoyun Shi

    2003-01-01

    Full Text Available In this paper we derived some simple criteria for non-existence and partial non-existence Laurent polynomial first integrals for a general nonlinear systems of ordinary differential equations $\\dot x = f(x$, $x \\in \\mathbb{R}^n$ with $f(0 = 0$. We show that if the eigenvalues of the Jacobi matrix of the vector field $f(x$ are $\\mathbb{Z}$-independent, then the system has no nontrivial Laurent polynomial integrals.

  10. Existence of solitary waves in dipolar quantum gases

    KAUST Repository

    Antonelli, Paolo; Sparber, Christof

    2011-01-01

    We study a nonlinear Schrdinger equation arising in the mean field description of dipolar quantum gases. Under the assumption of sufficiently strong dipolar interactions, the existence of standing waves, and hence solitons, is proved together with some of their properties. This gives a rigorous argument for the possible existence of solitary waves in BoseEinstein condensates, which originate solely due to the dipolar interaction between the particles. © 2010 Elsevier B.V. All rights reserved.

  11. The existence and persistence of household financial hardship

    OpenAIRE

    Brown, S.; Ghosh, P.; Taylor, K.

    2012-01-01

    We investigate the existence and persistence of financial hardship at the household level using data from the British Household Panel Survey. Our modelling strategy makes three important contributions to the existing literature on household finances. Firstly, we model nine different types of household financial problems within a joint framework, allowing for correlation in the random effects across the nine equations. Secondly, we develop a dynamic framework in order to model the persistence ...

  12. Existence of solutions to quasilinear Schrodinger equations with indefinite potential

    Directory of Open Access Journals (Sweden)

    Zupei Shen

    2015-04-01

    Full Text Available In this article, we study the existence and multiplicity of solutions of the quasilinear Schrodinger equation $$ -u''+V(xu-(|u| ^2''u=f(u $$ on $\\mathbb{R}$, where the potential $V$ allows sign changing and the nonlinearity satisfies conditions weaker than the classical Ambrosetti-Rabinowitz condition. By a local linking theorem and the fountain theorem, we obtain the existence and multiplicity of solutions for the equation.

  13. How Do We Know Protons, Electrons, and Quarks Really Exist?

    Science.gov (United States)

    Robertson, Bill

    2005-01-01

    Scientific explanations often make use of things that cannot be seen or felt, such as protons, electrons, and quarks. Do these things really exist? If so, how do is it known that they exist? Imagine being enclosed in a completely dark room with no light at all and not being able to see a thing. Being chained to a chair somewhere in the room, and…

  14. Existence of solitary waves in dipolar quantum gases

    KAUST Repository

    Antonelli, Paolo

    2011-02-01

    We study a nonlinear Schrdinger equation arising in the mean field description of dipolar quantum gases. Under the assumption of sufficiently strong dipolar interactions, the existence of standing waves, and hence solitons, is proved together with some of their properties. This gives a rigorous argument for the possible existence of solitary waves in BoseEinstein condensates, which originate solely due to the dipolar interaction between the particles. © 2010 Elsevier B.V. All rights reserved.

  15. Neurotensin is an antagonist of the human neurotensin NT2 receptor expressed in Chinese hamster ovary cells.

    Science.gov (United States)

    Vita, N; Oury-Donat, F; Chalon, P; Guillemot, M; Kaghad, M; Bachy, A; Thurneyssen, O; Garcia, S; Poinot-Chazel, C; Casellas, P; Keane, P; Le Fur, G; Maffrand, J P; Soubrie, P; Caput, D; Ferrara, P

    1998-11-06

    The human levocabastine-sensitive neurotensin NT2 receptor was cloned from a cortex cDNA library and stably expressed in Chinese hamster ovary (CHO) cells in order to study its binding and signalling characteristics. The receptor binds neurotensin as well as several other ligands already described for neurotensin NT1 receptor. It also binds levocabastine, a histamine H1 receptor antagonist that is not recognised by neurotensin NT1 receptor. Neurotensin binding to recombinant neurotensin NT2 receptor expressed in CHO cells does not elicit a biological response as determined by second messenger measurements. Levocabastine, and the peptides neuromedin N and xenin were also ineffective on neurotensin NT2 receptor activation. Experiments with the neurotensin NT1 receptor antagonists SR48692 and SR142948A, resulted in the unanticipated discovery that both molecules are potent agonists on neurotensin NT2 receptor. Both compounds, following binding to neurotensin NT2 receptor, enhance inositol phosphates (IP) formation with a subsequent [Ca2+]i mobilisation; induce arachidonic acid release; and stimulate mitogen-activated protein kinase (MAPK) activity. Interestingly, these activities are antagonised by neurotensin and levocabastine in a concentration-dependent manner. These activities suggest that the human neurotensin NT2 receptor may be of physiological importance and that a natural agonist for the receptor may exist.

  16. International Union of Pharmacology. XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors.

    Science.gov (United States)

    Poyner, David R; Sexton, Patrick M; Marshall, Ian; Smith, David M; Quirion, Remi; Born, Walter; Muff, Roman; Fischer, Jan A; Foord, Steven M

    2002-06-01

    The calcitonin family of peptides comprises calcitonin, amylin, two calcitonin gene-related peptides (CGRPs), and adrenomedullin. The first calcitonin receptor was cloned in 1991. Its pharmacology is complicated by the existence of several splice variants. The receptors for the other members the family are made up of subunits. The calcitonin-like receptor (CL receptor) requires a single transmembrane domain protein, termed receptor activity modifying protein, RAMP1, to function as a CGRP receptor. RAMP2 and -3 enable the same CL receptor to behave as an adrenomedullin receptor. Although the calcitonin receptor does not require RAMP to bind and respond to calcitonin, it can associate with the RAMPs, resulting in a series of receptors that typically have high affinity for amylin and varied affinity for CGRP. This review aims to reconcile what is observed when the receptors are reconstituted in vitro with the properties they show in native cells and tissues. Experimental conditions must be rigorously controlled because different degrees of protein expression may markedly modify pharmacology in such a complex situation. Recommendations, which follow International Union of Pharmacology guidelines, are made for the nomenclature of these multimeric receptors.

  17. Quantitative analysis of receptor imaging

    International Nuclear Information System (INIS)

    Fu Zhanli; Wang Rongfu

    2004-01-01

    Model-based methods for quantitative analysis of receptor imaging, including kinetic, graphical and equilibrium methods, are introduced in detail. Some technical problem facing quantitative analysis of receptor imaging, such as the correction for in vivo metabolism of the tracer and the radioactivity contribution from blood volume within ROI, and the estimation of the nondisplaceable ligand concentration, is also reviewed briefly

  18. Coronavirus spike-receptor interactions

    NARCIS (Netherlands)

    Mou, H.

    2015-01-01

    Coronaviruses cause important diseases in humans and animals. Coronavirus infection starts with the virus binding with its spike proteins to molecules present on the surface of host cells that act as receptors. This spike-receptor interaction is highly specific and determines the virus’ cell, tissue

  19. Interfacing the existing cask fleet with the MRS

    International Nuclear Information System (INIS)

    Doman, J.W.; Hahn, R.E.

    1992-01-01

    This paper reports that the Department of Energy (DOE) is considering the possibility of using the existing fleet of casks to achieve spent fuel receipt at the Monitored Retrievable Storage (MRS) facility. The existing cask fleet includes the NLI-1/2, the NAC-LWT, the TN-8 (and TN-8L), the TN-9, and the IF-300 casks. Other casks may be available, but their status is not certain. Use of the existing cask fleet at the MRS places additional design requirements on the system, and specifically affects the cask-to-MRS interface. The decision to use the existing cask fleet also places additional demands on training needs and operator certification, and the configuration management system. Some existing cask designs may not be able to mate with a bottom opening hot cell MRS. Use of the existing cask fleet also greatly increases the number of shipments that must be received, to the point that a facility larger than originally envisioned may be required

  20. Study of structural reliability of existing concrete structures

    Science.gov (United States)

    Druķis, P.; Gaile, L.; Valtere, K.; Pakrastiņš, L.; Goremikins, V.

    2017-10-01

    Structural reliability of buildings has become an important issue after the collapse of a shopping center in Riga 21.11.2013, caused the death of 54 people. The reliability of a building is the practice of designing, constructing, operating, maintaining and removing buildings in ways that ensure maintained health, ward suffered injuries or death due to use of the building. Evaluation and improvement of existing buildings is becoming more and more important. For a large part of existing buildings, the design life has been reached or will be reached in the near future. The structures of these buildings need to be reassessed in order to find out whether the safety requirements are met. The safety requirements provided by the Eurocodes are a starting point for the assessment of safety. However, it would be uneconomical to require all existing buildings and structures to comply fully with these new codes and corresponding safety levels, therefore the assessment of existing buildings differs with each design situation. This case study describes the simple and practical procedure of determination of minimal reliability index β of existing concrete structures designed by different codes than Eurocodes and allows to reassess the actual reliability level of different structural elements of existing buildings under design load.

  1. Reduced post-synaptic serotonin type 1A receptor binding in bipolar depression

    Science.gov (United States)

    Nugent, Allison C.; Bain, Earle E.; Carlson, Paul J.; Neumeister, Alexander; Bonne, Omer; Carson, Richard E.; Eckelman, William; Herscovitch, Peter; Zarate, Carlos A.; Charney, Dennis S.; Drevets, Wayne C.

    2013-01-01

    Multiple lines of evidence suggest that serotonin type 1A (5-HT1A) receptor dysfunction is involved in the pathophysiology of mood disorders, and that alterations in 5-HT1A receptor function play a role in the mechanisms of antidepressant and mood stabilizer treatment. The literature is in disagreement, however, as to whether 5-HT1A receptor binding abnormalities exist in bipolar disorder (BD). We acquired PET images of 5-HT1A receptor binding in 26 unmedicated BD subjects and 37 healthy controls using [18F]FCWAY, a highly selective 5-HT1A receptor radio-ligand. The mean 5-HT1A receptor binding potential (BPP) was significantly lower in BD subjects compared to controls in cortical regions where 5-HT1A receptors are expressed post-synaptically, most prominently in the mesiotemporal cortex. Post-hoc assessments involving other receptor specific binding parameters suggested that this difference particularly affected the females with BD. The mean BPP did not differ between groups in the raphe nucleus, however, where 5-HT1A receptors are predominantly expressed pre-synaptically. Across subjects the BPP in the mesiotemporal cortex was inversely correlated with trough plasma cortisol levels, consistent with preclinical literature indicating that hippocampal 5-HT1A receptor expression is inhibited by glucocorticoid receptor stimulation. These findings suggest that 5-HT1A receptor binding is abnormally reduced in BD, and this abnormality may particularly involve the postsynaptic 5-HT1A receptor system of individuals with a tendency toward cortisol hypersecretion. PMID:23434290

  2. Regulation of AMPA receptor localization in lipid rafts

    Science.gov (United States)

    Hou, Qingming; Huang, Yunfei; Amato, Stephen; Snyder, Solomon H.; Huganir, Richard L.; Man, Heng-Ye

    2009-01-01

    Lipid rafts are special microdomains enriched in cholesterol, sphingolipids and certain proteins, and play important roles in a variety of cellular functions including signal transduction and protein trafficking. We report that in cultured cortical and hippocampal neurons the distribution of lipid rafts is development-dependent. Lipid rafts in mature neurons exist on the entire cell-surface and display a high degree of mobility. AMPA receptors co-localize and associate with lipid rafts in the plasma membrane. The association of AMPARs with rafts is under regulation; through the NOS–NO pathway, NMDA receptor activity increases AMPAR localization in rafts. During membrane targeting, AMPARs insert into or at close proximity of the surface raft domains. Perturbation of lipid rafts dramatically suppresses AMPA receptor exocytosis, resulting in significant reduction in AMPAR cell-surface expression. PMID:18411055

  3. Neurobeachin regulates neurotransmitter receptor trafficking to synapses

    NARCIS (Netherlands)

    Nair, R.; Lauks, J.; Jung, S; Cooke, N.E.; de Wit, H.; Brose, N.; Kilimann, M.W.; Verhage, M.; Rhee, J.

    2013-01-01

    The surface density of neurotransmitter receptors at synapses is a key determinant of synaptic efficacy. Synaptic receptor accumulation is regulated by the transport, postsynaptic anchoring, and turnover of receptors, involving multiple trafficking, sorting, motor, and scaffold proteins. We found

  4. A Novel Mechanism of Androgen Receptor Action

    National Research Council Canada - National Science Library

    Roberts, Jr, Charles T

    2006-01-01

    .... Specifically, the authors had determined that the androgen receptor controls the expression of the cell-surface receptor for the hormone IGF-1 at the level of translation of the IGF-1 receptor mRNA...

  5. Quantitative densitometry of neurotransmitter receptors

    International Nuclear Information System (INIS)

    Rainbow, T.C.; Bleisch, W.V.; Biegon, A.; McEwen, B.S.

    1982-01-01

    An autoradiographic procedure is described that allows the quantitative measurement of neurotransmitter receptors by optical density readings. Frozen brain sections are labeled in vitro with [ 3 H]ligands under conditions that maximize specific binding to neurotransmitter receptors. The labeled sections are then placed against the 3 H-sensitive LKB Ultrofilm to produce the autoradiograms. These autoradiograms resemble those produced by [ 14 C]deoxyglucose autoradiography and are suitable for quantitative analysis with a densitometer. Muscarinic cholinergic receptors in rat and zebra finch brain and 5-HT receptors in rat brain were visualized by this method. When the proper combination of ligand concentration and exposure time are used, the method provides quantitative information about the amount and affinity of neurotransmitter receptors in brain sections. This was established by comparisons of densitometric readings with parallel measurements made by scintillation counting of sections. (Auth.)

  6. Dopamine Receptors and Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Shin Hisahara

    2011-01-01

    Full Text Available Parkinson's disease (PD is a progressive extrapyramidal motor disorder. Pathologically, this disease is characterized by the selective dopaminergic (DAergic neuronal degeneration in the substantia nigra. Correcting the DA deficiency in PD with levodopa (L-dopa significantly attenuates the motor symptoms; however, its effectiveness often declines, and L-dopa-related adverse effects emerge after long-term treatment. Nowadays, DA receptor agonists are useful medication even regarded as first choice to delay the starting of L-dopa therapy. In advanced stage of PD, they are also used as adjunct therapy together with L-dopa. DA receptor agonists act by stimulation of presynaptic and postsynaptic DA receptors. Despite the usefulness, they could be causative drugs for valvulopathy and nonmotor complication such as DA dysregulation syndrome (DDS. In this paper, physiological characteristics of DA receptor familyare discussed. We also discuss the validity, benefits, and specific adverse effects of pharmaceutical DA receptor agonist.

  7. Molecular characterization of opioid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Howard, A.D.

    1986-01-01

    The aim of this research was to purify and characterize active opioid receptors and elucidate molecular aspects of opioid receptor heterogeneity. Purification to apparent homogeneity of an opioid binding protein from bovine caudate was achieved by solubilization in the non-ionic detergent, digitonin, followed by sequential chromatography on the opiate affinity matrix, ..beta..-naltrexylethylenediamine-CH-Sepharose 4B, and on the lectine affinity matrix, wheat germ agglutinin-agarose. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE) followed by autoradiography revealed that radioiodinated purified receptor gave a single band. Purified receptor preparations showed a specific activity of 12,000-15,000 fmol of opiate bound per mg of protein. Radioiodinated human beta-endorphin (/sup 125/I-beta-end/sub H/) was used as a probe to investigate the ligand binding subunits of mu and delta opioid receptors. /sup 125/I-beta-end/sub H/ was shown to bind to a variety of opioid receptor-containing tissues with high affinity and specificity with preference for mu and delta sites, and with little, if any, binding to kappa sites. Affinity crosslinking techniques were employed to covalently link /sup 125/I-beta-end/sub H/ to opioid receptors, utilizing derivatives of bis-succinimidyl esters that are bifunctional crosslinkers with specificities for amino and sulfhydryl groups. This, and competition experiments with high type-selective ligands, permitted the assignment of two labeled peptides to their receptor types, namely a peptide of M/sub r/ = 65,000 for mu receptors and one of M/sub r/ = 53,000 for delta receptors.

  8. AMP Is an Adenosine A1 Receptor Agonist*

    Science.gov (United States)

    Rittiner, Joseph E.; Korboukh, Ilia; Hull-Ryde, Emily A.; Jin, Jian; Janzen, William P.; Frye, Stephen V.; Zylka, Mark J.

    2012-01-01

    Numerous receptors for ATP, ADP, and adenosine exist; however, it is currently unknown whether a receptor for the related nucleotide adenosine 5′-monophosphate (AMP) exists. Using a novel cell-based assay to visualize adenosine receptor activation in real time, we found that AMP and a non-hydrolyzable AMP analog (deoxyadenosine 5′-monophosphonate, ACP) directly activated the adenosine A1 receptor (A1R). In contrast, AMP only activated the adenosine A2B receptor (A2BR) after hydrolysis to adenosine by ecto-5′-nucleotidase (NT5E, CD73) or prostatic acid phosphatase (PAP, ACPP). Adenosine and AMP were equipotent human A1R agonists in our real-time assay and in a cAMP accumulation assay. ACP also depressed cAMP levels in mouse cortical neurons through activation of endogenous A1R. Non-selective purinergic receptor antagonists (pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid and suramin) did not block adenosine- or AMP-evoked activation. Moreover, mutation of His-251 in the human A1R ligand binding pocket reduced AMP potency without affecting adenosine potency. In contrast, mutation of a different binding pocket residue (His-278) eliminated responses to AMP and to adenosine. Taken together, our study indicates that the physiologically relevant nucleotide AMP is a full agonist of A1R. In addition, our study suggests that some of the physiological effects of AMP may be direct, and not indirect through ectonucleotidases that hydrolyze this nucleotide to adenosine. PMID:22215671

  9. Morbillivirus receptors and tropism: multiple pathways for infection

    Directory of Open Access Journals (Sweden)

    Hiroki eSato

    2012-03-01

    Full Text Available Morbilliviruses, which include measles virus (MeV, canine distemper virus, and rinderpest virus, are among the most important pathogens in their respective hosts and cause severe syndromes. Morbilliviruses are enveloped viruses with 2 envelope proteins, one of which is hemagglutinin (H protein, which plays a role in binding to cellular receptors. During morbillivirus infection, the virus initially targets lymphoid cells and replicates efficiently in the lymph nodes. The principal cellular receptor for morbillivirus is signaling lymphocyte activation molecule (SLAM, also called CD150, which is exclusively expressed on immune cells. This feature reflects the strong lymphoid cell tropism and viral spread in the infected body. Morbillivirus infection, however, affects various tissues in the body, including the lung, kidney, gastrointestinal tract, vascular endothelium, and brain. Thus, other receptors for morbilliviruses in addition to SLAM might exist. Recently, nectin-4 has been identified as a novel epithelial cell receptor for MeV. The expression of nectin-4 is localized to polarized epithelial cells, and this localization supports the notion of cell tropism since MeV also grows well in the epithelial cells of the respiratory tract. Although 2 major receptors for lymphoid and epithelial cells in natural infection have been identified, morbillivirus can still infect many other types of cells with low infectivity, suggesting the existence of inefficient but ubiquitously expressed receptors. We have identified other molecules that are implicated in morbillivirus infection of SLAM-negative cells by alternative mechanisms. These findings indicate that morbillivirus utilizes multiple pathways for establishment of infection. These studies will advance our understanding of morbillivirus tropism and pathogenesis.

  10. Existence conditions of optimal trajectories in dynamic control processes; Conditions d'existence de trajectoires optimales des processus dynamiques commandes

    Energy Technology Data Exchange (ETDEWEB)

    Bonnemay-Juricek, L [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1968-07-01

    The existence of solutions in the optimal control problems with free endpoints is studied in this report and existence conditions are established without the usual assumption that the control region is convex. Furthermore the results, in order to be of some utility in physical applications, are expressed only by means of conditions on the parameters defining the system. (author) [French] Ce rapport etudie l'existence de solutions optimales dans les problemes de commande ou le point terminal est libre et ou la duree de l'evolution du systeme a optimiser est connue. Des conditions d'existence y sont formulees sans recourir a l'hypothese usuelle de convexite du domaine des valeurs des commandes. De plus on a cherche a rendre utilisables les resultats en ne faisant porter les conditions que sur les parametres directement accessibles du systeme. (auteur)

  11. Proofs concerning the existence, in the blood of hypertensive patients, of some serum factors influencing the vascular smooth muscle and the myocardium physiology.

    Science.gov (United States)

    Mocanu, M; Botea, S; Dragomir, C T

    1991-01-01

    Starting from the existence of some autoimmune diseases (i.e. bronchial asthma or miastenia gravis) we asked ourselves if some plasmatic factors do exist, influencing the receptor--mediator relations in cardiovascular system during some illnesses having unknown etiology, as arterial hypertension. For this reason, in this work was tested the hypothesis that, in some chronic cardiovascular diseases would exist factors circulating and affecting the functions of the cellular membranes of the arterial wall, particularly of the smooth muscle cells and myocardial cells. Our results show a significant modification of the calcium fluxes and of some neuromediators uptake at the hypertensive patients.

  12. Greening Existing Buildings in Contemporary Iraqi Urban Reality/ Virtual Model

    Directory of Open Access Journals (Sweden)

    Saba Jabar Neama Al-Khafaji

    2015-11-01

    Full Text Available The approach of greening existing buildings, is an urgent necessity, because the greening operation provides the speed and optimal efficiency in the environmental performance, as well as keeping up with the global green architecture revolution. Therefore, greening existing buildings in Iraq is important for trends towards renewable energies, because of what the country went through economic conditions and crises and wars which kept the country away from what took place globally in this issue. The research problem is: insufficient knowledge about the importance and the mechanism of the greening of existing buildings, including its environmental and economic dimensions, by rationalization of energy consumption and preserving the environment. The research objective is: clarifying the importance of greening existing buildings environmentally and economically, providing a virtual experience for greening the presidency building of Baghdad University, through advanced computer program. The main conclusions is: there is difference representing by reducing the disbursed thermal loads amount for cooling in summer and heating in winter through the use of computerized program (DesignBuilder and that after the implementation of greening operations on the building envelope, which confirms its effectiveness in raising the energy performance efficiency inside the building. Hence, the importance of the application of greening existing buildings approach in Iraq, to bring back Iraqi architecture to environmental and local track proper.

  13. Seismic performance of existing R.C. framed buildings

    Directory of Open Access Journals (Sweden)

    Sameh A. El-Betar

    2017-08-01

    Full Text Available The earthquakes disasters basically occur due to buildings damage not because of the earth shaking. Therefore, the countries have being updated the seismic codes. The seismic loads for buildings design in Egyptian Code have been changed from (EC-1994 to (ECP-201, 2012. On the other hand, the need is raised to study the vulnerability of existing buildings, which can be divided into the buildings designed to resist the gravity loads only (GLD and the buildings designed according to Egyptian code (EC-1994. Comparison between forces due to Egyptian code for loads (EC-1994 and (ECP-201, 2012 is carried out on the multi-stories R.C. framed buildings which are the most common type of existing buildings in Egypt. To investigate the vulnerability of existing buildings, nonlinear static pushover analysis is conducted to evaluate the real strength of the existing buildings. Moreover, it is considered a useful and effective tool for the performance of three framed buildings: 3, 6 and 10 stories due to expected future earthquakes. Finally, it is found that the vulnerability of existing GLD buildings occurs at expected ground accelerations (ag greater than 0.125 g in Egyptian seismic map, while the EC-94 designed buildings behave elastically up to (ag equals to 0.2 g and above that a slight damage may occur.

  14. Energy and architecture: improvement of energy performance in existing buildings

    Energy Technology Data Exchange (ETDEWEB)

    Haase, Matthias; Wycmans, Annemie; Solbraa, Anne; Grytli, Eir

    2011-07-01

    This book aims to give an overview of different aspects of retrofitting existing buildings. The target group is students of architecture and building engineering as well as building professionals. Eight out of ten buildings which we will inhabit in 2050 already exist. This means that a great potential for reducing our carbon footprint lies in the existing building stock. Students from NTNU have used the renovation of a 1950s school building at Linesoeya in Soer-Trondelag as a case to increase their awareness and knowledge about the challenges building professionals need to overcome to unite technical details and high user quality into good environmental performance. The students were invited by the building owners and initiators of LIPA Eco Project to contribute to its development: By retrofitting an existing building to passive house standards and combining this with energy generated on site, LIPA Eco Project aims to provide a hands-on example with regard to energy efficiency, architectural design and craftsmanship for a low carbon society. The overall goal for this project is to raise awareness regarding resource efficiency measures in architecture and particularly in existing building mass.(au)

  15. Cloning and expression of a cDNA coding for the human platelet-derived growth factor receptor: Evidence for more than one receptor class

    International Nuclear Information System (INIS)

    Gronwald, R.G.K.; Grant, F.J.; Haldeman, B.A.; Hart, C.E.; O'Hara, P.J.; Hagen, F.S.; Ross, R.; Bowen-Pope, D.F.; Murray, M.J.

    1988-01-01

    The complete nucleotide sequence of a cDNA encoding the human platelet-derived growth factor (PDGF) receptor is presented. The cDNA contains an open reading frame that codes for a protein of 1106 amino acids. Comparison to the mouse PDGF receptor reveals an overall amino acid sequence identity of 86%. This sequence identity rises to 98% in the cytoplasmic split tyrosine kinase domain. RNA blot hybridization analysis of poly(A) + RNA from human dermal fibroblasts detects a major and a minor transcript using the cDNA as a probe. Baby hamster kidney cells, transfected with an expression vector containing the receptor cDNA, express an ∼ 190-kDa cell surface protein that is recognized by an anti-human PDGF receptor antibody. The recombinant PDGF receptor is functional in the transfected baby hamster kidney cells as demonstrated by ligand-induced phosphorylation of the receptor. Binding properties of the recombinant PDGF receptor were also assessed with pure preparations of BB and AB isoforms of PDGF. Unlike human dermal fibroblasts, which bind both isoforms with high affinity, the transfected baby hamster kidney cells bind only the BB isoform of PDGF with high affinity. This observation is consistent with the existence of more than one PDGF receptor class

  16. Captodiamine, a putative antidepressant, enhances hypothalamic BDNF expression in vivo by synergistic 5-HT2c receptor antagonism and sigma-1 receptor agonism.

    Science.gov (United States)

    Ring, Rebecca M; Regan, Ciaran M

    2013-10-01

    The putative antidepressant captodiamine is a 5-HT2c receptor antagonist and agonist at sigma-1 and D3 dopamine receptors, exerts an anti-immobility action in the forced swim paradigm, and enhances dopamine turnover in the frontal cortex. Captodiamine has also been found to ameliorate stress-induced anhedonia, reduce the associated elevations of hypothalamic corticotrophin-releasing factor (CRF) and restore the reductions in hypothalamic BDNF expression. Here we demonstrate chronic administration of captodiamine to have no significant effect on hypothalamic CRF expression through sigma-1 receptor agonism; however, both sigma-1 receptor agonism or 5-HT2c receptor antagonism were necessary to enhance BDNF expression. Regulation of BDNF expression by captodiamine was associated with increased phosphorylation of transcription factor CREB and mediated through sigma-1 receptor agonism but blocked by 5-HT2c receptor antagonism. The existence of two separate signalling pathways was confirmed by immunolocalisation of each receptor to distinct cell populations in the paraventricular nucleus of the hypothalamus. Increased BDNF induced by captodiamine was also associated with enhanced expression of synapsin, but not PSD-95, suggesting induction of long-term structural plasticity between hypothalamic synapses. These unique features of captodiamine may contribute to its ability to ameliorate stress-induced anhedonia as the hypothalamus plays a prominent role in regulating HPA axis activity.

  17. Structure and organization of heteromeric AMPA-type glutamate receptors.

    Science.gov (United States)

    Herguedas, Beatriz; García-Nafría, Javier; Cais, Ondrej; Fernández-Leiro, Rafael; Krieger, James; Ho, Hinze; Greger, Ingo H

    2016-04-29

    AMPA-type glutamate receptors (AMPARs), which are central mediators of rapid neurotransmission and synaptic plasticity, predominantly exist as heteromers of the subunits GluA1 to GluA4. Here we report the first AMPAR heteromer structures, which deviate substantially from existing GluA2 homomer structures. Crystal structures of the GluA2/3 and GluA2/4 N-terminal domains reveal a novel compact conformation with an alternating arrangement of the four subunits around a central axis. This organization is confirmed by cysteine cross-linking in full-length receptors, and it permitted us to determine the structure of an intact GluA2/3 receptor by cryogenic electron microscopy. Two models in the ligand-free state, at resolutions of 8.25 and 10.3 angstroms, exhibit substantial vertical compression and close associations between domain layers, reminiscent of N-methyl-D-aspartate receptors. Model 1 resembles a resting state and model 2 a desensitized state, thus providing snapshots of gating transitions in the nominal absence of ligand. Our data reveal organizational features of heteromeric AMPARs and provide a framework to decipher AMPAR architecture and signaling. Copyright © 2016, American Association for the Advancement of Science.

  18. Preliminary Molecular Dynamic Simulations of the Estrogen Receptor Alpha Ligand Binding Domain from Antagonist to Apo

    Directory of Open Access Journals (Sweden)

    Adrian E. Roitberg

    2008-06-01

    Full Text Available Estrogen receptors (ER are known as nuclear receptors. They exist in the cytoplasm of human cells and serves as a DNA binding transcription factor that regulates gene expression. However the estrogen receptor also has additional functions independent of DNA binding. The human estrogen receptor comes in two forms, alpha and beta. This work focuses on the alpha form of the estrogen receptor. The ERα is found in breast cancer cells, ovarian stroma cells, endometrium, and the hypothalamus. It has been suggested that exposure to DDE, a metabolite of DDT, and other pesticides causes conformational changes in the estrogen receptor. Before examining these factors, this work examines the protein unfolding from the antagonist form found in the 3ERT PDB crystal structure. The 3ERT PDB crystal structure has the estrogen receptor bound to the cancer drug 4-hydroxytamoxifen. The 4-hydroxytamoxifen ligand was extracted before the simulation, resulting in new conformational freedom due to absence of van der Waals contacts between the ligand and the receptor. The conformational changes that result expose the binding clef of the co peptide beside Helix 12 of the receptor forming an apo conformation. Two key conformations in the loops at either end of the H12 are produced resulting in the antagonist to apo conformation transformation. The results were produced over a 42ns Molecular Dynamics simulation using the AMBER FF99SB force field.

  19. TAM Receptors Are Not Required for Zika Virus Infection in Mice

    Directory of Open Access Journals (Sweden)

    Andrew K. Hastings

    2017-04-01

    Full Text Available Summary: Tyro3, Axl, and Mertk (TAM receptors are candidate entry receptors for infection with the Zika virus (ZIKV, an emerging flavivirus of global public health concern. To investigate the requirement of TAM receptors for ZIKV infection, we used several routes of viral inoculation and compared viral replication in wild-type versus Axl−/−, Mertk−/−, Axl−/−Mertk−/−, and Axl−/−Tyro3−/− mice in various organs. Pregnant and non-pregnant mice treated with interferon-α-receptor (IFNAR-blocking (MAR1-5A3 antibody and infected subcutaneously with ZIKV showed no reliance on TAMs for infection. In the absence of IFNAR-blocking antibody, adult female mice challenged intravaginally with ZIKV showed no difference in mucosal viral titers. Similarly, in young mice that were infected with ZIKV intracranially or intraperitoneally, ZIKV replication occurred in the absence of TAM receptors, and no differences in cell tropism were observed. These findings indicate that, in mice, TAM receptors are not required for ZIKV entry and infection. : TAM receptors have been implicated as entry receptors for the Zika virus. In this study, Hastings et al. used genetic knockout mouse models to demonstrate that they are not necessary for the infection of mice via multiple routes of viral challenge. These results suggest the existence of redundant entry receptors for ZIKV in mice. Keywords: viral entry, flavivirus, neurotropic virus, CNS, pregnancy, congenital infection

  20. Rapid synthesis of acetylcholine receptors at neuromuscular junctions.

    Science.gov (United States)

    Ramsay, D A; Drachman, D B; Pestronk, A

    1988-10-11

    The rate of acetylcholine receptor (AChR) degradation in mature, innervated mammalian neuromuscular junctions has recently been shown to be biphasic; up to 20% are rapidly turned over (RTOs; half life less than 1 day) whereas the remainder are lost more slowly ('stable' AChRs; half life 10-12 days). In order to maintain normal junctional receptor density, synthesis and insertion of AChRs should presumably be sufficiently rapid to replace both the RTOs and the stable receptors. We have tested this prediction by blocking pre-existing AChRs in the mouse sternomastoid muscle with alpha-bungarotoxin (alpha-BuTx), and monitoring the subsequent appearance of 'new' junctional AChRs at intervals of 3 h to 20 days by labeling them with 125I-alpha-BuTx. The results show that new receptors were initially inserted rapidly (16% at 24 h and 28% at 48 h). The rate of increase of 'new' 125I-alpha-BuTx binding sites gradually slowed down during the remainder of the time period studied. Control observations excluded possible artifacts of the experimental procedure including incomplete blockade of AChRs, dissociation of toxin-receptor complexes, or experimentally induced alteration of receptor synthesis. The present demonstration of rapid synthesis and incorporation of AChRs at innervated neuromuscular junctions provides support for the concept of a subpopulation of rapidly turned over AChRs. The RTOs may serve as precursors for the larger population of stable receptors and have an important role in the metabolism of the neuromuscular synapse.

  1. Relationship between peripheral leptin receptor and leptin in obese subjects

    International Nuclear Information System (INIS)

    Sun Junjiang; Du Tongxin; Wang Zizheng; Wang Shukui; Huang Min

    2002-01-01

    Objective: To investigate the relationship between leptin resistance and leptin receptor in obese subjects. Methods: Forty-four individuals undergoing surgery, exclusive of diabetic mellitus, chronic inflammatory and malignant diseases, were divided into 3 groups according to the body mass index (BMI), normal controls (n=15), weight excess (n=14), and obesity group (n=15). Fasting serum leptin were detected via ELISA kits, leptin receptor (Bmax) in peripheral adipose tissues was detected by radioligand assay. Results: Serum leptin levels were higher significantly in weight excess and obesity cases groups (10.3±4.45 and 13.2±3.26 vs 5.51±3.23 μg/L, both P<0.05, respectively) compared with normal control group, suggesting the existence of leptin resistance, while the leptin receptor of the weight excess and obese groups decreased significantly than that of normal control group (36.9 ± 5.89 and 24.3 ± 3.95 vs 76.5 ± 35.3 fmol/mg protein, both P<0.01, respectively), there was no statistical differences for Kd value among three groups. Also, there was a negative correlation between BMI and leptin receptor (r=-0.613, P<0.05), and no significant correlation was found between serum leptin and peripheral leptin receptor. Conclusion: The result suggested that there was expression of leptin receptor in peripheral adipose tissues and low level of leptin receptor expression may contribute to the development of leptin resistance and obesity

  2. Communication networks in the brain: neurons, receptors, neurotransmitters, and alcohol.

    Science.gov (United States)

    Lovinger, David M

    2008-01-01

    Nerve cells (i.e., neurons) communicate via a combination of electrical and chemical signals. Within the neuron, electrical signals driven by charged particles allow rapid conduction from one end of the cell to the other. Communication between neurons occurs at tiny gaps called synapses, where specialized parts of the two cells (i.e., the presynaptic and postsynaptic neurons) come within nanometers of one another to allow for chemical transmission. The presynaptic neuron releases a chemical (i.e., a neurotransmitter) that is received by the postsynaptic neuron's specialized proteins called neurotransmitter receptors. The neurotransmitter molecules bind to the receptor proteins and alter postsynaptic neuronal function. Two types of neurotransmitter receptors exist-ligand-gated ion channels, which permit rapid ion flow directly across the outer cell membrane, and G-protein-coupled receptors, which set into motion chemical signaling events within the cell. Hundreds of molecules are known to act as neurotransmitters in the brain. Neuronal development and function also are affected by peptides known as neurotrophins and by steroid hormones. This article reviews the chemical nature, neuronal actions, receptor subtypes, and therapeutic roles of several transmitters, neurotrophins, and hormones. It focuses on neurotransmitters with important roles in acute and chronic alcohol effects on the brain, such as those that contribute to intoxication, tolerance, dependence, and neurotoxicity, as well as maintained alcohol drinking and addiction.

  3. Existence domains of dust-acoustic solitons and supersolitons

    International Nuclear Information System (INIS)

    Maharaj, S. K.; Bharuthram, R.; Singh, S. V.; Lakhina, G. S.

    2013-01-01

    Using the Sagdeev potential method, the existence of large amplitude dust-acoustic solitons and supersolitons is investigated in a plasma comprising cold negative dust, adiabatic positive dust, Boltzmann electrons, and non-thermal ions. This model supports the existence of positive potential supersolitons in a certain region in parameter space in addition to regular solitons having negative and positive potentials. The lower Mach number limit for supersolitons coincides with the occurrence of double layers whereas the upper limit is imposed by the constraint that the adiabatic positive dust number density must remain real valued. The upper Mach number limits for negative potential (positive potential) solitons coincide with limiting values of the negative (positive) potential for which the negative (positive) dust number density is real valued. Alternatively, the existence of positive potential solitons can terminate when positive potential double layers occur

  4. The Existence of a Sticking Region in Free Weight Squats

    Directory of Open Access Journals (Sweden)

    Tillaar Roland van den

    2014-10-01

    Full Text Available The aim of this study was to investigate the existence of the sticking region in two legged free weight squats. Fifteen resistance-training males (age 24 ± 4 years, body mass 82 ± 11 kg, body height 179 ± 6 cm with 6 ± 3 years of resistance-training experience performed 6-RM in free weight squats. The last repetition was analyzed for the existence of a sticking region. Only in 10 out of 15 participants a sticking region was observed. The observed sticking region was much shorter than in the bench press. Furthermore, rectus femoris decreased the EMG activity in contrast to increased EMG activity in biceps femoris around the sticking and surrounding region. No significant change in EMG activity was found for the lateral and medial vastus muscles. It is suggested that a combination of these muscle activity changes could be one of the causes of the existence of the sticking region in free weight squats

  5. The existence of a sticking region in free weight squats.

    Science.gov (United States)

    van den Tillaar, Roland; Andersen, Vidar; Saeterbakken, Atle Hole

    2014-09-29

    The aim of this study was to investigate the existence of the sticking region in two legged free weight squats. Fifteen resistance-training males (age 24 ± 4 years, body mass 82 ± 11 kg, body height 179 ± 6 cm) with 6 ± 3 years of resistance-training experience performed 6-RM in free weight squats. The last repetition was analyzed for the existence of a sticking region. Only in 10 out of 15 participants a sticking region was observed. The observed sticking region was much shorter than in the bench press. Furthermore, rectus femoris decreased the EMG activity in contrast to increased EMG activity in biceps femoris around the sticking and surrounding region. No significant change in EMG activity was found for the lateral and medial vastus muscles. It is suggested that a combination of these muscle activity changes could be one of the causes of the existence of the sticking region in free weight squats.

  6. Islamic Banking Existence and Domestic Credit: Study at Seven Countries

    Directory of Open Access Journals (Sweden)

    Hamdan Yuafi

    2017-05-01

    Full Text Available This paper empirically investigates the determinants of domestic credit across a wide range of 7 countries; these are United Kingdom, Malaysia, Egypt, Kuwait, Qatar, Bahrain and Indonesia. We use dynamic panel estimation to examine effects of exchange rate, inflation, lending interest rate, banking crisis and existence of wholesale Islamic banking on domestic credit. We obtain several notable empirical results. First, the lending interest rate, banking crisis negatively and insignificantly contribute to domestic credit. The existence of Islamic bank has positive and insignificant contribution to domestic credit, while exchange rate positively and significantly contributes to domestic credit.  Inflation negatively and significantly contributes to domestic credit. Second, banking crisis and existence of wholesale Islamic banking show insignificant effect on domestic credit. Third, we find that today’s domestic credit is depended on domestic credit in the previous year.DOI: 10.15408/aiq9i2.4906

  7. Existing sustainable renovation concepts for single-family houses

    DEFF Research Database (Denmark)

    Tommerup, Henrik M.; Vanhoutteghem, Lies; Svendsen, Svend

    2010-01-01

    In the Nordic Innovation Centre Project, SuccessFamilies, the main objective is to change the business environment in order to speed up the implementation of sustainable renovation of single-family houses – proposing new service concepts that will combine both the technical solutions, financing...... with individual solutions, traditional warehouses ”do-it-yourself-shops” and some actors marketing single products. To speed up the implementation of sustainable renovation of single-family houses there is a great need for full-service packages. Existing technical renovation concepts, typically focusing...... services as well as other promoting issues to overcome the behavioural, organizational, legal and social barriers that exist in sustainable renovation. A starting point for such a change has been to get an overview of the existing sustainable renovation concepts, i.e. full-service concepts and technical...

  8. Intersubjective Dimension of Existence in the Philosophy of Gabriel Marcel

    Directory of Open Access Journals (Sweden)

    Martín Grassi

    2016-05-01

    Full Text Available The present work intends to introduce the reader to the essential dimension of intersubjectivity in personal existence in Gabriel Marcel’s philosophy. We will first attend to the characterization of persona; secondly, how we should understand the terms I and the other in concrete interpersonal relationships; in the third place, we will analize the way in which the other is given as an other, through the notion of presence. The main objective of this article is to show that personal existence is uncomprehensible without its reference to the other, that is to say, that identity has no sense without alterity. Moreover, the essential intencionality of identity to alterity does not imply only a practical or accidental character, but a metaphysical one, as communion constitutes the very being of personal existence.

  9. Stargazin Modulation of AMPA Receptors

    Directory of Open Access Journals (Sweden)

    Sana A. Shaikh

    2016-10-01

    Full Text Available Fast excitatory synaptic signaling in the mammalian brain is mediated by AMPA-type ionotropic glutamate receptors. In neurons, AMPA receptors co-assemble with auxiliary proteins, such as stargazin, which can markedly alter receptor trafficking and gating. Here, we used luminescence resonance energy transfer measurements to map distances between the full-length, functional AMPA receptor and stargazin expressed in HEK293 cells and to determine the ensemble structural changes in the receptor due to stargazin. In addition, we used single-molecule fluorescence resonance energy transfer to study the structural and conformational distribution of the receptor and how this distribution is affected by stargazin. Our nanopositioning data place stargazin below the AMPA receptor ligand-binding domain, where it is well poised to act as a scaffold to facilitate the long-range conformational selection observations seen in single-molecule experiments. These data support a model of stargazin acting to stabilize or select conformational states that favor activation.

  10. Radioiodinated ligands for dopamine receptors

    International Nuclear Information System (INIS)

    Kung, H.F.

    1994-01-01

    The dopamine receptor system is important for normal brain function; it is also the apparent action site for various neuroleptic drugs for the treatment of schizophrenia and other metal disorders. In the past few years radioiodinated ligands for single photon emission tomography (SPECT) have been successfully developed and tested in humans: [ 123 I]TISCH for D1 dopamine receptors; [ 123 I]IBZM, epidepride, IBF and FIDA2, four iodobenzamide derivatives, for D2/D3 dopamine receptors. In addition, [ 123 I]β-CIT (RTI-55) and IPT, cocaine derivatives, for the dopamine reuptake site are potentially useful for diagnosis of loss of dopamine neurons. The first iodinated ligand, (R)trans-7-OH-PIPAT, for D3 dopamine receptors, was synthesized and characterized with cloned cell lines (Spodoptera frugiperda, Sf9) expressing the D2 and D3 dopamine receptors and with rat basal forebrain membrane preparations. Most of the known iodobenzamides displayed similar potency in binding to both D2 and D3 dopamine receptors expressed in the cell lines. Initial studies appear to suggest that by fine tuning the structures it may be possible to develop agents specific for D2 and D3 dopamine receptors. It is important to investigate D2/D3 selectivity for this series of potent ligands

  11. Labeled receptor ligands for spect

    International Nuclear Information System (INIS)

    Kung, H.F.

    1989-01-01

    Receptor specific imaging agents for single photon emission computed tomography (SPECT) can potentially be useful in the understanding of basic biochemistry and pharmacology of receptors. SPECT images may also provide tools for evaluation of density and binding kinetics of a specific receptor, information important for diagnosis and patient management. Basic requirements for receptor imaging agents are: (a) they are labeled with short-lived isotopes, (b) they show high selectivity and specific uptake, (c) they exhibit high target/background ratio, and (d) they can be modeled to obtain quantitative information. Several good examples of CNS receptor specific ligands labeled with I-123 have been developed, including iodoQNB, iodoestrogen iodobenzadiazepine, iodobenazepine, iodobenzamides for muscarinic, estrogen benzadiazepine, D-1 and D-2 dopamine receptors. With the advent of newer and faster SPECT imaging devices, it may be feasible to quantitate the receptor density by in vivo imaging techniques. These new brain imaging agents can provide unique diagnostic information, which may not be available through other imaging modalities, such as CT and MRI

  12. Existing PON Infrastructure Supported Hybrid Fiber-Wireless Sensor Networks

    DEFF Research Database (Denmark)

    Yu, Xianbin; Zhao, Ying; Deng, Lei

    2012-01-01

    We propose a hybrid fiber wireless sensor network based on the existing PON infrastructure. The feasibility of remote sensing and PON convergence is experimentally proven by transmitting direct-sequence spread-spectrum wireless sensing and 2.5Gbps GPON signals.......We propose a hybrid fiber wireless sensor network based on the existing PON infrastructure. The feasibility of remote sensing and PON convergence is experimentally proven by transmitting direct-sequence spread-spectrum wireless sensing and 2.5Gbps GPON signals....

  13. Existing and Expected Service Quality of Grameenphone Users in Bangladesh

    Directory of Open Access Journals (Sweden)

    Azmat Ullah

    2015-12-01

    Full Text Available The Grameenphone (GP is a market leader in the telecommunication industry in Bangladesh. This study investigates the existing and expected service quality of Grameenphone users in Bangladesh. The Study reveals that there are significant gap between existing and expected perceived service network, 3G, customer care, physical facilities, billing cost, information service, mobile banking and GP offers. The study concludes that customer satisfaction is a dynamic phenomenon. Maintaining desired level of customer satisfaction requires corporate proactive responsiveness in accessing, building & retaining satisfied customers for sustainable competitive advantages in the marketplace.

  14. Principle of space existence and De Sitter metric

    International Nuclear Information System (INIS)

    Mal'tsev, V.K.

    1990-01-01

    The selection principle for the solutions of the Einstein equations suggested in a series of papers implies the existence of space (g ik ≠ 0) only in the presence of matter (T ik ≠0). This selection principle (principle of space existence, in the Markov terminology) implies, in the general case, the absence of the cosmological solution with the De Sitter metric. On the other hand, the De Sitter metric is necessary for describing both inflation and deflation periods of the Universe. It is shown that the De Sitter metric is also allowed by the selection principle under discussion if the metric experiences the evolution into the Friedmann metric

  15. [Does the right to die with dignity exist?].

    Science.gov (United States)

    Toro Flores, Rafael

    2008-12-01

    Death is one of the few certainties in human beings. This reality generates uneasiness regarding how death will occur especially in circumstances of loneliness or suffering which can become agony. In this report, the author first analyzes the existence of the right to die with dignity as a human right which takes on the nature of being a subjective right. In continuation, the author describes the existing problematic in the application of this right to die in relationship to the so-called double effect mechanism and euthanasia. The author concludes this article by proposing previous instructions or anticipated desires as ideal measures to make the right to die with dignity valid.

  16. On the existence of n-dimensional indecomposable vector bundles

    International Nuclear Information System (INIS)

    Tan Xiaojiang.

    1991-09-01

    Let X be an arbitrary smooth irreducible complex projective curve of genus g with g ≥ 4. In this paper we extend the existence theorem of special divisors to high dimensional indecomposable vector bundles. We give a necessary and sufficient condition on the existence of n-dimensional indecomposable vector bundles E with deg(E) = d, dimH 0 (X,E) ≥ h. We also determine under what condition the set of all such vector bundles will be finite and how many elements it contains. (author). 9 refs

  17. FMDP reactor alternative summary report. Volume 1 - existing LWR alternative

    International Nuclear Information System (INIS)

    Greene, S.R.; Bevard, B.B.

    1996-01-01

    Significant quantities of weapons-usable fissile materials [primarily plutonium and highly enriched uranium (HEU)] are becoming surplus to national defense needs in both the United States and Russia. These stocks of fissile materials pose significant dangers to national and international security. The dangers exist not only in the potential proliferation of nuclear weapons but also in the potential for environmental, safety, and health (ES ampersand H) consequences if surplus fissile materials are not properly managed. This document summarizes the results of analysis concerned with existing light water reactor plutonium disposition alternatives

  18. Existence of core localized toroidicity-induced Alfven eigenmode

    International Nuclear Information System (INIS)

    Fu, G.Y.

    1995-02-01

    The core-localized toroidicity-induced Alfven eigenmode (TAE) is shown to exist at finite plasma pressure due to finite aspect ratio effects in tokamak plasma. The new critical beta for the existence of the TAE mode is given by α∼ 3ε + 2s 2 , where ε = r/R is the inverse aspect ratio, s is the magnetic shear and α = -Rq 2 dβ/dr is the normalized pressure gradient. In contrast, previous critical α is given by α ∼ s 2 . In the limit of s << √r/R, the new critical α is greatly enhanced by the finite aspect ratio effects

  19. FMDP reactor alternative summary report. Volume 1 - existing LWR alternative

    Energy Technology Data Exchange (ETDEWEB)

    Greene, S.R.; Bevard, B.B. [and others

    1996-10-07

    Significant quantities of weapons-usable fissile materials [primarily plutonium and highly enriched uranium (HEU)] are becoming surplus to national defense needs in both the United States and Russia. These stocks of fissile materials pose significant dangers to national and international security. The dangers exist not only in the potential proliferation of nuclear weapons but also in the potential for environmental, safety, and health (ES&H) consequences if surplus fissile materials are not properly managed. This document summarizes the results of analysis concerned with existing light water reactor plutonium disposition alternatives.

  20. Microsomal receptor for steroid hormones: functional implications for nuclear activity.

    Science.gov (United States)

    Muldoon, T G; Watson, G H; Evans, A C; Steinsapir, J

    1988-01-01

    microsomal binding sites extracted. These observations suggest three possible roles for the microsomal receptor-like proteins: (a) modulation of estrogen access to nuclear binding sites; (b) formation of functional complexes which diffuse to other extranuclear sites to alter non-genomic cellular processes; (c) regulation of nuclear concentration of estrogen-receptor complexes by virtue of producing microsomal acceptor sites for uptake of free or loosely associated nuclear complexes, previously thought to exist in the cytoplasm.

  1. Regulation of AMPA receptor localization in lipid rafts

    OpenAIRE

    Hou, Qingming; Huang, Yunfei; Amato, Stephen; Snyder, Solomon H.; Huganir, Richard L.; Man, Heng-Ye

    2008-01-01

    Lipid rafts are special microdomains enriched in cholesterol, sphingolipids and certain proteins, and play important roles in a variety of cellular functions including signal transduction and protein trafficking. We report that in cultured cortical and hippocampal neurons the distribution of lipid rafts is development-dependent. Lipid rafts in mature neurons exist on the entire cell-surface and display a high degree of mobility. AMPA receptors co-localize and associate with lipid rafts in the...

  2. XMRV: usage of receptors and potential co-receptors

    Directory of Open Access Journals (Sweden)

    Gaddam Durga

    2011-09-01

    Full Text Available Abstract Background XMRV is a gammaretrovirus first identified in prostate tissues of Prostate Cancer (PC patients and later in the blood cells of patients with Chronic Fatigue Syndrome (CFS. Although XMRV is thought to use XPR1 for cell entry, it infects A549 cells that do not express XPR1, suggesting usage of other receptors or co-receptors. Methods To study the usage of different receptors and co- receptors that could play a role in XMRV infection of lymphoid cells and GHOST (GFP- Human osteosarcoma cells expressing CD4 along with different chemokine receptors including CCR1, CCR2, etc., were infected with XMRV. Culture supernatants and cells were tested for XMRV replication using real time quantitative PCR. Results Infection and replication of XMRV was seen in a variety of GHOST cells, LNCaP, DU145, A549 and Caski cell lines. The levels of XMRV replication varied in different cell lines showing differential replication in different cell lines. However, replication in A549 which lacks XPR1 expression was relatively higher than DU145 but lower than, LNCaP. XMRV replication varied in GHOST cell lines expressing CD4 and each of the co- receptors CCR1-CCR8 and bob. There was significant replication of XMRV in CCR3 and Bonzo although it is much lower when compared to DU145, A549 and LNCaP. Conclusion XMRV replication was observed in GHOST cells that express CD4 and each of the chemokine receptors ranging from CCR1- CCR8 and BOB suggesting that infectivity in hematopoietic cells could be mediated by use of these receptors.

  3. Existing and emerging therapies for managing constipation and diarrhea.

    Science.gov (United States)

    Bharucha, Adil E; Wouters, Mira M; Tack, Jan

    2017-12-01

    Functional bowel disorders (i.e., constipation and diarrhea) are characterized by abdominal pain, bloating, distention, and/or bowel habit abnormalities in the absence of obvious anatomic or physiologic abnormalities on routine diagnostic tests. These symptoms are attributable to gastrointestinal sensorimotor dysfunctions resulting from peripheral and/or central mechanisms. Available drugs target the underlying bowel disturbance (i.e., constipation, diarrhea, or both), supplemented when necessary by management of pain. Osmotic and stimulant laxatives, secretagogues, and serotonin 5-HT 4 receptor agonists are approved for treating constipation. Loperamide, anticholinergic agents, rifaximin, bile-acid binding agents, eluxadoline, and clonidine are used to treat diarrhea. Several exciting new compounds, some of which have been evaluated in humans, are currently under development. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. GABAA receptor: Positive and negative allosteric modulators.

    Science.gov (United States)

    Olsen, Richard W

    2018-01-31

    gamma-Aminobutyric acid (GABA)-mediated inhibitory neurotransmission and the gene products involved were discovered during the mid-twentieth century. Historically, myriad existing nervous system drugs act as positive and negative allosteric modulators of these proteins, making GABA a major component of modern neuropharmacology, and suggesting that many potential drugs will be found that share these targets. Although some of these drugs act on proteins involved in synthesis, degradation, and membrane transport of GABA, the GABA receptors Type A (GABA A R) and Type B (GABA B R) are the targets of the great majority of GABAergic drugs. This discovery is due in no small part to Professor Norman Bowery. Whereas the topic of GABA B R is appropriately emphasized in this special issue, Norman Bowery also made many insights into GABA A R pharmacology, the topic of this article. GABA A R are members of the ligand-gated ion channel receptor superfamily, a chloride channel family of a dozen or more heteropentameric subtypes containing 19 possible different subunits. These subtypes show different brain regional and subcellular localization, age-dependent expression, and potential for plastic changes with experience including drug exposure. Not only are GABA A R the targets of agonist depressants and antagonist convulsants, but most GABA A R drugs act at other (allosteric) binding sites on the GABA A R proteins. Some anxiolytic and sedative drugs, like benzodiazepine and related drugs, act on GABA A R subtype-dependent extracellular domain sites. General anesthetics including alcohols and neurosteroids act at GABA A R subunit-interface trans-membrane sites. Ethanol at high anesthetic doses acts on GABA A R subtype-dependent trans-membrane domain sites. Ethanol at low intoxicating doses acts at GABA A R subtype-dependent extracellular domain sites. Thus GABA A R subtypes possess pharmacologically specific receptor binding sites for a large group of different chemical classes of

  5. Photoaffinity labeling of the follitropin receptor

    International Nuclear Information System (INIS)

    Shin, J.; Ji, T.H.

    1985-01-01

    A photoactivatable derivative of human follitropin was used to identify the follitropin receptor on porcine granulosa cells. The hormone was condensed with a heterobifunctional reagent, the N-hydroxysuccinimide ester of 4-azidobenzoylglycine, and radioiodinated. The 125 I-labeled hormone derivative associated with the same number of receptors as 125 I-hormone itself, but with a slightly lower Ka, 1.12 X 10(10) M-1 compared with 1.4 X 10(10) M-1 for the 125 I-hormone. The binding could be blocked with untreated hormone. Its alpha and beta subunits could be cross-linked to produce alpha beta dimer by photolysis. When the 125 I-hormone derivative bound to the cells was photolyzed for crosslinking and the products resolved by electrophoresis on sodium dodecyl sulfate-polyacrylamide gels under reducing conditions, two new bands (106 and 61 kDa) of lower electrophoretic mobility appeared in addition to the alpha, beta, and alpha beta bands. Formation of these crosslinked complexes required photolysis, and the 125 I-hormone derivative specifically bound to cells bearing the receptor. Binding could be blocked by excess untreated follitropin but not with human choriogonadotropin and thyrotropin. Under nonreducing conditions, one major band (104 kDa) of cross-linked complexes appeared. Upon reduction with dithiothreitol and second-dimensional electrophoresis, the 104-kDa band produced two smaller complexes of 75 and 61 kDa, indicating the loss of two components and the existence of intercomponent disulfides. Successful production of the 104-kDa complex requires blocking of free sulfhydryl groups with N-ethylmaleimide. It is, however, independent of various protease inhibitors or the temperature and the time period of hormone incubation with cells or the plasma membrane fraction. The mass estimates and the interaction with the hormone of the photoaffinity-labeled components are discussed

  6. Photoaffinity labeling of the follitropin receptor

    Energy Technology Data Exchange (ETDEWEB)

    Shin, J.; Ji, T.H.

    1985-11-15

    A photoactivatable derivative of human follitropin was used to identify the follitropin receptor on porcine granulosa cells. The hormone was condensed with a heterobifunctional reagent, the N-hydroxysuccinimide ester of 4-azidobenzoylglycine, and radioiodinated. The SVI-labeled hormone derivative associated with the same number of receptors as SVI-hormone itself, but with a slightly lower Ka, 1.12 X 10(10) M-1 compared with 1.4 X 10(10) M-1 for the SVI-hormone. The binding could be blocked with untreated hormone. Its alpha and beta subunits could be cross-linked to produce alpha beta dimer by photolysis. When the SVI-hormone derivative bound to the cells was photolyzed for crosslinking and the products resolved by electrophoresis on sodium dodecyl sulfate-polyacrylamide gels under reducing conditions, two new bands (106 and 61 kDa) of lower electrophoretic mobility appeared in addition to the alpha, beta, and alpha beta bands. Formation of these crosslinked complexes required photolysis, and the SVI-hormone derivative specifically bound to cells bearing the receptor. Binding could be blocked by excess untreated follitropin but not with human choriogonadotropin and thyrotropin. Under nonreducing conditions, one major band (104 kDa) of cross-linked complexes appeared. Upon reduction with dithiothreitol and second-dimensional electrophoresis, the 104-kDa band produced two smaller complexes of 75 and 61 kDa, indicating the loss of two components and the existence of intercomponent disulfides. Successful production of the 104-kDa complex requires blocking of free sulfhydryl groups with N-ethylmaleimide. It is, however, independent of various protease inhibitors or the temperature and the time period of hormone incubation with cells or the plasma membrane fraction. The mass estimates and the interaction with the hormone of the photoaffinity-labeled components are discussed.

  7. Purification of the active C5a receptor from human polymorphonuclear leukocytes as a receptor - G sub i complex

    Energy Technology Data Exchange (ETDEWEB)

    Rollins, T.E.; Siciliano, S.; Kobayashi, S.; Cianciarulo, D.N.; Bonilla-Argudo, V.; Collier, K.; Springer, M.S. (Merck Sharp and Dohme Research Lab., Rahway, NJ (United States))

    1991-02-01

    The authors have isolated, in an active state, the C5a receptor from human polymorphonuclear leukocytes. The purification was achieved in a single step using a C5a affinity column in which the C5a molecule was coupled to the resin through its N terminus. The purified receptor, like the crude solubilized molecule, exhibited a single class of high-affinity binding sites with a K{sub d} of 30 pM. Further, the binding of C5a retained its sensitivity to guanine nucleotides, implying that the purified receptor contained a guanine nucleotide-binding protein (G protein). SDS/PAGE revealed the presence of three polypeptides with molecular masses of 42, 40, and 36 kDa, which were determined to be the C5a-binding subunit and the {alpha} and {beta} subunits of G{sub i}, respectively. The 36- and 40-kDa polypeptides were identified by immunoblotting and by the ability of pertussis toxin to ADP-ribosylate the 40-kDa molecule. These results confirm their earlier hypothesis that the receptor exists as a complex with a G protein in the presence or absence of C5a. The tight coupling between the receptor and G protein should make possible the identification of the G protein(s) involved in the transduction pathways used by C5a to produce its many biological effects.

  8. Purification of the active C5a receptor from human polymorphonuclear leukocytes as a receptor - Gi complex

    International Nuclear Information System (INIS)

    Rollins, T.E.; Siciliano, S.; Kobayashi, S.; Cianciarulo, D.N.; Bonilla-Argudo, V.; Collier, K.; Springer, M.S.

    1991-01-01

    The authors have isolated, in an active state, the C5a receptor from human polymorphonuclear leukocytes. The purification was achieved in a single step using a C5a affinity column in which the C5a molecule was coupled to the resin through its N terminus. The purified receptor, like the crude solubilized molecule, exhibited a single class of high-affinity binding sites with a K d of 30 pM. Further, the binding of C5a retained its sensitivity to guanine nucleotides, implying that the purified receptor contained a guanine nucleotide-binding protein (G protein). SDS/PAGE revealed the presence of three polypeptides with molecular masses of 42, 40, and 36 kDa, which were determined to be the C5a-binding subunit and the α and β subunits of G i , respectively. The 36- and 40-kDa polypeptides were identified by immunoblotting and by the ability of pertussis toxin to ADP-ribosylate the 40-kDa molecule. These results confirm their earlier hypothesis that the receptor exists as a complex with a G protein in the presence or absence of C5a. The tight coupling between the receptor and G protein should make possible the identification of the G protein(s) involved in the transduction pathways used by C5a to produce its many biological effects

  9. Taking two to tango: a role for ghrelin receptor heterodimerization in stress and reward.

    Science.gov (United States)

    Schellekens, Harriët; Dinan, Timothy G; Cryan, John F

    2013-08-30

    The gut hormone, ghrelin, is the only known peripherally derived orexigenic signal. It activates its centrally expressed receptor, the growth hormone secretagogue receptor (GHS-R1a), to stimulate food intake. The ghrelin signaling system has recently been suggested to play a key role at the interface of homeostatic control of appetite and the hedonic aspects of food intake, as a critical role for ghrelin in dopaminergic mesolimbic circuits involved in reward signaling has emerged. Moreover, enhanced plasma ghrelin levels are associated with conditions of physiological stress, which may underline the drive to eat calorie-dense "comfort-foods" and signifies a role for ghrelin in stress-induced food reward behaviors. These complex and diverse functionalities of the ghrelinergic system are not yet fully elucidated and likely involve crosstalk with additional signaling systems. Interestingly, accumulating data over the last few years has shown the GHS-R1a receptor to dimerize with several additional G-protein coupled receptors (GPCRs) involved in appetite signaling and reward, including the GHS-R1b receptor, the melanocortin 3 receptor (MC3), dopamine receptors (D1 and D2), and more recently, the serotonin 2C receptor (5-HT2C). GHS-R1a dimerization was shown to affect downstream signaling and receptor trafficking suggesting a potential novel mechanism for fine-tuning GHS-R1a receptor mediated activity. This review summarizes ghrelin's role in food reward and stress and outlines the GHS-R1a dimer pairs identified to date. In addition, the downstream signaling and potential functional consequences of dimerization of the GHS-R1a receptor in appetite and stress-induced food reward behavior are discussed. The existence of multiple GHS-R1a heterodimers has important consequences for future pharmacotherapies as it significantly increases the pharmacological diversity of the GHS-R1a receptor and has the potential to enhance specificity of novel ghrelin-targeted drugs.

  10. Impact of cell type and epitope tagging on heterologous expression of G protein-coupled receptor: a systematic study on angiotensin type II receptor.

    Directory of Open Access Journals (Sweden)

    Lili Jiang

    Full Text Available Despite heterologous expression of epitope-tagged GPCR is widely adopted for functional characterization, there is lacking of systematic analysis of the impact of expression host and epitope tag on GPCR expression. Angiotensin type II (AT2 receptor displays agonist-dependent and -independent activities, coupling to a spectrum of signaling molecules. However, consensus has not been reached on the subcellular distributions, signaling cascades and receptor-mediated actions. To examine the contributions of host cell and epitope tag on receptor expression and activity, epitope-tagged AT2 receptor variants were transiently or stably expressed in HEK293, CHO-K1 and PC12 cells. The epitope-tagged AT2 receptor variants were detected both on the cell membrane and in the perinuclear region. In transiently transfected HEK293 cells, Myc-AT2 existed predominantly as monomer. Additionally, a ladder of ubiquitinated AT2 receptor proteins was detected. By contrast, stably expressed epitope-tagged AT2 receptor variants existed as both monomer and high molecular weight complexes, and the latter was enriched in cell surface. Glycosylation promoted cell surface expression of Myc-AT2 but had no effect on AT2-GFP in HEK293 cells. In cells that stably expressed Myc-AT2, serum starvation induced apoptosis in CHO-K1 cells but not in HEK293 or PC12 cells. Instead, HEK293 and PC12 cells stably expressing Myc-AT2 exhibited partial cell cycle arrest with cells accumulating at G1 and S phases, respectively. Taken together, these results suggest that expression levels, subcellular distributions and ligand-independent constitutive activities of AT2 receptor were cell type-dependent while posttranslational processing of nascent AT2 receptor protein was modulated by epitope tag and mode of expression.

  11. How Far Does a Receptor Influence Vibrational Properties of an Odorant?

    Science.gov (United States)

    Reese, Anna; List, Nanna Holmgaard; Kongsted, Jacob; Solov'yov, Ilia A

    2016-01-01

    The biophysical mechanism of the sense of smell, or olfaction, is still highly debated. The mainstream explanation argues for a shape-based recognition of odorant molecules by olfactory receptors, while recent investigations suggest the primary olfactory event to be triggered by a vibrationally-assisted electron transfer reaction. We consider this controversy by studying the influence of a receptor on the vibrational properties of an odorant in atomistic details as the coupling between electronic degrees of freedom of the receptor and the vibrations of the odorant is the key parameter of the vibrationally-assisted electron transfer. Through molecular dynamics simulations we elucidate the binding specificity of a receptor towards acetophenone odorant. The vibrational properties of acetophenone inside the receptor are then studied by the polarizable embedding density functional theory approach, allowing to quantify protein-odorant interactions. Finally, we judge whether the effects of the protein provide any indications towards the existing theories of olfaction.

  12. Specific olfactory receptor populations projecting to identified glomeruli in the rat olfactory bulb.

    Science.gov (United States)

    Jastreboff, P J; Pedersen, P E; Greer, C A; Stewart, W B; Kauer, J S; Benson, T E; Shepherd, G M

    1984-08-01

    A critical gap exists in our knowledge of the topographical relationship between the olfactory epithelium and olfactory bulb. The present report describes the application to this problem of a method involving horseradish peroxidase conjugated to wheat germ agglutinin. This material was iontophoretically delivered to circumscribed glomeruli in the olfactory bulb and the characteristics and distribution of retrogradely labeled receptor cells were assessed. After discrete injections into small glomerular groups in the caudomedial bulb, topographically defined populations of receptor cells were labeled. Labeled receptor cell somata appeared at several levels within the epithelium. The receptor cell apical dendrites followed a tight helical course towards the surface of the epithelium. The data thus far demonstrate that functional units within the olfactory system may include not only glomeruli as previously suggested but, in addition, a corresponding matrix of receptor cells possessing functional and topographical specificity.

  13. Probabilistic risk assessment for new and existing chemicals: Example calculations

    NARCIS (Netherlands)

    Jager T; Hollander HA den; Janssen GB; Poel P van der; Rikken MGJ; Vermeire TG; ECO; CSR; LAE; CSR

    2000-01-01

    In the risk assessment methods for new and existing chemicals in the EU, "risk" is characterised by means of the deterministic quotient of exposure and effects (PEC/PNEC or Margin of Safety). From a scientific viewpoint, the uncertainty in the risk quotient should be accounted for explicitly in the

  14. 40 CFR 407.14 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for existing sources. 407.14 Section 407.14 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS CANNED AND PRESERVED FRUITS AND VEGETABLES PROCESSING POINT SOURCE...

  15. 40 CFR 407.34 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for existing sources. 407.34 Section 407.34 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS CANNED AND PRESERVED FRUITS AND VEGETABLES PROCESSING POINT SOURCE...

  16. 40 CFR 407.24 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for existing sources. 407.24 Section 407.24 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS CANNED AND PRESERVED FRUITS AND VEGETABLES PROCESSING POINT SOURCE...

  17. 40 CFR 406.14 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for existing sources. 406.14 Section 406.14 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GRAIN MILLS POINT SOURCE CATEGORY Corn Wet Milling Subcategory § 406.14...

  18. 40 CFR 406.24 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for existing sources. 406.24 Section 406.24 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GRAIN MILLS POINT SOURCE CATEGORY Corn Dry Milling Subcategory § 406.24...

  19. Building OOC layers on top of existing courses

    DEFF Research Database (Denmark)

    Bang, Jørgen; Dalsgaard, Christian; Kjær, Arne

    2016-01-01

    prefer the term "Open Online Courses", MOOCs (Massive Open Online Courses) without the M. This paper will present our approach to building OOCs on top of existing campusbased courses at Aarhus University, Denmark. Consequently, participants of an 'OOC track' will engage in collaboration and discussions...

  20. 40 CFR 421.275 - Pretreatment standards for existing sources.

    Science.gov (United States)

    2010-07-01

    ... Nickel 0.000 0.000 (e) Sodium hypochlorite filter backwash. PSES for the Primary Rare Earth Metals...) EFFLUENT GUIDELINES AND STANDARDS NONFERROUS METALS MANUFACTURING POINT SOURCE CATEGORY Primary Rare Earth Metals Subcategory § 421.275 Pretreatment standards for existing sources. Except as provided in 40 CFR...