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Sample records for endogenous prolactin-releasing peptide

  1. Prolactin-releasing peptide: a new tool for obesity treatment

    Czech Academy of Sciences Publication Activity Database

    Kuneš, Jaroslav; Pražienková, Veronika; Popelová, Andrea; Mikulášková, Barbora; Zemenová, Jana; Maletínská, Lenka

    2016-01-01

    Roč. 230, č. 2 (2016), R51-R58 ISSN 0022-0795 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:61388963 Keywords : prolactin-releasing peptide * lipidization * obesity * GPR10 * anorexigenic * mice Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 4.706, year: 2016

  2. Prolactin-releasing peptide: a new tool for obesity treatment

    Czech Academy of Sciences Publication Activity Database

    Kuneš, Jaroslav; Pražienková, V.; Popelová, A.; Mikulášková, Barbora; Zemenová, J.; Maletínská, L.

    2016-01-01

    Roč. 230, č. 2 (2016), R51-R58 ISSN 0022-0795 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:67985823 Keywords : prolactin-releasing peptide * lipidization * obesity * GPR10 * anorexigenic * mice Subject RIV: ED - Physiology Impact factor: 4.706, year: 2016

  3. Lipidized prolactin-releasing peptide analogs: A new tool for obesity treatment

    Czech Academy of Sciences Publication Activity Database

    Maletínská, Lenka; Pražienková, Veronika; Zemenová, Jana; Popelová, Andrea; Blechová, Miroslava; Mikulášková, Barbora; Holubová, Martina; Železná, Blanka; Kuneš, Jaroslav

    2016-01-01

    Roč. 22, Suppl S2 (2016), S179-S180 ISSN 1075-2617. [European Peptide Symposium /34./ and International Peptide Symposium /8./. 04.09.2016-09.09.2016, Leipzig] R&D Projects: GA TA ČR(CZ) TE01020028; GA ČR(CZ) GA15-08679S Institutional support: RVO:61388963 Keywords : prolactin-releasing peptide * food intake * obesity Subject RIV: CE - Biochemistry

  4. Pharmacological characterization of lipidized analogs of prolactin-releasing peptide with a modified C-terminal aromatic ring

    Czech Academy of Sciences Publication Activity Database

    Pražienková, Veronika; Tichá, Anežka; Blechová, Miroslava; Špolcová, Andrea; Železná, Blanka; Maletínská, Lenka

    2016-01-01

    Roč. 67, č. 1 (2016), s. 121-128 ISSN 0867-5910 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:61388963 Keywords : prolactin-releasing peptide * blood-brain barrier * food intake * lipidization * phenylalanine derivatives Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 2.883, year: 2016 http://www.jpp.krakow.pl/journal/archive/02_16/articles/11_article.html

  5. Neuropeptide FF and prolactin-releasing peptide decrease cortical excitability through activation of NPFF receptors.

    Science.gov (United States)

    Buffel, Ine; Meurs, Alfred; Portelli, Jeanelle; Raedt, Robrecht; De Herdt, Veerle; Sioncke, Lynn; Wadman, Wytse; Bihel, Frederic; Schmitt, Martine; Vonck, Kristl; Bourguignon, Jean-Jacques; Simonin, Frederic; Smolders, Ilse; Boon, Paul

    2015-03-01

    Drugs with a novel mechanism of action are needed to reduce the number of people with epilepsy that are refractory to treatment. Increasing attention is paid to neuropeptide systems and several anticonvulsant neuropeptides have already been described, such as galanin, ghrelin, and neuropeptide Y (NPY). Many others, however, have not been investigated for their ability to affect epileptic seizures. In this study, the potential anticonvulsant activities of three members of the RF-amide neuropeptide family, neuropeptide FF (NPFF), prolactin-releasing peptide (PrRP), and kisspeptin (Kp) and other receptor ligands (NPFF1/2 R, GPR10, and GRP54, respectively) were tested in the motor cortex stimulation model. A train of pulses with increasing intensity (0-10 mA over 150 s, 50 Hz, pulse width 2 msec) was delivered to the motor cortex of rats. The threshold intensity for eliciting a motor response (i.e., motor threshold) was determined through behavioral observation and used as a measure for cortical excitability. The threshold was determined before, during, and after the intracerebroventricular (i.c.v.) administration of various NPFF1/2 R, GPR10, and GPR54 receptor ligands. NPFF and PrRP significantly increased the motor threshold by a maximum of 143 ± 27 and 83 ± 13 μA, respectively, for the doses of 1 nmol/h (p < 0.05). The increase of motor threshold by NPFF and PrRP was prevented by pretreatment and co-treatment with the NPFF1/2 R antagonist RF9. Pretreatment with a selective NPFF1 R antagonist also prevented the threshold increase induced by NPFF. Kp did not increase motor threshold. Intracerebroventricular infusion of NPFF or PrRP decreases cortical excitability in rats through activation of NPFFRs. Furthermore, the NPFF1 R is required for the NPFF-induced decrease in cortical excitability. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

  6. Effect of palmitoylated prolactin-releasing peptide on food intake and neural activation after different routes of peripheral administration in rats

    Czech Academy of Sciences Publication Activity Database

    Mikulášková, Barbora; Zemenová, Jana; Pirník, Zdenko; Pražienková, Veronika; Bednárová, Lucie; Železná, Blanka; Maletínská, Lenka; Kuneš, Jaroslav

    2016-01-01

    Roč. 75, Jan (2016), s. 109-117 ISSN 0196-9781 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:61388963 Keywords : prolactin-releasing peptide * lipidization * food intake * c-Fos * pharmacokinetics * CD spectroscopy Subject RIV: CE - Biochemistry Impact factor: 2.778, year: 2016

  7. Novel lipidized analogs of prolactin-releasing peptide have prolonged half-lives and exert anti-obesity effects after peripheral administration

    Czech Academy of Sciences Publication Activity Database

    Maletínská, L.; Nagelová, V.; Tichá, A.; Zemenová, J.; Pirník, Z.; Holubová, M.; Špolcová, A.; Mikulášková, Barbora; Blechová, M.; Sýkora, D.; Lacinová, Z.; Haluzík, M.; Železná, B.; Kuneš, Jaroslav

    2015-01-01

    Roč. 39, č. 6 (2015), s. 986-993 ISSN 0307-0565 R&D Projects: GA TA ČR(CZ) TE01020028 Institutional support: RVO:67985823 Keywords : food intake * prolactin-releasing peptide * GPR10 receptor Subject RIV: CE - Biochemistry Impact factor: 5.337, year: 2015

  8. Effect of palmitoylated prolactin-releasing peptide on food intake and neural activation after different routes of peripheral administration in rats

    Czech Academy of Sciences Publication Activity Database

    Mikulášková, Barbora; Zemenová, J.; Pirník, Z.; Pražienková, V.; Bednárová, L.; Železná, B.; Maletínská, L.; Kuneš, Jaroslav

    2016-01-01

    Roč. 75, Jan (2016), s. 109-117 ISSN 0196-9781 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:67985823 Keywords : prolactin-releasing peptide * lipidization * food intake * c-Fos * pharmacokinetics * CD spectroscopy Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 2.778, year: 2016

  9. Peripheral administration of palmitoylated prolactin-releasing peptide induces Fos expression in hypothalamic neurons involved in energy homeostasis in NMRI male mice

    Czech Academy of Sciences Publication Activity Database

    Pirník, Zdenko; Železná, Blanka; Kiss, A.; Maletínská, Lenka

    2015-01-01

    Roč. 1625, Nov 2 (2015), s. 151-158 ISSN 0006-8993 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:61388963 Keywords : hypothalamus * prolactin-releasing peptide * Fos * oxytocin * hypocretin * mice Subject RIV: CE - Biochemistry Impact factor: 2.561, year: 2015

  10. LC-MS/MS analysis of lipidized analogs of prolactin-releasing peptide utilizing a monolithic column and simple sample preparation

    Czech Academy of Sciences Publication Activity Database

    Zemenová, Jana; Sýkora, D.; Freislebenová, A.; Maletínská, Lenka

    2017-01-01

    Roč. 9, č. 17 (2017), s. 1319-1328 ISSN 1757-6180 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:61388963 Keywords : LC-MS * lipopeptides * monolithic column * prolactin-releasing peptide * stability Subject RIV: CE - Biochemistry OBOR OECD: Biochemical research methods Impact factor: 2.673, year: 2016

  11. Novel lipidized analogs of prolactin-releasing peptide have prolonged half-lives and exert anti-obesity effects after peripheral administration

    Czech Academy of Sciences Publication Activity Database

    Maletínská, Lenka; Nagelová, Veronika; Tichá, Anežka; Zemenová, Jana; Pirník, Zdenko; Holubová, Martina; Špolcová, Andrea; Mikulášková, Barbora; Blechová, Miroslava; Sýkora, D.; Lacinová, Z.; Haluzík, M.; Železná, Blanka; Kuneš, Jaroslav

    2015-01-01

    Roč. 39, č. 6 (2015), s. 986-993 ISSN 0307-0565 R&D Projects: GA ČR GAP303/10/1368; GA ČR GAP303/12/0576; GA TA ČR(CZ) TE01020028 Institutional support: RVO:61388963 Keywords : food intake * prolactin-releasing peptide * GPR10 receptor Subject RIV: CE - Biochemistry Impact factor: 5.337, year: 2015

  12. Characterization of prolactin-releasing peptide binding, signaling and hormone secretion in rodent pituitary cell lines

    Czech Academy of Sciences Publication Activity Database

    Maletínská, Lenka; Maixnerová, Jana; Špolcová, Andrea; Pýchová, Miroslava; Blechová, Miroslava; Železná, Blanka

    2010-01-01

    Roč. 16, S1 (2010), s. 153-153 ISSN 1075-2617. [European Peptide Symposium /31./. 05.09.2010-09.09.2010, Copenhagen] R&D Projects: GA ČR GAP303/10/1368 Institutional research plan: CEZ:AV0Z40550506 Keywords : PrRP * GPR10 * pituitary cell lines * RC-4B/C cells Subject RIV: CC - Organic Chemistry

  13. Characterization of prolactin-releasing peptide: Binding, signaling and hormone secretion in rodent pituitary cell lines endogenously expressing its receptor

    Czech Academy of Sciences Publication Activity Database

    Maixnerová, Jana; Špolcová, Andrea; Pýchová, Miroslava; Blechová, Miroslava; Elbert, Tomáš; Řezáčová, M.; Železná, Blanka; Maletínská, Lenka

    2011-01-01

    Roč. 32, č. 4 (2011), s. 811-817 ISSN 0196-9781 R&D Projects: GA ČR GAP303/10/1368 Institutional research plan: CEZ:AV0Z40550506 Keywords : PrRP * pituitary cell lines * food intake Subject RIV: CC - Organic Chemistry Impact factor: 2.434, year: 2011

  14. Novel Endogenous Antimicrobial Peptides

    OpenAIRE

    Nordahl, Emma

    2009-01-01

    Antimicrobial peptides serve as a first line of defence against invading microorganisms and are an essential part of our fast innate immune system. They are ancient molecules found in all classes of life. Antimicrobial peptides rapidly kill a broad spectrum of microbes and are immunomodulatory, i.e. having additional actions influencing inflammation and other innate immune responses. Results presented in this thesis demonstrate that proteases of common human pathogens degrade and inactivate t...

  15. Involvement of arachidonate metabolism in neurotensin-induced prolactin release in vitro

    International Nuclear Information System (INIS)

    Canonico, P.L.; Speciale, C.; Sortino, M.A.; Scapagnini, U.

    1985-01-01

    Neurotensin increased in a concentration-dependent manner the level of hypophyseal [ 3 H]arachidonic acid in vitro as well as prolactin release from hemipituitary glands. The effect of 1 microM neurotensin on arachidonate release was already present at 2.5 min, maximal at 5, and disappeared after a 10-min incubation. Neurotensin analogues produced an enhancement of hypophyseal arachidonate similar to their relative potencies in other cellular systems, whereas other peptides (somatostatin and vasoactive intestinal peptide) were devoid of any effect on the concentration of the fatty acid in the pituitary. Seventy micromoles RHC 80267, a rather selective inhibitor of diacylglycerol lipase, completely prevented the neurotensin-stimulated prolactin release and decreased arachidonate release both in basal or in neurotensin-induced conditions. Similar results were obtained with 50 microM quinacrine, a phospholipase A2 inhibitor. To clarify whether arachidonate released by neurotensin requires a further metabolism through specific pathways to stimulate prolactin release, the authors used indomethacin and BW 755c, two blockers of cyclooxygenase and lipoxygenase pathways. Thirty micromoles indomethacin, a dose active to inhibit cyclooxygenase, did not affect unesterified arachidonate levels either in basal or in neurotensin-induced conditions; moreover, the drug did not modify basal prolactin release but slightly potentiated the stimulatory effect of neurotensin on the release of the hormone. On the other hand, 250 microM BW 755c, an inhibitor of both cyclooxygenase and lipoxygenase pathways, significantly inhibited both basal and neurotensin-stimulated prolactin release and further potentiated the increase of the fatty acid concentrations produced by 1 microM neurotensin

  16. Excitatory and inhibitory effects of prolactin release activated by nerve stimulation in rat anterior pituitary

    Directory of Open Access Journals (Sweden)

    Gao Li-Zhi

    2009-12-01

    Full Text Available Abstract Background A series of studies showed the presence of substantial amount of nerve fibers and their close relationship with the anterior pituitary gland cells. Our previous studies have suggested that aside from the classical theory of humoral regulation, the rat anterior pituitary has direct neural regulation on adrenocorticotropic hormone release. In rat anterior pituitary, typical synapses are found on every type of the hormone-secreting cells, many on lactotrophs. The present study was aimed at investigating the physiological significance of this synaptic relationship on prolactin release. Methods The anterior pituitary of rat was sliced and stimulated with electrical field in a self-designed perfusion chamber. The perfusate was continuously collected in aliquots and measured by radioimmunoassay for prolactin levels. After statistic analysis, differences of prolactin concentrations within and between groups were outlined. Results The results showed that stimulation at frequency of 2 Hz caused a quick enhancement of prolactin release, when stimulated at 10 Hz, prolactin release was found to be inhibited which came slower and lasted longer. The effect of nerve stimulation on prolactin release is diphasic and frequency dependent. Conclusions The present in vitro study offers the first physiological evidence that stimulation of nerve fibers can affect prolactin release in rat anterior pituitary. Low frequency stimulation enhances prolactin release and high frequency mainly inhibits it.

  17. Endogenous opioid peptides as neurotransmitters in the rat hippocampus

    International Nuclear Information System (INIS)

    Neumaier, J.F.

    1989-01-01

    The role of endogenous opioid peptides as neurotransmitters in the rat hippocampus was investigated by using extracellular recording and radioligand binding techniques in the hippocampal slice preparation. Synaptic conductances from endogenously released opioid peptides have been difficult to detect. This problem was approach by designing a novel assay of opioid peptide release, in which release was detected by measuring binding competition between endogenous opioids and added radioligand. Membrane depolarization displaced [ 3 H]-diprenorphine binding in a transient, calcium-dependent, and peptidase-sensitive manner. Autoradiographic localization of the sites of [ 3 H]-diprenorphine binding displacement showed that significant opioid peptide release and receptor occupancy occurred in each major subregion of the hippocampal slices. This assay method can not be used to define optimal electrical stimulation conditions for releasing endogenous opioids. The binding displacement method was extended to the study of the sigma receptor. Depolarization of hippocampal slices was found to reduce the binding of the sigma-selective radioligand [ 3 H]-ditolylguanidine in a transient and calcium-dependent manner with no apparent direct effects on sigma receptor affinity

  18. Dopamine inhibits maitotoxin-stimulated pituitary 45Ca2+ efflux and prolactin release

    International Nuclear Information System (INIS)

    Login, I.S.; Judd, A.M.; MacLeod, R.M.

    1986-01-01

    The authors examined the hypothesis that dopaminergic inhibition of prolactin release is coupled to modulation of cellular calcium flux. Dispersed female rat pituitary cells were prelabeled in 45 Ca 2+ and perifused to determine simultaneously fractional calcium efflux and prolactin release, as stimulated by maitotoxin, a calcium channel activator. The integrated response of each parameter to 5 ng/ml maitotoxin was obtained in individual perifusion columns in the absence or presence of various concentrations of dopamine. Maitotoxin-stimulated calcium efflux was suppressed by dopamine concentrations of 0.01 μM and greater and achieved a maximal effect at ∼0.1 μM, at which calcium efflux was reduced by 50%. Maitotoxin-stimulated prolactin release was inhibited by 0.03 μM dopamine and greater concentrations, and at a concentration of ∼10.0 μM dopamine the effect became maximal at ∼85% suppression. Haloperidol (0.1 μM) blocked the effects of 0.1 μM dopamine on both parameters. Simultaneous suppression of maitotoxin-stimulated calcium efflux and prolactin release by concentrations of dopamine within the nonomolar range suggests that dopamine receptor activation is negatively coupled to modulation of calcium flux in the physiological regulation of prolactin secretion

  19. Prolactin release in children treated with risperidone - Impact and role of CYP2D6 metabolism

    NARCIS (Netherlands)

    Troost, Pieter W.; Lahuis, Bertine E.; Hermans, Mirjam H.; Buitelaar, Jan K.; van Engeland, Herman; Scahill, Lawrence; Minderaa, Ruud B.; Hoekstra, Pieter J.

    Objective: Little is known about the role of CYP2136 polymorphism in risperidone-induced prolactin release in children. Method: Twenty-five children (aged 5-15 years) with pervasive developmental disorders were genotyped for CYP2D6 polymorphisms. Serum prolactin, risperidone, and

  20. Methylmercury inhibits prolactin release in a cell line of pituitary origin

    Directory of Open Access Journals (Sweden)

    L.A.L. Maués

    2015-08-01

    Full Text Available Heavy metals, such as methylmercury, are key environmental pollutants that easily reach human beings by bioaccumulation through the food chain. Several reports have demonstrated that endocrine organs, and especially the pituitary gland, are potential targets for mercury accumulation; however, the effects on the regulation of hormonal release are unclear. It has been suggested that serum prolactin could represent a biomarker of heavy metal exposure. The aim of this study was to evaluate the effect of methylmercury on prolactin release and the role of the nitrergic system using prolactin secretory cells (the mammosomatotroph cell line, GH3B6. Exposure to methylmercury (0-100 μM was cytotoxic in a time- and concentration-dependent manner, with an LC50 higher than described for cells of neuronal origin, suggesting GH3B6 cells have a relative resistance. Methylmercury (at exposures as low as 1 μM for 2 h also decreased prolactin release. Interestingly, inhibition of nitric oxide synthase by N-nitro-L-arginine completely prevented the decrease in prolactin release without acute neurotoxic effects of methylmercury. These data indicate that the decrease in prolactin production occurs via activation of the nitrergic system and is an early effect of methylmercury in cells of pituitary origin.

  1. Some aspects of physiology and pharmacology of endogenous opioid peptides.

    Science.gov (United States)

    Przewłocki, R

    1984-01-01

    The review, based largely on our own results describes the present state of knowledge of some aspects of opioid peptides and their physiological role. Studies on the effect of opioid peptides and opiates on brain function and the changes of brain level of endogenous opioids under various conditions have demonstrated, among others, the role of opioids in stress and stress-induced analgesia, the involvement of various opioid receptors in spinal mechanisms of analgesia, the inhibitory role of dynorphin in seizures in contrast to proconvulsant action of beta-endorphin system and mu receptor, and led to postulation of the role of beta-endorphin interaction with serotonin for ingestive behavior and a possible involvement of beta-endorphin system in the mechanism of action of antidepressant treatments.

  2. Combinations of physiologic estrogens with xenoestrogens alter calcium and kinase responses, prolactin release, and membrane estrogen receptor trafficking in rat pituitary cells

    Directory of Open Access Journals (Sweden)

    Watson Cheryl S

    2010-10-01

    Full Text Available Abstract Background Xenoestrogens such as alkylphenols and the structurally related plastic byproduct bisphenol A have recently been shown to act potently via nongenomic signaling pathways and the membrane version of estrogen receptor-α. Though the responses to these compounds are typically measured individually, they usually contaminate organisms that already have endogenous estrogens present. Therefore, we used quantitative medium-throughput screening assays to measure the effects of physiologic estrogens in combination with these xenoestrogens. Methods We studied the effects of low concentrations of endogenous estrogens (estradiol, estriol, and estrone at 10 pM (representing pre-development levels, and 1 nM (representing higher cycle-dependent and pregnancy levels in combinations with the same levels of xenoestrogens in GH3/B6/F10 pituitary cells. These levels of xenoestrogens represent extremely low contamination levels. We monitored calcium entry into cells using Fura-2 fluorescence imaging of single cells. Prolactin release was measured by radio-immunoassay. Extracellular-regulated kinase (1 and 2 phospho-activations and the levels of three estrogen receptors in the cell membrane (ERα, ERβ, and GPER were measured using a quantitative plate immunoassay of fixed cells either permeabilized or nonpermeabilized (respectively. Results All xenoestrogens caused responses at these concentrations, and had disruptive effects on the actions of physiologic estrogens. Xenoestrogens reduced the % of cells that responded to estradiol via calcium channel opening. They also inhibited the activation (phosphorylation of extracellular-regulated kinases at some concentrations. They either inhibited or enhanced rapid prolactin release, depending upon concentration. These latter two dose-responses were nonmonotonic, a characteristic of nongenomic estrogenic responses. Conclusions Responses mediated by endogenous estrogens representing different life stages are

  3. Combinations of physiologic estrogens with xenoestrogens alter calcium and kinase responses, prolactin release, and membrane estrogen receptor trafficking in rat pituitary cells.

    Science.gov (United States)

    Jeng, Yow-Jiun; Kochukov, Mikhail; Watson, Cheryl S

    2010-10-15

    Xenoestrogens such as alkylphenols and the structurally related plastic byproduct bisphenol A have recently been shown to act potently via nongenomic signaling pathways and the membrane version of estrogen receptor-α. Though the responses to these compounds are typically measured individually, they usually contaminate organisms that already have endogenous estrogens present. Therefore, we used quantitative medium-throughput screening assays to measure the effects of physiologic estrogens in combination with these xenoestrogens. We studied the effects of low concentrations of endogenous estrogens (estradiol, estriol, and estrone) at 10 pM (representing pre-development levels), and 1 nM (representing higher cycle-dependent and pregnancy levels) in combinations with the same levels of xenoestrogens in GH3/B6/F10 pituitary cells. These levels of xenoestrogens represent extremely low contamination levels. We monitored calcium entry into cells using Fura-2 fluorescence imaging of single cells. Prolactin release was measured by radio-immunoassay. Extracellular-regulated kinase (1 and 2) phospho-activations and the levels of three estrogen receptors in the cell membrane (ERα, ERβ, and GPER) were measured using a quantitative plate immunoassay of fixed cells either permeabilized or nonpermeabilized (respectively). All xenoestrogens caused responses at these concentrations, and had disruptive effects on the actions of physiologic estrogens. Xenoestrogens reduced the % of cells that responded to estradiol via calcium channel opening. They also inhibited the activation (phosphorylation) of extracellular-regulated kinases at some concentrations. They either inhibited or enhanced rapid prolactin release, depending upon concentration. These latter two dose-responses were nonmonotonic, a characteristic of nongenomic estrogenic responses. Responses mediated by endogenous estrogens representing different life stages are vulnerable to very low concentrations of these structurally

  4. Gastrointestinal Endogenous Proteins as a Source of Bioactive Peptides - An In Silico Study

    Science.gov (United States)

    Dave, Lakshmi A.; Montoya, Carlos A.; Rutherfurd, Shane M.; Moughan, Paul J.

    2014-01-01

    Dietary proteins are known to contain bioactive peptides that are released during digestion. Endogenous proteins secreted into the gastrointestinal tract represent a quantitatively greater supply of protein to the gut lumen than those of dietary origin. Many of these endogenous proteins are digested in the gastrointestinal tract but the possibility that these are also a source of bioactive peptides has not been considered. An in silico prediction method was used to test if bioactive peptides could be derived from the gastrointestinal digestion of gut endogenous proteins. Twenty six gut endogenous proteins and seven dietary proteins were evaluated. The peptides present after gastric and intestinal digestion were predicted based on the amino acid sequence of the proteins and the known specificities of the major gastrointestinal proteases. The predicted resultant peptides possessing amino acid sequences identical to those of known bioactive peptides were identified. After gastrointestinal digestion (based on the in silico simulation), the total number of bioactive peptides predicted to be released ranged from 1 (gliadin) to 55 (myosin) for the selected dietary proteins and from 1 (secretin) to 39 (mucin-5AC) for the selected gut endogenous proteins. Within the intact proteins and after simulated gastrointestinal digestion, angiotensin converting enzyme (ACE)-inhibitory peptide sequences were the most frequently observed in both the dietary and endogenous proteins. Among the dietary proteins, after in silico simulated gastrointestinal digestion, myosin was found to have the highest number of ACE-inhibitory peptide sequences (49 peptides), while for the gut endogenous proteins, mucin-5AC had the greatest number of ACE-inhibitory peptide sequences (38 peptides). Gut endogenous proteins may be an important source of bioactive peptides in the gut particularly since gut endogenous proteins represent a quantitatively large and consistent source of protein. PMID:24901416

  5. Gastrointestinal endogenous proteins as a source of bioactive peptides--an in silico study.

    Science.gov (United States)

    Dave, Lakshmi A; Montoya, Carlos A; Rutherfurd, Shane M; Moughan, Paul J

    2014-01-01

    Dietary proteins are known to contain bioactive peptides that are released during digestion. Endogenous proteins secreted into the gastrointestinal tract represent a quantitatively greater supply of protein to the gut lumen than those of dietary origin. Many of these endogenous proteins are digested in the gastrointestinal tract but the possibility that these are also a source of bioactive peptides has not been considered. An in silico prediction method was used to test if bioactive peptides could be derived from the gastrointestinal digestion of gut endogenous proteins. Twenty six gut endogenous proteins and seven dietary proteins were evaluated. The peptides present after gastric and intestinal digestion were predicted based on the amino acid sequence of the proteins and the known specificities of the major gastrointestinal proteases. The predicted resultant peptides possessing amino acid sequences identical to those of known bioactive peptides were identified. After gastrointestinal digestion (based on the in silico simulation), the total number of bioactive peptides predicted to be released ranged from 1 (gliadin) to 55 (myosin) for the selected dietary proteins and from 1 (secretin) to 39 (mucin-5AC) for the selected gut endogenous proteins. Within the intact proteins and after simulated gastrointestinal digestion, angiotensin converting enzyme (ACE)-inhibitory peptide sequences were the most frequently observed in both the dietary and endogenous proteins. Among the dietary proteins, after in silico simulated gastrointestinal digestion, myosin was found to have the highest number of ACE-inhibitory peptide sequences (49 peptides), while for the gut endogenous proteins, mucin-5AC had the greatest number of ACE-inhibitory peptide sequences (38 peptides). Gut endogenous proteins may be an important source of bioactive peptides in the gut particularly since gut endogenous proteins represent a quantitatively large and consistent source of protein.

  6. Kinetics of circulating endogenous insulin, C-peptide, and proinsulin in fasting nondiabetic man

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Tronier, B; Bülow, J B

    1987-01-01

    Plasma concentrations of insulin, C-peptide, and proinsulin were measured in different vascular beds in order to determine renal, hepatic, and systemic kinetics of the endogenous peptides in the fasting condition. Nineteen nondiabetic subjects were studied, two were normal, nine had minor vascular...

  7. Suckling-induced prolactin release potentiates mifepristone-induced lactogenesis in pregnant rats.

    Science.gov (United States)

    Deis, R P; Carrizo, D G; Jahn, G A

    1989-09-01

    Suckling, starting at 19:00 h on Day 18 of pregnancy, induced a significant increase in serum prolactin concentration at 20:00 h on Day 19 of pregnancy, but no increase in mammary gland casein or lactose content. Mifepristone (2 mg/kg) injection at 08:00 h on Day 19 of pregnancy induced significant increases in casein, but not in lactose, 24 h after administration. Mifepristone alone did not induce prolactin secretion, indicating that lactogenesis was induced by placental lactogen in the absence of progesterone action. When mifepristone was injected into suckling rats, serum prolactin concentrations were higher than in the untreated suckling rats. Casein in these rats increased significantly 12 h after mifepristone administration and lactose at 24 h after. If the suckling mifepristone-treated rats were given two injections of bromocriptine (1.5 mg/kg) at 12:00 h on Days 18 and 19 of pregnancy, serum prolactin concentrations were not increased by suckling, but casein and lactose concentrations in the mammary gland showed values similar to those obtained in the mifepristone-treated non-suckling rats. Mifepristone can therefore potentiate suckling-induced prolactin release in pregnant rats, demonstrating a direct central inhibitory action of progesterone on prolactin secretion. This suckling-induced prolactin secretion, unable to induce casein or lactose synthesis in the presence of progesterone, enhanced significantly synthesis of these milk components in the absence of progesterone action (rats treated with mifepristone). Fatty acid synthase, which is stimulated by the suckling stimulus in lactating rats, was not modified by mifepristone or suckling in pregnant rats.

  8. Recognition of GPCRs by peptide ligands and membrane compartments theory: structural studies of endogenous peptide hormones in membrane environment.

    Science.gov (United States)

    Sankararamakrishnan, Ramasubbu

    2006-04-01

    One of the largest family of cell surface proteins, G-protein coupled receptors (GPCRs) regulate virtually all known physiological processes in mammals. With seven transmembrane segments, they respond to diverse range of extracellular stimuli and represent a major class of drug targets. Peptidergic GPCRs use endogenous peptides as ligands. To understand the mechanism of GPCR activation and rational drug design, knowledge of three-dimensional structure of receptor-ligand complex is important. The endogenous peptide hormones are often short, flexible and completely disordered in aqueous solution. According to "Membrane Compartments Theory", the flexible peptide binds to the membrane in the first step before it recognizes its receptor and the membrane-induced conformation is postulated to bind to the receptor in the second step. Structures of several peptide hormones have been determined in membrane-mimetic medium. In these studies, micelles, reverse micelles and bicelles have been used to mimic the cell membrane environment. Recently, conformations of two peptide hormones have also been studied in receptor-bound form. Membrane environment induces stable secondary structures in flexible peptide ligands and membrane-induced peptide structures have been correlated with their bioactivity. Results of site-directed mutagenesis, spectroscopy and other experimental studies along with the conformations determined in membrane medium have been used to interpret the role of individual residues in the peptide ligand. Structural differences of membrane-bound peptides that belong to the same family but differ in selectivity are likely to explain the mechanism of receptor selectivity and specificity of the ligands. Knowledge of peptide 3D structures in membrane environment has potential applications in rational drug design.

  9. Endogenous peptide profile for elucidating biosynthetic processing of the ghrelin precursor.

    Science.gov (United States)

    Tsuchiya, Takashi; Iwakura, Hiroshi; Minamino, Naoto; Kangawa, Kenji; Sasaki, Kazuki

    2017-09-02

    Ghrelin is an orexigenic peptide primarily produced by gastric endocrine cells. The biosynthetic cleavage site of ghrelin has been well documented, but how its downstream region undergoes proteolytic processing remains poorly explored. Here, we provide the first snapshot of endogenous peptides from the ghrelin precursor by profiling the secretopeptidome of cultured mouse ghrelin-producing cells during exocytosis. Mapping of MS/MS sequenced peptides to the precursor highlighted three atypical monobasic processing sites, including the established C-terminus of ghrelin and the N-terminal cleavage site for obestatin, a putative 23-amino-acid C-terminally amidated peptide. However, we found that mouse obestatin does not occur in the form originally reported, but that a different amidation site is used to generate a shorter peptide. These data can be extended to study and characterize the precursor-derived peptides located downstream of ghrelin in different biological contexts. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Peptidomic Analysis of Fetal Heart Tissue for Identification of Endogenous Peptides Involved in Tetralogy of Fallot.

    Science.gov (United States)

    Zhang, Jingjing; Liang, Dong; Cheng, Qing; Cao, Li; Wu, Yun; Wang, Yan; Han, Shuping; Yu, Zhangbin; Cui, Xianwei; Xu, Tianhui; Ma, Dingyuan; Hu, Ping; Xu, Zhengfeng

    2017-06-01

    Tetralogy of fallot (TOF) is one of the most prevalent types of congenital heart diseases. As a category of bioactive molecules, peptides have been proved to participate in various biological processes. However, the role of endogenous peptides in the pathogenesis of TOF has not been studied. In this study, we performed a comparative peptidomic profile in the fetal heart of TOF and the control group for the first time by liquid chromatography-tandem mass spectrometry. Our data demonstrated that a total of 201 peptides derived from 176 precursor proteins were differentially expressed in the heart tissues of TOF fetuses compared with normal controls, including 41 upregulated peptides and 160 downregulated peptides. After analyzing the characteristics of these differentially expressed peptides and their precursor proteins, we found that these peptides were potentially involved in different biological processes, especially cardiogenesis and congenital anomaly of the cardiovascular system. Interestingly, we detected several extracellular matrix-derived peptides involved in our differentially expressed peptidomic profile. In summary, our study constructed a comparative peptidomic profile from the heart tissues of TOF fetuses and normal controls, and it identified a series of peptides that could potentially participate in heart development and TOF formation. The emergence of our peptidomics study indicated a new perspective to explore the pathogenesis of abnormal heart morphology, especially TOF.

  11. Biased Agonism of Endogenous Opioid Peptides at the μ-Opioid Receptor.

    Science.gov (United States)

    Thompson, Georgina L; Lane, J Robert; Coudrat, Thomas; Sexton, Patrick M; Christopoulos, Arthur; Canals, Meritxell

    2015-08-01

    Biased agonism is having a major impact on modern drug discovery, and describes the ability of distinct G protein-coupled receptor (GPCR) ligands to activate different cell signaling pathways, and to result in different physiologic outcomes. To date, most studies of biased agonism have focused on synthetic molecules targeting various GPCRs; however, many of these receptors have multiple endogenous ligands, suggesting that "natural" bias may be an unappreciated feature of these GPCRs. The μ-opioid receptor (MOP) is activated by numerous endogenous opioid peptides, remains an attractive therapeutic target for the treatment of pain, and exhibits biased agonism in response to synthetic opiates. The aim of this study was to rigorously assess the potential for biased agonism in the actions of endogenous opioids at the MOP in a common cellular background, and compare these to the effects of the agonist d-Ala2-N-MePhe4-Gly-ol enkephalin (DAMGO). We investigated activation of G proteins, inhibition of cAMP production, extracellular signal-regulated kinase 1 and 2 phosphorylation, β-arrestin 1/2 recruitment, and MOP trafficking, and applied a novel analytical method to quantify biased agonism. Although many endogenous opioids displayed signaling profiles similar to that of DAMGO, α-neoendorphin, Met-enkephalin-Arg-Phe, and the putatively endogenous peptide endomorphin-1 displayed particularly distinct bias profiles. These may represent examples of natural bias if it can be shown that they have different signaling properties and physiologic effects in vivo compared with other endogenous opioids. Understanding how endogenous opioids control physiologic processes through biased agonism can reveal vital information required to enable the design of biased opioids with improved pharmacological profiles and treat diseases involving dysfunction of the endogenous opioid system. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  12. Endogenous human milk peptide release is greater after preterm birth than term birth.

    Science.gov (United States)

    Dallas, David C; Smink, Christina J; Robinson, Randall C; Tian, Tian; Guerrero, Andres; Parker, Evan A; Smilowitz, Jennifer T; Hettinga, Kasper A; Underwood, Mark A; Lebrilla, Carlito B; German, J Bruce; Barile, Daniela

    2015-03-01

    Hundreds of naturally occurring milk peptides are present in term human milk. Preterm milk is produced before complete maturation of the mammary gland, which could change milk synthesis and secretion processes within the mammary gland, leading to differences in protein expression and enzymatic activity, thereby resulting in an altered peptide profile. This study examined differences in peptides present between milk from women delivering at term and women delivering prematurely. Nano-LC tandem mass spectrometry was employed to identify naturally occurring peptides and compare their abundances between term and preterm human milk samples at multiple time points over lactation. Term milk samples were collected from 8 mothers and preterm milk was collected from 14 mothers. The 28 preterm and 32 term human milk samples were divided into 4 groups based on day of collection (term milk. Bioinformatic analysis of the cleavage sites for peptides identified suggested that plasmin was more active in preterm milk than term milk and that cytosol aminopeptidase and carboxypeptidase B2 likely contribute to extensive milk protein breakdown. Many identified milk peptides in both term and preterm milk overlapped with known functional peptides, including antihypertensive, antimicrobial, and immunomodulatory peptides. The high protein degradation by endogenous proteases in preterm milk might attenuate problems because of the preterm infant's immature digestive system. This trial was registered at clinicaltrials.gov as NCT01817127. © 2015 American Society for Nutrition.

  13. Endogenous Antimicrobial Peptide Expression in Response to Bacterial Epidermal Colonization

    Directory of Open Access Journals (Sweden)

    Michael Brandwein

    2017-11-01

    Full Text Available Bacterial commensal colonization of human skin is vital for the training and maintenance of the skin’s innate and adaptive immune functions. In addition to its physical barrier against pathogen colonization, the skin expresses a variety of antimicrobial peptides (AMPs which are expressed constitutively and induced in response to pathogenic microbial stimuli. These AMPs are differentially effective against a suite of microbial skin colonizers, including both bacterial and fungal residents of the skin. We review the breadth of microorganism-induced cutaneous AMP expression studies and their complementary findings on the efficacy of skin AMPs against different bacterial and fungal species. We suggest further directions for skin AMP research based on emerging skin microbiome knowledge in an effort to advance our understanding of the nuanced host–microbe balance on human skin. Such advances should enable the scientific community to bridge the gap between descriptive disease-state AMP studies and experimental single-species in vitro studies, thereby enabling research endeavors that more closely mimic the natural skin environs.

  14. Role of endogenous opioid peptides in the pathogenesis of motion sickness

    Energy Technology Data Exchange (ETDEWEB)

    Yasnetsov, V.V.; Il' ina, S.L.; Karsanova, S.K.; Medvedev, O.S.; Mokrousova, A.V.; Sabaev, V.V.; Shashkov, V.A.; Tigranyan, R.A.; Vakulina, O.P

    1986-01-01

    This paper examines the pathogenesis of motion sickness and the role of the various neurochemical systems of the body in the genesis of the condition. It has been shown that the endogenous opioid system participates in the genesis of several pathological processes; this was the motivation for the study. The plasma beta-endorphin level was determined in samples from 19 clinically healthy males. Considering the positive prophylactic and therapeutic effect of naloxone against motion sickness it can be postulated that endogenous opioid peptides participate in the genesis of the vestibulo-autonomic disorders in motion sickness.

  15. Role of endogenous opioid peptides in the pathogenesis of motion sickness

    International Nuclear Information System (INIS)

    Yasnetsov, V.V.; Il'ina, S.L.; Karsanova, S.K.; Medvedev, O.S.; Mokrousova, A.V.; Sabaev, V.V.; Shashkov, V.A.; Tigranyan, R.A.; Vakulina, O.P

    1986-01-01

    This paper examines the pathogenesis of motion sickness and the role of the various neurochemical systems of the body in the genesis of the condition. It has been shown that the endogenous opioid system participates in the genesis of several pathological processes; this was the motivation for the study. The plasma beta-endorphin level was determined in samples from 19 clinically healthy males. Considering the positive prophylactic and therapeutic effect of naloxone against motion sickness it can be postulated that endogenous opioid peptides participate in the genesis of the vestibulo-autonomic disorders in motion sickness

  16. Immunoneutralization of endogenous glucagon-like peptide-2 reduces adaptive intestinal growth in diabetic rats

    DEFF Research Database (Denmark)

    Hartmann, Bolette; Thulesen, Jesper; Hare, Kristine Juul

    2002-01-01

    in the proximal part of the small intestine (10.84+/-0.44 mm(2)). Antibody treatment had no effect on body weight, blood glucose concentrations and food intake. Thus, blocking of endogenous GLP-2 in a model of adaptive intestinal growth reduces the growth response, providing strong evidence for a physiological......Supraphysiological doses of glucagon-like peptide-2 (GLP-2) have been shown to induce intestinal growth by increasing villus height and crypt depth and by decreasing apoptosis, but a physiological effect of GLP-2 has not yet been demonstrated. Earlier, we found elevated levels of endogenous GLP-2...... in untreated streptozotocin diabetic rats associated with marked intestinal growth. In the present study, we investigated the role of endogenous GLP-2 for this adaptive response. We included four groups of six rats: (1) diabetic rats treated with saline, (2) diabetic rats treated with non-specific antibodies...

  17. Cortisol rapidly reduces prolactin release and cAMP and 45Ca2+ accumulation in the cichlid fish pituitary in vitro

    International Nuclear Information System (INIS)

    Borski, R.J.; Helms, L.M.H.; Richman, N.H. III; Grau, E.G.

    1991-01-01

    During in vitro incubation, prolactin release is inhibited in a dose-related manner by cortisol. This action is mimicked by the synthetic glucocorticoid agonist dexamethasone but not by other steroids tested. Perifusion studies indicate that the inhibition of [ 3 H]prolactin release by cortisol occurs within 20 min. Cortisol (50 nM) also inhibits cAMP accumulation and reduces 45 Ca 2+ accumulation in the tilapia rostral pars distalis within 15 min. Cortisol's action on prolactin release is blocked in the presence of either the Ca 2+ ionophore A23187 or a combination of dibutyryl cAMP and 3-isobutyl-1-methylxanthine, which increase intracellular Ca 2+ and cAMP, respectively. Taken together, these findings suggest that cortisol may play a physiologically relevant role in the rapid modulation of prolactin secretion in vivo. These studies also suggest that the inhibition of prolactin release by cortisol is a specific glucocorticoid action that may be mediated, in part, through cortisol's ability to inhibit intracellular cAMP and Ca 2+ metabolism

  18. Cortisol rapidly reduces prolactin release and cAMP and sup 45 Ca sup 2+ accumulation in the cichlid fish pituitary in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Borski, R.J.; Helms, L.M.H.; Richman, N.H., III; Grau, E.G. (Univ. of Hawaii, Honolulu (United States))

    1991-04-01

    During in vitro incubation, prolactin release is inhibited in a dose-related manner by cortisol. This action is mimicked by the synthetic glucocorticoid agonist dexamethasone but not by other steroids tested. Perifusion studies indicate that the inhibition of ({sup 3}H)prolactin release by cortisol occurs within 20 min. Cortisol (50 nM) also inhibits cAMP accumulation and reduces {sup 45}Ca{sup 2+} accumulation in the tilapia rostral pars distalis within 15 min. Cortisol's action on prolactin release is blocked in the presence of either the Ca{sup 2+} ionophore A23187 or a combination of dibutyryl cAMP and 3-isobutyl-1-methylxanthine, which increase intracellular Ca{sup 2+} and cAMP, respectively. Taken together, these findings suggest that cortisol may play a physiologically relevant role in the rapid modulation of prolactin secretion in vivo. These studies also suggest that the inhibition of prolactin release by cortisol is a specific glucocorticoid action that may be mediated, in part, through cortisol's ability to inhibit intracellular cAMP and Ca{sup 2+} metabolism.

  19. SDF-1α peptide tethered polyester facilitates tissue repair by endogenous cell mobilization and recruitment.

    Science.gov (United States)

    Shafiq, Muhammad; Kong, Deling; Kim, Soo Hyun

    2017-10-01

    The design of bioactive scaffolds that can invoke host's own regenerative capabilities and facilitate endogenous tissue repair hold great promise. This study aims to evaluate the potential of stromal cell-derived factor 1 alpha (SDF-1α)-derived peptide and heparin tethered poly(L-lactide-co-ε-caprolactone) (PLCL) copolymers for blood vessel regeneration applications. Amino acid analysis and toluidine blue assays confirm successful conjugation of SDF-1α peptide and heparin with the PLCL copolymers. Assessment of biocompatibility after subcutaneous implantation in rats discloses higher cell infiltration in SDF-1α peptide (SDF-1 group) or SDF-1 peptide and heparin (SDF-1/heparin group) than the control group. SDF-1 and SDF-1/heparin grafts also show more numbers of laminin + blood vessels, CD90 + stem cells, and alpha smooth muscle actin + cells than the control group. However, SDF-1 and SDF-1/heparin groups did not significantly differ in terms of blood vessel regeneration and stem cell recruitment. Evaluation of the inflammatory response reveal less numbers of CD68 + macrophages in SDF-1 and SDF-1/heparin groups compared with the control group; whereas three groups show similar numbers of CD206 + macrophages. These results indicate that completely synthetic, cell-free grafts can attract endogenous cells and enhance tissue repair. Bioactive polyesters can be fabricated into different shapes and structures for various tissue engineering applications. © 2017 Wiley Periodicals, Inc. J Biomater Res Part A: 105A: 2670-2684, 2017. © 2017 Wiley Periodicals, Inc.

  20. Endogenous calcitonin gene-related peptide suppresses ischemic brain injuries and progression of cognitive decline.

    Science.gov (United States)

    Zhai, Liuyu; Sakurai, Takayuki; Kamiyoshi, Akiko; Ichikawa-Shindo, Yuka; Kawate, Hisaka; Tanaka, Megumu; Xian, Xian; Hirabayashi, Kazutaka; Dai, Kun; Cui, Nanqi; Tanimura, Keiya; Liu, Teng; Wei, Yangxuan; Tanaka, Masaaki; Tomiyama, Haruka; Yamauchi, Akihiro; Igarashi, Kyoko; Shindo, Takayuki

    2018-04-01

    Calcitonin gene-related peptide (CGRP) is a 37-amino acid peptide and produced by alternative splicing of the transcript of the calcitonin/CGRP gene. Originally identified as a strong vasodilatory and hypotensive peptide, CGRP is now known to be a pleiotropic molecule distributed in various organs, including the brain. In this study, we used CGRP knockout mice (CGRP-/-) to examine the actions of endogenous CGRP during cerebral ischemia. To induce acute and chronic cerebral ischemia, mice were subjected to middle cerebral artery occlusion (MCAO) and bilateral common carotid artery stenosis (BCAS). In the cerebral cortex of wild-type mice, CGRP expression was upregulated after acute infarction. In CGRP-/- subjected to MCAO or BCAS, recovery of cerebral blood flow was slower and exhibited more extensive neuronal cell death. Expression of the inflammatory cytokines was higher in CGRP-/- than wild type in the acute phase of ischemia. Pathological analysis during the chronic phase revealed more extensive neuronal cell loss and demyelination and higher levels of oxidative stress in CGRP-/- than wild-type. CGRP-/- also showed less compensatory capillary growth. In an eight-arm radial maze test, CGRP-/- exhibited poorer reference memory than wild-type. On the other hand, CGRP administration promoted cerebral blood flow recovery after cerebral ischemia. We also found that CGRP directly inhibited the cell death of primary cortical neurons. These results indicate endogenous CGRP is protective against ischemia-induced neuronal cell injury. CGRP could, thus, be a novel candidate for use in the treatment of both cerebral ischemia and progression of cognitive decline.

  1. Impact of novel palmitoylated prolactin-releasing peptide analogs on metabolic changes in mice with diet-induced obesity

    Czech Academy of Sciences Publication Activity Database

    Pražienková, Veronika; Holubová, Martina; Pelantová, Helena; Bugáňová, Martina; Pirník, Z.; Mikulášková, Barbora; Popelová, Andrea; Blechová, Miroslava; Haluzík, M.; Železná, Blanka; Kuzma, Marek; Kuneš, Jaroslav; Maletínská, Lenka

    2017-01-01

    Roč. 12, č. 8 (2017), č. článku e0183449. E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GA15-08679S; GA ČR GA13-14105S Institutional support: RVO:61388963 ; RVO:61388971 Keywords : food intake regulation * peroxisome proliferation * lipidized analogs Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition OBOR OECD: Endocrinology and metabolism (including diabetes, hormones) Impact factor: 2.806, year: 2016 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183449

  2. Biological properties of prolactin-releasing peptide analogs with a modified aromatic ring of a C-terminal phenylalanine amide

    Czech Academy of Sciences Publication Activity Database

    Maletínská, Lenka; Špolcová, Andrea; Maixnerová, Jana; Blechová, Miroslava; Železná, Blanka

    2011-01-01

    Roč. 32, č. 9 (2011), s. 1887-1892 ISSN 0196-9781 R&D Projects: GA ČR GAP303/10/1368 Institutional research plan: CEZ:AV0Z40550506 Keywords : pituitary cells * PrRP analogs * food intake Subject RIV: CC - Organic Chemistry Impact factor: 2.434, year: 2011

  3. CD1d-Restricted Type II NKT Cells Reactive With Endogenous Hydrophobic Peptides.

    Science.gov (United States)

    Nishioka, Yusuke; Masuda, Sakiko; Tomaru, Utano; Ishizu, Akihiro

    2018-01-01

    NKT cells belong to a distinct subset of T cells that recognize hydrophobic antigens presented by major histocompatibility complex class I-like molecules, such as CD1d. Because NKT cells stimulated by antigens can activate or suppress other immunocompetent cells through an immediate production of a large amount of cytokines, they are regarded as immunological modulators. CD1d-restricted NKT cells are classified into two subsets, namely, type I and type II. CD1d-restricted type I NKT cells express invariant T cell receptors (TCRs) and react with lipid antigens, including the marine sponge-derived glycolipid α-galactosylceramide. On the contrary, CD1d-restricted type II NKT cells recognize a wide variety of antigens, including glycolipids, phospholipids, and hydrophobic peptides, by their diverse TCRs. In this review, we focus particularly on CD1d-restricted type II NKT cells that recognize endogenous hydrophobic peptides presented by CD1d. Previous studies have demonstrated that CD1d-restricted type I NKT cells usually act as pro-inflammatory cells but sometimes behave as anti-inflammatory cells. It has been also demonstrated that CD1d-restricted type II NKT cells play opposite roles to CD1d-restricted type I NKT cells; thus, they function as anti-inflammatory or pro-inflammatory cells depending on the situation. In line with this, CD1d-restricted type II NKT cells that recognize type II collagen peptide have been demonstrated to act as anti-inflammatory cells in diverse inflammation-induction models in mice, whereas pro-inflammatory CD1d-restricted type II NKT cells reactive with sterol carrier protein 2 peptide have been demonstrated to be involved in the development of small vessel vasculitis in rats.

  4. FOLATE CYCLE GENE POLYMORPHISM AND ENDOGENOUS PEPTIDES IN CHILDREN WITH COW’S MILK PROTEIN ALLERGY

    Directory of Open Access Journals (Sweden)

    T. A. Shumatova

    2016-01-01

    Full Text Available Folate cycle gene polymorphisms and the levels of endogenous antimicrobial peptides and proteins in the blood and coprofiltrates were studied in 45 children aged 3 to 12 months with cow’s milk protein allergy. The polymorphic variants of the MTHFR, MTRR, and MTR genes were shown to be considered as a risk factor for the development of allergy. There was a significant increase in the levels of zonulin, β-defensin 2, transthyretin, and eosinophil cationic protein in the coprofiltrates and in those of eotaxin, fatty acidbinding proteins, and membrane permeability-increasing protein in the serum (p<0.05. The finding can improve the diagnosis of the disease for a predictive purpose for the evaluation of the efficiency of performed therapy.

  5. Importance of Endogenous Atrial and Brain Natriuretic Peptides in Murine Embryonic Vascular and Organ Development.

    Science.gov (United States)

    Tokudome, Takeshi; Kishimoto, Ichiro; Shindo, Takayuki; Kawakami, Hayato; Koyama, Teruhide; Otani, Kentaro; Nishimura, Hirohito; Miyazato, Mikiya; Kohno, Masakazu; Nakao, Kazuwa; Kangawa, Kenji

    2016-01-01

    Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) bind to the receptor guanylyl cyclase (GC)-A, leading to diuresis, natriuresis, and blood vessel dilation. In addition, ANP and BNP have various angiogenic properties in ischemic tissue. When breeding mice devoid of GC-A, we noted significant skewing of the Mendelian ratio in the offspring, suggesting embryonic lethality due to knockout of GC-A. Consequently, we here investigated the roles of endogenous ANP and BNP in embryonic neovascularization and organ morphogenesis. Embryos resulting from GC-A(-/-) × GC-A(+/-) crosses developed hydrops fetalis (HF) beginning at embryonic day (E)14.5. All embryos with HF had the genotype GC-A(-/-). At E17.5, 33.3% (12 of 36) of GC-A(-/-) embryos had HF, and all GC-A(-/-) embryos with HF were dead. Beginning at E16.0, HF-GC-A(-/-) embryos demonstrated poorly developed superficial vascular vessels and sc hemorrhage, the fetal side of the placenta appeared ischemic, and vitelline vessels on the yolk sac were poorly developed. Furthermore, HF-GC-A(-/-) embryos also showed abnormal constriction of umbilical cord vascular vessels, few cardiac trabeculae and a thin compact zone, hepatic hemorrhage, and poor bone development. Electron microscopy of E16.5 HF-GC-A(-/-) embryos revealed severe vacuolar degeneration in endothelial cells, and the expected 3-layer structure of the smooth muscle wall of the umbilical artery was indistinct. These data demonstrate the importance of the endogenous ANP/BNP-GC-A system not only in the neovascularization of ischemic tissues but also in embryonic vascular development and organ morphogenesis.

  6. TRH [thyrotropin-releasing hormone] and BAY K 8644 synergistically stimulate prolactin release but not 45Ca2+ uptake

    International Nuclear Information System (INIS)

    Pachter, J.A.; Law, G.J.; Dannies, P.S.

    1988-01-01

    Thyrotropin-releasing hormone (TRH) and the Ca 2+ -channel agonist BAY K 8644 each induced transient increases in prolactin secretion from primary cultures of rat anterior pituitary cells in perfusion. When BAY K 8644 was added after a TRH-induced secretory peak, the additional effect of BAY K 8644 on prolactin release was approximately twofold greater over a 30-min period than the effect of BAY K 8644 on previously untreated cells. TRH and BAY K 8644 were also synergistic when added in the opposite order or simultaneously. Substitution of other agents for BAY K 8644 revealed that only high K + was at least additive with TRH in stimulating prolactin secretion; treatment with TRH inhibited, rather than facilitated, subsequent stimulation of prolactin secretion by angiotensin II or the ionophore A23187. The cooperative effect was not specific for TRH because BAY K 8644 also acted synergistically with angiotensin II or 40 mM K + . In GH 4 C 1 cells, in which TRH and BAY K 8644 were also synergistic in releasing prolactin, measurements with the fluorescent indicator indo-1 showed that TRH and BAY K 8644 could each elevate cytosolic Ca 2+ above the level stimulated by the other. Unexpectedly, TRH was found to inhibit BAY K 8644-stimulated 45 Ca 2+ uptake in both GH 4 C 1 and primary cultured cells. These results indicate that BAY K 8644 and TRH synergistically stimulate prolactin secretion by a mechanism other than a cooperative effect on the activity of dihydropyridine-sensitive Ca 2+ channels

  7. Different serotonin receptor types participate in 5-hydroxytryptophan-induced gonadotropins and prolactin release in the female infantile rat.

    Science.gov (United States)

    Lacau-Mengido, I M; Libertun, C; Becú-Villalobos, D

    1996-05-01

    Serotonin (5-HT) receptors can be classified into at least three, possibly up to seven, classes of receptors. They comprise the 5-HT1, 5-HT2, and 5-HT3 classes, the "uncloned' 5-HT4 receptor and the recombinant receptors 5-ht5, 5-ht6 and 5-ht7. We investigated the role of different serotonin receptor types in a neuroendocrine response to the activation of the serotonergic system. Female immature rats were chosen as an experimental model as it has been shown that during the 3rd week of life, and not at later developmental stages, 5-hydroxytryptophan (5-HTP, a serotonin precursor) induces gonadotropin release in females and not in males. Besides, at this age, serotonin releases prolactin in both sexes. 5-HTP (50 mg/kg) released prolactin, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) as expected. Ketanserin (5-HT2A antagonist) and methysergide (5-HT2C antagonist) blocked 5-HTP-induced prolactin release, but did not block the LH or FSH responses. Ondansetron (5-HT3 receptor antagonist) did not modify prolactin response to 5-HTP, whereas it blocked 5-HTP-induced LH and FSH release. Propranolol (5-HT1 and beta-adrenergic antagonist) blocked prolactin, LH and FSH release induced by 5-HTP. The 5-HT2C agonist 1-(3-chlorophenyl)piperazine dihydrochloride released prolactin, without modifying LH or FSH release. Methyl-quipazine and phenylbiguanide (5-HT3 agonists) increased both LH and FSH levels, without altering prolactin secretion. The present experiments indicate that serotonin acting at the 5-HT3 receptor mediates LH and FSH release in infantile female rats, whereas 5-HT2C or 2A receptor types participate in the release of prolactin at this age. 5-HT1 receptor type may be involved in the release of the three hormones, though a beta-adrenergic component of the response cannot be discarded.

  8. Involvement of endogenous glucagon-like peptide-1 in regulation of gastric motility and pancreatic endocrine secretion

    DEFF Research Database (Denmark)

    Witte, Anne-Barbara; Grybäck, Per; Jacobsson, Hans

    2011-01-01

    Objective. To study the role of endogenous glucagon-like peptide-1 (GLP-1) on gastric emptying rates of a solid meal as well as postprandial hormone secretion and glucose disposal. Material and methods. In nine healthy subjects, gastric emptying of a 310-kcal radio-labelled solid meal and plasma ...

  9. Downregulation of the endogenous opioid peptides in the dorsal striatum of human alcoholics

    Directory of Open Access Journals (Sweden)

    Daniil eSarkisyan

    2015-05-01

    Full Text Available The endogenous opioid peptides dynorphins and enkephalins may be involved in brain-area specific synaptic adaptations relevant for different stages of an addiction cycle. We compared the levels of prodynorphin (PDYN and proenkephalin (PENK mRNAs (by qRT-PCR, and dynorphins and enkephalins (by radioimmunoassay in the caudate nucleus and putamen between alcoholics and control subjects. We also evaluated whether PDYN promoter variant rs1997794 associated with alcoholism affects PDYN expression. Postmortem specimens obtained from 24 alcoholics and 26 controls were included in final statistical analysis. PDYN mRNA and Met-enkephalin-Arg-Phe, a marker of PENK were downregulated in the caudate of alcoholics, while PDYN mRNA and Leu-enkephalin-Arg, a marker of PDYN were decreased in the putamen of alcoholics carrying high risk rs1997794 C allele. Downregulation of opioid peptides in the dorsal striatum may contribute to development of alcoholism including changes in goal directed behavior and formation of a compulsive habit in alcoholics.

  10. Endogenous Glucagon-Like Peptide-1 Reduces Drinking Behavior and Is Differentially Engaged by Water and Food Intakes in Rats

    OpenAIRE

    McKay, Naomi J.; Galante, Daniela L.; Daniels, Derek

    2014-01-01

    Glucagon-like peptide-1 (GLP-1) is produced in the ileum and the nucleus of the solitary tract. It is well known that GLP-1 controls food intake, but there is a growing literature indicating that GLP-1 also is involved in fluid intake. It is not known, however, if the observed effects are pharmacological or if endogenous GLP-1 and its receptor contribute to physiological fluid intake control. Accordingly, we blocked endogenous GLP-1 by application of a receptor antagonist and measured subsequ...

  11. Human gut endogenous proteins as a potential source of angiotensin-I-converting enzyme (ACE-I)-, renin inhibitory and antioxidant peptides.

    Science.gov (United States)

    Dave, Lakshmi A; Hayes, Maria; Montoya, Carlos A; Rutherfurd, Shane M; Moughan, Paul J

    2016-02-01

    It is well known that endogenous bioactive proteins and peptides play a substantial role in the body's first line of immunological defence, immune-regulation and normal body functioning. Further, the peptides derived from the luminal digestion of proteins are also important for body function. For example, within the peptide database BIOPEP (http://www.uwm.edu.pl/biochemia/index.php/en/biopep) 12 endogenous antimicrobial and 64 angiotensin-I-converting enzyme (ACE-I) inhibitory peptides derived from human milk and plasma proteins are listed. The antimicrobial peptide database (http://aps.unmc.edu/AP/main.php) lists over 111 human host-defence peptides. Several endogenous proteins are secreted in the gut and are subject to the same gastrointestinal digestion processes as food proteins derived from the diet. The human gut endogenous proteins (GEP) include mucins, serum albumin, digestive enzymes, hormones, and proteins from sloughed off epithelial cells and gut microbiota, and numerous other secreted proteins. To date, much work has been carried out regarding the health altering effects of food-derived bioactive peptides but little attention has been paid to the possibility that GEP may also be a source of bioactive peptides. In this review, we discuss the potential of GEP to constitute a gut cryptome from which bioactive peptides such as ACE-I inhibitory, renin inhibitory and antioxidant peptides may be derived. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Thrombocyte HLA molecules retain nonrenewable endogenous peptides of megakaryocyte lineage and do not stimulate direct allocytotoxicity in vitro.

    Science.gov (United States)

    Gouttefangeas, C; Diehl, M; Keilholz, W; Hörnlein, R F; Stevanović, S; Rammensee, H G

    2000-05-15

    The origin and the function of HLA class I molecules present on the surface of human platelets are still unclear. In particular, it is controversial which fraction of these class I molecules represents integral membrane components derived from the megakaryocyte-platelet lineage versus soluble plasma HLA molecules acquired by adsorption. Results of the present study show that HLA-A2 ligands isolated from platelets possess the same peptide motif as described for HLA-A2-associated peptides obtained from nucleated cells. Sequencing of these platelet-derived peptides reveals that they originate mainly from ubiquitously expressed proteins also present in the megakaryocyte-platelet lineage. Moreover, one of these peptides derives from the GPIX protein, which is specifically expressed by platelets and their precursors. Platelet HLA molecules are unstable in vitro at 37 degrees C, but can be partially stabilized by addition of exogenous beta(2)-microglobulin and HLA class I binding peptide, suggesting that platelets cannot load HLA molecules with endogenous peptides. In in vitro experiments platelets were used to stimulate peripheral blood mononuclear cells. No allospecific cytotoxicity was observed after primary stimulation, or secondary restimulation, with allogenic resting or activated platelets, even in the presence of additional third-party helper activity. These data indicate that HLA class I molecules from platelets cannot directly induce allogenic CD8(+) cytotoxic T-cell response in vitro.

  13. Endogenous Plasma Peptide Detection and Identification in the Rat by a Combination of Fractionation Methods and Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Fabrice Bertile

    2007-01-01

    Full Text Available Mass spectrometry-based analyses are essential tools in the field of biomarker research. However, detection and characterization of plasma low abundance and/or low molecular weight peptides is challenged by the presence of highly abundant proteins, salts and lipids. Numerous strategies have already been tested to reduce the complexity of plasma samples. The aim of this study was to enrich the low molecular weight fraction of rat plasma. To this end, we developed and compared simple protocols based on membrane filtration, solid phase extraction, and a combination of both. As assessed by UV absorbance, an albumin depletion 99% was obtained. The multistep fractionation strategy (including reverse phase HPLC allowed detection, in a reproducible manner (CV [1] 30%–35%, of more than 450 peaks below 3000 Da by MALDI-TOF/MS. A MALDI-TOF/MS-determined LOD as low as 1 fmol/μL was obtained, thus allowing nanoLC-Chip/ MS/MS identification of spiked peptides representing ∼10–6% of total proteins, by weight. Signal peptide recovery ranged between 5%–100% according to the spiked peptide considered. Tens of peptide sequence tags from endogenous plasma peptides were also obtained and high confidence identifications of low abundance fibrinopeptide A and B are reported here to show the efficiency of the protocol. It is concluded that the fractionation protocol presented would be of particular interest for future differential (high throughput analyses of the plasma low molecular weight fraction.

  14. GSK2374697, a long duration glucagon-like peptide-1 (GLP-1) receptor agonist, reduces postprandial circulating endogenous total GLP-1 and peptide YY in healthy subjects.

    Science.gov (United States)

    Lin, J; Hodge, R J; O'Connor-Semmes, R L; Nunez, D J

    2015-10-01

    We investigated the effects of a long-duration glucagon-like peptide-1 (GLP-1) receptor agonist, GSK2374697, on postprandial endogenous total GLP-1 and peptide YY (PYY). Two cohorts of healthy subjects, one normal/overweight and one obese, were randomized to receive GSK2374697 2 mg (n = 8 each) or placebo (n = 4 and n = 2) subcutaneously on days 1, 4 and 7. Samples for plasma endogenous GLP-1 and PYY were collected after breakfast on days -1 and 12. Weighted mean area under the curve (0-4 h) of total GLP-1 and PYY in treated subjects was reduced compared with placebo. The least squares mean difference for change from baseline was -1.24 pmol/l [95% confidence interval (CI) -2.33, -0.16] and -4.47 pmol/l (95% CI -8.74, -0.20) for total GLP-1 and PYY, respectively, in normal/overweight subjects (p GLP-1). In healthy subjects, GSK2374697 reduced postprandial total GLP-1 and PYY levels, suggesting feedback suppression of enteroendocrine L-cell secretion of these peptides. © 2015 John Wiley & Sons Ltd.

  15. Endogenous collagen peptide activation of CD1d-restricted NKT cells ameliorates tissue-specific inflammation in mice.

    Science.gov (United States)

    Liu, Yawei; Teige, Anna; Mondoc, Emma; Ibrahim, Saleh; Holmdahl, Rikard; Issazadeh-Navikas, Shohreh

    2011-01-01

    NKT cells in the mouse recognize antigen in the context of the MHC class I-like molecule CD1d and play an important role in peripheral tolerance and protection against autoimmune and other diseases. NKT cells are usually activated by CD1d-presented lipid antigens. However, peptide recognition in the context of CD1 has also been documented, although no self-peptide ligands have been reported to date. Here, we have identified an endogenous peptide that is presented by CD1d to activate mouse NKT cells. This peptide, the immunodominant epitope from mouse collagen type II (mCII707-721), was not associated with either MHC class I or II. Activation of CD1d-restricted mCII707-721-specific NKT cells was induced via TCR signaling and classical costimulation. In addition, mCII707-721-specific NKT cells induced T cell death through Fas/FasL, in an IL-17A-independent fashion. Moreover, mCII707-721-specific NKT cells suppressed a range of in vivo inflammatory conditions, including delayed-type hypersensitivity, antigen-induced airway inflammation, collagen-induced arthritis, and EAE, which were all ameliorated by mCII707-721 vaccination. The findings presented here offer new insight into the intrinsic roles of NKT cells in health and disease. Given the results, endogenous collagen peptide activators of NKT cells may offer promise as novel therapeutics in tissue-specific autoimmune and inflammatory diseases.

  16. Chronic liraglutide therapy induces an enhanced endogenous glucagon-like peptide-1 secretory response in early type 2 diabetes.

    Science.gov (United States)

    Kramer, Caroline K; Zinman, Bernard; Choi, Haysook; Connelly, Philip W; Retnakaran, Ravi

    2017-05-01

    Sustained exogenous stimulation of a hormone-specific receptor can affect endogenous hormonal regulation. In this context, little is known about the impact of chronic treatment with glucagon-like peptide-1 (GLP-1) agonists on the endogenous GLP-1 response. We therefore evaluated the impact of chronic liraglutide therapy on endogenous GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) response to an oral glucose challenge. A total of 51 people with type 2 diabetes of 2.6 ± 1.9 years' duration were randomized to daily subcutaneous liraglutide or placebo injection and followed for 48 weeks, with an oral glucose tolerance test (OGTT) every 12 weeks. GLP-1 and GIP responses were assessed according to their respective area under the curve (AUC) from measurements taken at 0, 30, 60, 90 and 120 minutes during each OGTT. There were no differences in AUC GIP between the groups. By contrast, although fasting GLP-1 was unaffected, the liraglutide arm had ~2-fold higher AUC GLP -1 at 12 weeks ( P  endogenous GLP-1 response, highlighting the need for further study of the long-term effects of incretin mimetics on L-cell physiology. © 2017 John Wiley & Sons Ltd.

  17. Effect of Leu-enkephalin and delta sleep inducing peptide (DSIP) on endogenous noradrenaline release by rat brain synaptosomes

    Energy Technology Data Exchange (ETDEWEB)

    Lozhanets, V.V.; Anosov, A.K.

    1986-01-01

    The nonapeptide delta-sleep inducing peptide (DSIP) causes specific changes in the encephalogram of recipient animals: It prolongs the phase of long-wave or delta sleep. The cellular mechanism of action of DSIP has not yet been explained. To test the hyporhesis that this peptide or its degradation product may be presynaptic regulators of catecholamine release, the action of Leu-enkephaline, DSIP, and amino acids composing DSIP on release of endogenous noradrenalin (NA) from synaptosomes during depolarization was compared. Subcellular fractions from cerebral hemisphere of noninbred male albino rats were isolated. Lactate dehydrogenase activity was determined in the suspension of synaptosomes before and after addition of 0.5% Triton X-100. The results were subjected to statistical analysis, using the Wilcoxon-Mann-Whitney nonparametric test.

  18. Effect of Leu-enkephalin and delta sleep inducing peptide (DSIP) on endogenous noradrenaline release by rat brain synaptosomes

    International Nuclear Information System (INIS)

    Lozhanets, V.V.; Anosov, A.K.

    1986-01-01

    The nonapeptide delta-sleep inducing peptide (DSIP) causes specific changes in the encephalogram of recipient animals: It prolongs the phase of long-wave or delta sleep. The cellular mechanism of action of DSIP has not yet been explained. To test the hyporhesis that this peptide or its degradation product may be presynaptic regulators of catecholamine release, the action of Leu-enkephaline, DSIP, and amino acids composing DSIP on release of endogenous noradrenalin (NA) from synaptosomes during depolarization was compared. Subcellular fractions from cerebral hemisphere of noninbred male albino rats were isolated. Lactate dehydrogenase activity was determined in the suspension of synaptosomes before and after addition of 0.5% Triton X-100. The results were subjected to statistical analysis, using the Wilcoxon-Mann-Whitney nonparametric test

  19. Endogenous collagen peptide activation of CD1d-restricted NKT cells ameliorates tissue-specific inflammation in mice

    DEFF Research Database (Denmark)

    Liu, Yawei; Teige, Anna; Mondoc, Emma

    2011-01-01

    NKT cells in the mouse recognize antigen in the context of the MHC class I-like molecule CD1d and play an important role in peripheral tolerance and protection against autoimmune and other diseases. NKT cells are usually activated by CD1d-presented lipid antigens. However, peptide recognition...... in the context of CD1 has also been documented, although no self-peptide ligands have been reported to date. Here, we have identified an endogenous peptide that is presented by CD1d to activate mouse NKT cells. This peptide, the immunodominant epitope from mouse collagen type II (mCII707-721), was not associated...... with either MHC class I or II. Activation of CD1d-restricted mCII707-721-specific NKT cells was induced via TCR signaling and classical costimulation. In addition, mCII707-721-specific NKT cells induced T cell death through Fas/FasL, in an IL-17A-independent fashion. Moreover, mCII707-721-specific NKT cells...

  20. Endogenous Glucagon-like Peptide-1 Receptor Signaling in the Nucleus Tractus Solitarius is Required for Food Intake Control.

    Science.gov (United States)

    Alhadeff, Amber L; Mergler, Blake D; Zimmer, Derek J; Turner, Christopher A; Reiner, David J; Schmidt, Heath D; Grill, Harvey J; Hayes, Matthew R

    2017-06-01

    Alhough the glucagon-like peptide-1 (GLP-1) system is critical to energy balance control and is a target for obesity pharmacotherapies, the receptor-population-mediating effects of endogenous GLP-1 signaling are not fully understood. To address this, we developed a novel adeno-associated virus (AAV-GLP-1R) that utilizes short hairpin RNA to chronically knock down GLP-1 receptors (GLP-1R) in rats. As pharmacological studies highlight the hindbrain nucleus tractus solitarius (NTS) as a brain region important for GLP-1R-mediated effects on energy balance, AAV-GLP-1R was injected into the NTS to examine the role of endogenous NTS GLP-1R signaling in energy balance control. Chow intake and meal size were significantly increased following chronic NTS GLP-1R knockdown. In addition, NTS GLP-1R knockdown significantly increased self-administration of palatable food under both fixed and progressive ratio schedules of reinforcement. Collectively, these data demonstrate that endogenous NTS GLP-1R signaling is required for the control of food intake and motivation to feed, and provide a new strategy to investigate the importance of distinct GLP-1R populations in the control of a variety of functions.

  1. γ-Preprotachykinin-(72-92)-peptide amide: An endogenous preprotachykinin I gene-derived peptide that preferentially binds to neurokinin-2 receptors

    International Nuclear Information System (INIS)

    Dam, T.V.; Takeda, Y.; Krause, J.E.; Escher, E.; Quirion, R.

    1990-01-01

    The presence of N-terminally extended forms of neurokinin A has recently been reported in the mammalian brain. Among them, gamma-preprotachykinin-(72-92)-peptide amide [gamma-PPT-(72-92)-NH2], a peptide derived by posttranslational processing of gamma-preprotachykinin, is most prominent. We report here that this peptide most likely acts on neurokinin-2 receptor sites since neurokinin A (a putative neurokinin-2 agonist) and gamma-PPT-(72-92)-NH2 are potent competitors of 125I-labeled gamma-PPT-(72-92)-NH2 binding whereas selective neurokinin-1 and -3 agonists are not. Moreover, the distribution of 125I-labeled gamma-PPT-(72-92)-NH2 and 125I-labeled neurokinin A binding sites are very similar in rat brain. On the other hand, 125I-labeled Bolton-Hunter-substance P (a neurokinin-1 ligand) and 125I-labeled Bolton-Hunter-eledoisin (a neurokinin-3 ligand) binding sites are differentially located in this tissue. Thus, it appears that gamma-PPT-(72-92)-NH2 binds to neurokinin-2 receptors and should be considered as a putative endogenous ligand for this receptor class

  2. Endogenous glucagon-like peptide-1 reduces drinking behavior and is differentially engaged by water and food intakes in rats.

    Science.gov (United States)

    McKay, Naomi J; Galante, Daniela L; Daniels, Derek

    2014-12-03

    Glucagon-like peptide-1 (GLP-1) is produced in the ileum and the nucleus of the solitary tract. It is well known that GLP-1 controls food intake, but there is a growing literature indicating that GLP-1 also is involved in fluid intake. It is not known, however, if the observed effects are pharmacological or if endogenous GLP-1 and its receptor contribute to physiological fluid intake control. Accordingly, we blocked endogenous GLP-1 by application of a receptor antagonist and measured subsequent drinking. Furthermore, we measured changes in GLP-1-associated gene expression after water intake, and compared the effects of fluid intake to those caused by food intake. Rats injected with the antagonist exendin-9 (Ex-9) drank more fluid in response to either subcutaneous hypertonic saline or water deprivation with partial rehydration than did vehicle-treated rats. Analysis of licking behavior showed that Ex-9 increased fluid intake by increasing the number of licking bursts, without having an effect on the number of licks per burst, suggesting that endogenous GLP-1 suppresses fluid intake by influencing satiety. Subsequent experiments showed that water intake had a selective effect on central GLP-1-related gene expression, unlike food intake, which affected both central and peripheral GLP-1. Although water and food intakes both affected central GLP-1-relevant gene expression, there were notable differences in the timing of the effect. These results show a novel role of the endogenous GLP-1 system in fluid intake, and indicate that elements of the GLP-1 system can be engaged separately by different forms of ingestive behavior. Copyright © 2014 the authors 0270-6474/14/3416417-07$15.00/0.

  3. Investigation into the antimicrobial action and mechanism of a novel endogenous peptide β-casein 197 from human milk.

    Science.gov (United States)

    Fu, Yanrong; Ji, Chenbo; Chen, Xiaohui; Cui, Xianwei; Wang, Xing; Feng, Jie; Li, Yun; Qin, Rui; Guo, Xirong

    2017-12-01

    A novel endogenous peptide cleaved from 197-213 AA of β-casein, named β-casein 197, was identified by tandem mass spectrometry. β-casein 197 constituted a significant proportion of the peptide content in preterm milk. This study investigated the antibacterial effects and mechanisms against common pathogenic bacteria. Six bacterial strains were selected for this study: Escherichia coli, Staphylococcus aureus, Yersinia enterocolitica, Listeria monocytogenes, Klebsiella pneumonia and Bacillus subtilis. After synthesis, serial twofold dilutions of β-casein 197 were added to select for sensitive bacteria. The disk diffusion method and analysis of bacterial staining were used to identify antibacterial effect, while DNA-binding, scanning electron microscopy and transmission electron microscopy were used to explore antimicrobial mechanisms. Disk diffusion showed that E. coli, S. aureus and Y. enterocolitica were sensitive to the β-casein 197. In addition, live/dead fluorescent staining also confirmed antibacterial effects. Scanning electron and transmission electron microscopy revealed affected extracellular and intracellular structure for three species of bacteria, while a DNA-binding assay showed that the antimicrobial activity did not occur through DNA binding. This study suggests that β-casein 197 has antimicrobial activity against common pathogenic bacteria in newborns with infection. The peptide induced membrane permeabilization but did not bind to genomic DNA. Based on our findings, β-casein 197 has potential clinical value for preventing infections of premature infants.

  4. Endogenous human milk Peptide release is greater after preterm birth than term birth

    NARCIS (Netherlands)

    Dallas, D.C.; Smink, C.J.; Robinson, R.C.; Tian, T.; Guerrero, A.; Parker, E.A.; Smilowitz, J.T.; Hettinga, K.A.; Underwood, M.A.; Lebrilla, C.B.; German, J.B.; Barile, D.

    2015-01-01

    Background: Hundreds of naturally occurring milk peptides are present in term human milk. Preterm milk is produced before complete maturation of the mammary gland, which could change milk synthesis and secretion processes within the mammary gland, leading to differences in protein expression and

  5. Oxytocin in the periaqueductal gray participates in pain modulation in the rat by influencing endogenous opiate peptides.

    Science.gov (United States)

    Yang, Jun; Liang, Jin-Ying; Li, Peng; Pan, Yan-Juan; Qiu, Pei-Yong; Zhang, Jing; Hao, Fang; Wang, Da-Xin

    2011-06-01

    Periaqueductal gray (PAG) plays a very important role in pain modulation through endogenous opiate peptides including leucine-enkephalin (L-Ek), methionine-enkephalin (M-Ek), β-endorphin (β-Ep) and dynorphin A(1-13) (DynA(1-13)). Our pervious study has demonstrated that intra-PAG injection of oxytocin (OXT) increases the pain threshold, and local administration of OXT receptor antagonist decreases the pain threshold, in which the antinociceptive role of OXT can be reversed by pre-PAG administration of OXT receptor antagonist. The experiment was designed to investigate the effect of OXT on endogenous opiate peptides in the rat PAG during the pain process. The results showed that (1) the concentrations of OXT, L-Ek, M-Ek and β-Ep, not DynA(1-13) in the PAG perfusion liquid were increased after the pain stimulation; (2) the concentrations of L-Ek, M-Ek and β-Ep, not DynA(1-13) in the PAG perfusion liquid were decreased by the OXT receptor antagonist; (3) the increased pain threshold induced by the OXT was attenuated by naloxone, an opiate receptor antagonist; and (4) the concentrations of L-Ek, M-Ek and β-Ep, not DynA(1-13) in the PAG perfusion liquid were increased by exogenous OXT administration. The data suggested that OXT in the PAG could influence the L-Ek, M-Ek and β-Ep rather than DynA(1-13) to participate in pain modulation, i.e. OXT in the PAG participate in pain modulation by influencing the L-Ek, M-Ek and β-Ep rather than DynA(1-13). Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Lysosomal Cathepsin A Plays Significant Role In The Processing Of Endogenous Bioactive Peptides

    Directory of Open Access Journals (Sweden)

    Zehra Timur

    2016-10-01

    Full Text Available Lysosomal serine carboxypeptidase Cathepsin A (CTSA is a multifunctional enzyme with distinct protective and catalytic function. CTSA that is present in the lysosomal multienzyme complex facilitates correct lysosomal routing, stability and activation of betagalactosidase and alpha-neuraminidase. In addition, CTSA plays a role in the inactivation of bioactive peptides including bradykinin, substances P, oxytocin, angiotensin I and endothelin-I by cleavage of one or two amino acid(s from the C-terminal ends. In this study, we aimed to elucidate the regulatory role of CTSA on bioactive peptides in a knock-in mouse model of CTSAS190A. We evaluated the levels of bradykinin, substances P, oxytocin, angiotensin I and endothelin-I in the kidney, liver, lung, brain and serum of the CTSAS190A mouse model at three- and six-months of age. Our results suggest that CTSA selectively contributes to the processing of bioactive peptides in different tissues of CTSAS190A mice compared to those of age-matched wild-type mice.

  7. Data on endogenous bovine ovarian follicular cells peptides and small proteins obtained through Top-down High Resolution Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Valérie Labas

    2017-08-01

    Full Text Available The endogenous peptides and small proteins extracted from bovine ovarian follicular cells (oocytes, cumulus and granulosa cells were identified by Top-down High Resolution Mass Spectrometry (TD-HR-MS/MS in order to annotate peptido- and proteoforms detected using qualitative and quantitative profiling method based on ICM-MS (Intact Cell Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. The description and analysis of these Top-down MS data in the context of oocyte quality biomarkers research are available in the original research article of Labas et al. (2017 http://dx.doi.org/10.1016/j.jprot.2017.03.027 [1]. Raw data derived from this peptidomic/proteomic analysis have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository (dataset identifier PXD004892. Here, we described the inventory of all identified peptido- and proteoforms including their biochemical and structural features, and functional annotation of correspondent proteins. This peptide/protein inventory revealed that TD-HR-MS/MS was appropriate method for both global and targeted proteomic analysis of ovarian tissues, and it can be further employed as a reference for other studies on follicular cells including single oocytes.

  8. Possible participation of endogenous opioid peptides on the mechanism involved in analgesia induced by vouacapan.

    Science.gov (United States)

    Duarte, I D; Ferreira-Alves, D L; Nakamura-Craig, M

    1992-01-01

    The involvement of opioid peptides in the mechanism of action of vouacapan, a new experimental compound extracted from seeds of Pterodon poligalaeflorus Benth, was investigated both in mice utilizing acetic acid writhing response and in rats utilizing inflammatory hyperalgesia induced by carrageenan and modified Randall-Selitto method. Vouacapan, in both models, caused a dose-dependent analgesia when injected p.o., s.c. and i.p. The analgesic effect was partially blocked by naloxone, nalorphine and n-methyl-nalorphine. Significant tolerance to analgesic effect was observed following repeated administration of vouacapan or morphine. On the last day of treatment, cross administration revealed symmetrical and asymmetrical cross-tolerance between vouacapan and morphine, in rats and mice, respectively. We conclude that a release of endorphins could be involved in the analgesic mechanism of vouacapan in both models tudied.

  9. A comparison of two semi-mechanistic models for prolactin release and prediction of receptor occupancy following administration of dopamine D2 receptor antagonists in rats.

    Science.gov (United States)

    Taneja, Amit; Vermeulen, An; Huntjens, Dymphy R H; Danhof, Meindert; De Lange, Elizabeth C M; Proost, Johannes H

    2016-10-15

    We compared the model performance of two semi-mechanistic pharmacokinetic-pharmacodynamic models, the precursor pool model and the agonist-antagonist interaction model, to describe prolactin response following the administration of the dopamine D2 receptor antagonists risperidone, paliperidone or remoxipride in rats. The time course of pituitary dopamine D2 receptor occupancy was also predicted. Male Wistar rats received a single dose (risperidone, paliperidone, remoxipride) or two consecutive doses (remoxipride). Population modeling was applied to fit the pool and interaction models to the prolactin data. The pool model was modified to predict the time course of pituitary D2 receptor occupancy. Unbound plasma concentrations of the D2 receptor antagonists were considered the drivers of the prolactin response. Both models were used to predict prolactin release following multiple doses of paliperidone. Both models described the data well and model performance was comparable. Estimated unbound EC50 for risperidone and paliperidone was 35.1nM (relative standard error 51%) and for remoxipride it was 94.8nM (31%). KI values for these compounds were 11.1nM (21%) and 113nM (27%), respectively. Estimated pituitary D2 receptor occupancies for risperidone and remoxipride were comparable to literature findings. The interaction model better predicted prolactin profiles following multiple paliperidone doses, while the pool model predicted tolerance better. The performance of both models in describing the prolactin profiles was comparable. The pool model could additionally describe the time course of pituitary D2 receptor occupancy. Prolactin response following multiple paliperidone doses was better predicted by the interaction model. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Neuroprotective effect of the endogenous neural peptide apelin in cultured mouse cortical neurons

    International Nuclear Information System (INIS)

    Zeng, Xiang Jun; Yu, Shan Ping; Zhang, Like; Wei, Ling

    2010-01-01

    The adipocytokine apelin and its G protein-coupled APJ receptor were initially isolated from a bovine stomach and have been detected in the brain and cardiovascular system. Recent studies suggest that apelin can protect cardiomyocytes from ischemic injury. Here, we investigated the effect of apelin on apoptosis in mouse primary cultures of cortical neurons. Exposure of the cortical cultures to a serum-free medium for 24 h induced nuclear fragmentation and apoptotic death; apelin-13 (1.0-5.0 nM) markedly prevented the neuronal apoptosis. Apelin neuroprotective effects were mediated by multiple mechanisms. Apelin-13 reduced serum deprivation (SD)-induced ROS generation, mitochondria depolarization, cytochrome c release and activation of caspase-3. Apelin-13 prevented SD-induced changes in phosphorylation status of Akt and ERK1/2. In addition, apelin-13 attenuated NMDA-induced intracellular Ca 2+ accumulation. These results indicate that apelin is an endogenous neuroprotective adipocytokine that may block apoptosis and excitotoxic death via cellular and molecular mechanisms. It is suggested that apelins may be further explored as a potential neuroprotective reagent for ischemia-induced brain damage.

  11. Neuroprotective effect of the endogenous neural peptide apelin in cultured mouse cortical neurons

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Xiang Jun [Department of Pathophysiology, Capital Medical University, Beijing 100069 (China); Department of Anesthesiology, 101 Woodruff Circle, Suite 617, Emory University School of Medicine, Atlanta, GA 30322 (United States); Yu, Shan Ping [Department of Anesthesiology, 101 Woodruff Circle, Suite 617, Emory University School of Medicine, Atlanta, GA 30322 (United States); Zhang, Like [Department of Pathophysiology, Capital Medical University, Beijing 100069 (China); Wei, Ling, E-mail: lwei7@emory.edu [Department of Anesthesiology, 101 Woodruff Circle, Suite 617, Emory University School of Medicine, Atlanta, GA 30322 (United States)

    2010-07-01

    The adipocytokine apelin and its G protein-coupled APJ receptor were initially isolated from a bovine stomach and have been detected in the brain and cardiovascular system. Recent studies suggest that apelin can protect cardiomyocytes from ischemic injury. Here, we investigated the effect of apelin on apoptosis in mouse primary cultures of cortical neurons. Exposure of the cortical cultures to a serum-free medium for 24 h induced nuclear fragmentation and apoptotic death; apelin-13 (1.0-5.0 nM) markedly prevented the neuronal apoptosis. Apelin neuroprotective effects were mediated by multiple mechanisms. Apelin-13 reduced serum deprivation (SD)-induced ROS generation, mitochondria depolarization, cytochrome c release and activation of caspase-3. Apelin-13 prevented SD-induced changes in phosphorylation status of Akt and ERK1/2. In addition, apelin-13 attenuated NMDA-induced intracellular Ca{sup 2+} accumulation. These results indicate that apelin is an endogenous neuroprotective adipocytokine that may block apoptosis and excitotoxic death via cellular and molecular mechanisms. It is suggested that apelins may be further explored as a potential neuroprotective reagent for ischemia-induced brain damage.

  12. Essential role of endogenous calcitonin gene-related peptide in pain-associated plasticity in the central amygdala.

    Science.gov (United States)

    Shinohara, Kei; Watabe, Ayako M; Nagase, Masashi; Okutsu, Yuya; Takahashi, Yukari; Kurihara, Hiroki; Kato, Fusao

    2017-09-01

    The role of the neuropeptide calcitonin gene-related peptide (CGRP) is well established in nociceptive behaviors. CGRP is highly expressed in the projection pathway from the parabrachial nucleus to the laterocapsular region of the central amygdala (CeC), which plays a critical role in relaying nociceptive information. The CeC is a key structure in pain behavior because it integrates and modulates nociceptive information along with other sensory signals. Previous studies have demonstrated that blockade of the amygdalar CGRP-signaling cascade attenuates nociceptive behaviors in pain models, while CGRP application facilitates amygdalar synaptic transmission and induces pain behaviors. Despite these lines of evidence, it remains unclear whether endogenous CGRP is involved in the development of nociceptive behaviors accompanied with amygdalar plasticity in a peripheral inflammation model in vivo. To directly address this, we utilized a previously generated CGRP knockout (KO) mouse to longitudinally study formalin-induced plasticity and nociceptive behavior. We found that synaptic potentiation in the right PB-CeC pathway that was observed in wild-type mice was drastically attenuated in the CGRP KO mice 6 h post-inflammation, when acute nociceptive behavior was no longer observed. Furthermore, the bilateral tactile allodynia 6 h post-inflammation was significantly decreased in the CGRP KO mice. In contrast, the acute nociceptive behavior immediately after the formalin injection was reduced only at 20-25 min post-injection in the CGRP KO mice. These results suggest that endogenous CGRP contributes to peripheral inflammation-induced synaptic plasticity in the amygdala, and this plasticity may underlie the exaggerated nociception-emotion linkage in pain chronification. © 2017 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  13. The thermogenic effect of leptin is dependent on a distinct population of prolactin-releasing peptide neurons in the dorsomedial hypothalamus.

    Science.gov (United States)

    Dodd, Garron T; Worth, Amy A; Nunn, Nicolas; Korpal, Aaron K; Bechtold, David A; Allison, Margaret B; Myers, Martin G; Statnick, Michael A; Luckman, Simon M

    2014-10-07

    Leptin is a critical regulator of metabolism, which acts on brain receptors (Lepr) to reduce energy intake and increase energy expenditure. Some of the cellular pathways mediating leptin's anorectic actions are identified, but those mediating the thermogenic effects have proven more difficult to decipher. We define a population of neurons in the dorsomedial hypothalamic nucleus (DMH) containing the RFamide PrRP, which is activated by leptin. Disruption of Lepr selectively in these cells blocks thermogenic responses to leptin and causes obesity. A separate population of leptin-insensitive PrRP neurons in the brainstem is required, instead, for the satiating actions of the gut-derived hormone cholecystokinin (CCK). Global deletion of PrRP (in a loxSTOPlox-PrRP mouse) results in obesity and attenuated responses to leptin and CCK. Cre-recombinase-mediated reactivation of PrRP in brainstem rescues the anorectic actions of CCK, but reactivation in the hypothalamus is required to re-establish the thermogenic effect of leptin. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Urinary C-peptide: a useful tool for evaluating the endogenous insulin reserve in cohort and longitudinal studies of diabetes in childhood.

    Science.gov (United States)

    de Beaufort, C E; den Boer, N C; Bruining, G J; Eilers, G A; van Strik, R; Weterings, T

    1988-09-01

    Increasing research into the remission phase of type I diabetes mellitus stresses the importance of a non-traumatic and reliable method for the evaluation of endogenous insulin production. We compared 24-h urinary C-peptide excretion (UCE) with plasma C-peptide values before and after stimulation with 1 mg glucagon in 24 type I diabetic children. Fasting plasma C-peptide values and stimulated plasma C-peptide values showed a linear correlation with 24 h UCE. Mean plasma C-peptide levels correlated inversely with the exogenous insulin dose. A slightly better correlation was found between the exogenous insulin dose and 24 h UCE. Control data of 24 h UCE were obtained from healthy siblings. A linear correlation with age was found up to 10 years of age above which UCE values seem to reach a plateau. This effect of age, as well as the frequency of sampling was taken into account in the derivation of 95% reference intervals for UCE. The measurement of 24 h UCE appears to be a useful parameter to assess endogenous insulin production in diabetic children, provided that age is taken into account.

  15. The Signal Peptide of a Recently Integrated Endogenous Sheep Betaretrovirus Envelope Plays a Major Role in Eluding Gag-Mediated Late Restriction ▿

    Science.gov (United States)

    Armezzani, Alessia; Arnaud, Frédérick; Caporale, Marco; di Meo, GiuliaPia; Iannuzzi, Leopoldo; Murgia, Claudio; Palmarini, Massimo

    2011-01-01

    The exogenous and pathogenic Jaagsiekte sheep retrovirus (JSRV) coexists with highly related and biologically active endogenous retroviruses (enJSRVs). The endogenous enJS56A1 locus possesses a defective Gag polyprotein which blocks the late replication steps of related exogenous and endogenous retroviruses by a mechanism known as JSRV late restriction (JLR). Conversely, enJSRV-26, which most likely integrated into the sheep genome less than 200 years ago, is able to escape JLR. In this study, we demonstrate that the ability of enJSRV-26 to escape JLR is due to a single-amino-acid substitution in the signal peptide (SP) of its envelope glycoprotein. We show that enJSRV-26 SP does not localize to the nucleolus, unlike the functional SPs of related exogenous and endogenous sheep betaretroviruses. In addition, enJSRV-26 SP function as a posttranscriptional regulator of viral gene expression is impaired. enJSRV-26 JLR escape relies on the presence of the functional enJS56A1 SP. Moreover, we show that the ratio between enJSRV-26 and enJS56A1 Gag is critical to elude JLR. Interestingly, we found that the domestic sheep has acquired, by genome amplification, several copies of the enJS56A1 provirus. These data further reinforce the notion that transdominant enJSRV proviruses have been positively selected in domestic sheep, and that the coevolution between endogenous and exogenous sheep betaretroviruses and their host is still occurring. PMID:21593182

  16. Summary data of potency and parameter information from semi-mechanistic PKPD modeling of prolactin release following administration of the dopamine D2 receptor antagonists risperidone, paliperidone and remoxipride in rats

    Directory of Open Access Journals (Sweden)

    Amit Taneja

    2016-09-01

    Full Text Available We provide the reader with relevant data related to our recently published paper, comparing two mathematical models to describe prolactin turnover in rats following one or two doses of the dopamine D2 receptor antagonists risperidone, paliperidone and remoxipride, “A comparison of two semi-mechanistic models for prolactin release and prediction of receptor occupancy following administration of dopamine D2 receptor antagonists in rats” (Taneja et al., 2016 [1]. All information is tabulated. Summary level data on the in vitro potencies and the physicochemical properties is presented in Table 1. Model parameters required to explore the precursor pool model are presented in Table 2. In Table 3, estimated parameter comparisons for both models are presented, when separate potencies are estimated for risperidone and paliperidone, as compared to a common potency for both drugs. In Table 4, parameter estimates are compared when the drug effect is parameterized in terms of drug concentration or receptor occupancy.

  17. Role of endogenous opioid peptides in the infarct size-limiting effect of adaptation to chronic continuous hypoxia

    Czech Academy of Sciences Publication Activity Database

    Maslov, L. N.; Naryzhnaya, N. V.; Tsibulnikov, S.Yu.; Kolář, František; Zhang, Y.; Wang, H.; Gusakova, A. M.; Lishmanov, Yu. B.

    2013-01-01

    Roč. 93, 9-11 (2013), s. 373-379 ISSN 0024-3205 R&D Projects: GA ČR(CZ) GAP303/12/1162 Institutional support: RVO:67985823 Keywords : chronic hypoxia * myocardial infarction * cardioprotection * opioid peptides * opioid receptors Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.296, year: 2013

  18. Cannabidiol and endogenous opioid peptide-mediated mechanisms modulate antinociception induced by transcutaneous electrostimulation of the peripheral nervous system.

    Science.gov (United States)

    Gonçalves, Thais Cristina Teixeira; Londe, Anna Karla; Albano, Rafael Isaac Pires; de Araújo Júnior, Artur Teixeira; de Aguiar Azeredo, Mariana; Biagioni, Audrey Francisco; Vasconcellos, Thiago Henrique Ferreira; Dos Reis Ferreira, Célio Marcos; Teixeira, Dulcinéa Gonçalves; de Souza Crippa, José Alexandre; Vieira, Débora; Coimbra, Norberto Cysne

    2014-12-15

    Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological therapy for the treatment of pain. The present work investigated the effect of cannabidiol, naloxone and diazepam in combination with 10 Hz and 150 Hz TENS. Male Wistar rats were submitted to the tail-flick test (baseline), and each rodent received an acute administration (intraperitoneal) of naloxone (3.0mg/kg), diazepam (1.5mg/kg) or cannabidiol (0.75 mg/kg, 1.5mg/kg, 3.0mg/kg, 4.5mg/kg, 6.0mg/kg and 12.0mg/kg); 10 min after the acute administration, 10 Hz or 150 Hz TENS or a sham procedure was performed for 30 min. Subsequently, tail-flick measures were recorded over a 90-min period, at 5-min intervals. 10 Hz TENS increased the nociceptive threshold during the 90-min period. This antinociceptive effect was reversed by naloxone pre-treatment, was not altered by diazepam pre-treatment and was abolished by cannabidiol pre-treatment (1.5mg/kg). Moreover, 150 Hz TENS increased tail-flick latencies by 35 min post-treatment, which was partially inhibited by naloxone pre-treatment and totally inhibited by cannabidiol (1.5mg/kg). These data suggest the involvement of the endogenous opioid system and the cannabinoid-mediated neuromodulation of the antinociception induced by transcutaneous electrostimulation at 10 Hz and 150 Hz TENS. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Xenoestrogens at Picomolar to Nanomolar Concentrations Trigger Membrane Estrogen Receptor-α–Mediated Ca2+ Fluxes and Prolactin Release in GH3/B6 Pituitary Tumor Cells

    Science.gov (United States)

    Wozniak, Ann L.; Bulayeva, Nataliya N.; Watson, Cheryl S.

    2005-01-01

    Xenoestrogens (XEs) are widespread in our environment and are known to have deleterious effects in animal (and perhaps human) populations. Acting as inappropriate estrogens, XEs are thought to interfere with endogenous estrogens such as estradiol (E2) to disrupt normal estrogenic signaling. We investigated the effects of E2 versus several XEs representing organochlorine pesticides (dieldrin, endosulfan, o′p′-dichlorodiphenylethylene), plastics manufacturing by-products/detergents (nonylphenol, bisphenol A), a phytoestrogen (coumestrol), and a synthetic estrogen (diethylstilbestrol) on the pituitary tumor cell subline GH3/B6/F10, previously selected for expression of high levels of membrane estrogen receptor-α. Picomolar to nanomolar concentrations of both E2 and XEs caused intracellular Ca2+ changes within 30 sec of administration. Each XE produced a unique temporal pattern of Ca2+ elevation. Removing Ca2+ from the extracellular solution abolished both spontaneous and XE-induced intracellular Ca2+ changes, as did 10 μM nifedipine. This suggests that XEs mediate their actions via voltage-dependent L-type Ca2+ channels in the plasma membrane. None of the Ca2+ fluxes came from intracellular Ca2+ stores. E2 and each XE also caused unique time- and concentration-dependent patterns of prolactin (PRL) secretion that were largely complete within 3 min of administration. PRL secretion was also blocked by nifedipine, demonstrating a correlation between Ca2+ influx and PRL secretion. These data indicate that at very low concentrations, XEs mediate membrane-initiated intracellular Ca2+ increases resulting in PRL secretion via a mechanism similar to that for E2, but with distinct patterns and potencies that could explain their abilities to disrupt endocrine functions. PMID:15811834

  20. Anti-inflammatory and vasoprotective activity of a retroviral-derived peptide, homologous to human endogenous retroviruses: endothelial cell effects.

    Directory of Open Access Journals (Sweden)

    George J Cianciolo

    Full Text Available Malignant and inflammatory tissues sometimes express endogenous retroviruses or their proteins. A highly-conserved sequence from retroviral transmembrane (TM proteins, termed the "immunosuppressive domain (ID", is associated with inhibition of immune and inflammatory functions. An octadecapeptide (MN10021 from the ID of retroviral TM protein p15E inhibits in vitro release of pro-inflammatory cytokines and increases synthesis of anti-inflammatory IL-10. We sought to determine if MN10021 has significant in vivo effects. MN10021, prepared by solid-phase synthesis, was dimerized through a naturally-occurring, carboxy-terminal cysteine. In vivo anti-inflammatory activity was determined using a murine model of sodium periodate (NaIO(4-induced peritonitis. In vivo vasoprotective effects were determined using: (1 a carrageenan-induced model of disseminated intravascular coagulation (DIC in mice; (2 a reverse passive Arthus model in guinea pigs; and (3 vasoregulatory effects in spontaneously hypertensive rats (SHR. In vitro studies included: (1 binding/uptake of MN10021 using human monocytes, cultured fibroblasts, and vascular endothelial cells (VEC; (2 gene expression by RT-PCR of MN10021-treated VEC; and (3 apoptosis of MN10021-treated VEC exposed to staurosporine or TNF-α. One-tenth nmol MN10021 inhibits 50 percent of the inflammatory response in the mouse peritonitis model. Furthermore, 73 nmol MN10021 completely protects mice in a lethal model of carrageenan-induced DIC and inhibits vascular leak in both the mouse DIC model and a guinea pig reverse passive Arthus reaction. MN10021 binds to and is taken up in a specific manner by both human monocytes and VEC but not by cultured human fibroblasts. Surprisingly, orally-administered MN10021 lowers blood pressure in SHR rats by 10-15% within 1 h suggesting a direct or indirect effect on the vascular endothelium. MN10021 and derived octapeptides induce iNOS (inducible nitric oxide synthase mRNA in VEC

  1. Effects of endogenous nitric oxide on adrenergic nerve-mediated vasoconstriction and calcitonin gene-related peptide-containing nerve-mediated vasodilation in pithed rats.

    Science.gov (United States)

    Yamawaki, Kousuke; Zamami, Yoshito; Kawasaki, Hiromu; Takatori, Shingo

    2017-05-05

    Vascular adrenergic nerves mainly regulate the tone of blood vessels. Calcitonin gene-related peptide-containing (CGRPergic) vasodilator nerves also participate in the regulation of vascular tone. Furthermore, there are nitric oxide (NO)-containing (nitrergic) nerves, which include NO in blood vessels as vasodilator nerves, but it remains unclear whether nitrergic nerves participate in vascular regulation. The present study investigated the role of nitrergic nerves in vascular responses to spinal cord stimulation (SCS) and vasoactive agents in pithed rats. Wistar rats were anesthetized and pithed, and vasopressor responses to SCS and injections of norepinephrine were observed. To evaluate vasorelaxant responses, the BP was increased by a continuous infusion of methoxamine with hexamethonium to block autonomic outflow. After the elevated BP stabilized, SCS and injections of acetylcholine (ACh), sodium nitroprusside (SNP), and CGRP were intravenously administered. We then evaluated the effects of the NO synthase (NOS) inhibitor, N-ω-nitro-L-arginine methylester hydrochloride (L-NAME), on these vascular responses. Pressor responses to SCS and norepinephrine in pithed rats were enhanced by L-NAME, while the combined infusion of L-NAME and L-arginine had no effect on these responses. L-NAME infusion significantly increased the release of norepinephrine evoked by SCS. In pithed rats with artificially increased BP and L-NAME infusion, depressor response to ACh (except for 0.05nmol/kg) was suppressed and SNP (only 2nmol/kg) was enhanced. However, depressor responses to SCS and CGRP were similar to control responses. The present results suggest endogenous NO regulates vascular tone through endothelium function and inhibition of adrenergic neurotransmission, but not through CGRPergic nerves. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Endogenous Expression of ODN-Related Peptides in Astrocytes Contributes to Cell Protection Against Oxidative Stress: Astrocyte-Neuron Crosstalk Relevance for Neuronal Survival.

    Science.gov (United States)

    Ghouili, Ikram; Bahdoudi, Seyma; Morin, Fabrice; Amri, Fatma; Hamdi, Yosra; Coly, Pierre Michael; Walet-Balieu, Marie-Laure; Leprince, Jérôme; Zekri, Sami; Vaudry, Hubert; Vaudry, David; Castel, Hélène; Amri, Mohamed; Tonon, Marie-Christine; Masmoudi-Kouki, Olfa

    2017-07-11

    Astroglial cells are important actors in the defense of brain against oxidative stress injuries. Glial cells synthesize and release the octadecaneuropeptide ODN, a diazepam-binding inhibitor (DBI)-related peptide, which acts through its metabotropic receptor to protect neurons and astrocytes from oxidative stress-induced apoptosis. The purpose of the present study is to examine the contribution of the endogenous ODN in the protection of astrocytes and neurons from moderate oxidative stress. The administration of H 2 O 2 (50 μM, 6 h) induced a moderate oxidative stress in cultured astrocytes, i.e., an increase in reactive oxygen species, malondialdehyde, and carbonyl group levels, but it had no effect on astrocyte death. Mass spectrometry and QPCR analysis revealed that 50 μM H 2 O 2 increased ODN release and DBI mRNA levels. The inhibition of ODN release or pharmacological blockage of the effects of ODN revealed that in these conditions, 50 μM H 2 O 2 induced the death of astrocytes. The transfection of astrocytes with DBI siRNA increased the vulnerability of cells to moderate stress. Finally, the addition of 1 nM ODN to culture media reversed cell death observed in DBI-deficient astrocytes. The treatment of neurons with media from 50 μM H 2 O 2 -stressed astrocytes significantly reduced the neuronal death induced by H 2 O 2 ; this effect is greatly attenuated by the administration of an ODN metabotropic receptor antagonist. Overall, these results indicate that astrocytes produce authentic ODN, notably in a moderate oxidative stress situation, and this glio- and neuro-protective agent may form part of the brain defense mechanisms against oxidative stress injury.

  3. Comparison of the endogenous ileal and faecal amino acid excretion in the dog (Canis familiaris) and the rat (Rattus rattus) determined under protein-free feeding and peptide alimentation.

    Science.gov (United States)

    Hendriks, W H; Sritharan, K; Hodgkinson, S M

    2002-10-01

    The aim of the study was to determine and compare the endogenous ileal excretions of nitrogen and amino acids under protein-free and peptide alimentation by the dog and rat. Two diets were prepared, one that was devoid of protein and the other containing 23% enzyme hydrolysed casein. Chromic oxide was included in the diets as an indigestible marker. A total of 10 mixed breed dogs were fed hourly either a protein-free or enzymatically hydrolysed casein diet for a total of 10 days. A faecal sample was obtained from each dog on day 9 while digesta was obtained from the terminal 20 cm of the ileum directly after euthanasia on day 10. A total of 12 8-week-old Sprague-Dawley rats received the same diets as the dogs. A faecal sample from each rat was obtained on day 7 while ileal digesta samples were obtained on day 8. The endogenous ileal excretions of most amino acids were greater in the dogs and rats that received the enzymatically hydrolysed casein diet compared with those receiving the protein free diet. Whereas the pattern of endogenous amino acid excretion was similar in the rats and dogs, the dogs excreted a significantly greater amount of nitrogen (1.91 vs. 2.27 and 1.63 vs. 4.12 g/kg dry matter intake for the protein-free and peptide alimentation method, respectively) and all amino acids except for glycine, isoleucine and leucine. Endogenous ileal amino acid excretions are higher in dogs compared to omnivorous animals such as rats and pigs but similar to the carnivorous cat.

  4. Different binding motifs of the celiac disease-associated HLA molecules DQ2.5, DQ2.2, and DQ7.5 revealed by relative quantitative proteomics of endogenous peptide repertoires

    DEFF Research Database (Denmark)

    Bergseng, Elin; Dørum, Siri; Arntzen, Magnus Ø.

    2014-01-01

    Celiac disease is caused by intolerance to cereal gluten proteins, and HLA-DQ molecules are involved in the disease pathogenesis by presentation of gluten peptides to CD4+ T cells. The α- or β-chain sharing HLA molecules DQ2.5, DQ2.2, and DQ7.5 display different risks for the disease...... established binding motifs. The binding motif of DQ2.2 was strikingly different from that of DQ2.5 with position P3 being a major anchor having a preference for threonine and serine. This is notable as three recently identified epitopes of gluten recognized by T cells of DQ2.2 celiac patients harbor serine...... at position P3. This study demonstrates that relative quantitative comparison of endogenous peptides sampled from our protein metabolism by HLA molecules provides clues to understand HLA association with disease....

  5. Ciprofloxacin Affects Host Cells by Suppressing Expression of the Endogenous Antimicrobial Peptides Cathelicidins and Beta-Defensin-3 in Colon Epithelia

    Directory of Open Access Journals (Sweden)

    Protim Sarker

    2014-07-01

    Full Text Available Antibiotics exert several effects on host cells including regulation of immune components. Antimicrobial peptides (AMPs, e.g., cathelicidins and defensins display multiple functions in innate immunity. In colonic mucosa, cathelicidins are induced by butyrate, a bacterial fermentation product. Here, we investigated the effect of antibiotics on butyrate-induced expression of cathelicidins and beta-defensins in colon epithelial cells. Real-time PCR analysis revealed that ciprofloxacin and clindamycin reduce butyrate-induced transcription of the human cathelicidin LL-37 in the colonic epithelial cell line HT-29. Suppression of LL-37 peptide/protein by ciprofloxacin was confirmed by Western blot analysis. Immunohistochemical analysis demonstrated that ciprofloxacin suppresses the rabbit cathelicidin CAP-18 in rectal epithelia of healthy and butyrate-treated Shigella-infected rabbits. Ciprofloxacin also down-regulated butyrate-induced transcription of the human beta-defensin-3 in HT-29 cells. Microarray analysis of HT-29 cells revealed upregulation by butyrate with subsequent down-regulation by ciprofloxacin of additional genes encoding immune factors. Dephosphorylation of histone H3, an epigenetic event provided a possible mechanism of the suppressive effect of ciprofloxacin. Furthermore, LL-37 peptide inhibited Clostridium difficile growth in vitro. In conclusion, ciprofloxacin and clindamycin exert immunomodulatory function by down-regulating AMPs and other immune components in colonic epithelial cells. Suppression of AMPs may contribute to the overgrowth of C. difficile, causing antibiotic-associated diarrhea.

  6. Endogenous opiates and behavior: 2014.

    Science.gov (United States)

    Bodnar, Richard J

    2016-01-01

    This paper is the thirty-seventh consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2014 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (endogenous opioids and receptors), and the roles of these opioid peptides and receptors in pain and analgesia (pain and analgesia); stress and social status (human studies); tolerance and dependence (opioid mediation of other analgesic responses); learning and memory (stress and social status); eating and drinking (stress-induced analgesia); alcohol and drugs of abuse (emotional responses in opioid-mediated behaviors); sexual activity and hormones, pregnancy, development and endocrinology (opioid involvement in stress response regulation); mental illness and mood (tolerance and dependence); seizures and neurologic disorders (learning and memory); electrical-related activity and neurophysiology (opiates and conditioned place preferences (CPP)); general activity and locomotion (eating and drinking); gastrointestinal, renal and hepatic functions (alcohol and drugs of abuse); cardiovascular responses (opiates and ethanol); respiration and thermoregulation (opiates and THC); and immunological responses (opiates and stimulants). This paper is the thirty-seventh consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2014 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular

  7. The application of strand invasion phenomenon, directed by peptide nucleic acid (PNA) and single-stranded DNA binding protein (SSB) for the recognition of specific sequences of human endogenous retroviral HERV-W family.

    Science.gov (United States)

    Machnik, Grzegorz; Bułdak, Łukasz; Ruczyński, Jarosław; Gąsior, Tomasz; Huzarska, Małgorzata; Belowski, Dariusz; Alenowicz, Magdalena; Mucha, Piotr; Rekowski, Piotr; Okopień, Bogusław

    2017-05-01

    The HERV-W family of human endogenous retroviruses represents a group of numerous sequences that show close similarity in genetic composition. It has been documented that some members of HERV-W-derived expression products are supposed to play significant role in humans' pathology, such as multiple sclerosis or schizophrenia. Other members of the family are necessary to orchestrate physiological processes (eg, ERVWE1 coding syncytin-1 that is engaged in syncytiotrophoblast formation). Therefore, an assay that would allow the recognition of particular form of HERV-W members is highly desirable. A peptide nucleic acid (PNA)-mediated technique for the discrimination between multiple sclerosis-associated retrovirus and ERVWE1 sequence has been developed. The assay uses a PNA probe that, being fully complementary to the ERVWE1 but not to multiple sclerosis-associated retrovirus (MSRV) template, shows high selective potential. Single-stranded DNA binding protein facilitates the PNA-mediated, sequence-specific formation of strand invasion complex and, consequently, local DNA unwinding. The target DNA may be then excluded from further analysis in any downstream process such as single-stranded DNA-specific exonuclease action. Finally, the reaction conditions have been optimized, and several PNA probes that are targeted toward distinct loci along whole HERV-W env sequences have been evaluated. We believe that PNA/single-stranded DNA binding protein-based application has the potential to selectively discriminate particular HERV-W molecules as they are at least suspected to play pathogenic role in a broad range of medical conditions, from psycho-neurologic disorders (multiple sclerosis and schizophrenia) and cancers (breast cancer) to that of an auto-immunologic background (psoriasis and lupus erythematosus). Copyright © 2016 John Wiley & Sons, Ltd.

  8. Human endogenous retroviruses and cancer.

    Science.gov (United States)

    Gonzalez-Cao, María; Iduma, Paola; Karachaliou, Niki; Santarpia, Mariacarmela; Blanco, Julià; Rosell, Rafael

    2016-12-01

    Human endogenous retroviruses (HERVs) are retroviruses that infected human genome millions of years ago and have persisted throughout human evolution. About 8% of our genome is composed of HERVs, most of which are nonfunctional because of epigenetic control or deactivating mutations. However, a correlation between HERVs and human cancer has been described and many tumors, such as melanoma, breast cancer, germ cell tumors, renal cancer or ovarian cancer, express HERV proteins, mainly HERV-K (HML6) and HERV-K (HML2). Although the causative role of HERVs in cancer is controversial, data from animal models demonstrated that endogenous retroviruses are potentially oncogenic. HERV protein expression in human cells generates an immune response by activating innate and adaptive immunities. Some HERV-derived peptides have antigenic properties. For example, HERV-K (HML-6) encodes the HER-K MEL peptide recognized by CD8+ lymphocytes. In addition, HERVs are two-edged immunomodulators. HERVs show immunosuppressive activity. The presence of genomic retroviral elements in host-cell cytosol may activate an interferon type I response. Therefore, targeting HERVs through cellular vaccines or immunomodulatory drugs combined with checkpoint inhibitors is attracting interest because they could be active in human tumors.

  9. Endogenous Lunar Volatiles

    Science.gov (United States)

    McCubbin, F. M.; Liu, Y.; Barnes, J. J.; Anand, M.; Boyce, J. W.; Burney, D.; Day, J. M. D.; Elardo, S. M.; Hui, H.; Klima, R. L.; Magna, T.; Ni, P.; Steenstra, E.; Tartèse, R.; Vander Kaaden, K. E.

    2018-04-01

    This abstract discusses numerous outstanding questions on the topic of endogenous lunar volatiles that will need to be addressed in the coming years. Although substantial insights into endogenous lunar volatiles have been gained, more work remains.

  10. Comparative Effects of the Endogenous Agonist Glucagon-Like Peptide-1 (GLP-1)-(7-36) Amide and the Small-Molecule Ago-Allosteric Agent “Compound 2” at the GLP-1 Receptor

    OpenAIRE

    Coopman, Karen; Huang, Yan; Johnston, Neil; Bradley, Sophie J.; Wilkinson, Graeme F.; Willars, Gary B.

    2010-01-01

    Glucagon-like peptide-1 (GLP-1) mediates antidiabetogenic effects through the GLP-1 receptor (GLP-1R), which is targeted for the treatment of type 2 diabetes. Small-molecule GLP-1R agonists have been sought due to difficulties with peptide therapeutics. Recently, 6,7-dichloro-2-methylsulfonyl-3-N-tert-butylaminoquinoxaline (compound 2) has been described as a GLP-1R allosteric modulator and agonist. Using human embryonic kidney-293 cells expressing human GLP-1Rs, we extended this work to cons...

  11. Endogenous Prospect Theory

    OpenAIRE

    Schmidt, Ulrich; Zank, Horst

    2010-01-01

    In previous models of (cumulative) prospect theory reference-dependence of preferences is imposed beforehand and the location of the reference point is exogenously determined. This paper provides an axiomatization of a new specification of cumulative prospect theory, termed endogenous prospect theory, where reference-dependence is derived from preference conditions and a unique reference point arises endogenously.

  12. Endogenous Locus Reporter Assays.

    Science.gov (United States)

    Liu, Yaping; Hermes, Jeffrey; Li, Jing; Tudor, Matthew

    2018-01-01

    Reporter gene assays are widely used in high-throughput screening (HTS) to identify compounds that modulate gene expression. Traditionally a reporter gene assay is built by cloning an endogenous promoter sequence or synthetic response elements in the regulatory region of a reporter gene to monitor transcriptional activity of a specific biological process (exogenous reporter assay). In contrast, an endogenous locus reporter has a reporter gene inserted in the endogenous gene locus that allows the reporter gene to be expressed under the control of the same regulatory elements as the endogenous gene, thus more accurately reflecting the changes seen in the regulation of the actual gene. In this chapter, we introduce some of the considerations behind building a reporter gene assay for high-throughput compound screening and describe the methods we have utilized to establish 1536-well format endogenous locus reporter and exogenous reporter assays for the screening of compounds that modulate Myc pathway activity.

  13. WHAT IS ENDOGENOUS IN ENDOGENOUS GROWTH MODEL?

    OpenAIRE

    Öztürkler, Harun; Bozgeyik, Yusuf

    2014-01-01

    The neoclassical growth model predicts that as soon as technologic improvements and innovations are not provided the growth in per capita income would stop in long term. However, the long-run data for many countries indicate that positive rates of per capita income growth can persist over the long term. Growth theorists of the 1950s and 1960s recognized this modeling deficiency and usually patched it up by assuming that technological progress occurs in an exogenous manner. The endogenous grow...

  14. The Endogenous Exposome

    Science.gov (United States)

    Nakamura, Jun; Mutlu, Esra; Sharma, Vyom; Collins, Leonard; Bodnar, Wanda; Yu, Rui; Lai, Yongquan; Moeller, Benjamin; Lu, Kun; Swenberg, James

    2014-01-01

    The concept of the Exposome, is a compilation of diseases and one’s lifetime exposure to chemicals, whether the exposure comes from environmental, dietary, or occupational exposures; or endogenous chemicals that are formed from normal metabolism, inflammation, oxidative stress, lipid peroxidation, infections, and other natural metabolic processes such as alteration of the gut microbiome. In this review, we have focused on the Endogenous Exposome, the DNA damage that arises from the production of endogenous electrophilic molecules in our cells. It provides quantitative data on endogenous DNA damage and its relationship to mutagenesis, with emphasis on when exogenous chemical exposures that produce identical DNA adducts to those arising from normal metabolism cause significant increases in total identical DNA adducts. We have utilized stable isotope labeled chemical exposures of animals and cells, so that accurate relationships between endogenous and exogenous exposures can be determined. Advances in mass spectrometry have vastly increased both the sensitivity and accuracy of such studies. Furthermore, we have clear evidence of which sources of exposure drive low dose biology that results in mutations and disease. These data provide much needed information to impact quantitative risk assessments, in the hope of moving towards the use of science, rather than default assumptions. PMID:24767943

  15. Comparative effects of the endogenous agonist glucagon-like peptide-1 (GLP-1)-(7-36) amide and the small-molecule ago-allosteric agent "compound 2" at the GLP-1 receptor.

    Science.gov (United States)

    Coopman, Karen; Huang, Yan; Johnston, Neil; Bradley, Sophie J; Wilkinson, Graeme F; Willars, Gary B

    2010-09-01

    Glucagon-like peptide-1 (GLP-1) mediates antidiabetogenic effects through the GLP-1 receptor (GLP-1R), which is targeted for the treatment of type 2 diabetes. Small-molecule GLP-1R agonists have been sought due to difficulties with peptide therapeutics. Recently, 6,7-dichloro-2-methylsulfonyl-3-N-tert-butylaminoquinoxaline (compound 2) has been described as a GLP-1R allosteric modulator and agonist. Using human embryonic kidney-293 cells expressing human GLP-1Rs, we extended this work to consider the impact of compound 2 on G protein activation, Ca(2+) signaling and receptor internalization and particularly to compare compound 2 and GLP-1 across a range of functional assays in intact cells. GLP-1 and compound 2 activated Galpha(s) in cell membranes and increased cellular cAMP in intact cells, with compound 2 being a partial and almost full agonist, respectively. GLP-1 increased intracellular [Ca(2+)] by release from intracellular stores, which was mimicked by compound 2, with slower kinetics. In either intact cells or membranes, the orthosteric antagonist exendin-(9-39), inhibited GLP-1 cAMP generation but increased the efficacy of compound 2. GLP-1 internalized enhanced green fluorescent protein-tagged GLP-1Rs, but the speed and magnitude evoked by compound 2 were less. Exendin-(9-39) inhibited internalization by GLP-1 and also surprisingly that by compound 2. Compound 2 displays GLP-1R agonism consistent with action at an allosteric site, although an orthosteric antagonist increased its efficacy on cAMP and blocked compound 2-mediated receptor internalization. Full assessment of the properties of compound 2 was potentially hampered by damaging effects that were particularly manifest in either longer term assays with intact cells or in acute assays with membranes.

  16. Decisions with endogenous frames

    NARCIS (Netherlands)

    Dalton, P.S.; Ghosal, S.

    2012-01-01

    We develop a model of decision-making with endogenous frames and contrast the normative implications of our model to those of choice theoretic models in which observed choices are determined by exogenous frames or ancillary conditions. We argue that, frames, though they may be taken as given by the

  17. The Endogenous Feedback Network

    DEFF Research Database (Denmark)

    Augustenborg, Claudia Carrara

    2010-01-01

    proposals, it will first be considered the extents of their reciprocal compatibility, tentatively shaping an integrated, theoretical profile of consciousness. A new theory, the Endogenous Feedback Network (EFN) will consequently be introduced which, beside being able to accommodate the main tenets...

  18. Does liver-intestine significantly degrade circulating endogenous substance P in man?

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Schaffalitzky de Muckadell, O B; Bülow, J B

    1986-01-01

    Elevated concentrations of circulating substance P in patients with liver insufficiency have been ascribed to decreased hepatic degradation. To establish a possible biodegradation of the peptide in liver-intestine and kidneys, the concentration of endogenous immunoreactive substance P was determi......Elevated concentrations of circulating substance P in patients with liver insufficiency have been ascribed to decreased hepatic degradation. To establish a possible biodegradation of the peptide in liver-intestine and kidneys, the concentration of endogenous immunoreactive substance P....... The results indicate that degradation of circulating endogenous substance P in man is not confined to liver-intestine or kidney but may take place in many tissues....

  19. Endogenous growth and the environment

    NARCIS (Netherlands)

    Withagen, C.A.A.M.; Vellinga, N.

    2001-01-01

    This paper examines the relationship between environmental policy and growth, from the perspective of endogenous growth theory. In particular three standard endogenous growth models are supplemented with environmental issues, such as pollution and exhaustibility of natural resources. It is found

  20. Endogenous Entry in Contests

    OpenAIRE

    John Morgan; Henrik Orzen; Martin Sefton

    2008-01-01

    We report the results of laboratory experiments on rent-seeking contests with endogenous participation. Theory predicts that (a) contest entry and rent-seeking expenditures increase with the size of the prize; and (b) earnings are equalized between the contest and the outside option. While the directional predictions offered in (a) are supported in the data, the level predictions are not. Prediction (b) is not supported in the data: When the prize is large, contest participants earn more than...

  1. Stimulating endogenous cardiac regeneration

    Directory of Open Access Journals (Sweden)

    Amanda eFinan

    2015-09-01

    Full Text Available The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration,a combination of these approaches couldameliorate the overall repair process to incorporate the participation ofmultiple cell players.

  2. NCBI nr-aa BLAST: CBRC-DRER-17-0052 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DRER-17-0052 ref|NP_001019756.1| prolactin releasing peptide receptor-like [Ga...llus gallus] gb|AAS77862.1| prolactin releasing peptide receptor-like protein [Gallus gallus] NP_001019756.1 1e-117 60% ...

  3. NCBI nr-aa BLAST: CBRC-MEUG-01-1879 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MEUG-01-1879 ref|NP_001120643.1| prolactin-releasing peptide receptor-like pro...tein [Gallus gallus] gb|ABW96907.1| prolactin-releasing peptide receptor-like protein precursor [Gallus gallus] NP_001120643.1 1e-129 68% ...

  4. NCBI nr-aa BLAST: CBRC-TGUT-08-0014 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TGUT-08-0014 ref|NP_001019756.1| prolactin releasing peptide receptor-like [Ga...llus gallus] gb|AAS77862.1| prolactin releasing peptide receptor-like protein [Gallus gallus] NP_001019756.1 1e-178 87% ...

  5. NCBI nr-aa BLAST: CBRC-ACAR-01-0391 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-ACAR-01-0391 ref|NP_001019756.1| prolactin releasing peptide receptor-like [Ga...llus gallus] gb|AAS77862.1| prolactin releasing peptide receptor-like protein [Gallus gallus] NP_001019756.1 1e-154 76% ...

  6. NCBI nr-aa BLAST: CBRC-MEUG-01-1879 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MEUG-01-1879 ref|NP_001108618.1| brain prolactin-releasing peptide receptor-li...ke protein 2 [Danio rerio] gb|ABY25269.1| brain prolactin-releasing peptide receptor-like protein 2 [Danio rerio] NP_001108618.1 1e-118 61% ...

  7. NCBI nr-aa BLAST: CBRC-GGAL-05-0010 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-GGAL-05-0010 ref|NP_001019756.1| prolactin releasing peptide receptor-like [Ga...llus gallus] gb|AAS77862.1| prolactin releasing peptide receptor-like protein [Gallus gallus] NP_001019756.1 0.0 97% ...

  8. NCBI nr-aa BLAST: CBRC-OLAT-22-0015 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OLAT-22-0015 ref|NP_001019756.1| prolactin releasing peptide receptor-like [Ga...llus gallus] gb|AAS77862.1| prolactin releasing peptide receptor-like protein [Gallus gallus] NP_001019756.1 1e-103 56% ...

  9. NCBI nr-aa BLAST: CBRC-FRUB-02-0068 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-FRUB-02-0068 ref|NP_001019756.1| prolactin releasing peptide receptor-like [Ga...llus gallus] gb|AAS77862.1| prolactin releasing peptide receptor-like protein [Gallus gallus] NP_001019756.1 1e-101 55% ...

  10. NCBI nr-aa BLAST: CBRC-GACU-15-0002 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-GACU-15-0002 ref|NP_001019756.1| prolactin releasing peptide receptor-like [Ga...llus gallus] gb|AAS77862.1| prolactin releasing peptide receptor-like protein [Gallus gallus] NP_001019756.1 1e-100 56% ...

  11. NCBI nr-aa BLAST: CBRC-PMAR-01-0684 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PMAR-01-0684 ref|NP_001019756.1| prolactin releasing peptide receptor-like [Ga...llus gallus] gb|AAS77862.1| prolactin releasing peptide receptor-like protein [Gallus gallus] NP_001019756.1 3e-44 55% ...

  12. NCBI nr-aa BLAST: CBRC-MDOM-01-0092 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MDOM-01-0092 ref|NP_001108618.1| brain prolactin-releasing peptide receptor-li...ke protein 2 [Danio rerio] gb|ABY25269.1| brain prolactin-releasing peptide receptor-like protein 2 [Danio rerio] NP_001108618.1 1e-117 66% ...

  13. NCBI nr-aa BLAST: CBRC-OLAT-13-0068 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OLAT-13-0068 ref|NP_001019756.1| prolactin releasing peptide receptor-like [Ga...llus gallus] gb|AAS77862.1| prolactin releasing peptide receptor-like protein [Gallus gallus] NP_001019756.1 1e-100 54% ...

  14. Peptide dendrimers

    Czech Academy of Sciences Publication Activity Database

    Niederhafner, Petr; Šebestík, Jaroslav; Ježek, Jan

    2005-01-01

    Roč. 11, - (2005), 757-788 ISSN 1075-2617 R&D Projects: GA ČR(CZ) GA203/03/1362 Institutional research plan: CEZ:AV0Z40550506 Keywords : multiple antigen peptides * peptide dendrimers * synthetic vaccine * multipleantigenic peptides Subject RIV: CC - Organic Chemistry Impact factor: 1.803, year: 2005

  15. The Endogenous Feedback Network

    DEFF Research Database (Denmark)

    Augustenborg, Claudia Carrara

    2010-01-01

    proposals, it will first be considered the extents of their reciprocal compatibility, tentatively shaping an integrated, theoretical profile of consciousness. A new theory, the Endogenous Feedback Network (EFN) will consequently be introduced which, beside being able to accommodate the main tenets...... of the reviewed theories, appears able to compensate for the explanatory gaps they leave behind. The EFN proposes consciousness as the phenomenon emerging from a distinct network of neural paths broadcasting the neural changes associated to any mental process. It additionally argues for the need to include a 5th...

  16. Endogenous cannabinoids and appetite.

    Science.gov (United States)

    Kirkham, T C; Williams, C M

    2001-06-01

    Since pre-history, Cannabis sativa has been exploited for its potent and manifold pharmacological actions. Amongst the most renowned of these actions is a tendency to provoke ravenous eating. The characterization of the psychoactive principals in cannabis (exogenous cannabinoids) and, more recently, the discovery of specific brain cannabinoid receptors and their endogenous ligands (endocannabinoids) has stimulated research into the physiological roles of endocannabinoid systems. In this review, we critically discuss evidence from the literature that describe studies on animals and human subjects to support endocannabinoid involvement in the control of appetite. We describe the hyperphagic actions of the exogenous cannabinoid, Delta9-tetrahydrocannabinol, and the endogenous CB1 ligands, anandamide and 2-arachidonylglycerol, and present evidence to support a specific role of endocannabinoid systems in appetitive processes related to the incentive and reward properties of food. A case is made for more comprehensive and systematic analyses of cannabinoid actions on eating, in the anticipation of improved therapies for disorders of appetite and body weight, and a better understanding of the biopsychological processes underlying hunger.

  17. Combining Semi-Endogenous and Fully Endogenous Growth: a Generalization.

    OpenAIRE

    Cozzi, Guido

    2017-01-01

    This paper shows that combining the semi-endogenous and the fully endogenous growth mechanisms with a general CES aggregator, either growth process can prevail in the balanced growth path depending on their degree of complementarity/substitutability. Policy-induced long-run economic switches to the fully endogenous steady state as the R&D employment ratio surpasses a positive threshold are possible if the two growth engines are gross substitutes.

  18. [Biosynthesis of opioid peptides].

    Science.gov (United States)

    Rossier, J

    1988-01-01

    The endogenous opioid peptides all contain the enkephalin sequence Tyr-Gly-Gly-Phe-Met and Tyr-Gly-Gly-Phe-Leu at their aminoterminus. Three distinct families of these peptides (endorphins, enkephalins and dynorphins) are present in different neuronal pathways within the central nervous system. Molecular genetics have shown that these three families of opioid peptides are derived from three distinct precursors. Pro-opiomelanocortin gives rise to the endorphins, as well as adrenocorticotropic hormone (ACTH) and the melanotropic hormones (MSH's). [Met] enkephalin, [Leu] enkephalin and the related heptapeptide [Met] enkephalin-Arg6-Phe7 and octapeptide [Met] enkephalin-Arg6-Gly7-Leu8 are derived from proenkephalin. The third family is derived from prodynorphin and includes dynorphin A, dynorphin B (also known as rimorphin) and alpha- and beta-neo-endorphin. The structure of the genes coding for these precursors are similar, suggesting the possibility of one common ancestral gene. The most common scheme for enzymatic maturation of precursors proposes the action of a trypsin-like endopeptidase followed by a carboxypeptidase B-like exopeptidase. However, we have provided evidence that this combination of trypsin-like and carboxypeptidase B-like enzymes may not be the only mechanism for liberating enkephalin from low molecular weight enkephalin-containing peptides. Indeed, endo-oligopeptidase A, an enzyme, known to hydrolyze the Phe5-Ser6 bond of bradykinin and the Arg8-Arg9 bond of neurotensin, has been shown to produce, by a single cleavage, [Leu] enkephalin or [Met] enkephalin from small enkephalin-containing peptides, (Camargo et al., 1987, J. Neurochem. 48, 1258-1263).(ABSTRACT TRUNCATED AT 250 WORDS)

  19. An antioxidant peptide produced by autolysis reactions from wheat ...

    African Journals Online (AJOL)

    Wheat germ was incubated in a buffer solution of sodium citrate and dibasic sodium phosphate and its proteins were hydrolyzed by endogenous proteases to produce peptides. A peptide with high antioxidant activity was purified using ultrafiltration, Sephadex G-25 gel filtration column and consecutive chromatographic ...

  20. Endogenous Monetary Policy Regime Change

    OpenAIRE

    Troy Davig; Eric M. Leeper

    2006-01-01

    This paper makes changes in monetary policy rules (or regimes) endogenous. Changes are triggered when certain endogenous variables cross specified thresholds. Rational expectations equilibria are examined in three models of threshold switching to illustrate that (i) expectations formation effects generated by the possibility of regime change can be quantitatively important; (ii) symmetric shocks can have asymmetric effects; (iii) endogenous switching is a natural way to formally model preempt...

  1. Endogeneity Of Indonesian Money Supply

    OpenAIRE

    Rachma, Meutia Safrina

    2010-01-01

    There has been a long debate about the endogeneity of money supply. The main objective of this article is to identify whether money supply in Indonesia is an exogenous or an endogenous variable. Using a Vector Autoregressive model and monthly data 1997(5)-2010(6), the estimation result shows that money supply in Indonesia is an endogenous variable. The movement of broad money supply does influence the movement of base money and Consumer Price Index. Consequently, the central bank does not hav...

  2. Habits, aspirations and endogenous fertility

    OpenAIRE

    Luciano Fanti

    2012-01-01

    Motivated by the increasing literature on endogenous preferences as well as on endogenous fertility, this paper investigates the implications of the interaction of the endogenous determination of the number of children with habit and aspiration formation in an OLG model. In contrast with the previous literature, we show that greater aspirations may lead to higher savings, and more interestingly, always increase the neoclassical economic growth.

  3. ENDOGENEITY OF INDONESIAN MONEY SUPPLY

    OpenAIRE

    Rachma, Meutia Safrina

    2011-01-01

    There has been a long debate about the endogeneity of money supply. The main objective of this article is to identify whether money supply in Indonesia is an exogenous or an endogenous variable. Using a Vector Autoregressive model and monthly data 1997(5)-2010(6), the estimation result shows that money supply in Indonesia is an endogenous variable. The movement of broad money supply does influence the movement of base money and Consumer Price Index. Consequently, the central bank does not hav...

  4. Endogenous Lunar Volatiles

    Science.gov (United States)

    McCubbin, F. M.; Liu, Y.; Barnes, J. J.; Boyce, J. W.; Day, J. M. D.; Elardo, S. M.; Hui, H.; Magna, T.; Ni, P.; Tartese, R.; hide

    2017-01-01

    The chapter will begin with an introduction that defines magmatic volatiles (e.g., H, F, Cl, S) versus geochemical volatiles (e.g., K, Rb, Zn). We will discuss our approach of understanding both types of volatiles in lunar samples and lay the ground work for how we will determine the overall volatile budget of the Moon. We will then discuss the importance of endogenous volatiles in shaping the "Newer Views of the Moon", specifically how endogenous volatiles feed forward into processes such as the origin of the Moon, magmatic differentiation, volcanism, and secondary processes during surface and crustal interactions. After the introduction, we will include a re-view/synthesis on the current state of 1) apatite compositions (volatile abundances and isotopic compositions); 2) nominally anhydrous mineral phases (moderately to highly volatile); 3) volatile (moderately to highly volatile) abundances in and isotopic compositions of lunar pyroclastic glass beads; 4) volatile (moderately to highly volatile) abundances in and isotopic compositions of lunar basalts; 5) volatile (moderately to highly volatile) abundances in and isotopic compositions of melt inclusions; and finally 6) experimental constraints on mineral-melt partitioning of moderately to highly volatile elements under lunar conditions. We anticipate that each section will summarize results since 2007 and focus on new results published since the 2015 Am Min review paper on lunar volatiles [9]. The next section will discuss how to use sample abundances of volatiles to understand the source region and potential caveats in estimating source abundances of volatiles. The following section will include our best estimates of volatile abundances and isotopic compositions (where permitted by available data) for each volatile element of interest in a number of important lunar reservoirs, including the crust, mantle, KREEP, and bulk Moon. The final section of the chapter will focus upon future work, outstanding questions

  5. Endogenous fertility and development traps with endogenous lifetime

    OpenAIRE

    Fanti, Luciano; Gori, Luca

    2010-01-01

    We extend the literature on endogenous lifetime and economic growth by Chakraborty (2004) and Bunzel and Qiao (2005) to endogenous fertility. We show that development traps due to underinvestments in health cannot appear when fertility is an economic decision variable and the costs of children are represented by a constant fraction of the parents' income used for their upbringing.

  6. Human milk peptides differentiate between the preterm and term infant and across varying lactational stages

    NARCIS (Netherlands)

    Dingess, Kelly A.; de Waard, Marita; Boeren, Sjef; Vervoort, Jacques; Lambers, Tim T.; van Goudoever, Johannes B.; Hettinga, Kasper

    2017-01-01

    Variations in endogenous peptide profiles, functionality, and the enzymes responsible for the formation of these peptides in human milk are understudied. Additionally, there is a lack of knowledge regarding peptides in donor human milk, which is used to feed preterm infants when mother's own milk is

  7. Role of Endogenous Peptides and Enzymes in the Pathogenesis of ...

    African Journals Online (AJOL)

    pathogenesis mechanism of acute pancreatitis that are related to various inflammatory and pro- inflammatory mediators. Keywords: Acute ... cytokines which are released by neutrophils and macrophages during acute pancreatitis, ... platelet activating factor have been shown to play significant roles in the pathogenesis of ...

  8. Role of Endogenous Peptides and Enzymes in the Pathogenesis of ...

    African Journals Online (AJOL)

    Acute pancreatitis is an inflammatory disease with the clinical manifestation of acute abdominal pain. Several factors are involved in the pathogenesis of acute pancreatitis. The exact mechanism(s) by which diverse etiological factors induce an attack are still unclear. However, one of the proposed mechanisms for induction ...

  9. Endogenous uveitis in children.

    Science.gov (United States)

    Merritt, J C

    1979-07-01

    Endogenous uveitis, with its ocular sequalae, accounts for a significant number of blind children in the world today. Even though these children are asymptomatic by ophthalmic history, they usually present with ocular pathology compatible with chronic intraocular inflammation. Although loss of vision is invariably due to cataract formation, fluorescein angiogram, binocular indirect ophthalmoloscopy, and fundus contact lens examination often reveal pathology of the optic nerve and retina, accounting for a significant degree of visual loss. While actual etiologic agents are usually not identified in the majority of children, toxoplasmosis, sarcoidosis, and childhood arthropathies occur with such high frequency that mention is made of these diseases. Conventional surgical procedures for ocular sequalae such as cataract and glaucoma, are known to yield poor results. Corticosteroids administered either topically, periocularly, or systemically appear to be of value in the treatment of these diseases, although control studies have not been done. Efforts to lessen the visual morbidity in these children should begin by a cross-fertilization of information between primary care physicians, pediatricians, and ophthalmologists.

  10. 59 eyes with endogenous endophthalmitis

    DEFF Research Database (Denmark)

    Bjerrum, Søren Solborg; la Cour, Morten

    2017-01-01

    BACKGROUND: To study the epidemiology of patients with endogenous endophthalmitis in Denmark. MATERIAL AND METHODS: Retrospective and prospective case series of 59 eyes in patients with endogenous endophthalmitis in Denmark between 2000 and 2016. RESULTS: The age of the patients ranged from 28...... identified microorganisms. The sources of endogenous endophthalmitis were diverse and were not identified in 36% of the patients. Diabetes (36%) was the most predisposing medical illness. A total of 15% of the patients died within the first year after surgery for endophthalmitis and half of the patients died...... during follow up. The mortality of patients was 22.6 times higher compared to a Danish background population. Culture positive patients had a higher mortality compared to culture negative patients. CONCLUSIONS: Endogenous endophthalmitis is a heterogeneous condition which is reflected in the age...

  11. ENDOGENEITY OF INDONESIAN MONEY SUPPLY

    Directory of Open Access Journals (Sweden)

    Meutia Safrina Rachma

    2011-09-01

    Full Text Available There has been a long debate about the endogeneity of money supply. The main objective of this article is to identify whether money supply in Indonesia is an exogenous or an endogenous variable. Using a Vector Autoregressive model and monthly data 1997(5-2010(6, the estimation result shows that money supply in Indonesia is an endogenous variable. The movement of broad money supply does influence the movement of base money and Consumer Price Index. Consequently, the central bank does not have control power on money supply. The bank is only able to maintain the stability and control the movement of broad money supply. Keywords: Endogenous variable, money supply, vector autoregressionJEL classification numbers: E51, E52, E58

  12. Discovery and Characterization of an Endogenous CXCR4 Antagonist

    Directory of Open Access Journals (Sweden)

    Onofrio Zirafi

    2015-05-01

    Full Text Available CXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPI-X4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation.

  13. Endogenous scheduling preferences and congestion

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; Small, Kenneth

    2017-01-01

    We consider the timing of activities through a dynamic model of commuting with congestion, in which workers care solely about leisure and consumption. Implicit preferences for the timing of the commute form endogenously due to temporal agglomeration economies. Equilibrium exists uniquely and is i......We consider the timing of activities through a dynamic model of commuting with congestion, in which workers care solely about leisure and consumption. Implicit preferences for the timing of the commute form endogenously due to temporal agglomeration economies. Equilibrium exists uniquely...

  14. Endogenous scheduling preferences and congestion

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; Small, Kenneth

    2010-01-01

    and leisure, but agglomeration economies at home and at work lead to scheduling preferences forming endogenously. Using bottleneck congestion technology, we obtain an equilibrium queuing pattern consistent with a general version of the Vickrey bottleneck model. However, the policy implications are different...

  15. Monopoly Insurance and Endogenous Information

    DEFF Research Database (Denmark)

    Lagerlöf, Johan N. M.; Schottmüller, Christoph

    2018-01-01

    We study a monopoly insurance model with endogenous information acquisi- tion. Through a continuous effort choice, consumers can determine the precision of a privately observed signal that is informative about their accident risk. The equilibrium effort is, depending on parameter values, either...

  16. Antimicrobial Peptides

    Directory of Open Access Journals (Sweden)

    Ali Adem Bahar

    2013-11-01

    Full Text Available The rapid increase in drug-resistant infections has presented a serious challenge to antimicrobial therapies. The failure of the most potent antibiotics to kill “superbugs” emphasizes the urgent need to develop other control agents. Here we review the history and new development of antimicrobial peptides (AMPs, a growing class of natural and synthetic peptides with a wide spectrum of targets including viruses, bacteria, fungi, and parasites. We summarize the major types of AMPs, their modes of action, and the common mechanisms of AMP resistance. In addition, we discuss the principles for designing effective AMPs and the potential of using AMPs to control biofilms (multicellular structures of bacteria embedded in extracellular matrixes and persister cells (dormant phenotypic variants of bacterial cells that are highly tolerant to antibiotics.

  17. Endogenous opioids and feeding behavior: A decade of further progress (2004-2014). A Festschrift to Dr. Abba Kastin.

    Science.gov (United States)

    Bodnar, Richard J

    2015-10-01

    Functional elucidation of the endogenous opioid system temporally paralleled the creation and growth of the journal, Peptides, under the leadership of its founding editor, Dr. Abba Kastin. He was prescient in publishing annual and uninterrupted reviews on Endogenous Opiates and Behavior that served as a microcosm for the journal under his stewardship. This author published a 2004 review, "Endogenous opioids and feeding behavior: a thirty-year historical perspective", summarizing research in this field between 1974 and 2003. The present review "closes the circle" by reviewing the last 10 years (2004-2014) of research examining the role of endogenous opioids and feeding behavior. The review summarizes effects upon ingestive behavior following administration of opioid receptor agonists, in opioid receptor knockout animals, following administration of general opioid receptor antagonists, following administration of selective mu, delta, kappa and ORL-1 receptor antagonists, and evaluating opioid peptide and opioid receptor changes in different food intake models. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Isotocin Regulates Growth Hormone but Not Prolactin Release From the Pituitary of Ricefield Eels

    Directory of Open Access Journals (Sweden)

    Wei Yang

    2018-04-01

    Full Text Available The neurohypophyseal hormone oxytocin (Oxt has been shown to stimulate prolactin (Prl synthesis and release from the adenohypophysis in rats. However, little is known about the functional roles of Oxt-like neuropeptides in the adenohypophysis of non-mammalian vertebrates. In this study, cDNAs encoding ricefield eel oxytocin-like receptors (Oxtlr, namely isotocin (Ist receptor 1 (Istr1 and 2 (Istr2, were isolated and specific antisera were generated, respectively. RT-PCR and Western blot analysis detected the presence of both Istr1 and Istr2 in the brain and pituitary, but differential expression in some peripheral tissues, including the liver and kidney, where only Istr1 was detected. In the pituitary, immunoreactive Istr1 and Istr2 were differentially distributed, with the former mainly in adenohypophyseal cell layers adjacent to the neurohypophysis, whereas the latter in peripheral areas of the adenohypophysis. Double immunofluorescent images showed that immunostaining of Istr1, but not Istr2 was localized to growth hormone (Gh cells, but neither of them was expressed in Prl cells. Ist inhibited Gh release in primary pituitary cells of ricefield eels and increased Gh contents in the pituitary gland of ricefield eels at 6 h after in vivo administration. Ist inhibition of Gh release is probably mediated by cAMP, PKC/DAG, and IP3/Ca2+ pathways. In contrast, Ist did not affect either prl gene expression or Prl contents in primary pituitary cells. Results of this study demonstrated that Ist may not be involved in the regulation of Prl, but inhibit Gh release via Istr1 rather than Istr2 in ricefield eels, and provided evidence for the direct regulation of Gh cells by oxytocin-like neuropeptides in the pituitary of non-mammalian vertebrates.

  19. Isotocin Regulates Growth Hormone but Not Prolactin Release From the Pituitary of Ricefield Eels

    Science.gov (United States)

    Yang, Wei; Zhang, Ning; Shi, Boyang; Zhang, Shen; Zhang, Lihong; Zhang, Weimin

    2018-01-01

    The neurohypophyseal hormone oxytocin (Oxt) has been shown to stimulate prolactin (Prl) synthesis and release from the adenohypophysis in rats. However, little is known about the functional roles of Oxt-like neuropeptides in the adenohypophysis of non-mammalian vertebrates. In this study, cDNAs encoding ricefield eel oxytocin-like receptors (Oxtlr), namely isotocin (Ist) receptor 1 (Istr1) and 2 (Istr2), were isolated and specific antisera were generated, respectively. RT-PCR and Western blot analysis detected the presence of both Istr1 and Istr2 in the brain and pituitary, but differential expression in some peripheral tissues, including the liver and kidney, where only Istr1 was detected. In the pituitary, immunoreactive Istr1 and Istr2 were differentially distributed, with the former mainly in adenohypophyseal cell layers adjacent to the neurohypophysis, whereas the latter in peripheral areas of the adenohypophysis. Double immunofluorescent images showed that immunostaining of Istr1, but not Istr2 was localized to growth hormone (Gh) cells, but neither of them was expressed in Prl cells. Ist inhibited Gh release in primary pituitary cells of ricefield eels and increased Gh contents in the pituitary gland of ricefield eels at 6 h after in vivo administration. Ist inhibition of Gh release is probably mediated by cAMP, PKC/DAG, and IP3/Ca2+ pathways. In contrast, Ist did not affect either prl gene expression or Prl contents in primary pituitary cells. Results of this study demonstrated that Ist may not be involved in the regulation of Prl, but inhibit Gh release via Istr1 rather than Istr2 in ricefield eels, and provided evidence for the direct regulation of Gh cells by oxytocin-like neuropeptides in the pituitary of non-mammalian vertebrates.

  20. Dependence of spontaneous electrical activity and basal prolactin release on nonselective cation channels in pituitary lactotrophs

    Czech Academy of Sciences Publication Activity Database

    Kučka, M.; Kretschmannová, K.; Stojilkovic, S. S.; Zemková, Hana; Tomic, M.

    2012-01-01

    Roč. 61, č. 3 (2012), s. 267-275 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA305/07/0681; GA ČR(CZ) GBP304/12/G069 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : TRPC channels * pituitary * GH3 cells * calcium influx * action potentials * resting membrane potential Subject RIV: ED - Physiology Impact factor: 1.531, year: 2012

  1. Leptin stimulates pituitary prolactin release through an extracellular signal-regulated kinase-dependent pathway

    DEFF Research Database (Denmark)

    Tipsmark, Christian K; Strom, Christina N; Bailey, Sean T

    2008-01-01

    pituitary model system. This advantageous system allows isolation of a nearly pure population of lactotropes in their natural, in situ aggregated state. The rostral pars distalis were dissected from tilapia pituitaries and exposed to varying concentrations of leptin (0, 1, 10, 100 nM) for 1 h. Release...

  2. Human milk peptides differentiate between the preterm and term infant and across varying lactational stages.

    Science.gov (United States)

    Dingess, Kelly A; de Waard, Marita; Boeren, Sjef; Vervoort, Jacques; Lambers, Tim T; van Goudoever, Johannes B; Hettinga, Kasper

    2017-10-18

    Variations in endogenous peptide profiles, functionality, and the enzymes responsible for the formation of these peptides in human milk are understudied. Additionally, there is a lack of knowledge regarding peptides in donor human milk, which is used to feed preterm infants when mother's own milk is not (sufficiently) available. To assess this, 29 human milk samples from the Dutch Human Milk Bank were analyzed as three groups, preterm late lactation stage (LS) (n = 12), term early (n = 8) and term late LS (n = 9). Gestational age (GA) groups were defined as preterm (24-36 weeks) and term (≥37 weeks). LS was determined as days postpartum as early (16-36 days) or late (55-88 days). Peptides, analyzed by LC-MS/MS, and parent proteins (proteins from matched peptide sequences) were identified and quantified, after which peptide functionality and the enzymes responsible for protein cleavage were determined. A total of 16 different parent proteins were identified from human milk, with no differences by GA or LS. We identified 1104 endogenous peptides, of which, the majority were from the parent proteins β-casein, polymeric immunoglobulin receptor, α s1 -casein, osteopontin, and κ-casein. The absolute number of peptides differed by GA and LS with 30 and 41 differing sequences respectively (p analysis showed that plasmin/trypsin enzymes most likely cleaved the identified human milk peptides. These results explain some of the variation in endogenous peptides in human milk, leading to future targets that may be studied for functionality.

  3. Automated multi-dimensional liquid chromatography : sample preparation and identification of peptides from human blood filtrate

    NARCIS (Netherlands)

    Machtejevas, Egidijus; John, Harald; Wagner, Knut; Standker, Ludger; Marko-Varga, Gyorgy; Georg Forssmann, Wolf; Bischoff, Rainer; K. Unger, Klaus

    2004-01-01

    A comprehensive on-line sample clean-up with an integrated two-dimensional HPLC system was developed for the analysis of natural peptides. Samples comprised of endogenous peptides with molecular weights up to 20 kDa were generated from human hemofiltrate (HF) obtained from patients with chronic

  4. Endogenous respiration of Polyporus sulphureus

    International Nuclear Information System (INIS)

    Li, S.M.W.; Siehr, D.J.

    1980-01-01

    Thirty percent of the dry weight of the basidiomycete Polyporus sulphureus is triterpenoid acid. The endogenous respiratory quotient of this organism is 0.8 indicating that the triterpenoid is being used as an endogenous storage material. Monosaccharides did not seem to be utilized as exogenous substrates but Krebs-cycle intermediates stimulated oxygen uptake. Pyruvic acid inhibited oxygen uptake. Studies with 14 C-labeled glucose indicated that 27% of the glucose was metabolized by way of glycolysis. The hexose-monophosphate pathway was the major metabolic path for the utilization of glucose. Despite the fact that P. sulphureus is associated with brown rot, its carbon metabolism suggests that it utilizes substances associated with the degradation of lignin more readily than it does glucose

  5. Exogenic and endogenic Europa minerals

    Science.gov (United States)

    Maynard-Casely, H. E.; Brand, H. E. A.; Wilson, S. A.

    2016-12-01

    The Galileo Near Infrared Mapping Spectrometer (NIMS) identified a significant `non-ice' component upon the surface of Jupiter's moon Europa. Current explanations invoke both endogenic and exogenic origins for this material. It has long been suggested that magnesium and sodium sulfate minerals could have leached from the rock below a putative ocean (endogenic) 1 and that sulfuric acid hydrate minerals could have been radiologically produced from ionised sulfur originally from Io's volcanoes (exogenic) 2. However, a more recent theory proposes that the `non-ice' component could be radiation damaged NaCl leached from Europa's speculative ocean 3. What if the minerals are actually from combination of both endogenic and exogenic sources? To investigate this possibility we have focused on discovering new minerals that might form in the combination of the latter two cases, that is a mixture of leached sulfates hydrates with radiologically produced sulfuric acid. To this end we have explored a number of solutions in the MgSO4-H2SO4-H2O and Na2SO4-H2SO4-H2O systems, between 80 and 280 K with synchrotron x-ray powder diffraction. We report a number of new materials formed in this these ternary systems. This suggests that it should be considered that the `non-ice' component of the Europa's surface could be a material derived from endogenic and exogenic components. 1 Kargel, J. S. Brine volcanism and the interior structures of asteroids and icy satellites. Icarus 94, 368-390 (1991). 2 Carlson, R. W., Anderson, M. S., Mehlman, R. & Johnson, R. E. Distribution of hydrate on Europa: Further evidence for sulfuric acid hydrate. Icarus 177, 461-471, doi:10.1016/j.icarus.2005.03.026 (2005). 3 Hand, K. P. & Carlson, R. W. Europa's surface color suggests an ocean rich with sodium chloride. Geophysical Research Letters, 2015GL063559, doi:10.1002/2015gl063559 (2015).

  6. Money, banks and endogenous volatility

    OpenAIRE

    Pere Gomis-Porqueras

    2000-01-01

    In this paper I consider a monetary growth model in which banks provide liquidity, and the government fixes a constant rate of money creation. There are two underlying assets in the economy, money and capital. Money is dominated in rate of return. In contrast to other papers with a larger set of government liabilities, I find a unique equilibrium when agents' risk aversion is moderate. However, indeterminacies and endogenous volatility can be observed when agents are relatively risk averse.

  7. Endogenous Population and Environmental Quality

    OpenAIRE

    Phu NGUYEN VAN

    2002-01-01

    This paper provides with empirical and theoretical studies of the relationship between population, economic growth and environmental quality. Using a simple endogenous growth model we obtain results close to empirical findings. We show existence of a sustainable balanced growth path (BGP) equilibrium in which perpetual economic growth goes in parallel with environmental quality preservation. At the BGP equilibrium, when all exogenous factors are controlled, a negative relationship between fer...

  8. REFERENCE MODELS OF ENDOGENOUS ECONOMIC GROWTH

    OpenAIRE

    GEAMĂNU MARINELA

    2012-01-01

    The new endogenous growth theories are a very important research area for shaping the most effective policies and long term sustainable development strategies. Endogenous growth theory has emerged as a reaction to the imperfections of neoclassical theory, by the fact that the economic growth is the endogenous product of an economical system.

  9. Coffee, hunger, and peptide YY.

    Science.gov (United States)

    Greenberg, James A; Geliebter, Allan

    2012-06-01

    There is evidence from several empirical studies suggesting that coffee may help people control body weight. Our objective was to assess the effects of caffeine, caffeinated coffee, and decaffeinated coffee, both alone and in combination with 75 g of glucose, on perceived hunger and satiety and related peptides. We conducted a placebo-controlled single-blinded randomized 4-way crossover trial. Eleven healthy male volunteers (mean age, 23.5 ± 5.7 years; mean BMI, 23.6 ± 4.2 kg/m(2)) ingested 1 of 3 test beverages (caffeine in water, caffeinated coffee, or decaffeinated coffee) or placebo (water), and 60 minutes later they ingested the glucose. Eight times during each laboratory visit, hunger and satiety were assessed by visual analog scales, and blood samples were drawn to measure 3 endogenous peptides associated with hunger and satiety: ghrelin, peptide YY (PYY), and leptin. Compared to placebo, decaffeinated coffee yielded significantly lower hunger during the whole 180-minute study period and higher plasma PYY for the first 90 minutes (p hunger or PYY. Caffeinated coffee showed a pattern between that of decaffeinated coffee and caffeine in water. These findings suggest that one or more noncaffeine ingredients in coffee may have the potential to decrease body weight. Glucose ingestion did not change the effects of the beverages. Our randomized human trial showed that decaffeinated coffee can acutely decrease hunger and increase the satiety hormone PYY.

  10. Antimicrobial Peptides: Multifunctional Drugs for Different Applications

    Directory of Open Access Journals (Sweden)

    Lea-Jessica Albrecht

    2012-02-01

    Full Text Available Antimicrobial peptides (APs are an important part of the innate immune system in epithelial and non-epithelial surfaces. So far, many different antimicrobial peptides from various families have been discovered in non-vertebrates and vertebrates. They are characterized by antibiotic, antifungal and antiviral activities against a variety of microorganisms. In addition to their role as endogenous antimicrobials, APs participate in multiple aspects of immunity. They are involved in septic and non-septic inflammation, wound repair, angiogenesis, regulation of the adaptive immune system and in maintaining homeostasis. Due to those characteristics AP could play an important role in many practical applications. Limited therapeutic efficiency of current antimicrobial agents and the emerging resistance of pathogens require alternate antimicrobial drugs. The purpose of this review is to highlight recent literature on functions and mechanisms of APs. It also shows their current practical applications as peptide therapeutics and bioactive polymers and discusses the possibilities of future clinical developments.

  11. Synthetic antifreeze peptide

    OpenAIRE

    1991-01-01

    A synthetic antifreeze peptide and a synthetic gene coding for the antifreeze peptide have been produced. The antifreeze peptide has a greater number of repeating amino acid sequences than is present in the native antifreeze peptides from winter flounder upon which the synthetic antifreeze peptide was modeled. Each repeating amino acid sequence has two polar amino acid residues which are spaced a controlled distance apart so that the antifreeze peptide may inhibit ice formation. The synthetic...

  12. Comparison of Caenorhabditis elegans NLP peptides with arthropod neuropeptides.

    Science.gov (United States)

    Husson, Steven J; Lindemans, Marleen; Janssen, Tom; Schoofs, Liliane

    2009-04-01

    Neuropeptides are small messenger molecules that can be found in all metazoans, where they govern a diverse array of physiological processes. Because neuropeptides seem to be conserved among pest species, selected peptides can be considered as attractive targets for drug discovery. Much can be learned from the model system Caenorhabditis elegans because of the availability of a sequenced genome and state-of-the-art postgenomic technologies that enable characterization of endogenous peptides derived from neuropeptide-like protein (NLP) precursors. Here, we provide an overview of the NLP peptide family in C. elegans and discuss their resemblance with arthropod neuropeptides and their relevance for anthelmintic discovery.

  13. Does liver-intestine significantly degrade circulating endogenous substance P in man?

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Schaffalitzky de Muckadell, O B; Bülow, J B

    1986-01-01

    Elevated concentrations of circulating substance P in patients with liver insufficiency have been ascribed to decreased hepatic degradation. To establish a possible biodegradation of the peptide in liver-intestine and kidneys, the concentration of endogenous immunoreactive substance P...... was determined in various vascular beds during a right-sided catheterization in 13 subjects without liver insufficiency. All subjects had normal values of circulating substance P, and no significant difference was found between systemic plasma and hepatic venous or renal venous concentrations of substance P....... The results indicate that degradation of circulating endogenous substance P in man is not confined to liver-intestine or kidney but may take place in many tissues....

  14. Flow cytometric assay detecting cytotoxicity against human endogenous retrovirus antigens expressed on cultured multiple sclerosis cells

    DEFF Research Database (Denmark)

    Møller-Larsen, A; Brudek, T; Petersen, T

    2013-01-01

    expressing increased amounts of human endogenous retrovirus antigens. MS patients also have increased antibody levels to these antigens. The target cells are spontaneously growing peripheral blood mononuclear cells (PBMCs) of B cell lineage, expressing human endogenous retrovirus HERV epitopes...... on their surface. Polyclonal antibodies against defined peptides in the Env- and Gag-regions of the HERVs were raised in rabbits and used in antibody-dependent cell-mediated cytotoxicity (ADCC) -assays. Rituximab® (Roche), a chimeric monoclonal antibody against CD20 expressed primarily on B cells, was used...

  15. On the origins of endogenous thoughts.

    Science.gov (United States)

    Tillas, Alexandros

    2017-05-01

    Endogenous thoughts are thoughts that we activate in a top-down manner or in the absence of the appropriate stimuli. We use endogenous thoughts to plan or recall past events. In this sense, endogenous thinking is one of the hallmarks of our cognitive lives. In this paper, I investigate how it is that we come to possess endogenous control over our thoughts. Starting from the close relation between language and thinking, I look into speech production-a process motorically controlled by the inferior frontal gyrus (IFG). Interestingly, IFG is also closely related to silent talking, as well as volition. The connection between IFG and volition is important given that endogenous thoughts are or at least greatly resemble voluntary actions. Against this background, I argue that IFG is key to understanding the origins of conscious endogenous thoughts. Furthermore, I look into goal-directed thinking and show that IFG plays a key role also in unconscious endogenous thinking.

  16. 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...

  17. Mycobacteria attenuate nociceptive responses by formyl peptide receptor triggered opioid peptide release from neutrophils.

    Directory of Open Access Journals (Sweden)

    Heike L Rittner

    2009-04-01

    Full Text Available In inflammation, pain is regulated by a balance of pro- and analgesic mediators. Analgesic mediators include opioid peptides which are secreted by neutrophils at the site of inflammation, leading to activation of opioid receptors on peripheral sensory neurons. In humans, local opioids and opioid peptides significantly downregulate postoperative as well as arthritic pain. In rats, inflammatory pain is induced by intraplantar injection of heat inactivated Mycobacterium butyricum, a component of complete Freund's adjuvant. We hypothesized that mycobacterially derived formyl peptide receptor (FPR and/or toll like receptor (TLR agonists could activate neutrophils, leading to opioid peptide release and inhibition of inflammatory pain. In complete Freund's adjuvant-induced inflammation, thermal and mechanical nociceptive thresholds of the paw were quantified (Hargreaves and Randall-Selitto methods, respectively. Withdrawal time to heat was decreased following systemic neutrophil depletion as well as local injection of opioid receptor antagonists or anti-opioid peptide (i.e. Met-enkephalin, beta-endorphin antibodies indicating an increase in pain. In vitro, opioid peptide release from human and rat neutrophils was measured by radioimmunoassay. Met-enkephalin release was triggered by Mycobacterium butyricum and formyl peptides but not by TLR-2 or TLR-4 agonists. Mycobacterium butyricum induced a rise in intracellular calcium as determined by FURA loading and calcium imaging. Opioid peptide release was blocked by intracellular calcium chelation as well as phosphoinositol-3-kinase inhibition. The FPR antagonists Boc-FLFLF and cyclosporine H reduced opioid peptide release in vitro and increased inflammatory pain in vivo while TLR 2/4 did not appear to be involved. In summary, mycobacteria activate FPR on neutrophils, resulting in tonic secretion of opioid peptides from neutrophils and in a decrease in inflammatory pain. Future therapeutic strategies may aim

  18. Endogenous, Imperfectly Competitive Business Cycles

    DEFF Research Database (Denmark)

    Whitta-Jacobsen, Hans Jørgen

    by monopolistic competition. An implicit assumption of barriers to entry justifies that the number of firms is fixed even when positive profits occur. It turns out that both market power of firms on the product markets and market power of unions on the labor markets make the occurrence of cycles more likely......We investigate how imperfect competition affects the occurrence and the properties of endogenous, rational expectations business cycles in an overlapping generations model with constant returns to scale in production. The model has explicit product and labor markets all characterized...

  19. Endogenous Receptor Agonists: Resolving Inflammation

    Directory of Open Access Journals (Sweden)

    Gerhard Bannenberg

    2007-01-01

    Full Text Available Controlled resolution or the physiologic resolution of a well-orchestrated inflammatory response at the tissue level is essential to return to homeostasis. A comprehensive understanding of the cellular and molecular events that control the termination of acute inflammation is needed in molecular terms given the widely held view that aberrant inflammation underlies many common diseases. This review focuses on recent advances in the understanding of the role of arachidonic acid and ω-3 polyunsaturated fatty acids (PUFA–derived lipid mediators in regulating the resolution of inflammation. Using a functional lipidomic approach employing LC-MS-MS–based informatics, recent studies, reviewed herein, uncovered new families of local-acting chemical mediators actively biosynthesized during the resolution phase from the essential fatty acids eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. These new families of local chemical mediators are generated endogenously in exudates collected during the resolution phase, and were coined resolvins and protectins because specific members of these novel chemical families control both the duration and magnitude of inflammation in animal models of complex diseases. Recent advances on the biosynthesis, receptors, and actions of these novel anti-inflammatory and proresolving lipid mediators are reviewed with the aim to bring to attention the important role of specific lipid mediators as endogenous agonists in inflammation resolution.

  20. Human-Specific Endogenous Retroviruses

    Directory of Open Access Journals (Sweden)

    Anton Buzdin

    2007-01-01

    Full Text Available This review focuses on a small family of human-specific genomic repetitive elements, presented by 134 members that shaped ~330 kb of the human DNA. Although modest in terms of its copy number, this group appeared to modify the human genome activity by endogenizing ~50 functional copies of viral genes that may have important implications in the immune response, cancer progression, and antiretroviral host defense. A total of 134 potential promoters and enhancers have been added to the human DNA, about 50% of them in the close gene vicinity and 22% in gene introns. For 60 such human-specific promoters, their activity was confirmed by in vivo assays, with the transcriptional level varying ~1000-fold from hardly detectable to as high as ~3% of β-actin transcript level. New polyadenylation signals have been provided to four human RNAs, and a number of potential antisense regulators of known human genes appeared due to human-specific retroviral insertional activity. This information is given here in the context of other major genomic changes underlining differences between human and chimpanzee DNAs. Finally, a comprehensive database, is available for download, of human-specific and polymorphic endogenous retroviruses is presented, which encompasses the data on their genomic localization, primary structure, encoded viral genes, human gene neighborhood, transcriptional activity, and methylation status.

  1. Human peptide transporters

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Brodin, Birger; Jørgensen, Flemming Steen

    2002-01-01

    Peptide transporters are epithelial solute carriers. Their functional role has been characterised in the small intestine and proximal tubules, where they are involved in absorption of dietary peptides and peptide reabsorption, respectively. Currently, two peptide transporters, PepT1 and PepT2, wh...

  2. [SYNTHETIC PEPTIDE VACCINES].

    Science.gov (United States)

    Sergeyev, O V; Barinsky, I F

    2016-01-01

    An update on the development and trials of synthetic peptide vaccines is reviewed. The review considers the successful examples of specific protection as a result of immunization with synthetic peptides using various protocols. The importance of conformation for the immunogenicity of the peptide is pointed out. An alternative strategy of the protection of the organism against the infection using synthetic peptides is suggested.

  3. Ileal endogenous nitrogen recovery is increased and its amino acid pattern is altered in pigs fed quebracho extract

    NARCIS (Netherlands)

    Steendam, C.A.; Tamminga, S.; Boer, H.; Jong, de E.J.; Visser, G.H.; Verstegen, M.W.A.

    2004-01-01

    Ileal endogenous nitrogen recovery (ENR) in pigs (9 ± 0.6 kg body weight) was estimated simultaneously using the 15N-isotope dilution technique (15N-IDT) and the peptide alimentation ultrafiltration (UF) method. Diets were cornstarch, enzyme-hydrolyzed casein with no (control) or high (4%) content

  4. Ileal endogenous nitrogen recovery is increased and its amino acid pattern is altered in pigs fed quebracho extract

    NARCIS (Netherlands)

    Steendam, C.A.C.; Tamminga, S.; Boer, H.; de Jong, E.J.; Visser, G.H.; Verstegen, M.W.A.

    2004-01-01

    lleal endogenous nitrogen recovery (ENR) in pigs (9 +/- 0.6 kg body weight) was estimated simultaneously using the N-15-isotope dilution technique (N-15-IDT) and the peptide alimentation ultrafiltration (UF) method. Diets were cornstarch, enzyme-hydrolyzed casein with no (control) or high (4%)

  5. Probing protein sequences as sources for encrypted antimicrobial peptides.

    Science.gov (United States)

    Brand, Guilherme D; Magalhães, Mariana T Q; Tinoco, Maria L P; Aragão, Francisco J L; Nicoli, Jacques; Kelly, Sharon M; Cooper, Alan; Bloch, Carlos

    2012-01-01

    Starting from the premise that a wealth of potentially biologically active peptides may lurk within proteins, we describe here a methodology to identify putative antimicrobial peptides encrypted in protein sequences. Candidate peptides were identified using a new screening procedure based on physicochemical criteria to reveal matching peptides within protein databases. Fifteen such peptides, along with a range of natural antimicrobial peptides, were examined using DSC and CD to characterize their interaction with phospholipid membranes. Principal component analysis of DSC data shows that the investigated peptides group according to their effects on the main phase transition of phospholipid vesicles, and that these effects correlate both to antimicrobial activity and to the changes in peptide secondary structure. Consequently, we have been able to identify novel antimicrobial peptides from larger proteins not hitherto associated with such activity, mimicking endogenous and/or exogenous microorganism enzymatic processing of parent proteins to smaller bioactive molecules. A biotechnological application for this methodology is explored. Soybean (Glycine max) plants, transformed to include a putative antimicrobial protein fragment encoded in its own genome were tested for tolerance against Phakopsora pachyrhizi, the causative agent of the Asian soybean rust. This procedure may represent an inventive alternative to the transgenic technology, since the genetic material to be used belongs to the host organism and not to exogenous sources.

  6. Development of an enrichment method for endogenous phosphopeptide characterization in human serum.

    Science.gov (United States)

    La Barbera, Giorgia; Capriotti, Anna Laura; Cavaliere, Chiara; Ferraris, Francesca; Laus, Michele; Piovesana, Susy; Sparnacci, Katia; Laganà, Aldo

    2018-01-01

    The work describes the development of an enrichment method for the analysis of endogenous phosphopeptides in serum. Endogenous peptides can play significant biological roles, and some of them could be exploited as future biomarkers. In this context, blood is one of the most useful biofluids for screening, but a systematic investigation of the endogenous peptides, especially phosphorylated ones, is still lacking, mainly due to the lack of suitable analytical methods. Thus, in this paper, different phosphopeptide enrichment strategies were pursued, based either on metal oxide affinity chromatography (MOAC, in the form of commercial TiO 2 spin columns or magnetic graphitized carbon black-TiO 2 composite), or on immobilized metal ion affinity chromatography (IMAC, in the form of Ti 4+ -IMAC magnetic material or commercial Fe 3+ -IMAC spin columns). While MOAC strategies proved completely unsuccessful, probably due to interfering phospholipids displacing phosphopeptides, the IMAC materials performed very well. Different sample preparation strategies were tested, comprising direct dilution with the loading buffer, organic solvent precipitation, and lipid removal from the matrix, as well as the addition of phosphatase inhibitors during sample handling for maximized endogenous phosphopeptide enrichment. All data were acquired by a shotgun peptidomics approach, in which peptide samples were separated by reversed-phase nanoHPLC hyphenated with high-resolution tandem mass spectrometry. The devised method allowed the identification of 176 endogenous phosphopeptides in fresh serum added with inhibitors by the direct dilution protocol and the Ti 4+ -IMAC magnetic material enrichment, but good results could also be obtained from the commercial Fe 3+ -IMAC spin column adapted to the batch enrichment protocol.

  7. Arterial blood-pressure change and endogenous circulating substance P in man

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Kastrup, J; Schaffalitzky De Muckadell, O B

    1985-01-01

    Substance P (SP) is a powerful vasodilator and this peptide is today considered to be a chemical messenger. The potential effects on circulating SP of acute changes in arterial blood-pressure was investigated in nine subjects. An increase in arterial mean blood-pressure (+33%, P less than 0.001, ...... change in plasma SP, this seems to indicate that endogenous circulating SP has no significant role in the vascular tonus controlled by the arterial baroreflex....

  8. Endogenous money: the evolutionary versus revolutionary views

    OpenAIRE

    Louis-Philippe Rochon; Sergio Rossi

    2013-01-01

    The purpose of this paper is to shed light on the endogenous nature of money. Contrary to the established post-Keynesian, or evolutionary, view, this paper argues that money has always been endogenous, irrespective of the historical period. Instead of the evolutionary theory of money and banking that can be traced back to Chick (1986), this paper puts forward a revolutionary definition of endogenous money consistent with many aspects of post-Keynesian economics as well as with the monetary ci...

  9. Endogenous price flexibility and optimal monetary policy

    OpenAIRE

    Ozge Senay; Alan Sutherland

    2014-01-01

    Much of the literature on optimal monetary policy uses models in which the degree of nominal price flexibility is exogenous. There are, however, good reasons to suppose that the degree of price flexibility adjusts endogenously to changes in monetary conditions. This article extends the standard new Keynesian model to incorporate an endogenous degree of price flexibility. The model shows that endogenizing the degree of price flexibility tends to shift optimal monetary policy towards complete i...

  10. Endogenous Market Structures and International Trade

    OpenAIRE

    Etro Federico

    2010-01-01

    I extend the endogenous market structures approach to international trade theory and policy. When markets are characterized by strategic interactions and endogenous entry, opening up to trade decreases the price level, and increases concentration and the production of each firm, with a positive competition effect on welfare. With endogenous entry of foreign firms in the domestic market it is optimal to set a positive import tariff decreasing in the ratio between entry costs and market size. W...

  11. Binary choice models with endogenous regressors

    OpenAIRE

    Christopher Baum; Yingying Dong; Arthur Lewbel; Tao Yang

    2012-01-01

    Dong and Lewbel have developed the theory of simple estimators for binary choice models with endogenous or mismeasured regressors, depending on a `special regressor' as defined by Lewbel (J. Econometrics, 2000). `Control function' methods such as Stata's ivprobit are generally only valid when endogenous regressors are consistent. The estimators proposed here can be used with limited, censored, continuous or discrete endogenous regressors, and have significant advantages over alternatives such...

  12. Endogenous, Imperfectly Competitive Business Cycles

    DEFF Research Database (Denmark)

    Whitta-Jacobsen, Hans Jørgen

    We investigate how imperfect competition affects the occurrence and the properties of endogenous, rational expectations business cycles in an overlapping generations model with constant returns to scale in production. The model has explicit product and labor markets all characterized...... by monopolistic competition. An implicit assumption of barriers to entry justifies that the number of firms is fixed even when positive profits occur. It turns out that both market power of firms on the product markets and market power of unions on the labor markets make the occurrence of cycles more likely....... In particular, imperfect competition on the product markets and the positive profits associated with it may have the effect that there is a cycle even if the labor supply curve is increasing in the real-wage rate. For competitive cycles is required not only a decreasing labor supply curve, but a wage elasticity...

  13. Endogenous retroviruses and animal reproduction.

    Science.gov (United States)

    Prudhomme, S; Bonnaud, B; Mallet, F

    2005-01-01

    Endogenous retroviruses (ERV), as part of the host genetic heritage, are transmissible to the next generation in a Mendelian way. Their abundance in animal genomes and their expression primarily detected in germ cells, embryonic tissues and cancer cell lines, raised the question of their biological significance. This article reviews the possible role of ERVs in the physiology and diseases of animal reproduction, from Drosophila to human. In males, there is no trivial involvement of ERVs in a physiological process. Conversely, a spermatogenesis defect was associated in the human male with HERV-K expression and HERV15-induced chromosomal alteration, leading to cancer and infertility, respectively. In females, the study of insect ERVs (IERV) pointed out the overlap between genetics and virology with the genetic-dependent regulation of ZAM and the non-infectious and infectious life cycles of gypsy. The pattern of ERVs expression in rodent, ovine and human females suggest a hormone-dependent mechanism consistent with the mammalian oestrus cycle regulation. The differentiation of the mammary epithelium and breast tumorigenesis involving the mouse mammary tumour viruses (MMTV) illustrate the intimate connection between endogenous and exogenous retroviruses. Last, as a major site of ERVs transcription, placenta contributed to our understanding of ERVs modulation of neighbouring gene expression. As an interface, i.e. a site of conflicts and exchanges, placenta should resist infection and protect the foetus against the maternal immune system. Retroviral envelopes could theoretically provide such features due to receptor interference, immunosuppression and fusion properties, as shown by the HERV-W envelope involved in the syncytiotrophoblast formation. We conclude with an insight on the evolutionary and epigenetic consequences of the relationships of ERV guests with their animal hosts.

  14. Endogenous timing factors in bird migration

    Science.gov (United States)

    Gwinner, E. G.

    1972-01-01

    Several species of warbler birds were observed in an effort to determine what initiates and terminates migration. Environmental and endogenous timing mechanisms were analyzed. The results indicate that endogenous stimuli are dominant factors for bird migration especially for long distances. It was concluded that environmental factors act as an assist mechanism.

  15. Endogenous Peer Effects: Fact or Fiction?

    Science.gov (United States)

    Yeung, Ryan; Nguyen-Hoang, Phuong

    2016-01-01

    The authors examine endogenous peer effects, which occur when a student's behavior or outcome is a function of the behavior or outcome of his or her peer group. Endogenous peer effects have important implications for educational policies such as busing, school choice and tracking. In this study, the authors quantitatively review the literature on…

  16. Applying Endogenous Knowledge in the African Context ...

    African Journals Online (AJOL)

    The question presented in this article is how to improve the dispute resolution competence of practitioners in Africa. The response offered involves enhancing the endogenous knowledge of a dispute and how to resolve it. This requires not only an understanding of what endogenous knowledge is, but also an alignment of ...

  17. Dentin and dental pulp regeneration by the patient's endogenous cells.

    Science.gov (United States)

    Kim, Sahng G; Zheng, Ying; Zhou, Jian; Chen, Mo; Embree, Mildred C; Song, Karen; Jiang, Nan; Mao, Jeremy J

    2013-03-01

    The goal of regenerative endodontics is to restore the functions of the dental pulp-dentin complex. Two approaches are being applied toward dental pulp-dentin regeneration: cell transplantation and cell homing. The majority of previous approaches are based on cell transplantation by delivering ex vivo cultivated cells toward dental pulp or dentin regeneration. Many hurdles limit the clinical translation of cell transplantation such as the difficulty of acquiring and isolating viable cells, uncertainty of what cells or what fractions of cells to use, excessive cost of cell manipulation and transportation, and the risk of immune rejection, pathogen transmission, and tumorigenesis in associated with ex vivo cell manipulation. In contrast, cell homing relies on induced chemotaxis of endogenous cells and therefore circumvents many of the difficulties that are associated with cell transplantation. An array of proteins, peptides, and chemical compounds that are yet to be identified may orchestrate endogenous cells to regenerate dental pulp-dentin complex. Both cell transplantation and cell homing are scientifically valid approaches; however, cell homing offers a number of advantages that are compatible with the development of clinical therapies for dental pulp-dentin regeneration.

  18. Release of endogenous opioids from duodenal enteroendocrine cells requires Trpm5.

    Science.gov (United States)

    Kokrashvili, Zaza; Rodriguez, Deniliz; Yevshayeva, Valeriya; Zhou, Hang; Margolskee, Robert F; Mosinger, Bedrich

    2009-08-01

    Enteroendocrine cells, the largest and most diverse population of mammalian endocrine cells, comprise a number of different cell types in the gut mucosa that produce, store, and secrete small molecules, peptides, and/or larger proteins that regulate many aspects of gut physiology. Little is known about less typical endocrine cells in the intestinal mucosa that do not contain secretory granules, such as brush or caveolated cells. We studied a subset of these enteroendocrine cells in duodenum that produce several peptides, including endogenous opioids, and that also express the Trpm5 cation channel. We studied expression patterns of Trpm5 and other molecules by immunohistochemical and enzyme-linked immunosorbent assay analyses of intestinal tissues from transgenic mice that express green fluorescent protein from the Trpm5 promoter, as well as wild-type and Trpm5-null mice. We describe a type of enteroendocrine cell in mouse duodenum that is defined by the presence of Trpm5 and that does not contain typical secretory granules yet expresses endogenous opioids (beta-endorphin and Met-enkephalin) and uroguanylin in apical compartments close to the lumen of the gut. Solitary chemosensory cells that coexpress beta-endorphin, Met-enkephalin, uroguanylin, and Trpm5 exist in mouse duodenum. These cells are likely to secrete the bioactive peptides into the intestinal lumen in response to dietary factors; release of the opioid peptides requires the Trpm5 ion channel.

  19. Quantification of pharmaceutical peptides using selenium as an elemental detection label

    DEFF Research Database (Denmark)

    Møller, Laura Hyrup; Gabel-Jensen, Charlotte; Franzyk, Henrik

    2014-01-01

    analysis of cell samples by LC-ICP-MS showed mainly uptake of the intact peptides, while the amount of intact peptides in cell lysates was semi-quantitatively determined. The selenium-containing penetratin analogues were to some extent degraded in pure cell medium, while an extensive degradation...... studies. Most pharmaceutical peptides, including penetratin, are synthetic analogues of endogenous peptides, and incorporation of selenium may improve the critical assessment of the native drug or drug delivery candidate early in the drug development process....

  20. Human endogenous retroviruses and ADHD.

    Science.gov (United States)

    Balestrieri, Emanuela; Pitzianti, Mariabernarda; Matteucci, Claudia; D'Agati, Elisa; Sorrentino, Roberta; Baratta, Antonia; Caterina, Rosa; Zenobi, Rossella; Curatolo, Paolo; Garaci, Enrico; Sinibaldi-Vallebona, Paola; Pasini, Augusto

    2014-08-01

    Several lines of evidences suggest that human endogenous retroviruses (HERVs) are implicated in the development of many complex diseases with a multifactorial aetiology and a strong heritability, such as neurological and psychiatric diseases. Attention deficit hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that results from a complex interaction of environmental, biological and genetic factors. Our aim was to analyse the expression levels of three HERV families (HERV-H, K and W) in patients with ADHD. The expression of retroviral mRNAs from the three HERV families was evaluated in peripheral blood mononuclear cells (PBMCs) from 30 patients with ADHD and 30 healthy controls by quantitative RT-PCR. The expression levels of HERV-H are significantly higher in patients with ADHD compared to healthy controls, while there are no differences in the expression levels of HERV-K and W. Since the ADHD aetiology is due to a complex interaction of environmental, biological and genetic factors, HERVs may represent one link among these factors and clinical phenotype of ADHD. A future confirmation of HERV-H overexpression in a larger number of ADHD patients will make possible to identify it as a new parameter for this clinical condition, also contributing to deepen the study on the role of HERVs in the neurodevelopment diseases.

  1. PeptideAtlas

    Data.gov (United States)

    U.S. Department of Health & Human Services — PeptideAtlas is a multi-organism, publicly accessible compendium of peptides identified in a large set of tandem mass spectrometry proteomics experiments. Mass...

  2. Meat and meat products as a source of bioactive peptides

    Directory of Open Access Journals (Sweden)

    Alfonso Totosaus

    2016-12-01

    Full Text Available Meat is a high protein content food, with great nutritional and biological value. Meat protein hydrolysis begins with the muscle to meat conversion, during meat ageing. After slaughter, endogen enzymes are responsible of meat softening since myofibrillar anchorage proteins are degraded. Protein hydrolysis continues during food preparation. When meat reaches the stomach, pepsin is the first enzyme to interact. As the food travel trough out gastrointestinal tract, pancreatic enzymes degraded the remained protein and the peptidases made the final proteolysis process. The small proteins or peptides are the absorbed to the circulatory system and distributed to the rest of the body. Bioactive peptides activity of meat and meat products is anti-hypertensive mainly, where histidine, carnosine and anserine are the main peptides identified. Another peptide with anti-oxidant activity is glutathione. The content depends on animal species.

  3. [Regulatory peptides and psychomotor development in infants].

    Science.gov (United States)

    Sokolov, O Iu; Kost, N V; Kurasova, O B; Dmitriev, A D; Gabaeva, M V; Zolotarev, Iu A; Mikheeva, I G; Zozulia, A A

    2007-01-01

    Regulatory peptides (RP) are an important homeostatic factor. The maternal organism and placenta are substantial sources of RP for fetus during the prenatal period. Not only endogenous, but also exogenous RP play an important role during early postnatal period. In this study, the concentration of exogenous RP (casomorphins-7) and the activity of peptidases (enkephalinases) in the serum of breastfed and bottle-fed infants were estimated. Possible interrelation between these two parameters and the psychomotor development (PMD) of infants were evaluated. Using specially developed RIA, the investigators estimated the presence of human and bovine casomorphins immunoreactivity (CMir) in the serum of breastfed and bottle-fed infants. A distinct correlation of CMir with PMD was demonstrated. The activity of RP-degrading serum enzymes also correlated with PMD level. The role of endo- and exogenous peptides in normal PMD process and in the pathogenesis of early child autism is discussed in the article.

  4. Immunosuppressive peptides and their therapeutic applications☆

    Science.gov (United States)

    Thell, Kathrin; Hellinger, Roland; Schabbauer, Gernot; Gruber, Christian W.

    2014-01-01

    The immune system is vital for detecting and evading endogenous and exogenous threats to the body. Failure to regulate this homeostasis leads to autoimmunity, which is often associated with malfunctioning T cell signaling. Several medications are available to suppress over-reactive T lymphocytes, but many of the currently marketed drugs produce severe and life-threatening side-effects. Ribosomally synthesized peptides are gaining recognition from the pharmaceutical industry for their enhanced selectivity and decreased toxicity compared with small molecules; in particular, circular peptides exhibit remarkable stability and increased oral administration properties. For example, plant cyclotides effectively inhibit T lymphocyte proliferation. They are composed of a head-to-tail cyclized backbone and a cystine-knot motif, which confers them with remarkable stability, thus making them attractive pharmaceutical tools. PMID:24333193

  5. Designer Natriuretic Peptides

    Science.gov (United States)

    Lee, Candace Y. W.; Lieu, Hsiao; Burnett, John C.

    2011-01-01

    Designer natriuretic peptides (NPs) are novel hybrid peptides that are engineered from the native NPs through addition, deletion, or substitution of amino acid(s) with a goal toward optimization of pharmacological actions while minimizing undesirable effects. In this article, selected peptides that were designed in our laboratory are reviewed, and future directions for research and development of designer NPs are discussed. PMID:19158603

  6. PH dependent adhesive peptides

    Science.gov (United States)

    Tomich, John; Iwamoto, Takeo; Shen, Xinchun; Sun, Xiuzhi Susan

    2010-06-29

    A novel peptide adhesive motif is described that requires no receptor or cross-links to achieve maximal adhesive strength. Several peptides with different degrees of adhesive strength have been designed and synthesized using solid phase chemistries. All peptides contain a common hydrophobic core sequence flanked by positively or negatively charged amino acids sequences.

  7. Antimicrobial Peptides in 2014

    Directory of Open Access Journals (Sweden)

    Guangshun Wang

    2015-03-01

    Full Text Available This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release its cargo. Proline-rich peptides, previously known to bind to heat shock proteins, are shown to inhibit protein synthesis. A model antimicrobial peptide is demonstrated to have multiple hits on bacteria, including surface protein delocalization. While cell surface modification to decrease cationic peptide binding is a recognized resistance mechanism for pathogenic bacteria, it is also used as a survival strategy for commensal bacteria. The year 2014 also witnessed continued efforts in exploiting potential applications of antimicrobial peptides. We highlight 3D structure-based design of peptide antimicrobials and vaccines, surface coating, delivery systems, and microbial detection devices involving antimicrobial peptides. The 2014 results also support that combination therapy is preferred over monotherapy in treating biofilms.

  8. Peptide Nucleic Acid Synthons

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  9. Peptide-Carrier Conjugation

    DEFF Research Database (Denmark)

    Hansen, Paul Robert

    2015-01-01

    To produce antibodies against synthetic peptides it is necessary to couple them to a protein carrier. This chapter provides a nonspecialist overview of peptide-carrier conjugation. Furthermore, a protocol for coupling cysteine-containing peptides to bovine serum albumin is outlined....

  10. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2003-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  11. Peptide Nucleic Acids (PNA)

    DEFF Research Database (Denmark)

    2002-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  12. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    1998-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  13. Localization of endogenous amyloid-β to the coeruleo-cortical pathway: consequences of noradrenergic depletion.

    Science.gov (United States)

    Ross, Jennifer A; Reyes, Beverly A S; Thomas, Steven A; Van Bockstaele, Elisabeth J

    2018-01-01

    The locus coeruleus (LC)-norepinephrine (NE) system is an understudied circuit in the context of Alzheimer's disease (AD), and is thought to play an important role in neurodegenerative and neuropsychiatric diseases involving catecholamine neurotransmitters. Understanding the expression and distribution of the amyloid beta (Aβ) peptide, a primary component of AD, under basal conditions and under conditions of NE perturbation within the coeruleo-cortical pathway may be important for understanding its putative role in pathological states. Thus, the goal of this study is to define expression levels and the subcellular distribution of endogenous Aβ with respect to noradrenergic profiles in the rodent LC and medial prefrontal cortex (mPFC) and, further, to determine the functional relevance of NE in modulating endogenous Aβ 42 levels. We report that endogenous Aβ 42 is localized to tyrosine hydroxylase (TH) immunoreactive somatodendritic profiles of the LC and dopamine-β-hydroxylase (DβH) immunoreactive axon terminals of the infralimbic mPFC (ILmPFC). Male and female naïve rats have similar levels of amyloid precursor protein (APP) cleavage products demonstrated by western blot, as well as similar levels of endogenous Aβ 42 as determined by enzyme-linked immunosorbent assay. Two models of NE depletion, DSP-4 lesion and DβH knockout (KO) mice, were used to assess the functional relevance of NE on endogenous Aβ 42 levels. DSP-4 lesioned rats and DβH-KO mice show significantly lower levels of endogenous Aβ 42 . Noradrenergic depletion did not change APP-cleavage products resulting from β-secretase processing. Thus, resultant decreases in endogenous Aβ 42 may be due to decreased neuronal activity of noradrenergic neurons, or, by decreased stimulation of adrenergic receptors which are known to contribute to Aβ 42 production by enhancing γ-secretase processing under normal physiological conditions.

  14. Gravity effects on endogenous movements

    Science.gov (United States)

    Johnsson, Anders; Antonsen, Frank

    Gravity effects on endogenous movements A. Johnsson * and F. Antonsen *+ * Department of Physics, Norwegian University of Science and Technology,NO-7491, Trond-heim, Norway, E-mail: anders.johnsson@ntnu.no + Present address: Statoil Research Center Trondheim, NO-7005, Trondheim, Norway Circumnutations in stems/shoots exist in many plants and often consists of more or less regular helical movements around the plumb line under Earth conditions. Recent results on circumnu-tations of Arabidopsis in space (Johnsson et al. 2009) showed that minute amplitude oscilla-tions exist in weightlessness, but that centripetal acceleration (mimicking the gravity) amplified and/or created large amplitude oscillations. Fundamental mechanisms underlying these results will be discussed by modeling the plant tissue as a cylinder of cells coupled together. As a starting point we have modeled (Antonsen 1998) standing waves on a ring of biological cells, as first discussed in a classical paper (Turing 1952). If the coupled cells can change their water content, an `extension' wave could move around the ring. We have studied several, stacked rings of cells coupled into a cylinder that together represent a cylindrical plant tissue. Waves of extensions travelling around the cylinder could then represent the observable circumnutations. The coupling between cells can be due to cell-to-cell diffusion, or to transport via channels, and the coupling can be modeled to vary in both longitudinal and transversal direction of the cylinder. The results from ISS experiments indicate that this cylindrical model of coupled cells should be able to 1) show self-sustained oscillations without the impact of gravity (being en-dogenous) and 2) show how an environmental factor like gravity can amplify or generate the oscillatory movements. Gravity has been introduced in the model by a negative, time-delayed feed-back transport across the cylinder. This represents the physiological reactions to acceler

  15. Acylation of Therapeutic Peptides

    DEFF Research Database (Denmark)

    Trier, Sofie; Henriksen, Jonas Rosager; Jensen, Simon Bjerregaard

    to the harsh and selective gastrointestinal system, and development has lacked far behind injection therapy. Peptide acylation is a powerful tool to alter the pharmacokinetics, biophysical properties and chemical stability of injectable peptide drugs, primarily used to prolong blood circulation....... This work aims to characterize acylated analogues of two therapeutic peptides by systematically increasing acyl chain length in order to elucidate its influence on membrane interaction and intestinal cell translocation in vitro. The studied peptides are the 33 amino acid Glucagon-like peptide-2 (GLP-2...... peptides can increase in vitro intestinal permeability, modestly for GLP-2 and drastically for sCT, and might benefit oral delivery. GLP-2 results provide a well-founded predictive power for future peptide analogues, whereas sCT results hold great promise for future analogues, albeit with a larger...

  16. Endogenous Money, Output and Prices in India

    OpenAIRE

    Das, Rituparna

    2009-01-01

    This paper proposes to quantify the macroeconometric relationships among the variables broad money, lending by banks, price, and output in India using simultaneous equations system keeping in view the issue of endogeneity.

  17. A merge model with endogenous technological change

    Energy Technology Data Exchange (ETDEWEB)

    Kypreos, S.; Bahn, O.

    2002-03-01

    A new version of the MERGE model, called MERGE-ETL, has been developed to consider endogenous technological change in the energy system. The basic formulation of MERGE-ETL as well as some first results are reported here. (author)

  18. Endogenous vs. exogenous regulations in the commons

    DEFF Research Database (Denmark)

    Abatayo, Anna Lou; Lynham, John

    2016-01-01

    potential confounds in previous experiments. A key feature of our experimental design is to have the exact same regulations chosen endogenously as those that are imposed exogenously. When we compare the same regulations chosen endogenously to those externally imposed, we observe no differences in extraction...... levels among CPR users in a laboratory experiment. We also observe no differences between weak external regulations and no regulations, after controlling for a potential confound. However, when we add communication to our endogenous treatment, we observe significant behavioral differences between...... endogenous regulations with communication and exogenous regulations without communication. Our results suggest that externally imposed regulations do not crowd out intrinsic motivations in the lab and they confirm that communication facilitates cooperation to reduce extraction....

  19. Contagion risk in endogenous financial networks

    International Nuclear Information System (INIS)

    Li, Shouwei; Sui, Xin

    2016-01-01

    Highlights: • We propose an endogenous financial network model. • Endogenous networks include interbank networks, inter-firm networks and bank-firm networks. • We investigate contagion risk in endogenous financial networks. - Abstract: In this paper, we investigate contagion risk in an endogenous financial network, which is characterized by credit relationships connecting downstream and upstream firms, interbank credit relationships and credit relationships connecting firms and banks. The findings suggest that: increasing the number of potential lenders randomly selected can lead to an increase in the number of bank bankruptcies, while the number of firm bankruptcies presents a trend of increase after the decrease; after the intensity of choice parameter rises beyond a threshold, the number of bankruptcies in three sectors (downstream firms, upstream firms and banks) shows a relatively large margin of increase, and keeps at a relatively high level; there exists different trends for bankruptcies in different sectors with the change of the parameter of credits’ interest rates.

  20. Pronase E-Based Generation of Fluorescent Peptide Fragments: Tracking Intracellular Peptide Fate in Single Cells.

    Science.gov (United States)

    Mainz, Emilie R; Dobes, Nicholas C; Allbritton, Nancy L

    2015-08-04

    The ability to track intracellular peptide proteolysis at the single cell level is of growing interest, particularly as short peptide sequences continue to play important roles as biosensors, therapeutics, and endogenous participants in antigen processing and intracellular signaling. We describe a rapid and inexpensive methodology to generate fluorescent peptide fragments from a parent sequence with diverse chemical properties, including aliphatic, nonpolar, basic, acidic, and non-native amino acids. Four peptide sequences with existing biochemical applications were fragmented using incubation with Pronase E and/or formic acid, and in each case a complete set of fluorescent fragments was generated for use as proteolysis standards in chemical cytometry. Fragment formation and identity was monitored with capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) and matrix assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-MS) to confirm the presence of all sequences and yield fragmentation profiles across Pronase E concentrations which can readily be used by others. As a pilot study, Pronase E-generated standards from an Abl kinase sensor and an ovalbumin antigenic peptide were then employed to identify proteolysis products arising from the metabolism of these sequences in single cells. The Abl kinase sensor fragmented at 4.2 ± 4.8 zmol μM(-1) s(-1) and the majority of cells possessed similar fragment identities. In contrast, an ovalbumin epitope peptide was degraded at 8.9 ± 0.1 zmol μM(-1) s(-1), but with differential fragment formation between individual cells. Overall, Pronase E-generated peptide standards were a rapid and efficient method to identify proteolysis products from cells.

  1. Endogenous Money Supply and Money Demand

    OpenAIRE

    Woon Gyu Choi; Seonghwan Oh

    2000-01-01

    This paper explores the behavior of money demand by explicitly accounting for the money supply endogeneity arising from endogenous monetary policy and financial innovations. Our theoretical analysis indicates that money supply factors matter in the money demand function when the money supply partially responds to money demand. Our empirical results with U.S. data provide strong evidence for the relevance of the policy stance to the demand for MI under a regime in which monetary policy is subs...

  2. Some observations about the endogenous money theory

    OpenAIRE

    Bertocco Giancarlo

    2006-01-01

    The endogenous money theory constitutes the core element of the post-keynesian monetary theory. The first formulation of this theory can be found in the works of Kaldor published in the 1970s. Taking these studies as a starting point, the post-keynesians elaborated two versions of the endogenous money theory which differ in their assumptions about the behaviour of the monetary authorities and the banking system, and hence offer different conclusions about the slope of the money supply curve. ...

  3. Population aging and endogenous economic growth

    OpenAIRE

    Prettner, Klaus

    2010-01-01

    This article investigates the consequences of population aging for long-run economic growth perspectives. We introduce age specific heterogeneity of households into a model of research and development (R&D) based technological change. We show that the framework incorporates two standard specifications as special cases: endogenous growth models with scale e ects and semi-endogenous growth models without scale effects. The introduction of an age structured population implies that aggregate laws...

  4. ENDOGENOUS ENERGY. A CAUSE OF BIASET/ TRUE ...

    African Journals Online (AJOL)

    ENDOGENOUS ENERGY. A CAUSE OF. J.J. du Preez. Department of Poultry Scienc'e,. BIASET/ TRUE METABOLISABLE ENERGY VALUES. Receipr of MS 2l -05-81. J.P. Hayes and J.S. Duckitt. (.tn i vc r si t.y' o f S t e lle nb o sch, S t e lle nbo sc h, 7 6 0 0. (Key words: Endogenous energy, true metabolisable energ"t), ...

  5. Harnessing Endogenous Systems for Cancer Therapy

    DEFF Research Database (Denmark)

    Klauber, Thomas Christopher Bogh

    In the recent decade, two strategies in particular have attracted attention due to the prospect of significantly improving cancer treatment: Gene silencing therapy and immunotherapy. Both strategies work by manipulating endogenous mechanisms and theoretically promise very strong effect on the dis......In the recent decade, two strategies in particular have attracted attention due to the prospect of significantly improving cancer treatment: Gene silencing therapy and immunotherapy. Both strategies work by manipulating endogenous mechanisms and theoretically promise very strong effect...

  6. Cell Penetrating Peptides and Cationic Antibacterial Peptides

    Science.gov (United States)

    Rodriguez Plaza, Jonathan G.; Morales-Nava, Rosmarbel; Diener, Christian; Schreiber, Gabriele; Gonzalez, Zyanya D.; Lara Ortiz, Maria Teresa; Ortega Blake, Ivan; Pantoja, Omar; Volkmer, Rudolf; Klipp, Edda; Herrmann, Andreas; Del Rio, Gabriel

    2014-01-01

    Cell penetrating peptides (CPP) and cationic antibacterial peptides (CAP) have similar physicochemical properties and yet it is not understood how such similar peptides display different activities. To address this question, we used Iztli peptide 1 (IP-1) because it has both CPP and CAP activities. Combining experimental and computational modeling of the internalization of IP-1, we show it is not internalized by receptor-mediated endocytosis, yet it permeates into many different cell types, including fungi and human cells. We also show that IP-1 makes pores in the presence of high electrical potential at the membrane, such as those found in bacteria and mitochondria. These results provide the basis to understand the functional redundancy of CPPs and CAPs. PMID:24706763

  7. Salt sensitivity, endogenous ouabain and hypertension

    Science.gov (United States)

    Hamlyn, John M.; Blaustein, Mordecai P.

    2013-01-01

    Purpose of review Endogenous cardiotonic steroids (CTS) exert long-term effects on salt and blood pressure homeostasis. Here we discuss recent observations on mechanisms of salt sensitivity that involve endogenous ouabain and novel pathways in the brain and discuss their possible relationship to arterial and renal function in hypertension. Recent findings Chronic elevation of brain sodium promotes sustained hypertension mediated by central endogenous ouabain and the Na+ pump α-2 catalytic subunit. The intermediary pressor mechanism in the brain involves aldosterone biosynthesis, activation of mineralocorticoid receptors and increased epithelial sodium channel activity. In the periphery, elevated plasma CTS raise contractility and blood pressure by augmentation of sympathetic nerve responses, increasing arterial Ca2+ signaling and blunting nitric oxide production in the renal medulla and collecting ducts. Summary Endogenous ouabain in the brain appears to play a critical role in salt sensitivity and hypertension. In the periphery, the J-shaped relationship of plasma endogenous ouabain in response to short-term changes in salt balance in humans raises the possibility that endogenous ouabain contributes to the increased risk of adverse cardiovascular events associated with both low and high salt intakes. PMID:23207724

  8. Plant peptide hormone signalling.

    Science.gov (United States)

    Motomitsu, Ayane; Sawa, Shinichiro; Ishida, Takashi

    2015-01-01

    The ligand-receptor-based cell-to-cell communication system is one of the most important molecular bases for the establishment of complex multicellular organisms. Plants have evolved highly complex intercellular communication systems. Historical studies have identified several molecules, designated phytohormones, that function in these processes. Recent advances in molecular biological analyses have identified phytohormone receptors and signalling mediators, and have led to the discovery of numerous peptide-based signalling molecules. Subsequent analyses have revealed the involvement in and contribution of these peptides to multiple aspects of the plant life cycle, including development and environmental responses, similar to the functions of canonical phytohormones. On the basis of this knowledge, the view that these peptide hormones are pivotal regulators in plants is becoming increasingly accepted. Peptide hormones are transcribed from the genome and translated into peptides. However, these peptides generally undergo further post-translational modifications to enable them to exert their function. Peptide hormones are expressed in and secreted from specific cells or tissues. Apoplastic peptides are perceived by specialized receptors that are located at the surface of target cells. Peptide hormone-receptor complexes activate intracellular signalling through downstream molecules, including kinases and transcription factors, which then trigger cellular events. In this chapter we provide a comprehensive summary of the biological functions of peptide hormones, focusing on how they mature and the ways in which they modulate plant functions. © 2015 Authors; published by Portland Press Limited.

  9. A fossil protein chimera; difficulties in discriminating dinosaur peptide sequences from modern cross-contamination

    OpenAIRE

    Buckley, Michael; Warwood, Stacey; van Dongen, Bart; Kitchener, Andrew C.; Manning, Phillip L.

    2017-01-01

    A decade ago, reports that organic-rich soft tissue survived from dinosaurfossils were apparently supported by proteomics-derived sequence informationof exceptionally well-preserved bone. This initial claim to thesequencing of endogenous collagen peptides from an approximately68 Myr Tyrannosaurus rex fossil was highly controversial, largely on thegrounds of potential contamination from either bacterial biofilms or fromlaboratory practice. In a subsequent study, collagen peptide sequencesfrom ...

  10. Proteomics shows Hsp70 does not bind peptide sequences indiscriminately in vivo

    International Nuclear Information System (INIS)

    Grossmann, Michael E.; Madden, Benjamin J.; Gao, Fan; Pang, Yuan-Ping; Carpenter, John E.; McCormick, Daniel; Young, Charles Y.F.

    2004-01-01

    Heat shock protein 70 (Hsp70) binds peptide and has several functions that include protein folding, protein trafficking, and involvement with immune function. However, endogenous Hsp70-binding peptides had not previously been identified. Therefore, we eluted and identified several hundred endogenously bound peptides from Hsp70 using liquid chromatography ion trap mass spectrophotometry (LC-ITMS). Our work shows that the peptides are capable of binding Hsp70 as previously described. They are generally 8-26 amino acids in length and correspond to specific regions of many proteins. Through computationally assisted analysis of peptides eluted from Hsp70 we determined variable amino acid sequences, including a 5 amino acid core sequence that Hsp70 favorably binds. We also developed a computer algorithm that predicts Hsp70 binding within proteins. This work helps to define what peptides are bound by Hsp70 in vivo and suggests that Hsp70 facilitates peptide selection by aiding a funneling mechanism that is flexible but allows only a limited number of peptides to be processed

  11. 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...

  12. Antimicrobial Peptides in Reptiles

    Science.gov (United States)

    van Hoek, Monique L.

    2014-01-01

    Reptiles are among the oldest known amniotes and are highly diverse in their morphology and ecological niches. These animals have an evolutionarily ancient innate-immune system that is of great interest to scientists trying to identify new and useful antimicrobial peptides. Significant work in the last decade in the fields of biochemistry, proteomics and genomics has begun to reveal the complexity of reptilian antimicrobial peptides. Here, the current knowledge about antimicrobial peptides in reptiles is reviewed, with specific examples in each of the four orders: Testudines (turtles and tortosises), Sphenodontia (tuataras), Squamata (snakes and lizards), and Crocodilia (crocodilans). Examples are presented of the major classes of antimicrobial peptides expressed by reptiles including defensins, cathelicidins, liver-expressed peptides (hepcidin and LEAP-2), lysozyme, crotamine, and others. Some of these peptides have been identified and tested for their antibacterial or antiviral activity; others are only predicted as possible genes from genomic sequencing. Bioinformatic analysis of the reptile genomes is presented, revealing many predicted candidate antimicrobial peptides genes across this diverse class. The study of how these ancient creatures use antimicrobial peptides within their innate immune systems may reveal new understandings of our mammalian innate immune system and may also provide new and powerful antimicrobial peptides as scaffolds for potential therapeutic development. PMID:24918867

  13. Endogenous ACh tonically stimulates ANP secretion in rat atria.

    Science.gov (United States)

    Kim, Hye Yoom; Cho, Kyung Woo; Xu, Dong Yuan; Kang, Dae Gill; Lee, Ho Sub

    2013-10-01

    Exogenous acetylcholine (ACh) is known to stimulate atrial natriuretic peptide (ANP) secretion concomitantly with a decrease in atrial pulse pressure. However, the role of intrinsic ACh in the regulation of ANP secretion remains unknown. Recently, it was shown that nonneuronal and neuronal ACh is present in the cardiac atria. From this finding we hypothesize that endogenously released ACh is involved in the regulation of ANP secretion in an autocrine or paracrine manner in the atria. Experiments were performed in isolated beating rat atria. ANP was measured using radioimmunoassay. To increase the availability of the ACh in the extracellular space of the atrium, its degradation was inhibited with an inhibitor of acetylcholinesterase. Acetylcholinesterase inhibition with physostigmine increased ANP secretion concomitantly with a decrease in atrial dynamics in a concentration-dependent manner. Inhibitors of M2 muscarinic ACh receptor (mAChR), methoctramine, and ACh-activated K(+) (KACh(+)) channels, tertiapin-Q, abolished the physostigmine-induced changes. The effects were not observed in the atria from rats treated with pertussis toxin. Furthermore, the physostigmine-induced effects were attenuated by an inhibitor of high-affinity choline transporter, hemicholinium-3, which is a rate-limiting step of ACh synthesis. Inhibitors of the mAChR signaling pathway and ACh synthesis also attenuated the basal levels of ANP secretion and accentuated atrial dynamics. These findings suggest that endogenously released ACh tonically stimulates ANP secretion from atrial cardiomyocytes via activation of M2 mAChR-Gi/o-KACh(+) channel signaling. It is also suggested that the ACh-ANP signaling is implicated in cardiac physiology and pathophysiology.

  14. Natriuretic Hormones, Endogenous Ouabain, and Related Sodium Transport Inhibitors

    Directory of Open Access Journals (Sweden)

    John eHamlyn

    2014-12-01

    Full Text Available The work of deWardener and colleagues stimulated longstanding interest in natriuretic hormones (NH. In addition to the atrial peptides (APs, the circulation contains unidentified physiologically-relevant NHs. One NH is controlled by the central nervous system (CNS and likely secreted by the pituitary. Its circulating activity is modulated by salt intake and the prevailing sodium concentration of the blood and intracerebroventricular fluid, and contributes to postprandial and dehydration natriuresis. The other NH, mobilized by atrial stretch, promotes natriuresis by increasing the production of intrarenal dopamine and/or nitric oxide. Both NHs have short (<35 minutes circulating half lives, depress renotubular sodium transport, and neither requires the renal nerves. The search for NHs led to endogenous cardiotonic steroids (CTS including ouabain-, digoxin-, and bufadienolide-like materials. These CTS, given acutely in high nanomole to micromole amounts into the general or renal circulations, inhibit sodium pumps and are natriuretic. Among these CTS, only bufalin is cleared sufficiently rapidly to qualify for an NH-like role. Ouabain-like CTS are cleared slowly, and when given chronically in low daily nanomole amounts, promote sodium retention, augment arterial myogenic tone, reduce renal blood flow and glomerular filtration, suppress nitric oxide in the renal vasa recta, and increase sympathetic nerve activity and blood pressure. Moreover, lowering total body sodium raises circulating endogenous ouabain. Thus, ouabain-like CTS have physiological actions that, like aldosterone, support renal sodium retention and blood pressure. In conclusion, the mammalian circulation contains two non-AP NHs. Identification of the CNS NH should be a priority.

  15. A Probabilistic Framework for Peptide and Protein Quantification from Data-Dependent and Data-Independent LC-MS Proteomics Experiments

    DEFF Research Database (Denmark)

    Richardson, Katherine; Denny, R.; Hughes, C.

    2012-01-01

    that outliers of any type can be automatically reweighted. Two discrete normalization methods can be employed. The first method is based on a user-defined subset of peptides, while the second method relies on the presence of a dominant background of endogenous peptides for which the concentration is assumed...

  16. In vitro determination of the short-chain synthetic peptide RP13 antimicrobial activity.

    Science.gov (United States)

    Sánchez, Adrián; Calderón, Ernesto; Castañón-Alonso, Sandra L; Santos, Araceli; Hernández, Beatriz; Vázquez, Alfredo

    2014-01-01

    The proliferation of antibiotic-resistant microorganisms, along with the lack of new drugs against them, has elicited the interest of the scientific community on the study and development of endogenous synthetic compounds with bacteriostatic or bactericidal activity. In recent years, several short-chain, low molecular weight peptides isolated from natural sources such as plants and animals have demonstrated an array of antimicrobial activities. Despite having structural characteristics similar to microbicidal peptides isolated from human platelets, peptide RP11 does not exhibit antimicrobial activity. In vitro determination of the antimicrobial activity of the synthetic peptide RP13. Peptide RP13 was prepared modifying the original amino acids sequence of peptide RP11, reversing the position of the amino acids lysine and tyrosine in order to modify the conformation of the original peptide. These amino acids are localized close to the N-terminus of the peptidic chain. Peptide RP13 was prepared in solution using conventional methods for peptide synthesis. The antimicrobial activity of RP13 was assessed against the microorganisms S. aureus, E. faecalis and E. coli in a test solution and later evaluated by cultivation of plates during the first 2 h after inoculation of bacteria. RP13 activity antimicrobial was compared against tetracycline, a broad-spectrum antibiotic. The new peptide RP13, resulting form the structural modification of the amino acid sequence of peptide RP11, displayed antimicrobial activity. RP13 demonstrated to be more efficient inhibiting the growth of gram-positive than gramnegative bacteria. The structural modification of peptide RP11, obtained from human platelets, resulted in a new peptide with improved antimicrobial activity. These results clearly demonstrate that peptides of natural origin, as well as their synthetic analogs, represent an attractive alternative against pathogenic agents.

  17. The hallucinogen N,N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator.

    Science.gov (United States)

    Fontanilla, Dominique; Johannessen, Molly; Hajipour, Abdol R; Cozzi, Nicholas V; Jackson, Meyer B; Ruoho, Arnold E

    2009-02-13

    The sigma-1 receptor is widely distributed in the central nervous system and periphery. Originally mischaracterized as an opioid receptor, the sigma-1 receptor binds a vast number of synthetic compounds but does not bind opioid peptides; it is currently considered an orphan receptor. The sigma-1 receptor pharmacophore includes an alkylamine core, also found in the endogenous compound N,N-dimethyltryptamine (DMT). DMT acts as a hallucinogen, but its receptor target has been unclear. DMT bound to sigma-1 receptors and inhibited voltage-gated sodium ion (Na+) channels in both native cardiac myocytes and heterologous cells that express sigma-1 receptors. DMT induced hypermobility in wild-type mice but not in sigma-1 receptor knockout mice. These biochemical, physiological, and behavioral experiments indicate that DMT is an endogenous agonist for the sigma-1 receptor.

  18. Insulin C-peptide test

    Science.gov (United States)

    C-peptide ... the test depends on the reason for the C-peptide measurement. Ask your health care provider if ... C-peptide is measured to tell the difference between insulin the body produces and insulin someone injects ...

  19. Host-virus interactions of mammalian endogenous retroviruses

    OpenAIRE

    Farkašová, Helena

    2017-01-01

    Endogenous retroviruses (ERVs) originate by germline infection and subsequent mendelian inheritance of their exogenous counterparts. With notable exceptions, all mammalian ERVs are evolutionarily old and fixed in the population of its host species. Some groups of retroviruses were believed not to be able to form endogenous copies. We discovered an additional endogenous Lentivirus and a first endogenous Deltaretrovirus. Both of these groups were previously considered unable to form endogenous ...

  20. Endogenous Fusarium Endophthalmitis in Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    S. Balamurugan

    2016-01-01

    Full Text Available Endogenous endophthalmitis accounts for 2% to 8% of cases of endophthalmitis. Immunocompromised state and intravenous drug use are the 2 most common causes of endogenous endophthalmitis due to molds fungi. Aspergillus, Fusarium, and Scedosporium are the common organisms in mold endophthalmitis. We report a case of Fusarium endophthalmitis in a patient with uncontrolled diabetes. While diabetes mellitus is a well-known risk factor for endogenous endophthalmitis, we did not find any reported case of Fusarium endophthalmitis in a case of diabetes mellitus. The patient presented with granulomatous uveitis masquerading as noninfectious uveitis with a very good response to steroids. The characteristic clinical features were established late in the clinical course associated with poor outcome. This case highlights the significance of uncontrolled diabetes as a risk factor for Fusarium endophthalmitis and also the presentation of endophthalmitis as a masquerade syndrome. The clinician should have high index of suspicion as these cases have poor outcomes.

  1. Endogenous Turnover of Cyanogenic Glycosides in Plants

    DEFF Research Database (Denmark)

    Picmanova, Martina

    through the formation of β- cyanoalanine, or, potentially, in an alternative endogenous turnover pathway circumventing the release of HCN. The investigation of the latter is the primary focus of this PhD project. Scattered data from the literature indicated that CNglcs co-occur in plants...... revealed the formation of glycosides of amides, carboxylic acids and "anitriles", including their di- and triglycosides, evidently derived from CNglcs. Based on results common to the three phylogenetically unrelated plant species, a recycling endogenous turnover pathway for CNglcs was suggested in which...... with an N-terminal TCP domain, showed that these enzymes do not recognize CNglcs as their substrates. However, the activity of NIT4s on a nitrile glucoside indicates that the enzymatic formation of glycosylated turnover products might be an integral part of the endogenous turnover of CNglcs. The elucidation...

  2. Endogenous Generalized Weights under DEA Control

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    Non-parametric efficiency analysis, such as Data Envelopment Analysis (DEA) relies so far on endogenous local or exogenous general weights, based on revealed preferences or market prices. However, as DEA is gaining popularity in regulation and normative budgeting, the strategic interest of the ev......Non-parametric efficiency analysis, such as Data Envelopment Analysis (DEA) relies so far on endogenous local or exogenous general weights, based on revealed preferences or market prices. However, as DEA is gaining popularity in regulation and normative budgeting, the strategic interest...... of the evaluated industry calls for attention. We offer endogenous general prices based on a reformulation of DEA where the units collectively propose the set of weights that maximize their efficiency. Thus, the sector-wide efficiency is then a result of compromising the scores of more specialized smaller units...

  3. Endogenous cross-talk of fungal metabolites.

    Directory of Open Access Journals (Sweden)

    Kevin J Sheridan

    2015-01-01

    Full Text Available Non-ribosomal peptide synthesis in fungi requires a ready supply of proteogenic and non-proteogenic amino acids which are subsequently incorporated into the nascent non-ribosomal peptide via a thiotemplate mechanism catalysed by non-ribosomal peptide synthetases. Substrate amino acids can be modified prior to or during incorporation into the non-ribosomal peptide, or following incorporation into an early stage amino acid-containing biosynthetic intermediate. These post-incorporation modifications involve a range of additional enzymatic activities including but not exclusively, monooxygenases, methyltransferases, epimerases, oxidoreductases and glutathione transferases which are essential to effect biosynthesis of the final non-ribosomal peptide. Likewise, polyketide biosynthesis is directly by polyketide synthase megaenzymes and cluster-encoded ancilliary decorating enzymes. Additionally, a suite of additional primary metabolites, for example: CoA, acetyl CoA, S-adenosylmethionine, glutathione, NADPH, malonyl CoA and molecular oxygen, amongst others are required for non-ribosomal peptide and polyketide synthesis. Clearly these processes must involve exquisite orchestration to facilitate the simultaneous biosynthesis of different types of non-ribosomal peptides, polyketides, and related metabolites requiring identical or similar biosynthetic precursors or co-factors. Moreover, the near identical structures of many natural products within a given family (e.g., ergot alkaloids, along with localization to similar regions within fungi (e.g., conidia suggests that cross-talk may exist, in terms of biosynthesis and functionality. Finally, we speculate if certain biosynthetic steps involved in non-ribosomal peptide and polyketide synthesis play a role in cellular protection or environmental adaptation, and wonder if these enzymatic reactions are of equivalent importance to the actual biosynthesis of the final metabolite.

  4. Bioactive Peptides in Animal Food Products

    Directory of Open Access Journals (Sweden)

    Marzia Albenzio

    2017-05-01

    Full Text Available Proteins of animal origin represent physiologically active components in the human diet; they exert a direct action or constitute a substrate for enzymatic hydrolysis upon food processing and consumption. Bioactive peptides may descend from the hydrolysis by digestive enzymes, enzymes endogenous to raw food materials, and enzymes from microorganisms added during food processing. Milk proteins have different polymorphisms for each dairy species that influence the amount and the biochemical characteristics (e.g., amino acid chain, phosphorylation, and glycosylation of the protein. Milk from other species alternative to cow has been exploited for their role in children with cow milk allergy and in some infant pathologies, such as epilepsy, by monitoring the immune status. Different mechanisms concur for bioactive peptides generation from meat and meat products, and their functionality and application as functional ingredients have proven effects on consumer health. Animal food proteins are currently the main source of a range of biologically-active peptides which have gained special interest because they may also influence numerous physiological responses in the organism. The addition of probiotics to animal food products represent a strategy for the increase of molecules with health and functional properties.

  5. Bioactive Peptides in Animal Food Products.

    Science.gov (United States)

    Albenzio, Marzia; Santillo, Antonella; Caroprese, Mariangela; Della Malva, Antonella; Marino, Rosaria

    2017-05-09

    Proteins of animal origin represent physiologically active components in the human diet; they exert a direct action or constitute a substrate for enzymatic hydrolysis upon food processing and consumption. Bioactive peptides may descend from the hydrolysis by digestive enzymes, enzymes endogenous to raw food materials, and enzymes from microorganisms added during food processing. Milk proteins have different polymorphisms for each dairy species that influence the amount and the biochemical characteristics (e.g., amino acid chain, phosphorylation, and glycosylation) of the protein. Milk from other species alternative to cow has been exploited for their role in children with cow milk allergy and in some infant pathologies, such as epilepsy, by monitoring the immune status. Different mechanisms concur for bioactive peptides generation from meat and meat products, and their functionality and application as functional ingredients have proven effects on consumer health. Animal food proteins are currently the main source of a range of biologically-active peptides which have gained special interest because they may also influence numerous physiological responses in the organism. The addition of probiotics to animal food products represent a strategy for the increase of molecules with health and functional properties.

  6. Feeding Releases Endogenous Opioids in Humans.

    Science.gov (United States)

    Tuulari, Jetro J; Tuominen, Lauri; de Boer, Femke E; Hirvonen, Jussi; Helin, Semi; Nuutila, Pirjo; Nummenmaa, Lauri

    2017-08-23

    The endogenous opioid system supports a multitude of functions related to appetitive behavior in humans and animals, and it has been proposed to govern hedonic aspects of feeding thus contributing to the development of obesity. Here we used positron emission tomography to investigate whether feeding results in hedonia-dependent endogenous opioid release in humans. Ten healthy males were recruited for the study. They were scanned with the μ-opioid-specific ligand [ 11 C]carfentanil three times, as follows: after a palatable meal, a nonpalatable meal, and after an overnight fast. Subjective mood, satiety, and circulating hormone levels were measured. Feeding induced significant endogenous opioid release throughout the brain. This response was more pronounced following a nonpalatable meal versus a palatable meal, and independent of the subjective hedonic responses to feeding. We conclude that feeding consistently triggers cerebral opioid release even in the absence of subjective pleasure associated with feeding, suggesting that metabolic and homeostatic rather than exclusively hedonic responses play a role in the feeding-triggered cerebral opioid release. SIGNIFICANCE STATEMENT The endogenous opioid system supports both hedonic and homeostatic functions. It has been proposed that overeating and concomitant opioid release could downregulate opioid receptors and promote the development of obesity. However, it remains unresolved whether feeding leads to endogenous opioid release in humans. We used in vivo positron emission tomography to test whether feeding triggers cerebral opioid release and whether this response is associated with pleasurable sensations. We scanned volunteers using the μ-opioid receptor-specific radioligand [ 11 C]carfentanil three times, as follows: after an overnight fast, after consuming a palatable meal, and after consuming a nonpalatable meal. Feeding led to significant endogenous opioid release, and this occurred also in the absence of feeding

  7. Endogenous network of firms and systemic risk

    Science.gov (United States)

    Ma, Qianting; He, Jianmin; Li, Shouwei

    2018-02-01

    We construct an endogenous network characterized by commercial credit relationships connecting the upstream and downstream firms. Simulation results indicate that the endogenous network model displays a scale-free property which exists in real-world firm systems. In terms of the network structure, with the expansion of the scale of network nodes, the systemic risk increases significantly, while the heterogeneities of network nodes have no effect on systemic risk. As for firm micro-behaviors, including the selection range of trading partners, actual output, labor requirement, price of intermediate products and employee salaries, increase of all these parameters will lead to higher systemic risk.

  8. Endogenous Natural Complement Inhibitor Regulates Cardiac Development

    DEFF Research Database (Denmark)

    Mortensen, Simon A; Skov, Louise L; Kjaer-Sorensen, Kasper

    2017-01-01

    mechanisms during fetal development and adult homeostasis. In this article, we describe the function of an endogenous complement inhibitor, mannan-binding lectin (MBL)-associated protein (MAp)44, in regulating the composition of a serine protease-pattern recognition receptor complex, MBL-associated serine...... of MAp44 caused impaired cardiogenesis, lowered heart rate, and decreased cardiac output. These defects were associated with aberrant neural crest cell behavior. We found that MAp44 competed with MASP-3 for pattern recognition molecule interaction, and knockdown of endogenous MAp44 expression could...

  9. Endogenous thrombin potential in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Aziz, Mubeena; Sidelmann, Johannes J; Wissing, Marie Louise Muff

    2015-01-01

    OBJECTIVES: The objective of this study is to investigate plasma endogenous thrombin generation in four different phenotypes of polycystic ovary syndrome (PCOS) defined by Body Mass Index (BMI) and insulin resistance (IR). PCOS is diagnosed according to the Rotterdam criteria. DESIGN: Multicenter......: Endogenous thrombin potential (ETP). RESULTS: PCOS women with phenotype BMI > 25 + IR have increased potential of thrombin generation. ETP is associated with total body fat mass, IR, and CRP. CONCLUSIONS: Obese and insulin resistant women with PCOS have elevated level of ETP corresponding to increased risk...

  10. Peptide profiling of bovine kefir reveals 236 unique peptides released from caseins during its production by starter culture or kefir grains.

    Science.gov (United States)

    Ebner, Jennifer; Aşçı Arslan, Ayşe; Fedorova, Maria; Hoffmann, Ralf; Küçükçetin, Ahmet; Pischetsrieder, Monika

    2015-03-18

    Kefir has a long tradition in human nutrition due to its presupposed health promoting effects. To investigate the potential contribution of bioactive peptides to the physiological effects of kefir, comprehensive analysis of the peptide profile was performed by nano-ESI-LTQ-Orbitrap MS coupled to nano-ultrahigh-performance liquid chromatography. Thus, 257 peptides were identified, mainly released from β-casein, followed by αS1-, κ-, and αS2-casein. Most (236) peptides were uniquely detected in kefir, but not in raw milk indicating that the fermentation step does not only increase the proteolytic activity 1.7- to 2.4-fold compared to unfermented milk, but also alters the composition of the peptide fraction. The influence of the microflora was determined by analyzing kefir produced from traditional kefir grains or commercial starter culture. Kefir from starter culture featured 230 peptide sequences and showed a significantly, 1.4-fold higher proteolytic activity than kefir from kefir grains with 127 peptides. A match of 97 peptides in both varieties indicates the presence of a typical kefir peptide profile that is not influenced by the individual composition of the microflora. Sixteen of the newly identified peptides were previously described as bioactive, including angiotensin-converting enzyme (ACE)-inhibitory, antimicrobial, immunomodulating, opioid, mineral binding, antioxidant, and antithrombotic effects. The present study describes a comprehensive peptide profile of kefir comprising 257 sequences. The peptide list was used to identify 16 bioactive peptides with ACE-inhibitory, antioxidant, antithrombotic, mineral binding, antimicrobial, immunomodulating and opioid activity in kefir. Furthermore, it was shown that a majority of the kefir peptides were not endogenously present in the raw material milk, but were released from milk caseins by proteases of the microbiota and are therefore specific for the product. Consequently, the proteolytic activity and the

  11. Porcine major histocompatibility complex (MHC) class I molecules and analysis of their peptide-binding specificities

    Science.gov (United States)

    In all vertebrate animals, CD8+ cytotoxic T lymphocytes (CTLs) are controlled by major histocompatibility complex class I (MHC-I) molecules, which are highly polymorphic peptide receptors selecting and presenting endogenously derived epitopes to circulating cytotoxic lymphocytes (CTLs). The polymorp...

  12. Ligand binding and activation mechanism og the glucagon-like peptide-1 receptor

    DEFF Research Database (Denmark)

    Underwood, Christina Rye

    endogenous agonist, Glucagon-Like Peptide-1 (GLP-1), has a number of physiological effects that contribute to reducing blood sugar and body weight. Therefore, GLP-1R has become a promising target for the treatment of type 2 diabetes (T2D). The overall purpose of the Ph.D. project has been to investigate how...

  13. Endogenous MOV10 inhibits the retrotransposition of endogenous retroelements but not the replication of exogenous retroviruses

    Directory of Open Access Journals (Sweden)

    Arjan-Odedra Shetal

    2012-06-01

    Full Text Available Abstract Background The identification of cellular factors that regulate the replication of exogenous viruses and endogenous mobile elements provides fundamental understanding of host-pathogen relationships. MOV10 is a superfamily 1 putative RNA helicase that controls the replication of several RNA viruses and whose homologs are necessary for the repression of endogenous mobile elements. Here, we employ both ectopic expression and gene knockdown approaches to analyse the role of human MOV10 in the replication of a panel of exogenous retroviruses and endogenous retroelements. Results MOV10 overexpression substantially decreased the production of infectious retrovirus particles, as well the propagation of LTR and non-LTR endogenous retroelements. Most significantly, RNAi-mediated silencing of endogenous MOV10 enhanced the replication of both LTR and non-LTR endogenous retroelements, but not the production of infectious retrovirus particles demonstrating that natural levels of MOV10 suppress retrotransposition, but have no impact on infection by exogenous retroviruses. Furthermore, functional studies showed that MOV10 is not necessary for miRNA or siRNA-mediated mRNA silencing. Conclusions We have identified novel specificity for human MOV10 in the control of retroelement replication and hypothesise that MOV10 may be a component of a cellular pathway or process that selectively regulates the replication of endogenous retroelements in somatic cells.

  14. Endogenous MOV10 inhibits the retrotransposition of endogenous retroelements but not the replication of exogenous retroviruses

    Science.gov (United States)

    2012-01-01

    Background The identification of cellular factors that regulate the replication of exogenous viruses and endogenous mobile elements provides fundamental understanding of host-pathogen relationships. MOV10 is a superfamily 1 putative RNA helicase that controls the replication of several RNA viruses and whose homologs are necessary for the repression of endogenous mobile elements. Here, we employ both ectopic expression and gene knockdown approaches to analyse the role of human MOV10 in the replication of a panel of exogenous retroviruses and endogenous retroelements. Results MOV10 overexpression substantially decreased the production of infectious retrovirus particles, as well the propagation of LTR and non-LTR endogenous retroelements. Most significantly, RNAi-mediated silencing of endogenous MOV10 enhanced the replication of both LTR and non-LTR endogenous retroelements, but not the production of infectious retrovirus particles demonstrating that natural levels of MOV10 suppress retrotransposition, but have no impact on infection by exogenous retroviruses. Furthermore, functional studies showed that MOV10 is not necessary for miRNA or siRNA-mediated mRNA silencing. Conclusions We have identified novel specificity for human MOV10 in the control of retroelement replication and hypothesise that MOV10 may be a component of a cellular pathway or process that selectively regulates the replication of endogenous retroelements in somatic cells. PMID:22727223

  15. Immigration, Endogenous Technology Adoption and Wages

    NARCIS (Netherlands)

    Ray Chaudhuri, A.; Pandey, Manish

    2015-01-01

    We document that immigration to U.S. states has increased the mass of workers at the lower range of the skill distribution. We use this change in skill distribution of workers to analyze the effect of immigration on wages. Our model allows firms to endogenously respond to the immigration-induced

  16. The Limit of Public Policy : Endogenous Preferences

    NARCIS (Netherlands)

    Bar-Gill, O.; Fershtman, C.

    2000-01-01

    In designing public policy it is not enough to consider the possible reaction of individuals to the chosen policy.Public policy may also affect the formation of preferences and norms in a society.The endogenous evolution of preferences, in addition to introducing a conceptual difficulty in

  17. Baboon endogenous virus evolution and ecology

    NARCIS (Netherlands)

    van der Kuyl, A. C.; Dekker, J. T.; Goudsmit, J.

    1996-01-01

    Cross-species transmission of retroviruses among primates has recently been recognized as the source of the current epidemics of HIV-1, HIV-2 and human T cell leukemia virus type 1 (HTLV-1). The distribution of baboon endogenous virus among non-human primates resembles that of exogenous viruses and

  18. endogenous retrovirus sequences expressed in male mammalian

    African Journals Online (AJOL)

    2002-01-02

    Jan 2, 2002 ... the human genome. Because of such hypotheses, in this communication, we discuss the findings of various studies that have demonstrated expression of endogenous retrovirus-like particles in male mammalian reproductive tissues. In addition, we discuss the biological implications of the presence of these ...

  19. Essays on Policy Evaluation with Endogenous Adoption

    Science.gov (United States)

    Gentile, Elisabetta

    2011-01-01

    Over the last decade, experimental and quasi-experimental methods have been favored by researchers in empirical economics, as they provide unbiased causal estimates. However, when implementing a program, it is often not possible to randomly assign subjects to treatment, leading to a possible endogeneity bias. This dissertation consists of two…

  20. Evolution and Refinement with Endogenous Mistake Probabilities

    NARCIS (Netherlands)

    van Damme, E.E.C.; Weibull, J.

    1999-01-01

    Bergin and Lipman (1996) show that the refinement effect from the random mutations in the adaptive population dynamics in Kandori, Mailath and Rob (1993) and Young (1993) is due to restrictions on how these mutation rates vary across population states. We here model mutation rates as endogenously

  1. Maintenance Costs, Obsolescence, and Endogenous Growth

    NARCIS (Netherlands)

    K.G. Berden (Koen); J.G.M. van Marrewijk (Charles)

    2001-01-01

    textabstractWe analyze the impact of obsolescence of economic inventions by incorporating maintenance costs in the endogenous growth model of expanding product varieties. This contrasts with the existing literature, which ignores maintenance costs and uses the model of quality improvements to

  2. Hepatic, renal and endogenous antioxidant status modulatory ...

    African Journals Online (AJOL)

    Background: This study investigated the hepatic, renal and endogenous antioxidant status modulatory effects of chronic cosupplementation of rooibos and red palm oil (RPO) in male Wistar rats. Materials and Methods: Rats were randomized into four groups (n=10/group) and fed daily either standard rat chow (SRC) and ...

  3. Applying Endogenous Knowledge in the African Context ...

    African Journals Online (AJOL)

    This requires not only an understanding of what endogenous knowledge is, but also an alignment of personal values, innovative strategies and an attitude of activism. An integral part of an extensive skills set to implement specifi c dispute resolution strategies is the ability to facilitate the free sharing of information about all ...

  4. Place branding, embeddedness and endogenous rural development

    NARCIS (Netherlands)

    Donner, Mechthild; Horlings, Lummina; Fort, Fatiha; Vellema, Sietze

    2017-01-01

    This article deals with place branding on the regional scale, in the rural context of food and tourism networks in Europe. Place branding is linked to the concepts of endogenous rural development, territory and embeddedness, by analysing how the valorisation of specific rural assets takes shape.

  5. Environmental tax reform and endogenous growth

    NARCIS (Netherlands)

    Bovenberg, A.L.; de Mooij, R.A.

    1994-01-01

    This paper explores the effects of an environmental tax reform on pollution, economic growth and welfare in an endogenous growth model with pre-existing tax distortions. We find that a shift in the tax mix away from output towards pollution may raise economic growth through two channels. The first

  6. Endogeneity in Strategy-Performance Analysis

    DEFF Research Database (Denmark)

    Rocha, Vera; Van Praag, Mirjam; B. Folta, Timothy

    2018-01-01

    , such as employees, strategic partners, customers, or investors, whose choices and preferences also affect the final decision. We discuss how endogeneity can plague the measurement of the performance effects of these two-sided strategic decisions—which are more complex, but more realistic, than prior representations...

  7. Climate changes and farmers' endogenous adaptation strategies ...

    African Journals Online (AJOL)

    It has been claimed that climate changes impact studies often assume certain adaptations and little explicit examination of how, when, why, and under what conditions they occur. This research aims at analysing the endogenous strategies developed by farmers in agricultural land and crop management. With random ...

  8. Optimal income taxation with endogenous human capital

    NARCIS (Netherlands)

    Jacobs, B.

    2005-01-01

    This paper augments the theory of optimal linear income taxation by taking into account human capital accumulation as a dimension of labor supply. The distribution of earning potentials is endogenous because agents differ in the ability to learn. Taxation affects utilization rates of human capital

  9. Endogenous Markups, Firm Productivity and International Trade:

    DEFF Research Database (Denmark)

    Bellone, Flora; Musso, Patrick; Nesta, Lionel

    In this paper, we test key micro-level theoretical predictions ofMelitz and Ottaviano (MO) (2008), a model of international trade with heterogenous firms and endogenous mark-ups. At the firm-level, the MO model predicts that: 1) firm markups are negatively related to domestic market size; 2...

  10. Leveraging Endogenous Research and Innovation for Sustainable ...

    African Journals Online (AJOL)

    In this treatise, a quick look is taken at the spectrum (range) of research from pure basic, strategic basic, applied, experimental development or research and development (R&D) to endogenous research and innovation (ER&I). It also defines development, innovation, food security, poverty; and discusses some contemporary ...

  11. Endogenous retrovirus sequences expressed in male mammalian ...

    African Journals Online (AJOL)

    Objectives: To review the research findings on the expression of endogenous retroviruses and retroviral-related particles in male mammalian reproductive tissues, and to discuss their possible role in normal cellular events and association with disease conditions in male reproductive tissues. Data sources: Published ...

  12. Endogenous pancreatic polypeptide in different vascular beds

    DEFF Research Database (Denmark)

    Henriksen, J H; Schwartz, Tania; Bülow, J B

    1986-01-01

    The plasma concentration of pancreatic polypeptide (PP-like immunoreactivity) was measured in different vascular beds in order to determine regional kinetics of endogenous PP in fasting, supine subjects with normal or moderately decreased kidney function. Patients with kidney disease (n = 10) had...

  13. Changes in endogenous hormone concentrations during ...

    African Journals Online (AJOL)

    Administrator

    2011-09-14

    Sep 14, 2011 ... This study investigated the changes of five endogenous hormones in the shoot apex and the white bases of D-leaf during the inflorescence induction and development of 'Smooth Cayenne' pineapple, using 14-month-old pot-grown plants as material and ethephon as flower forcing agent. Results showed.

  14. Environmental policy, pollution, unemployment and endogenous growth

    DEFF Research Database (Denmark)

    Pedersen, Lars Haagen; Nielsen, Søren Bo; Sørensen, Peter Birch

    1995-01-01

    The paper develops a model of endogenous economic growth with pollution externalities and a labor market distorted by union monopoly power and by taxes and transfers. We study the optimal second-best pollution tax and abatement policy and find that a shift toward greener preferences will tend...

  15. Endogenous retroviruses are associated with autoimmune diseases

    DEFF Research Database (Denmark)

    Nexø, Bjørn A; Bisgaard Jensen, Sara; Hansen, Bettina

    2016-01-01

    Retroviruses can be transmitted in two fundamentally different ways: 1) They can be horizontally transmitted as infectious virus, or 2) they can integrate in the germ line and be transmitted to offspring and the offsprings' offspring as DNA. The latter is called endogenous viruses. The mode...

  16. Optimized Formation of Benzyl Isothiocyanate by Endogenous ...

    African Journals Online (AJOL)

    Purpose: To use endogenous myrosinase in Carica papaya seed to convert benzyl glucosinolate (BG) to benzyl isothiocyanate (BITC) and then extract it for further studies. Methods: Process variables including seed powder particle size, sample-to-solvent ratio, pH of buffer solution, enzymolysis temperature, enzymolysis ...

  17. Managing spillovers: an endogenous sunk cost approach

    Czech Academy of Sciences Publication Activity Database

    Senyuta, Olena; Žigić, Krešimir

    2016-01-01

    Roč. 35, June (2016), s. 45-64 ISSN 0167-6245 R&D Projects: GA ČR(CZ) GAP402/12/0961 Institutional support: PRVOUK-P23 Keywords : endogenous sunk costs * innovations * knowledge spillovers Subject RIV: AH - Economics Impact factor: 0.739, year: 2016

  18. climate changes and farmers' endogenous adaptation strategies

    African Journals Online (AJOL)

    Prof. Adipala Ekwamu

    CLIMATE CHANGES AND FARMERS' ENDOGENOUS ADAPTATION STRATEGIES: SOCIO ECONOMIC ANALYSIS OF THE DYNAMIC USE OF AGRICULTURAL LANDS IN. CENTRAL REGION OF BENIN. M.W. ABIDJI, H. DEDEHOUANOU, P. VISSOH, E. AGBOSSOU1 and H. GUIBERT1. University of Abomey-Calavi ...

  19. An endogenous policy model of hierarchical government

    NARCIS (Netherlands)

    Mazza, I.; van Winden, F.

    2008-01-01

    Endogenous policy models usually neglect that government policies are frequently the result of decisions taken at different tiers by different agents, each enjoying some degree of autonomy. In this paper, policies are the outcome of the choices made by two agents within a hierarchy. A legislator

  20. HERVd: the Human Endogenous Retrovirus Database: update

    Czech Academy of Sciences Publication Activity Database

    Pačes, Jan; Pavlíček, A.; Zíka, Radek; Jurka, J.; Pačes, Václav

    2004-01-01

    Roč. 32, č. 1 (2004), s. 50-50 ISSN 0305-1048 R&D Projects: GA MŠk LN00A079 Institutional research plan: CEZ:AV0Z5052915 Keywords : human * endogenous retrovirus * database Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.260, year: 2004

  1. Endogenous retrovirus sequences expressed in male mammalian ...

    African Journals Online (AJOL)

    Data sources: Published findings on endogenous retrovirus (ERV) expression in vertebrate reproductive tissues. Study selection: Relevant citations on ERVs and male reproduction by research groups worldwide. Data extraction: Literature search on Medline and Pubmed upto the year 2000, and retrieval of relevant articles ...

  2. Changes in endogenous hormone concentrations during ...

    African Journals Online (AJOL)

    Results showed that application of ethephon increased the level of endogenous ethylene (C2H4), abscisic acid (ABA) and 2-isopentyl adenine (2-iP) while it decreased the concentration of indole-3-acetic acid (IAA), gibberellic acid (GA3) and zeatin (ZT), and led to the transition of vegetative growth to inflorescence initiation ...

  3. Biofortification of rice with lysine using endogenous histones.

    Science.gov (United States)

    Wong, H W; Liu, Q; Sun, S S M

    2015-02-01

    Rice is the most consumed cereal grain in the world, but deficient in the essential amino acid lysine. Therefore, people in developing countries with limited food diversity who rely on rice as their major food source may suffer from malnutrition. Biofortification of stable crops by genetic engineering provides a fast and sustainable method to solve this problem. In this study, two endogenous rice lysine-rich histone proteins, RLRH1 and RLRH2, were over-expressed in rice seeds to achieve lysine biofortification. Their protein sequences passed an allergic sequence-based homology test. Their accumulations in rice seeds were raised to a moderate level by the use of a modified rice glutelin 1 promoter with lowered expression strength to avoid the occurrence of physiological abnormalities like unfolded protein response. The expressed proteins were further targeted to protein storage vacuoles for stable storage using a glutelin 1 signal peptide. The lysine content in the transgenic rice seeds was enhanced by up to 35 %, while other essential amino acids remained balanced, meeting the nutritional standards of the World Health Organization. No obvious unfolded protein response was detected. Different degrees of chalkiness, however, were detected in the transgenic seeds, and were positively correlated with both the levels of accumulated protein and lysine enhancement. This study offered a solution to the lysine deficiency in rice, while at the same time addressing concerns about food safety and physiological abnormalities in biofortified crops.

  4. Humanin is an endogenous activator of chaperone-mediated autophagy.

    Science.gov (United States)

    Gong, Zhenwei; Tasset, Inmaculada; Diaz, Antonio; Anguiano, Jaime; Tas, Emir; Cui, Lingguang; Kuliawat, Regina; Liu, Honghai; Kühn, Bernhard; Cuervo, Ana Maria; Muzumdar, Radhika

    2018-02-05

    Chaperone-mediated autophagy (CMA) serves as quality control during stress conditions through selective degradation of cytosolic proteins in lysosomes. Humanin (HN) is a mitochondria-associated peptide that offers cytoprotective, cardioprotective, and neuroprotective effects in vivo and in vitro. In this study, we demonstrate that HN directly activates CMA by increasing substrate binding and translocation into lysosomes. The potent HN analogue HNG protects from stressor-induced cell death in fibroblasts, cardiomyoblasts, neuronal cells, and primary cardiomyocytes. The protective effects are lost in CMA-deficient cells, suggesting that they are mediated through the activation of CMA. We identified that a fraction of endogenous HN is present at the cytosolic side of the lysosomal membrane, where it interacts with heat shock protein 90 (HSP90) and stabilizes binding of this chaperone to CMA substrates as they bind to the membrane. Inhibition of HSP90 blocks the effect of HNG on substrate translocation and abolishes the cytoprotective effects. Our study provides a novel mechanism by which HN exerts its cardioprotective and neuroprotective effects. © 2018 Gong et al.

  5. Yield improvement of heterologous peptides expressed in yps1-disrupted Saccharomyces cerevisiae strains.

    Science.gov (United States)

    Egel-Mitani; Andersen; Diers; Hach; Thim; Hastrup; Vad

    2000-06-01

    Heterologous protein expression levels in Saccharomyces cerevisiae fermentations are highly dependent on the susceptibility to endogenous yeast proteases. Small peptides, such as glucagon and glucagon-like-peptides (GLP-1 and GLP-2), featuring an open structure are particularly accessible for proteolytic degradation during fermentation. Therefore, homogeneous products cannot be obtained. The most sensitive residues are found at basic amino acid residues in the peptide sequence. These heterologous peptides are degraded mainly by the YPS1-encoded aspartic protease, yapsin1, when produced in the yeast. In this article, distinct degradation products were analyzed by HPLC and mass spectrometry, and high yield of the heterologous peptide production has been achieved by the disruption of the YPS1 gene (previously called YAP3). By this technique, high yield continuous fermentation of glucagon in S. cerevisiae is now possible.

  6. ENDOGENOUS ANALGESIA, DEPENDENCE, AND LATENT PAIN SENSITIZATION

    Science.gov (United States)

    Taylor, Bradley K; Corder, Gregory

    2015-01-01

    Endogenous activation of μ-opioid receptors (MORs) provides relief from acute pain. Recent studies have established that tissue inflammation produces latent pain sensitization (LS) that is masked by spinal MOR signaling for months, even after complete recovery from injury and re-establishment of normal pain thresholds. Disruption with MOR inverse agonists reinstates pain and precipitates cellular, somatic and aversive signs of physical withdrawal; this phenomenon requires N-methyl-D-aspartate receptor-mediated activation of calcium-sensitive adenylyl cyclase type 1 (AC1). In this review, we present a new conceptual model of the transition from acute to chronic pain, based on the delicate balance between LS and endogenous analgesia that develops after painful tissue injury. First, injury activates pain pathways. Second, the spinal cord establishes MOR constitutive activity (MORCA) as it attempts to control pain. Third, over time, the body becomes dependent on MORCA, which paradoxically sensitizes pain pathways. Stress or injury escalates opposing inhibitory and excitatory influences on nociceptive processing as a pathological consequence of increased endogenous opioid tone. Pain begets MORCA begets pain vulnerability in a vicious cycle. The final result is a silent insidious state characterized by the escalation of two opposing excitatory and inhibitory influences on pain transmission: LS mediated by AC1 (which maintains accelerator), and pain inhibition mediated by MORCA (which maintains the brake). This raises the prospect that opposing homeostatic interactions between MORCA analgesia and latent NMDAR–AC1-mediated pain sensitization create a lasting vulnerability to develop chronic pain. Thus, chronic pain syndromes may result from a failure in constitutive signaling of spinal MORs and a loss of endogenous analgesic control. An overarching long-term therapeutic goal of future research is to alleviate chronic pain by either: a) facilitating endogenous opioid

  7. Inhibitory effect of a novel peptide, H-RN, on keratitis induced by LPS or poly(I:C) in vitro and in vivo via suppressing NF-?B and MAPK activation

    OpenAIRE

    Zhu, Shaopin; Xu, Xun; Wang, Lili; Su, Li; Gu, Qing; Wei, Fang; Liu, Kun

    2017-01-01

    Background Keratitis is a common cause of blindness. Current anti-inflammatory drugs used in keratitis have profound side effects. Small peptides derived from endogenous proteins potentially display both desired efficiency and safety. We identified an 11-amino-acid peptide, H-RN, from hepatocyte growth factor (HGF), an endogenous protein with anti-inflammatory properties. We evaluated the effects of H-RN in keratitis in vitro and in vivo. Methods In vitro, corneal fibroblasts were stimulated ...

  8. Descriptors for antimicrobial peptides

    DEFF Research Database (Denmark)

    Jenssen, Håvard

    2011-01-01

    Introduction: A frightening increase in the number of isolated multidrug resistant bacterial strains linked to the decline in novel antimicrobial drugs entering the market is a great cause for concern. Cationic antimicrobial peptides (AMPs) have lately been introduced as a potential new class...... of antimicrobial drugs, and computational methods utilizing molecular descriptors can significantly accelerate the development of new peptide drug candidates. Areas covered: This paper gives a broad overview of peptide and amino-acid scale descriptors available for AMP modeling and highlights which...

  9. Tumor penetrating peptides

    Directory of Open Access Journals (Sweden)

    Tambet eTeesalu

    2013-08-01

    Full Text Available Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC, contains the integrin-binding RGD motif. RGD mediates tumor homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular zip code of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is

  10. Tumor-Penetrating Peptides

    Science.gov (United States)

    Teesalu, Tambet; Sugahara, Kazuki N.; Ruoslahti, Erkki

    2013-01-01

    Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC), contains the integrin-binding RGD motif. RGD mediates tumor-homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR) motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular “zip code” of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies, and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is present in the

  11. Dependence of electrical activity and calcium influx-controlled prolactin release on adenylyl cyclase signaling pathway in pituitary lactotrophs

    Czech Academy of Sciences Publication Activity Database

    Gonzalez-Iglesias, A. E.; Jiang, Y.; Tomič, M.; Kretschmannová, K.; Andric, S. A.; Zemková, Hana

    2006-01-01

    Roč. 20, č. 9 (2006), s. 2231-2246 ISSN 0888-8809 R&D Projects: GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : adenylyl cyclase * intracellular calcium concentration * lactotrophs Subject RIV: FH - Neurology Impact factor: 4.967, year: 2006

  12. MATERNAL EXPOSURE TO ATRAZINE DURING LACTATION SUPPRESSES SUCKLING-INDUCED PROLACTIN RELEASE AND RESULTS IN PROSTATITIS IN THE ADULT OFFSPRING

    Science.gov (United States)

    The availability of prolactin (PRL) to the neonatal brain is known to affect the development of the tuberoinfundibular (TIDA) neurons and, as a consequence, lead to alterations in subsequent PRL regulation. Without early lactational exposure to PRL (derived from the dam's milk), ...

  13. Involvement of the endogenous opioid system in the psychopharmacological actions of ethanol: the role of acetaldehyde

    Directory of Open Access Journals (Sweden)

    Laura eFont

    2013-07-01

    Full Text Available Significant evidence implicates the endogenous opioid system (opioid peptides and receptors in the mechanisms underlying the psychopharmacological effects of ethanol. Ethanol modulates opioidergic signaling and function at different levels, including biosynthesis, release, and degradation of opioid peptides, as well as binding of endogenous ligands to opioid receptors. The role of β-endorphin and µ-opioid receptors (OR have been suggested to be of particular importance in mediating some of the behavioral effects of ethanol, including psychomotor stimulation and sensitization, consumption and conditioned place preference. Ethanol increases the release of β-endorphin from the hypothalamic arcuate nucleus (NArc, which can modulate activity of other neurotransmitter systems such as mesolimbic dopamine. The precise mechanism by which ethanol induces a release of β-endorphin, thereby inducing behavioral responses, remains to be elucidated. The present review summarizes accumulative data suggesting that the first metabolite of ethanol, the psychoactive compound acetaldehyde, could participate in such mechanism. Two lines of research involving acetaldehyde are reviewed: 1 implications of the formation of acetaldehyde in brain areas such as the NArc, with high expression of ethanol metabolizing enzymes and presence of cell bodies of endorphinic neurons and 2 the formation of condensation products between DA and acetaldehyde such as salsolinol, which exerts its actions via OR.

  14. SORPTION РATHOGENETIC THERAPY OF ENDOGENOUS INTOXICATION OF PEDIATRIC CHRONIC INFLAMMATORY BOWEL DISEASES

    Directory of Open Access Journals (Sweden)

    O.V. Fedorova

    2009-01-01

    Full Text Available Gut endotoxicosis caused by penetration of bacterial and metabolic toxins from chime on the background of increasing permeability of gut wall is of great importance in pathogenesis of chronic inflammatory bowel diseases (nonspecific ulcerative colitis — NUC and Crohn’s disease. It is accompanied by disturbance of regulating homeostasis system with the following disturbances of organs and systems of toxication. Developed endotoxicosis accordingly contributes to maintain and to progress of metabolic and immunological changes. To obtain the precise degree and phase of development of endotoxicosis we estimated quantitative and qualitative changes of metabolic status in accordance with content in erythrocytes, plasma and urine LMMWP (low and medium molecular weight peptides. Taking into concideration the peculiarities of children endotoxicosis with, we suggested patogenetical absorption therapy. Therefore, the therapeutic complex was added enterosorbent ensoral, which absorb eczo and endogenic toxins and, moreover, positive influence for composition of intestinal microflora. Prominent clinical effect was accompanied by positive dynamics of laboratory-instrumental parameters.Key words: endogenous intoxication, inflammatory bowel diseases, nonspecific ulcerative colitis, Crohn’s disease, low and medium molecular weight peptides, enterosorbents, children.

  15. Differing effects of exogenous or endogenous cathelicidin on macrophage toll-like receptor signaling.

    Science.gov (United States)

    Pinheiro da Silva, Fabiano; Gallo, Richard L; Nizet, Victor

    2009-01-01

    Cathelicidins are mammalian defense peptides with direct antimicrobial activity and the potential to exert other immunomodulatory effects during the innate immune response. One such function of human cathelicidin is direct binding and inhibition of bacterially derived lipopolysaccharide (LPS), a ligand of toll-like receptor 4 (TLR4) . Here, we show that physiological concentrations of exogenous murine cathelicidin blunt activation of p38 and ERK mitogen-activated protein kinases (MAPKs) and decrease tumor necrosis factor-alpha (TNFalpha) release in murine macrophages exposed to LPS, but also other TLR agonists such as lipoteichoic acid and flagellin. In this context, CRAMP is capable of aborting MyD88 synthesis and MyD88/IRAK (interleukin-1 receptor-associated kinase)-4 association in the stimulated macrophages. Exogenous CRAMP can reverse diminished MAPK activation associated with LPS tolerance. By analyzing macrophages from CRAMP(-/-) mice, we find their endogenous production of cathelicidin does not inhibit LPS MAPK and cytokine activation, rather CRAMP(-/-) cells show slightly diminished responses. CRAMP deficiency does not render mice more susceptible to lethal LPS challenge. These studies indicate the immunomodulatory effects of cathelicidin on macrophage TLR response may vary both on the exogenous vs endogenous origin of peptide and the prior activation state of the cell.

  16. Peptide aldehyde inhibitors of bacterial peptide deformylases.

    Science.gov (United States)

    Durand, D J; Gordon Green, B; O'Connell, J F; Grant, S K

    1999-07-15

    Bacterial peptide deformylases (PDF, EC 3.5.1.27) are metalloenzymes that cleave the N-formyl groups from N-blocked methionine polypeptides. Peptide aldehydes containing a methional or norleucinal inhibited recombinant peptide deformylase from gram-negative Escherichia coli and gram-positive Bacillus subtilis. The most potent inhibitor was calpeptin, N-CBZ-Leu-norleucinal, which was a competitive inhibitor of the zinc-containing metalloenzymes, E. coli and B. subtilis PDF with Ki values of 26.0 and 55.6 microM, respectively. Cobalt-substituted E. coli and B. subtilis deformylases were also inhibited by these aldehydes with Ki values for calpeptin of 9.5 and 12.4 microM, respectively. Distinct spectral changes were observed upon binding of calpeptin to the Co(II)-deformylases, consistent with the noncovalent binding of the inhibitor rather than the formation of a covalent complex. In contrast, the chelator 1,10-phenanthroline caused the time-dependent inhibition of B. subtilis Co(II)-PDF activity with the loss of the active site metal. The fact that calpeptin was nearly equipotent against deformylases from both gram-negative and gram-positive bacterial sources lends further support to the idea that a single deformylase inhibitor might have broad-spectrum antibacterial activity. Copyright 1999 Academic Press.

  17. Endogenous endophthalmitis after severe burn: A case report

    Directory of Open Access Journals (Sweden)

    Seyedeh Maryam Hosseini

    2017-01-01

    Conclusion: Burn patients treated with broad-spectrum antibiotics are at risk of candidemia and its complications, including endogenous endophthalmitis. Early diagnosis of endogenous endophthalmitis in high risk patients could prevent visual loss.

  18. Endogeneity of Money Supply: Evidence From Turkey

    Directory of Open Access Journals (Sweden)

    Oguzhan Cepni

    2017-02-01

    Full Text Available There is a long discussion among academics and central bankers about the theories of money supply. According to the exogenous view, central banks have the full control over money supply via policy actions including the adjustments of interest rates and reserve ratios, both of which alter commercial banks’ lending decisions. However, the theory of endogenous money supply emphasizes the role of demand for bank loans in money creation. More specifically, banks create money by meeting the demand of economic agents. In this study, we investigate which of the money supply theories holds in Turkish economy for the period 2006-2015 by employing cointegration and causality tests. Our findings show that the causality runs from bank loans to money supply both in the short and long terms, which supports the endogenous view in a sense that central bank and the banks fully meet the total demand for money in Turkish economy.

  19. Endogenous Magnetic Reconnection in Solar Coronal Loops

    Science.gov (United States)

    Asgari-Targhi, M.; Coppi, B.; Basu, B.; Fletcher, A.; Golub, L.

    2017-12-01

    We propose that a magneto-thermal reconnection process occurring in coronal loops be the source of the heating of the Solar Corona [1]. In the adopted model, magnetic reconnection is associated with electron temperature gradients, anisotropic electron temperature fluctuations and plasma current density gradients [2]. The input parameters for our theoretical model are derived from the most recent observations of the Solar Corona. In addition, the relevant (endogenous) collective modes can produce high energy particle populations. An endogenous reconnection process is defined as being driven by factors internal to the region where reconnection takes place. *Sponsored in part by the U.S. D.O.E. and the Kavli Foundation* [1] Beafume, P., Coppi, B. and Golub, L., (1992) Ap. J. 393, 396. [2] Coppi, B. and Basu, B. (2017) MIT-LNS Report HEP 17/01.

  20. Post Keynesian Endogeneity of Money Supply: Panel Evidence

    OpenAIRE

    Nayan, Sabri; Ahmad, Mahyudin; Kadir, Norsiah; Abdullah, Mat Saad

    2013-01-01

    Post Keynesian economics is actually macroeconomics in a world of uncertainty and endogenous money. Post Keynesians posit that money supply in a market oriented production economy is endogenous or endogenously determined (rather than exogenous as claimed by Monetarists). Money supply is said to be endogenous if it is determined within the economic system itself. The present paper investigates this theory using a panel dataset of 177 countries from year 1970-2011 utilising dynamic ...

  1. Endogenous Growth, Monetary Shocks and Nominal Rigidities

    OpenAIRE

    Annicchiarico, Barbara; Pelloni, Alessandra; Lorenza, Rossi

    2010-01-01

    We introduce endogenous growth in an otherwise standard NK model with staggered prices and wages. Some results follow: (i) monetary volatility negatively affects long-run growth; (ii) the relation between nominal volatility and growth depends on the persistence of the nominal shocks and on the Taylor rule considered; (iii) a Taylor rule with smoothing increases the negative effect of nominal volatility on mean growth.

  2. Probabilistic political economy and endogenous money

    OpenAIRE

    Cockshott, W.P.; Cottrell, A.

    2008-01-01

    Since the foundational work of Farjoun and Machover , important contributions to the field of\\ud probabilistic economy have been made. In this context one naturally has conservation of money as a postulate. However\\ud it is questionable whether a capitalist economy could ever work with entirely exogenous money, and it\\ud is interesting to see to what extent probabilistic arguments can illuminate the evolution of the type of\\ud endogenous money system that characterizes contemporary capitalism....

  3. Toxicokinetics of endogenous substances: a neglected issue.

    Science.gov (United States)

    Marzo, A

    1996-01-01

    Some specific problems related to the pharmacokinetics and toxicokinetics of endogenous substances are reviewed in this paper with specific reference to baseline and its variation, reversible dynamic pools, saturable tubular reabsorption, the stability of the parent compound, poorly absorbed substances, analytical procedures and statistical analysis. Compared to xenobiotics, endogenous substances require special care in planning pharmacokinetic and toxicokinetic investigations as they possess homeostatic equilibria. The presence of a baseline, its variation according to specific rhythms, age, sex or simple fluctuation, active absorption and passive diffusion, saturable enzyme processes, renal threshold, the distribution of the exogenous drug in relation to that already present in the body and a possible balance between endogenous synthesis and dietary intake are the main mechanisms which allow homeostatic equilibria to be preserved and restored when impaired. The presence of multicomponent dynamic pools requires not only the substance administered but also the entire pool to be assayed, to determine the components that can be originated from the drug administered. Various analytical approaches are discussed and some specific examples given. The above mechanisms frequently involve saturable processes which lead to non-linear kinetics. Clearance and, for substances excreted via urine not interacting with plasma proteins, renal clearance, are important parameters to check linearity/non-linearity, and give more accurate information than the half-life of the elimination phase, which with this kind of substance varies in non-linearity and baseline fluctuation or rhythms. Appropriate statistical approaches are suggested to analyse proof of absorption, length of treatment, gender difference and the linearity/proportionality assessment of absorption. Possible discrepancies in the dose-absorption relationship when dose-linearity and dose non-proportionality are

  4. Population, Pensions, and Endogenous Economic Growth

    OpenAIRE

    Heer, Burkhard; Irmen, Andreas

    2008-01-01

    We study the effect of a declining labor force on the incentives to engage in labor-saving technical change and ask how this effect is influenced by institutional characteristics of the pension scheme. When labor is scarcer it becomes more expensive and innovation investments that increase labor productivity are more profitable. We incorporate this channel in a new dynamic general equilibrium model with endogenous economic growth and heterogeneous overlapping generations. We calibrate the mod...

  5. Capital, endogenous separations, and the business cycle

    OpenAIRE

    van Roye, Björn; Wesselbaum, Dennis

    2009-01-01

    We implement capital in an endogenous separations New Keynesian matching model. In contrast to the vintage capital theory, we suggest a more general approach, such that workers have unrestricted access to a proportional share of the capital stock. We find that the introduction of capital generates an important channel for the transmission of aggregate productivity shocks, using capital-labor trade-off. The model generates higher volatilities of key variables and therefore enhances the perform...

  6. A General Theory of Endogenous Market Structures

    OpenAIRE

    Federico Etro; Paolo Bertoletti

    2014-01-01

    We provide a unified approach to imperfect (monopolistic, Bertrand and Cournot) competition equilibria with demand functions derived from symmetric preferences over a large but finite number of goods. The equilibrium markups depend on the Morishima Elasticity of Substitution/Complementarity between goods, and can be derived directly from the utility functions and ranked unambiguously. We characterize the endogenous market structures, their dependence on market size, income and firms’ producti...

  7. Endogenous Time Preference and Strategic Growth

    OpenAIRE

    Carmen CAMACHO; Cagri SAGLAM; Agah TURAN

    2010-01-01

    This paper presents a strategic growth model that analyzes the impact of Endogenous preferences on equilibrium dynamics by employing the tools provided by lattice theory and supermodular games. Supermodular game structure of the model let us provide monotonicity results on the greatest and the least equilibrium without making any assumptions regarding the curvature of the production function. We also sharpen these results by showing the differentiability of the value function and the uniquene...

  8. Endogeneity of Money Supply: Evidence From Turkey

    OpenAIRE

    Oguzhan Cepni; Ibrahim Ethem Guney

    2017-01-01

    There is a long discussion among academics and central bankers about the theories of money supply. According to the exogenous view, central banks have the full control over money supply via policy actions including the adjustments of interest rates and reserve ratios, both of which alter commercial banks’ lending decisions. However, the theory of endogenous money supply emphasizes the role of demand for bank loans in money creation. More specifically, banks create money by meeting the demand ...

  9. Neoclassical vs. Endogenous Growth Analysis: An Overview

    OpenAIRE

    Bennett T. McCallum

    1996-01-01

    This paper begins with an exposition of neoclassical growth theory, including several analytical results such as the distinction between golden-rule and optimal steady states. Next it emphasizes that the neoclassical approach fails to provide any explanation of steady-state growth in per capita values of output and consumption, and also cannot plausibly explain actual growth differences by reference to transitional episodes. Three types of endogenous growth models, which attempt to provide ex...

  10. Buyer Search Costs and Endogenous Product Design

    OpenAIRE

    Dmitri Kuksov

    2004-01-01

    Buyer search costs for price are changing in many markets. Through a model of buyer and seller behavior, I consider the effects of changing search costs on prices both when product differentiation is fixed and when it is endogenously determined in equilibrium. If firms cannot change product design, lower buyer search costs for price lead to increased price competition. However, if product design is a decision variable, lower search costs for price may also lead to higher product differentiati...

  11. THE INDIAN GROWTH MIRACLE AND ENDOGENOUS GROWTH

    OpenAIRE

    Jakob B. Madsen; Shishir Saxena; James B. Ang

    2008-01-01

    Using over half a century of R&D data for India, this paper examines the extent to which India's recent growth experience can be explained by R&D, international R&D spillovers, catch-up to the technology frontier and financial liberalization. Furthermore, the paper also tests whether any of the competing second-generation endogenous growth theories can explain India's growth experience. The findings provide support for Schumpeterian growth theory and indicate that the recent high growth rates...

  12. On the Endogenous Generation of Emotion

    OpenAIRE

    Engen, Haakon

    2017-01-01

    The thesis investigates the endogenous generation of emotion (EnGE). Two main questions were pursued: 1) How is the volitional generation of emotion neurally and behaviourally implemented? and 2) How can this ability be used for emotional self- regulation? This was investigated in two projects: In the first project, neural, psychophysiological, and behavioural indices of EnGE were investigated in a large, representative sample. The second project investigated the behavioural, functional and s...

  13. The endogeneity of money and the eurosystem

    OpenAIRE

    Steiger, Otto

    2004-01-01

    The endogenous theory of money, developed by Basil Moore, argues that the supply of central bank money in modern economies is not under the control of the central bank. According to this view, a central bank typically supplies cash reserves automatically on demand at its minimum lending rate, resulting in a clearly horizontal money supply function. While the paper agrees with Moore that the supply of central bank money cannot be determined exogenously by the central bank, it wonders whether t...

  14. Asset Bubbles, Endogenous Growth, and Financial Frictions

    OpenAIRE

    Hirano, Tomohiro; Yanagawa, Noriyuki

    2016-01-01

    This paper analyzes the effects of bubbles in an infinitely-lived agent model of endogenous growth with financial frictions and heterogeneous agents. We provide a complete characterization on the relationship between financial frictions and the existence of bubbles. Our model predicts that if the degree of pledgeability is sufficiently high or sufficiently low, bubbles can not exist. They can only arise at an intermediate degree. This suggests that improving the financial market condition mig...

  15. Public Procurement of Innovation as Endogenous

    DEFF Research Database (Denmark)

    Rolfstam, Max

    Public procurement used as an innovation policy instrument has attracted attention the last decade. It has been argued that public procurement can be used to stimulate innovation from the demand-side. This paper problematizes ‘demand’ understood as a problem defined by a public procurer given to ...... underlying mechanisms critical for success. Instead the paper views public procurement of innovation as an instrument of endogenous- exogenous knowledge conversion....

  16. Unfunded pensions and endogenous labor supply

    DEFF Research Database (Denmark)

    Andersen, Torben M.; Bhattacharya, Joydeep

    A classic result in dynamic public economics, dating back to Aaron (1966) and Samuelson (1975), states that there is no welfare rationale for PAYG pensions in a dynamically-efficient neoclassical economy with exogenous labor supply. This paper argues that this result, under the fairly-mild restri......-mild restriction that the old be no less risk-averse than the young, extends to a neoclassical economy with endogenous labor supply....

  17. Firm Heterogeneity, Credit Constraints, and Endogenous Growth

    OpenAIRE

    Torben Klarl; Alfred Maussner

    2010-01-01

    This paper is concerned with the role of firm heterogeneity under credit constraints for economic growth. We focus on firm size, innovativeness and credit constraints in a semi-endogenous growth model reflecting recent empirical findings on firm heterogeneity. It allows for an explicit solution for transitional growth and balanced growth path productivity as well as the growth maximizing firm heterogeneity. This enables us to draw inference about the impact of key policy parameters of the mod...

  18. Endogenous gene tagging with fluorescent proteins.

    Science.gov (United States)

    Fetter, John; Samsonov, Andrey; Zenser, Nathan; Zhang, Fan; Zhang, Hongyi; Malkov, Dmitry

    2015-01-01

    Human genome manipulation has become a powerful tool for understanding the mechanisms of numerous diseases including cancer. Inserting reporter sequences in the desired locations in the genome of a cell can allow monitoring of endogenous activities of disease related genes. Native gene expression and regulation is preserved in these knock-in cells in contrast to cell lines with target overexpression under an exogenous promoter as in the case of transient transfection or stable cell lines with random integration. The fusion proteins created using the modern genome editing tools are expressed at their physiological level and thus are more likely to retain the characteristic expression profile of the endogenous proteins in the cell. Unlike biochemical assays or immunostaining, using a tagged protein under endogenous regulation avoids fixation artifacts and allows detection of the target's activity in live cells. Multiple gene targets could be tagged in a single cell line allowing for the creation of effective cell-based assays for compound screening to discover novel drugs.

  19. Endogenous growth theory and regional development policy

    Directory of Open Access Journals (Sweden)

    Cvetanović Slobodan

    2015-01-01

    Full Text Available The numerous versions of endogenous explanations of economic growth emphasize the importance of technological change driving forces, as well as the existence of appropriate institutional arrangements. Endogenous growth theory contributes to a better understanding of various experiences with long-term growth of countries and regions. It changes the key assumptions of the Neoclassical growth theory and participates in the modern regional development physiology explanation. Based on these conclusions, the paper: a explicates the most important theoretical postulates of the theory, b explains the most important factors of economic growth in the regions in light of the Endogenous growth theory messages and c emphasizes the key determinants of regional competitiveness which in our view is conceptually between the phenomena of micro- and macro-competitiveness and represents their necessary and unique connection. First of all, micro-competitiveness is transformed into a regional competitiveness; then regional competitiveness is transformed into a macro-competitiveness. In turn, macro - influences the microeconomic competitiveness, and the circle is closed. After that, the process starts over again.

  20. Endogenous cueing attenuates object substitution masking.

    Science.gov (United States)

    Germeys, Filip; Pomianowska, I; De Graef, P; Zaenen, P; Verfaillie, K

    2010-07-01

    Object substitution masking (OSM) is a form of visual masking in which a briefly presented target surrounded by four small dots is masked by the continuing presence of the four dots after target offset. A major parameter in the prediction of OSM is the time required for attention to be directed to the target following its onset. Object substitution theory (Di Lollo et al. in J Exp Psychol Gen 129:481-507, 2000) predicts that the sooner attention can be focused at the target's location, the less masking will ensue. However, recently Luiga and Bachmann (Psychol Res 71:634-640, 2007) presented evidence that precueing of attention to the target location prior to target-plus-mask onset by means of a central (endogenous) arrow cue does not reduce OSM. When attention was cued exogenously, OSM was attenuated. Based on these results, Luiga and Bachmann argued that object substitution theory should be adapted by differentiating the ways of directing attention to the target location. The goal of the present study was to further examine the dissociation between the effects of endogenous and exogenous precueing on OSM. Contrary to Luiga and Bachmann, our results show that prior shifts of attention to the target location initiated by both exogenous and endogenous cues reduce OSM as predicted by object substitution theory and its computational model CMOS.

  1. Endogenous Retroviruses in the Genomics Era.

    Science.gov (United States)

    Johnson, Welkin E

    2015-11-01

    Endogenous retroviruses comprise millions of discrete genetic loci distributed within the genomes of extant vertebrates. These sequences, which are clearly related to exogenous retroviruses, represent retroviral infections of the deep past, and their abundance suggests that retroviruses were a near-constant presence throughout the evolutionary history of modern vertebrates. Endogenous retroviruses contribute in myriad ways to the evolution of host genomes, as mutagens and as sources of genetic novelty (both coding and regulatory) to be acted upon by the twin engines of random genetic drift and natural selection. Importantly, the richness and complexity of endogenous retrovirus data can be used to understand how viruses spread and adapt on evolutionary timescales by combining population genetics and evolutionary theory with a detailed understanding of retrovirus biology (gleaned from the study of extant retroviruses). In addition to revealing the impact of viruses on organismal evolution, such studies can help us better understand, by looking back in time, how life-history traits, as well as ecological and geological events, influence the movement of viruses within and between populations.

  2. Endogenous lung regeneration: potential and limitations.

    Science.gov (United States)

    Rock, Jason; Königshoff, Melanie

    2012-12-15

    The exploration of the endogenous regenerative potential of the diseased adult human lung represents an innovative and exciting task. In this pulmonary perspective, we discuss three major components essential for endogenous lung repair and regeneration: epithelial progenitor populations, developmental signaling pathways that regulate their reparative and regenerative potential, and the surrounding extracellular matrix in the human diseased lung. Over the past years, several distinct epithelial progenitor populations have been discovered within the lung, all of which most likely respond to different injuries by varying degrees. It has become evident that several progenitor populations are mutually involved in maintenance and repair, which is highly regulated by developmental pathways, such as Wnt or Notch signaling. Third, endogenous progenitor cells and developmental signaling pathways act in close spatiotemporal synergy with the extracellular matrix. These three components define and refine the highly dynamic microenvironment of the lung, which is altered in a disease-specific fashion in several chronic lung diseases. The search for the right mixture to induce efficient and controlled repair and regeneration of the diseased lung is ongoing and will open completely novel avenues for the treatment of patients with chronic lung disease.

  3. Fanconi anemia proteins and endogenous stresses

    International Nuclear Information System (INIS)

    Pang Qishen; Andreassen, Paul R.

    2009-01-01

    Each of the thirteen identified Fanconi anemia (FA) genes is required for resistance to DNA interstrand crosslinking agents, such as mitomycin C, cisplatin, and melphalan. While these agents are excellent tools for understanding the function of FA proteins in DNA repair, it is uncertain whether a defect in the removal of DNA interstrand crosslinks (ICLs) is the basis for the pathophysiology of FA. For example, DNA interstrand crosslinking agents induce other types of DNA damage, in addition to ICLs. Further, other DNA-damaging agents, such as ionizing or ultraviolet radiation, activate the FA pathway, leading to monoubiquitination of FANCD2 and FANCI. Also, FA patients display congenital abnormalities, hematologic deficiencies, and a predisposition to cancer in the absence of an environmental source of ICLs that is external to cells. Here we consider potential sources of endogenous DNA damage, or endogenous stresses, to which FA proteins may respond. These include ICLs formed by products of lipid peroxidation, and other forms of oxidative DNA damage. FA proteins may also potentially respond to telomere shortening or replication stress. Defining these endogenous sources of DNA damage or stresses is critical for understanding the pathogenesis of deficiencies for FA proteins. We propose that FA proteins are centrally involved in the response to replication stress, including replication stress arising from oxidative DNA damage.

  4. Endogenous viral elements in animal genomes.

    Directory of Open Access Journals (Sweden)

    Aris Katzourakis

    2010-11-01

    Full Text Available Integration into the nuclear genome of germ line cells can lead to vertical inheritance of retroviral genes as host alleles. For other viruses, germ line integration has only rarely been documented. Nonetheless, we identified endogenous viral elements (EVEs derived from ten non-retroviral families by systematic in silico screening of animal genomes, including the first endogenous representatives of double-stranded RNA, reverse-transcribing DNA, and segmented RNA viruses, and the first endogenous DNA viruses in mammalian genomes. Phylogenetic and genomic analysis of EVEs across multiple host species revealed novel information about the origin and evolution of diverse virus groups. Furthermore, several of the elements identified here encode intact open reading frames or are expressed as mRNA. For one element in the primate lineage, we provide statistically robust evidence for exaptation. Our findings establish that genetic material derived from all known viral genome types and replication strategies can enter the animal germ line, greatly broadening the scope of paleovirological studies and indicating a more significant evolutionary role for gene flow from virus to animal genomes than has previously been recognized.

  5. Fanconi anemia proteins and endogenous stresses

    Energy Technology Data Exchange (ETDEWEB)

    Pang Qishen [Division of Experimental Hematology and Cancer Biology, Cincinnati Children' s Research Foundation, Cincinnati, OH (United States); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH (United States); Andreassen, Paul R., E-mail: Paul.Andreassen@cchmc.org [Division of Experimental Hematology and Cancer Biology, Cincinnati Children' s Research Foundation, Cincinnati, OH (United States); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH (United States)

    2009-07-31

    Each of the thirteen identified Fanconi anemia (FA) genes is required for resistance to DNA interstrand crosslinking agents, such as mitomycin C, cisplatin, and melphalan. While these agents are excellent tools for understanding the function of FA proteins in DNA repair, it is uncertain whether a defect in the removal of DNA interstrand crosslinks (ICLs) is the basis for the pathophysiology of FA. For example, DNA interstrand crosslinking agents induce other types of DNA damage, in addition to ICLs. Further, other DNA-damaging agents, such as ionizing or ultraviolet radiation, activate the FA pathway, leading to monoubiquitination of FANCD2 and FANCI. Also, FA patients display congenital abnormalities, hematologic deficiencies, and a predisposition to cancer in the absence of an environmental source of ICLs that is external to cells. Here we consider potential sources of endogenous DNA damage, or endogenous stresses, to which FA proteins may respond. These include ICLs formed by products of lipid peroxidation, and other forms of oxidative DNA damage. FA proteins may also potentially respond to telomere shortening or replication stress. Defining these endogenous sources of DNA damage or stresses is critical for understanding the pathogenesis of deficiencies for FA proteins. We propose that FA proteins are centrally involved in the response to replication stress, including replication stress arising from oxidative DNA damage.

  6. Immature transformed rat islet beta-cells differentially express C-peptides derived from the genes coding for insulin I and II as well as a transfected human insulin gene

    DEFF Research Database (Denmark)

    Blume, N; Petersen, J S; Andersen, L C

    1992-01-01

    is induced in the transformed heterogeneous rat islet cell clone, NHI-6F, by transient in vivo passage. During this process a transfected human insulin gene is coactivated with the endogenous nonallelic rat insulin I and II genes. Newly established cultures from NHI-6F insulinomas having a high frequency...... of insulin-producing cells showed highly differential expression at the cellular level of the three proinsulin C-peptide immunoreactivities, as follows: C-peptide I greater than human C-peptide greater than C-peptide II. The fractions of cells expressing human C-peptide and C-peptide II decreased in time...... species of proinsulin-C-peptide immunoreactivity but still at high levels. However, rat C-peptide II and human C-peptide were often colocalized, even in later passages. In situ hybridization studies combined with the immunocytochemical data suggest that the differential expression occurs at the level...

  7. Sensory Neuropeptides and Endogenous Opioids Expression in Human Dental Pulp with Asymptomatic Inflammation: In Vivo Study

    Directory of Open Access Journals (Sweden)

    Daniel Chavarria-Bolaños

    2015-01-01

    Full Text Available Purpose. This study quantified the expression of substance P (SP, calcitonin gene-related peptide (CGRP, β-endorphins (β-End, and methionine-enkephalin (Met-Enk in human dental pulp following orthodontic intrusion. Methods. Eight patients were selected according to preestablished inclusion criteria. From each patient, two premolars (indicated for extraction due to orthodontic reasons were randomly assigned to two different groups: the asymptomatic inflammation group (EXPg, which would undergo controlled intrusive force for seven days, and the control group (CTRg, which was used to determine the basal levels of each substance. Once extracted, dental pulp tissue was prepared to determine the expression levels of both neuropeptides and endogenous opioids by radioimmunoassay (RIA. Results. All samples from the CTRg exhibited basal levels of both neuropeptides and endogenous opioids. By day seven, all patients were asymptomatic, even when all orthodontic-intrusive devices were still active. In the EXPg, the SP and CGRP exhibited statistically significant different levels. Although none of the endogenous opioids showed statistically significant differences, they all expressed increasing trends in the EXPg. Conclusions. SP and CGRP were identified in dental pulp after seven days of controlled orthodontic intrusion movement, even in the absence of pain.

  8. Endogenously generated arachidonate-derived ligands for TRPV1 induce cardiac protection in sepsis.

    Science.gov (United States)

    Chen, Jianmin; Hamers, Alexander J P; Finsterbusch, Michaela; Massimo, Gianmichele; Zafar, Maleeha; Corder, Roger; Colas, Romain A; Dalli, Jesmond; Thiemermann, Christoph; Ahluwalia, Amrita

    2018-02-20

    The severity of cardiac dysfunction predicts mortality in sepsis. Activation of transient receptor potential vanilloid receptor type (TRPV)-1, a predominantly neuronal nonselective cation channel, has been shown to improve outcome in sepsis and endotoxemia. However, the role of TRPV1 and the identity of its endogenous ligands in the cardiac dysfunction caused by sepsis and endotoxemia are unknown. Using TRPV1 -/- and TRPV1 +/+ mice, we showed that endogenous activation of cardiac TRPV1 during sepsis is key to limiting the ensuing cardiac dysfunction. Use of liquid chromatography-tandem mass spectrometry lipid analysis and selective inhibitors of arachidonic metabolism suggest that the arachidonate-derived TRPV1 activator, 20-hydroxyeicosateraenoic acid (20-HETE), underlies a substantial component of TRPV1-mediated cardioprotection in sepsis. Moreover, using selective antagonists for neuropeptide receptors, we show that this effect of TRPV1 relates to the activity of neuronally released cardiac calcitonin gene-related peptide (CGRP) and that, accordingly, administration of CGRP can rescue cardiac dysfunction in severe endotoxemia. In sum activation of TRPV1 by 20-HETE leads to the release of CGRP, which protects the heart against the cardiac dysfunction in endotoxemia and identifies both TRPV1 and CGRP receptors as potential therapeutic targets in endotoxemia.-Chen, J., Hamers, A. J. P., Finsterbusch, M., Massimo, G., Zafar, M., Corder, R., Colas, R. A., Dalli, J., Thiemermann, C., Ahluwalia, A. Endogenously generated arachidonate-derived ligands for TRPV1 induce cardiac protection in sepsis.

  9. Endogenous opioids regulate alveolar bone loss in a periodontal disease model.

    Science.gov (United States)

    Queiroz-Junior, Celso M; Maltos, Kátia L M; Pacheco, Daniela F; Silva, Tarcília Aparecida; Albergaria, Juliano D S; Pacheco, Cinthia M F

    2013-10-06

    The anti-inflammatory effects of exogenous opioid compounds have been demonstrated in several conditions. Nevertheless, the function of endogenous opioid peptides released by the host during inflammatory processes deserves further characterization. The aim of this study was to verify whether endogenous opioids are involved in the progression of the inflammatory alveolar bone loss induced by ligature in rats. The experimental model of periodontal disease (PD) induced by ligature in rats was used throughout the study. A silk ligature was placed around the 2nd upper molar of male Holtzman rats, for 7 days. Rats received different doses of either the non-selective opioid antagonist naloxone or vehicle, locally into the afflicted gingival tissue, from the 3rd to the 5th day after ligature placement. In the 7th experimental day, rats were euthanized and their maxillae were collected for evaluation of alveolar bone and fiber attachment loss, presence of neutrophils (myeloperoxidase assay), osteoclast amount, and levels of cytokines IL-6, TNF-α, IL-8 and IL-10 in periodontal tissues. Naloxone increased alveolar bone loss significantly, in a dose-dependent manner, in relation to vehicle-treated rats. In contrast, the opioid antagonist did not affect the loss of fiber attachment. The treatment with naloxone also induced a significant increase in myeloperoxidase levels, osteoclast number and cytokines in periodontal tissues of rats with ligature-induced PD. Endogenous opioids protect the host from the progression of inflammatory alveolar bone loss that occurs in chronic periodontitis. © 2013.

  10. CD1a presentation of endogenous antigens by group 2 innate lymphoid cells.

    Science.gov (United States)

    Hardman, Clare S; Chen, Yi-Ling; Salimi, Maryam; Jarrett, Rachael; Johnson, David; Järvinen, Valtteri J; Owens, Raymond J; Repapi, Emmanouela; Cousins, David J; Barlow, Jillian L; McKenzie, Andrew N J; Ogg, Graham

    2017-12-22

    Group 2 innate lymphoid cells (ILC2) are effectors of barrier immunity, with roles in infection, wound healing, and allergy. A proportion of ILC2 express MHCII (major histocompatibility complex II) and are capable of presenting peptide antigens to T cells and amplifying the subsequent adaptive immune response. Recent studies have highlighted the importance of CD1a-reactive T cells in allergy and infection, activated by the presentation of endogenous neolipid antigens and bacterial components. Using a human skin challenge model, we unexpectedly show that human skin-derived ILC2 can express CD1a and are capable of presenting endogenous antigens to T cells. CD1a expression is up-regulated by TSLP (thymic stromal lymphopoietin) at levels observed in the skin of patients with atopic dermatitis, and the response is dependent on PLA2G4A. Furthermore, this pathway is used to sense Staphylococcus aureus by promoting Toll-like receptor-dependent CD1a-reactive T cell responses to endogenous ligands. These findings define a previously unrecognized role for ILC2 in lipid surveillance and identify shared pathways of CD1a- and PLA2G4A-dependent ILC2 inflammation amenable to therapeutic intervention. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  11. Endogenous laminin is required for human airway smooth muscle cell maturation

    Directory of Open Access Journals (Sweden)

    Tran Thai

    2006-09-01

    Full Text Available Abstract Background Airway smooth muscle (ASM contraction underlies acute bronchospasm in asthma. ASM cells can switch between a synthetic-proliferative phenotype and a contractile phenotype. While the effects of extracellular matrix (ECM components on modulation of ASM cells to a synthetic phenotype have been reported, the role of ECM components on maturation of ASM cells to a contractile phenotype in adult lung is unclear. As both changes in ECM components and accumulation of contractile ASM are features of airway wall remodelling in asthma, we examined the role of the ECM protein, laminin, in the maturation of contractile phenotype in human ASM cells. Methods Human ASM cells were made senescence-resistant by stable expression of human telomerase reverse transcriptase. Maturation to a contractile phenotype was induced by 7-day serum deprivation, as assessed by immunoblotting for desmin and calponin. The role of laminin on ASM maturation was investigated by comparing the effects of exogenous laminin coated on culture plates, and of soluble laminin peptide competitors. Endogenous expression of laminin chains during ASM maturation was also measured. Results Myocyte binding to endogenously expressed laminin was required for ASM phenotype maturation, as laminin competing peptides (YIGSR or GRGDSP significantly reduced desmin and calponin protein accumulation that otherwise occurs with prolonged serum deprivation. Coating of plastic cell culture dishes with different purified laminin preparations was not sufficient to further promote accumulation of desmin or calponin during 7-day serum deprivation. Expression of α2, β1 and γ1 laminin chains by ASM cells was specifically up-regulated during myocyte maturation, suggesting a key role for laminin-2 in the development of the contractile phenotype. Conclusion While earlier reports suggest exogenously applied laminin slows the spontaneous modulation of ASM to a synthetic phenotype, we show for the

  12. Granin-derived peptides.

    Science.gov (United States)

    Troger, Josef; Theurl, Markus; Kirchmair, Rudolf; Pasqua, Teresa; Tota, Bruno; Angelone, Tommaso; Cerra, Maria C; Nowosielski, Yvonne; Mätzler, Raphaela; Troger, Jasmin; Gayen, Jaur R; Trudeau, Vance; Corti, Angelo; Helle, Karen B

    2017-07-01

    The granin family comprises altogether 7 different proteins originating from the diffuse neuroendocrine system and elements of the central and peripheral nervous systems. The family is dominated by three uniquely acidic members, namely chromogranin A (CgA), chromogranin B (CgB) and secretogranin II (SgII). Since the late 1980s it has become evident that these proteins are proteolytically processed, intragranularly and/or extracellularly into a range of biologically active peptides; a number of them with regulatory properties of physiological and/or pathophysiological significance. The aim of this comprehensive overview is to provide an up-to-date insight into the distribution and properties of the well established granin-derived peptides and their putative roles in homeostatic regulations. Hence, focus is directed to peptides derived from the three main granins, e.g. to the chromogranin A derived vasostatins, betagranins, pancreastatin and catestatins, the chromogranin B-derived secretolytin and the secretogranin II-derived secretoneurin (SN). In addition, the distribution and properties of the chromogranin A-derived peptides prochromacin, chromofungin, WE14, parastatin, GE-25 and serpinins, the CgB-peptide PE-11 and the SgII-peptides EM66 and manserin will also be commented on. Finally, the opposing effects of the CgA-derived vasostatin-I and catestatin and the SgII-derived peptide SN on the integrity of the vasculature, myocardial contractility, angiogenesis in wound healing, inflammatory conditions and tumors will be discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Peptide Optical waveguides.

    Science.gov (United States)

    Handelman, Amir; Apter, Boris; Shostak, Tamar; Rosenman, Gil

    2017-02-01

    Small-scale optical devices, designed and fabricated onto one dielectric substrate, create integrated optical chip like their microelectronic analogues. These photonic circuits, based on diverse physical phenomena such as light-matter interaction, propagation of electromagnetic waves in a thin dielectric material, nonlinear and electro-optical effects, allow transmission, distribution, modulation, and processing of optical signals in optical communication systems, chemical and biological sensors, and more. The key component of these optical circuits providing both optical processing and photonic interconnections is light waveguides. Optical confinement and transmitting of the optical waves inside the waveguide material are possible due to the higher refractive index of the waveguides in comparison with their surroundings. In this work, we propose a novel field of bionanophotonics based on a new concept of optical waveguiding in synthetic elongated peptide nanostructures composed of ordered peptide dipole biomolecules. New technology of controllable deposition of peptide optical waveguiding structures by nanofountain pen technique is developed. Experimental studies of refractive index, optical transparency, and linear and nonlinear waveguiding in out-of-plane and in-plane diphenylalanine peptide nanotubes have been conducted. Optical waveguiding phenomena in peptide structures are simulated by the finite difference time domain method. The advantages of this new class of bio-optical waveguides are high refractive index contrast, wide spectral range of optical transparency, large optical nonlinearity, and electro-optical effect, making them promising for new applications in integrated multifunctional photonic circuits. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

  14. Endogenic Activity of the Earth and Moon

    Science.gov (United States)

    Marakushev, A. A.

    1998-01-01

    The endogenic activity of the Earth and Moon is created by the H fluid flows that ascends from their liquid cores and generates magnetic fields. In these flows, the generation of water together with hydrocarbons (3H2+CO = CH4+H2O), carbon (H2+CO=C+H2O), carbon dioxide (H2+3CO=C+CO2+H2O) and nitrogen (2H2+2NO=N2+2H2O) occurs. Water in fluids strongly lowers the melting temperature of rocks and thereby initiates magmatic activity and, making it to the surface, aids the generation of Earth's hydrosphere and aqueous ice covers of satellites. The endogenic activity of a planet or satellite stops after its complete consolidation; this occurs simultaneously with the disappearing of the magnetic field. Endogenic activity of the Earth continued for about 4.6 m.y. because of the existence of a liquid core rich with H. The other planets of the Earth's group lost their endogenic activity as well as magnetic fields due to complete consolidation. The Moon is the oldest known of the solar system bodies. Volcanic activity occurred on the Moon at 4.6-3.2 GA when it had a strong magnetic field, which is thought to be responsible for residual magnetization inherent in the samples. By analogy to the Moon, whose activity has been suppl.ied by its fluid reservoir for about 1.5 m .y., the current volcanic activity on Jupiter's satellite Io, (analogous to the Moon) suggest that Jupiter's satellite system is relatively young. This is confirmed by discoveries of the magnetic fields of Io, Europa, and Ganymede. However, Callisto is completely consolidated and has lots its magnetic field. The endogenic activity resulted in explosive volcanism on Io, and in the formation of aqueous ice covers on Europa and Ganymede. The ice cover of Europa si still forming, judging from the lack of meteoritic craters on its surface.

  15. Urodilatin. A renal natriuretic peptide

    International Nuclear Information System (INIS)

    Carstens, Jan

    1998-01-01

    Development and validation of a radioimmunoassay for endogenous URO in urine and synthetic URO in plasma is described. The first obstacle to overcome was to produce an antibody specific for URO. A polyclonal URO antibody with a cross-reactivity with the structural highly homologous atrial natriuretic peptide (ANP) was developed by immunization of rabbits with the whole URO(95-126). Purification of the polyclonal URO antiserum with CNBr-activated Sepharose affinity chromatography was a simple way of producing a URO-specific antibody without cross-reactivity with ANP analogues. A reliable 125 I-labelled URO tracer was made with the Iodo-Gen method. Prior to the assay, the urine samples were prepared by ethanol with a recovery of unlabelled URO between 80 - 100% and the plasma samples were Sep-Pak C 18 extracted with a recovery of about 50%. The radioimmunoassay is performed in 3 days, using polyethylene glycol for separation. The sensitivity of the assay was improved by sample preparation and concentration, reducing the amount of tracer and late addition, reducing the amount of antibody and increasing the incubation time and lowering the temperature of incubation. The infusion rate of 20 ng URO kg -1 min -1 was most potential and well tolerated in healthy subjects. The short-term natriuretic and diuretic effects were closely associated with a significant diminished sodium reabsorption in the distal nephron. Further studies are needed to exploit the therapeutical potential of URO, for example in patients with sodium-water retaining disorders. The therapeutical dose range will probably be narrow due to the blood pressure lowering effect of URO with infusion rates higher than 20-30 ng kg -1 min -1 . (EHS)

  16. Diversity-oriented peptide stapling

    DEFF Research Database (Denmark)

    Tran, Thu Phuong; Larsen, Christian Ørnbøl; Røndbjerg, Tobias

    2017-01-01

    The introduction of macrocyclic constraints in peptides (peptide stapling) is an important tool within peptide medicinal chemistry for stabilising and pre-organising peptides in a desired conformation. In recent years, the copper-catalysed azide-alkyne cycloaddition (CuAAC) has emerged as a power......The introduction of macrocyclic constraints in peptides (peptide stapling) is an important tool within peptide medicinal chemistry for stabilising and pre-organising peptides in a desired conformation. In recent years, the copper-catalysed azide-alkyne cycloaddition (CuAAC) has emerged...... incorporating two azide-modified amino acids with 1,3,5-triethynylbenzene efficiently provides (i, i+7)- and (i, i+9)-stapled peptides with a single free alkyne positioned on the staple, that can be further conjugated or dimerised. A unique feature of the present method is that it provides easy access...

  17. Peptide Integrated Optics.

    Science.gov (United States)

    Handelman, Amir; Lapshina, Nadezda; Apter, Boris; Rosenman, Gil

    2018-02-01

    Bio-nanophotonics is a wide field in which advanced optical materials, biomedicine, fundamental optics, and nanotechnology are combined and result in the development of biomedical optical chips. Silk fibers or synthetic bioabsorbable polymers are the main light-guiding components. In this work, an advanced concept of integrated bio-optics is proposed, which is based on bioinspired peptide optical materials exhibiting wide optical transparency, nonlinear and electrooptical properties, and effective passive and active waveguiding. Developed new technology combining bottom-up controlled deposition of peptide planar wafers of a large area and top-down focus ion beam lithography provides direct fabrication of peptide optical integrated circuits. Finding a deep modification of peptide optical properties by reconformation of biological secondary structure from native phase to β-sheet architecture is followed by the appearance of visible fluorescence and unexpected transition from a native passive optical waveguiding to an active one. Original biocompatibility, switchable regimes of waveguiding, and multifunctional nonlinear optical properties make these new peptide planar optical materials attractive for application in emerging technology of lab-on-biochips, combining biomedical photonic and electronic circuits toward medical diagnosis, light-activated therapy, and health monitoring. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Uncovering the Peptide-Binding Specificities of HLA-C: A General Strategy To Determine the Specificity of Any MHC Class I Molecule

    DEFF Research Database (Denmark)

    Rasmussen, Michael; Harndahl, Mikkel; Stryhn, Anette

    2014-01-01

    MHC class I molecules (HLA-I in humans) present peptides derived from endogenous proteins to CTLs. Whereas the peptide-binding specificities of HLA-A and -B molecules have been studied extensively, little is known about HLA-C specificities. Combining a positional scanning combinatorial peptide...... library approach with a peptide-HLA-I dissociation assay, in this study we present a general strategy to determine the peptide-binding specificity of any MHC class I molecule. We applied this novel strategy to 17 of the most common HLA-C molecules, and for 16 of these we successfully generated matrices...... representing their peptide-binding motifs. The motifs prominently shared a conserved C-terminal primary anchor with hydrophobic amino acid residues, as well as one or more diverse primary and auxiliary anchors at P1, P2, P3, and/or P7. Matrices were used to generate a large panel of HLA-C-specific peptide...

  19. Endogenous Peptide Apelin and Pathological Cardiac Remodeling in Hypertensive Patients with Diabetes Mellitus Type 2

    Directory of Open Access Journals (Sweden)

    S.M. Koval

    2015-08-01

    Full Text Available The study involved 63 patients with essential hypertension and diabetes mellitus type 2. The control group consisted of 16 apparently healthy individuals. Complex of examination included conventional clinical-laboratory and instrumental methods, ultrasound of the heart with Doppler sonography, determining apelin blood concentration by ELISA. Patients with essential hypertension and diabetes mellitus type 2 compared with the control group had a probable reduction in apelin level associated with the development of pathological cardiac remodeling, increasing the size of the left atrium and diastolic dysfunction of the heart.

  20. Peroxidase catalyzed conjugation of peptides, proteins and polysaccharides via endogenous and exogenous phenols.

    NARCIS (Netherlands)

    Oudgenoeg, G.

    2004-01-01

    The research was directed towards peroxidase mediated cross-linking of proteins and polysaccharides. Two approaches were explored, cross-linking by use of ferulic acid (FA)oand cross-linking by use

  1. Synthetic antibiofilm peptides.

    Science.gov (United States)

    de la Fuente-Núñez, César; Cardoso, Marlon Henrique; de Souza Cândido, Elizabete; Franco, Octavio Luiz; Hancock, Robert E W

    2016-05-01

    Bacteria predominantly exist as multicellular aggregates known as biofilms that are associated with at least two thirds of all infections and exhibit increased adaptive resistance to conventional antibiotic therapies. Therefore, biofilms are major contributors to the global health problem of antibiotic resistance, and novel approaches to counter them are urgently needed. Small molecules of the innate immune system called host defense peptides (HDPs) have emerged as promising templates for the design of potent, broad-spectrum antibiofilm agents. Here, we review recent developments in the new field of synthetic antibiofilm peptides, including mechanistic insights, synergistic interactions with available antibiotics, and their potential as novel antimicrobials against persistent infections caused by biofilms. This article is part of a Special Issue entitled: Antimicrobial peptides edited by Karl Lohner and Kai Hilpert. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. A fossil protein chimera; difficulties in discriminating dinosaur peptide sequences from modern cross-contamination.

    Science.gov (United States)

    Buckley, Michael; Warwood, Stacey; van Dongen, Bart; Kitchener, Andrew C; Manning, Phillip L

    2017-05-31

    A decade ago, reports that organic-rich soft tissue survived from dinosaur fossils were apparently supported by proteomics-derived sequence information of exceptionally well-preserved bone. This initial claim to the sequencing of endogenous collagen peptides from an approximately 68 Myr Tyrannosaurus rex fossil was highly controversial, largely on the grounds of potential contamination from either bacterial biofilms or from laboratory practice. In a subsequent study, collagen peptide sequences from an approximately 78 Myr Brachylophosaurus canadensis fossil were reported that have remained largely unchallenged. However, the endogeneity of these sequences relies heavily on a single peptide sequence, apparently unique to both dinosaurs. Given the potential for cross-contamination from modern bone analysed by the same team, here we extract collagen from bone samples of three individuals of ostrich, Struthio camelus The resulting LC-MS/MS data were found to match all of the proposed sequences for both the original Tyrannosaurus and Brachylophosaurus studies. Regardless of the true nature of the dinosaur peptides, our finding highlights the difficulty of differentiating such sequences with confidence. Our results not only imply that cross-contamination cannot be ruled out, but that appropriate measures to test for endogeneity should be further evaluated. © 2017 The Authors.

  3. Nicotine and endogenous opioids: neurochemical and pharmacological evidence.

    Science.gov (United States)

    Hadjiconstantinou, Maria; Neff, Norton H

    2011-06-01

    Although the mesolimbic dopamine hypothesis is the most influential theory of nicotine reward and reinforcement, there has been a consensus that other neurotransmitter systems contribute to the addictive properties of nicotine as well. In this regard, the brain opioidergic system is of interest. Striatum is rich in opioid peptides and opioid receptors, and striatal opioidergic neurons are engaged in a bidirectional communication with midbrain dopaminergic neurons, closely regulating each other's activity. Enkephalins and dynorphins exert opposing actions on dopaminergic neurons, increasing and decreasing dopamine release respectively, and are components of circuits promoting positive or negative motivational and affective states. Moreover, dopamine controls the synthesis of striatal enkephalins and dynorphins. Evidence suggests that opioidergic function is altered after nicotine and endogenous opioids are involved in nicotine's behavioral effects. 1) The synthesis and release of β-endorphin, met-enkephalin and dynorphin in brain, especially nucleus accumbens (NAc), are altered after acute or chronic nicotine treatment and during nicotine withdrawal. 2) Although opioid receptor binding and mRNA do not appear to change in the striatum during nicotine withdrawal, the activity of κ-opioid (KOPr) and δ-opioid (DOPr) receptors is attenuated in NAc. 3) The nicotine withdrawal syndrome reminisces that of opiates, and naloxone precipitates some of its somatic, motivational, and affective signs. 4) Genetic and pharmacological studies indicate that μ-opioid (MOPr) receptors are mainly involved in nicotine reward, while DOPrs contribute to the emotional and KOPrs to the aversive responses of nicotine. 5) Finally, MOPrs and enkephalin, but not β-endorphin or dynorphin, are necessary for the physical manifestations of nicotine withdrawal. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'. Copyright © 2010 Elsevier

  4. Cell-Penetrating Ability of Peptide Hormones: Key Role of Glycosaminoglycans Clustering

    Directory of Open Access Journals (Sweden)

    Armelle Tchoumi Neree

    2015-11-01

    Full Text Available Over the last two decades, the potential usage of cell-penetrating peptides (CPPs for the intracellular delivery of various molecules has prompted the identification of novel peptidic identities. However, cytotoxic effects and unpredicted immunological responses have often limited the use of various CPP sequences in the clinic. To overcome these issues, the usage of endogenous peptides appears as an appropriate alternative approach. The hormone pituitary adenylate-cyclase-activating polypeptide (PACAP38 has been recently identified as a novel and very efficient CPP. This 38-residue polycationic peptide is a member of the secretin/glucagon/growth hormone-releasing hormone (GHRH superfamily, with which PACAP38 shares high structural and conformational homologies. In this study, we evaluated the cell-penetrating ability of cationic peptide hormones in the context of the expression of cell surface glycosaminoglycans (GAGs. Our results indicated that among all peptides evaluated, PACAP38 was unique for its potent efficiency of cellular uptake. Interestingly, the abilities of the peptides to reach the intracellular space did not correlate with their binding affinities to sulfated GAGs, but rather to their capacity to clustered heparin in vitro. This study demonstrates that the uptake efficiency of a given cationic CPP does not necessarily correlate with its affinity to sulfated GAGs and that its ability to cluster GAGs should be considered for the identification of novel peptidic sequences with potent cellular penetrating properties.

  5. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...

  6. Peptide Vaccine Against Paracoccidioidomycosis.

    Science.gov (United States)

    Taborda, Carlos P; Travassos, Luiz R

    2017-01-01

    The chapter reviews methods utilized for the isolation and characterization of a promising immunogen candidate, aiming at a human vaccine against paracoccidioidomycosis. Peptide P10 carries a T-CD4+ epitope and was identified as an internal sequence of the major diagnostic antigen known as gp43 glycoprotein. It successfully treated massive intratracheal infections by virulent Paracoccidioides brasiliensis in combination with chemotherapy.An introduction about the systemic mycosis was found essential to understand the various options that were considered to design prophylactic and therapeutic vaccine protocols using peptide P10.

  7. Brazilian endogenous trade policy: 1991-1998

    Directory of Open Access Journals (Sweden)

    Geraldo Edmundo Silva Junior

    2011-12-01

    Full Text Available This paper presents an empirical contribution to the identification of Grossman-Helpman's "Protection for Sale" parameters model for Brazilian trade policy, based on robust estimations techniques, which means the use of instrumental variables in a 2SLS for Generalized Method of Moments and Limited Information Maximum Likelihood methods for weak instruments with corrections of size tests, in order to correct endogenous bias. The results suggest that the political economy of Brazil's trade policy is an outlier in international comparisons, as the identification of structural parameters for Protection for Sale model shows a low part of population represented by an interest group and low weight of the welfare function.

  8. ENDOGENOUS INTOxICATION AND SEPSIS

    Directory of Open Access Journals (Sweden)

    I. V. Aleksandrova

    2014-01-01

    Full Text Available RELEVANCE. Sepsis is always accompanied by endogenous intoxication (EI. It is very important to study EI in the patients with severe sepsis and septic shock.MATERIAL AND METHODS. Twenty seven patients with severe sepsis and thirteen with septic shock in the postoperative period were enrolled into the study. EI was assessed using the measurements of total and effective albumin concentrations (EAC, middle-molecular-weight proteins (MMWP and EI index (Kei=MMWP/ EACx1000.RESULTS. The use of the EI index in patients with severe sepsis and septic shock leads to improvement of diagnostic and therapy monitoring.

  9. Endogenous and exogenous factors in national development ...

    African Journals Online (AJOL)

    Endogenous and exogenous factors in national development: inferences from the metaphor of witchcraft (Àjé) in Olátúbòsún. Oládàpò's poetry. This work engages political commentary in the work of Olátúbòsún Oládàpò, a Yorùbá poet. Its focus is on the way that political ideas and values that are rooted in Nigerian culture ...

  10. Psychological rehabilitation of patients with endogenous disease

    Directory of Open Access Journals (Sweden)

    Tamara Kryvonis

    2013-07-01

    Full Text Available The rationale for early psychotherapeutic intervention in combination with psychopharmatherapy in patients with endogenous disorders is provided. The mechanisms of psychological defenses to deal with traumatic experience, used by personalities functioning on a psychotic level, are also described here. Characteristic behavior patterns of extended family members in terms of emotional codependence are provided. Individual pathopsychology is considered as a symptom of abnormal functioning of the family. Emphasis is placed on the importance of inclusion of family members in psychotherapeutic interaction in order to correct interpersonal relations.

  11. Comparative analysis of human milk and infant formula derived peptides following in vitro digestion.

    Science.gov (United States)

    Su, M-Y; Broadhurst, M; Liu, C-P; Gathercole, J; Cheng, W-L; Qi, X-Y; Clerens, S; Dyer, J M; Day, L; Haigh, B

    2017-04-15

    It has long been recognised that there are differences between human milk and infant formulas which lead to differences in health and nutrition for the neonate. In this study we examine and compare the peptide profile of human milk and an exemplar infant formula. The study identifies both similarities and differences in the endogenous and postdigestion peptide profiles of human milk and infant formula. This includes differences in the protein source of these peptides but also with the region within the protein producing the dominant proteins. Clustering of similar peptides around regions of high sequence identity and known bioactivity was also observed. Together the data may explain some of the functional differences between human milk and infant formula, while identifying some aspects of conserved function between bovine and human milks which contribute to the effectiveness of modern infant formula as a substitute for human milk. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. A distinct translation initiation mechanism generates cryptic peptides for immune surveillance.

    Directory of Open Access Journals (Sweden)

    Shelley R Starck

    Full Text Available MHC class I molecules present a comprehensive mixture of peptides on the cell surface for immune surveillance. The peptides represent the intracellular protein milieu produced by translation of endogenous mRNAs. Unexpectedly, the peptides are encoded not only in conventional AUG initiated translational reading frames but also in alternative cryptic reading frames. Here, we analyzed how ribosomes recognize and use cryptic initiation codons in the mRNA. We find that translation initiation complexes assemble at non-AUG codons but differ from canonical AUG initiation in response to specific inhibitors acting within the peptidyl transferase and decoding centers of the ribosome. Thus, cryptic translation at non-AUG start codons can utilize a distinct initiation mechanism which could be differentially regulated to provide peptides for immune surveillance.

  13. Forearm vascular response to nitric oxide and calcitonin gene-related peptide: comparison between migraine patients and control subjects.

    NARCIS (Netherlands)

    Hoon, J.N. de; Smits, P.; Troost, J.; Struijker-Boudier, H.A.; Bortel, L.M. van

    2006-01-01

    The forearm vascular response to nitric oxide (NO) and calcitonin gene-related peptide (CGRP) was investigated in 10 migraine patients and 10 matched control subjects. Changes in forearm blood flow (FBF) during intrabrachial infusion of: (i) serotonin (releasing endogenous NO), (ii) sodium

  14. Hypothalamic CART is a new anorectic peptide regulated by leptin.

    Science.gov (United States)

    Kristensen, P; Judge, M E; Thim, L; Ribel, U; Christjansen, K N; Wulff, B S; Clausen, J T; Jensen, P B; Madsen, O D; Vrang, N; Larsen, P J; Hastrup, S

    1998-05-07

    The mammalian hypothalamus strongly influences ingestive behaviour through several different signalling molecules and receptor systems. Here we show that CART (cocaine- and amphetamine-regulated transcript), a brain-located peptide, is a satiety factor and is closely associated with the actions of two important regulators of food intake, leptin and neuropeptide Y. Food-deprived animals show a pronounced decrease in expression of CART messenger RNA in the arcuate nucleus. In animal models of obesity with disrupted leptin signalling, CART mRNA is almost absent from the arcuate nucleus. Peripheral administration of leptin to obese mice stimulates CART mRNA expression. When injected intracerebroventricularly into rats, recombinant CART peptide inhibits both normal and starvation-induced feeding, and completely blocks the feeding response induced by neuropeptide Y. An antiserum against CART increases feeding in normal rats, indicating that CART may be an endogenous inhibitor of food intake in normal animals.

  15. NCAM Mimetic Peptides: An Update

    DEFF Research Database (Denmark)

    Berezin, Vladimir; Bock, Elisabeth

    2008-01-01

    of combinatorial peptide libraries. The C3 and NBP10 peptides target the first Ig module whereas the ENFIN2 and ENFIN11 peptides target fibronectin type III (FN3) modules of NCAM. A number of NCAM mimetics can induce neurite outgrowth and exhibit neuroprotective and synaptic plasticity modulating properties...

  16. Mindfulness Meditation Modulates Pain Through Endogenous Opioids.

    Science.gov (United States)

    Sharon, Haggai; Maron-Katz, Adi; Ben Simon, Eti; Flusser, Yuval; Hendler, Talma; Tarrasch, Ricardo; Brill, Silviu

    2016-07-01

    Recent evidence supports the beneficial effects of mindfulness meditation on pain. However, the neural mechanisms underlying this effect remain poorly understood. We used an opioid blocker to examine whether mindfulness meditation-induced analgesia involves endogenous opioids. Fifteen healthy experienced mindfulness meditation practitioners participated in a double-blind, randomized, placebo-controlled, crossover study. Participants rated the pain and unpleasantness of a cold stimulus prior to and after a mindfulness meditation session. Participants were then randomized to receive either intravenous naloxone or saline, after which they meditated again, and rated the same stimulus. A (3) × (2) repeated-measurements analysis of variance revealed a significant time effect for pain and unpleasantness scores (both P mindfulness meditation and after placebo, but not after naloxone. Furthermore, there was a positive correlation between the pain scores following naloxone vs placebo and participants' mindfulness meditation experience. These findings show, for the first time, that meditation involves endogenous opioid pathways, mediating its analgesic effect and growing resilient with increasing practice to external suggestion. This finding could hold promising therapeutic implications and further elucidate the fine mechanisms involved in human pain modulation. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Endogenous antispermatogenic agents: prospects for male contraception.

    Science.gov (United States)

    Ewing, L L; Robaire, B

    1978-01-01

    A review of endogenous antispermatogenic agents as prospects for male contraception is reported. It is demonstrated that endogenous compounds exert regulatory influences at 4 major levels in the male: 1) between germ cells; 2) between Sertoli and germ cells; 3) between Leydig cells and seminiferous tubules; and 4) between the central nervous system and the testis. Efforts to interrupt spermatogenesis have failed to find application as male contraceptives for various reasons: 1) some investigators ignored the vulnerable control points by utilizing nonspecific agents; 2) others attacked a vulnerable control point but used synthetic drugs that had deleterious side effects; and 3) still others attacked a vulnerable control point with a relatively innocuous drug but used an impractical mode of drug administration. The potential for devising innovative techniques for administering relatively innocuous drugs at dosages sufficient to produce sterility without causing deleterious side effects is demonstrated. The most promising solution for the development of an antispermatogenic male contraceptive is the interference with the adenohypophyseal-gonadal axis via the subcutaneous sustained release of steroid formulations containing either androgen-danazol, androgen-progestin, or androgen-estrogen formulations. Another promising agent would be luteinizing releasing hormone agonist-androgen formulation.

  18. Endogenous Technology Adoption and Medical Costs.

    Science.gov (United States)

    Lamiraud, Karine; Lhuillery, Stephane

    2016-09-01

    Despite the claim that technology has been one of the most important drivers of healthcare spending growth over the past decades, technology variables are rarely introduced explicitly in cost equations. Furthermore, technology is often considered exogenous. Using 1996-2007 panel data on Swiss geographical areas, we assessed the impact of technology availability on per capita healthcare spending covered by basic health insurance whilst controlling for the endogeneity of health technology availability variables. Our results suggest that medical research, patent intensity and the density of employees working in the medical device industry are influential factors for the adoption of technology and can be used as instruments for technology availability variables in the cost equation. These results are similar to previous findings: CT and PET scanner adoption is associated with increased healthcare spending, whilst increased availability of percutaneous transluminal coronary angioplasty facilities is associated with reductions in per capita spending. However, our results suggest that the magnitude of these relationships is much greater in absolute value than that suggested by previous studies that did not control for the possible endogeneity of the availability of technologies. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  19. ANAEROBIC ENDOGENOUS METABOLISM IN STREPTOCOCCUS FAECALIS.

    Science.gov (United States)

    WALKER, D J; FORREST, W W

    1964-02-01

    Walker, D. J. (CSIRO, University of Adelaide, Adelaide, South Australia), and W. W. Forrest. Endogenous metabolism in Streptococcus faecalis. J. Bacteriol. 87:256-262. 1964.-Washed suspensions of Streptococcus faecalis incubated in phosphate buffer (pH 6.0) under anaerobic conditions released amino acids into the suspending medium. Little or no carbohydrate was released in soluble form, and no acid production could be detected. Cell lipid was stable, and only a small amount of nucleotide (material absorbing at 260 mmu) was released. Estimates of total carbon produced in soluble form showed that this could be almost entirely accounted for as amino acid. Over the short period during which amino acid was produced (up to 5 hr), the glycolytic activity of the cells remained fairly constant, and fell slowly thereafter to low values in 24 to 48 hr; the rate of fall depended on cell concentration. Whereas exogenous sources of energy protected against loss of glycolytic activity, arsenate, hydroxylamine, or replacement of phosphate by other buffers accelerated loss of glycolytic activity. Restoration of glycolytic activity in aged cells could be achieved by incubation with amino acids plus an energy source, with concurrent synthesis of protein but no apparent growth. Ammonium ion was not effective in protecting or restoring glycolytic activity. The nature of changes which took place during endogenous metabolism are discussed.

  20. Human endogenous retroviruses in neurologic disease.

    Science.gov (United States)

    Christensen, Tove

    2016-01-01

    Endogenous retroviruses are pathogenic - in other species than the human. Disease associations for Human Endogenous RetroViruses (HERVs) are emerging, but so far an unequivocal pathogenetic cause-effect relationship has not been established. A role for HERVs has been proposed in neurological and neuropsychiatric diseases as diverse as multiple sclerosis (MS) and schizophrenia (SCZ). Particularly for MS, many aspects of the activation and involvement of specific HERV families (HERV-H/F and HERV-W/MSRV) have been reported, both for cells in the circulation and in the central nervous system. Notably envelope genes and their gene products (Envs) appear strongly associated with the disease. For SCZ, for ALS, and for HIV-associated dementia (HAD), indications are accumulating for involvement of the HERV-K family, and also HERV-H/F and/or HERV-W. Activation is reasonably a prerequisite for causality as most HERV sequences remain quiescent in non-pathological conditions, so the importance of regulatory pathways and epigenetics involved in regulating HERV activation, derepression, and also involvement of retroviral restriction factors, is emerging. HERV-directed antiretrovirals have potential as novel therapeutic paradigms in neurologic disease, particularly in MS. The possible protective or ameliorative effects of antiretroviral therapy in MS are substantiated by reports that treatment of HIV infection may be associated with a significantly decreased risk of MS. Further studies of HERVs, their role in neurologic diseases, and their potential as therapeutic targets are essential. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  1. Endogenous fibrinolysis facilitates clot retraction in vivo.

    Science.gov (United States)

    Samson, Andre L; Alwis, Imala; Maclean, Jessica A A; Priyananda, Pramith; Hawkett, Brian; Schoenwaelder, Simone M; Jackson, Shaun P

    2017-12-07

    Clot retraction refers to the process whereby activated platelets transduce contractile forces onto the fibrin network of a thrombus, which over time increases clot density and decreases clot size. This process is considered important for promoting clot stability and maintaining blood vessel patency. Insights into the mechanisms regulating clot retraction at sites of vascular injury have been hampered by a paucity of in vivo experimental models. By pairing localized vascular injury with thrombin microinjection in the mesenteric circulation of mice, we have demonstrated that the fibrin network of thrombi progressively compacts over a 2-hour period. This was a genuine retraction process, as treating thrombi with blebbistatin to inhibit myosin IIa-mediated platelet contractility prevented shrinkage of the fibrin network. Real-time confocal analysis of fibrinolysis after recombinant tissue-type plasminogen activator (tPA) administration revealed that incomplete proteolysis of fibrin polymers markedly facilitated clot retraction. Similarly, inhibiting endogenous fibrinolysis with tranexamic acid reduced retraction of fibrin polymers in vivo. In vitro clot retraction experiments indicated that subthreshold doses of tPA facilitated clot retraction through a plasmin-dependent mechanism. These effects correlated with changes in the elastic modulus of fibrin clots. These findings define the endogenous fibrinolytic system as an important regulator of clot retraction, and show that promoting clot retraction is a novel and complementary means by which fibrinolytic enzymes can reduce thrombus size. © 2017 by The American Society of Hematology.

  2. brain natriuretic peptide

    African Journals Online (AJOL)

    Background: Recently brain natriuretic peptide (BNP) level has been introduced as a screening test for congestive heart failure (CHF) in children. The current CHF assessment scores are not satisfactory as they use a large number of variables. Objective: To evaluate two CHF scores: a modified clinical score and an echo-.

  3. Brain Peptides and Psychopharmacology

    Science.gov (United States)

    Arehart-Treichel, Joan

    1976-01-01

    Proteins isolated from the brain and used as drugs can improve and apparently even transfer mental states and behavior. Much of the pioneering work and recent research with humans and animals is reviewed and crucial questions that are being posed about the psychologically active peptides are related. (BT)

  4. On Taxation in a Two-Sector Endogenous Growth Model with Endogenous Labor Supply

    NARCIS (Netherlands)

    P.A. de Hek (Paul)

    2003-01-01

    textabstractThis paper examines the effects of taxation on long-run growth in a two-sector endogenous growth model with (i) physical capital as an input in the education sector and (ii) leisure as an additional argument in the utility function. The analysis of the effects of taxation - including

  5. Annexin 1 and Melanocortin Peptide Therapy for Protection Against Ischaemic-Reperfusion Damage in the Heart

    Directory of Open Access Journals (Sweden)

    F.N.E. Gavins

    2006-01-01

    Full Text Available Cardiovascular disease is a major cause of mortality within the western world affecting 2.7 million British people. This review highlights the beneficial effects of naturally occurring hormones and their peptides, in myocardial ischaemic-injury (MI models, a disease pathology in which cytokines and neutrophils play a causal role. Here we discuss two distinct classes of endogenous peptides: the steroid inducible annexin 1 and the melanocortin peptides. Annexin 1 and the melanocortins counteract the most important part of the host inflammatory response, namely, the process of leukocyte extravasation, as well as release of proinflammatory mediators. Their biological effects are mediated via the seven transmembrane G-protein-coupled receptors, the fMLP receptor family (or FPR, and the melanocortin receptors, respectively. Pharmacological analysis has demonstrated that the first 24 amino acids of the N-terminus (termed Ac2-26 are the most active region. Both exogenous annexin 1 and its peptides demonstrate cardioprotectiveness and continuing work is required to understand this annexin 1/FPR relationship fully. The melanocortin peptides are derived from a precursor molecule called the POMC protein. These peptides display potent anti-inflammatory effects in human and animal models of disease. In MI, the MC3R has been demonstrated to play an important role in mediating the protective effects of these peptides. The potential anti-inflammatory role for endogenous peptides in cardiac disease is in its infancy. The inhibition of cell migration and release of cytokines and other soluble mediators appears to play an important role in affording protection in ischaemic injury and thus may lead to potential therapeutic targets.

  6. EpsinR, a target for pyrenocine B, role in endogenous MHC-II-restricted antigen presentation.

    Science.gov (United States)

    Shishido, Tatsuya; Hachisuka, Masami; Ryuzaki, Kai; Miura, Yuko; Tanabe, Atsushi; Tamura, Yasuaki; Kusayanagi, Tomoe; Takeuchi, Toshifumi; Kamisuki, Shinji; Sugawara, Fumio; Sahara, Hiroeki

    2014-11-01

    While the presentation mechanism of antigenic peptides derived from exogenous proteins by MHC class II molecules is well understood, relatively little is known about the presentation mechanism of endogenous MHC class II-restricted antigens. We therefore screened a chemical library of 200 compounds derived from natural products to identify inhibitors of the presentation of endogenous MHC class II-restricted antigens. We found that pyrenocine B, a compound derived from the fungus Pyrenochaeta terrestris, inhibits presentation of endogenous MHC class II-restricted minor histocompatibility antigen IL-4 inducible gene 1 (IL4I1) by primary dendritic cells (DCs). Phage display screening and surface plasmon resonance (SPR) analysis were used to investigate the mechanism of suppressive action by pyrenocine B. EpsinR, a target molecule for pyrenocine B, mediates endosomal trafficking through binding of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). Lentiviral-mediated short hairpin (sh) RNA downregulation of EpsinR expression in DCs resulted in a decrease in the responsiveness of CD4+ T cells. Our data thus suggest that EpsinR plays a role in antigen presentation, which provides insight into the mechanism of presentation pathway of endogenous MHC class II-restricted antigen. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Biochemical functionalization of peptide nanotubes with phage displayed peptides

    Science.gov (United States)

    Swaminathan, Swathi; Cui, Yue

    2016-09-01

    The development of a general approach for the biochemical functionalization of peptide nanotubes (PNTs) could open up existing opportunities in both fundamental studies as well as a variety of applications. PNTs are spontaneously assembled organic nanostructures made from peptides. Phage display has emerged as a powerful approach for identifying selective peptide binding motifs. Here, we demonstrate for the first time the biochemical functionalization of PNTs via peptides identified from a phage display peptide library. The phage-displayed peptides are shown to recognize PNTs. These advances further allow for the development of bifunctional peptides for the capture of bacteria and the self-assembly of silver particles onto PNTs. We anticipate that these results could provide significant opportunities for using PNTs in both fundamental studies and practical applications, including sensors and biosensors nanoelectronics, energy storage devices, drug delivery, and tissue engineering.

  8. NCBI nr-aa BLAST: CBRC-MEUG-01-1879 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MEUG-01-1879 ref|NP_001117065.1| prolactin-releasing peptide receptor [Salmo salar] gb|AAZ04129.1| prol...actin-releasing peptide receptor [Salmo salar] NP_001117065.1 1e-118 66% ...

  9. NCBI nr-aa BLAST: CBRC-MDOM-01-0092 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MDOM-01-0092 ref|NP_001117065.1| prolactin-releasing peptide receptor [Salmo salar] gb|AAZ04129.1| prol...actin-releasing peptide receptor [Salmo salar] NP_001117065.1 1e-118 66% ...

  10. Development of second generation peptides modulating cellular adiponectin receptor responses

    Directory of Open Access Journals (Sweden)

    Laszlo eOtvos

    2014-10-01

    Full Text Available The adipose tissue participates in the regulation of energy homeostasis as an important endocrine organ that secretes a number of biologically active adipokines, including adiponectin. Recently we developed and characterized a first-in-class peptide-based adiponectin receptor agonist by using in vitro and in vivo models of glioblastoma and breast cancer (BC. In the current study, we further explored the effects of peptide ADP355 in additional cellular models and found that ADP355 inhibited chronic myeloid leukemia (CML cell proliferation and renal myofibroblast differentiation with mid-nanomolar IC50 values. According to molecular modeling calculations, ADP355 was remarkably flexible in the global minimum with a turn present in the middle of the peptide. Considering these structural features of ADP355 and the fact that adiponectin normally circulates as multimeric complexes, we developed and tested the activity of a linear branched dimer (ADP399. The dimer exhibited approximately 20-fold improved cellular activity inhibiting K562 CML and MCF-7 cell growth with high pM - low nM relative IC50 values. Biodistribution studies suggested superior tissue dissemination of both peptides after subcutaneous administration relative to intraperitoneal inoculation. After screening of a 397-member adiponectin active site library, a novel octapeptide (ADP400 was designed that counteracted 10-1000 nM ADP355- and ADP399-mediated effects on CML and BC cell growth at nanomolar concentrations. ADP400 induced mitogenic effects in MCF-7 BC cells perhaps due to antagonizing endogenous adiponectin actions or acting as an inverse agonist. While the linear dimer agonist ADP399 meets pharmacological criteria of a contemporary peptide drug lead, the peptide showing antagonist activity (ADP400 at similar concentrations will be an important target validation tool to study adiponectin functions.

  11. Extraction of aggrecan-peptide from cartilage by tissue autolysis.

    Science.gov (United States)

    Nakano, Takuo; Srichamroen, Anchalee; Ozimek, Lech

    2014-01-01

    Aggrecan is a cartilage specific proteoglycan containing chondroitin sulfate (CS) and keratan sulfate (KS). CS is an acidic polysaccharide having wide range of applications in pharmaceutical, cosmetic, and food industries. CS is extracted from cartilage by tissue proteolysis with an exogenous proteinase or by activating endogenous proteinases (autolysis) to release aggrecan-peptides from the tissue. This review is focused on the latter technique. Bovine nasal and tracheal cartilages, and broiler chicken sternum cartilage have been used for autolysis studies. To extract aggrecan-peptide, cartilage tissues are cut into small pieces, and incubated in a monovalent or divalent salt solution (e.g., 0.1 M sodium or calcium acetate) at pH 4.5 and 37 °C for 7 - 24 h. Most (~80% or more) of total tissue uronic acid, a constituent sugar of aggrecan, is extracted and released into the salt solution during incubation. Reextraction of the tissue residue results in release of a small amount of uronic acid. Aggrecan-peptides purified using anion exchange chromatography are large compounds containing CS and KS. On gel chromatography, they are excluded from the column of Sephacryl S-300. Chemical composition analysis demonstrated that aggrecan-peptides from either bovine or chicken cartilage contain >90% CS with small amount (autolysis has been used as a plate coating antigen in enzyme- linked immunosorbent assay (ELISA) to determine KS.

  12. Analysis of Swine Leukocyte Antigen Peptide Binding Profiles and the Identification of T cell Epitopes by Tetramer Staining

    DEFF Research Database (Denmark)

    Pedersen, Lasse Eggers

    ) class I molecules, which are highly polymorphic peptide receptors which select and present endogenously derived peptides to circulating CTLs. Peptides that are recognized by CTLs in the context of MHC are epitopes, and represent a small sample of the pathogen proteome, making it possible for the immune...... fingerprint” of an individual can be identified by defining MHC alleles. This is classically called “tissue typing” and is done by analyzing the reactivity of peripheral blood cells with sera unique to MHC alleles. Such knowledge is paramount to analysis of the immune response regarding MHC restriction...... within a species makes immune escape almost impossible for any intruding pathogen. Characterization of the SLA class I and class II gene products and their peptide binding capacity defines the T cell epitopes of any given pathogen proteome. To date the analysis of MHC peptide interactions, strength...

  13. The emerging role of the mitochondrial-derived peptide humanin in stress resistance.

    Science.gov (United States)

    Yen, Kelvin; Lee, Changhan; Mehta, Hemal; Cohen, Pinchas

    2013-02-01

    The discovery of humanin, a novel, mitochondrial-derived peptide, has created a potentially new category of biologically active peptide. As more research unravels the endogenous role of humanin as well as its potential pharmacological use, its role in stress resistance has become clearer. Humanin protects cells from oxidative stress, serum starvation, hypoxia, and other insults in vitro and also improves cardiovascular disease as well as Alzheimer's disease in vivo. In this review, we discuss the emerging role of humanin in stress resistance and its proposed mechanism of action.

  14. Antibody Production with Synthetic Peptides.

    Science.gov (United States)

    Lee, Bao-Shiang; Huang, Jin-Sheng; Jayathilaka, Lasanthi P; Lee, Jenny; Gupta, Shalini

    2016-01-01

    Peptides (usually 10-20 amino acid residues in length) can be used as effectively as proteins in raising antibodies producing both polyclonal and monoclonal antibodies routinely with titers higher than 20,000. Peptide antigens do not function as immunogens unless they are conjugated to proteins. Production of high quality antipeptide antibodies is dependent upon peptide sequence selection, the success of peptide synthesis, peptide-carrier protein conjugation, the humoral immune response in the host animal, the adjuvant used, the peptide dose administered, the injection method, and the purification of the antibody. Peptide sequence selection is probably the most critical step in the production of antipeptide antibodies. Although the process for designing peptide antigens is not exact, several guidelines and computational B-cell epitope prediction methods can help maximize the likelihood of producing antipeptide antibodies that recognize the protein. Antibodies raised by peptides have become essential tools in life science research. Virtually all phospho-specific antibodies are now produced using phosphopeptides as antigens. Typically, 5-20 mg of peptide is enough for antipeptide antibody production. It takes 3 months to produce a polyclonal antipeptide antibody in rabbits that yields ~100 mL of serum which corresponds to ~8-10 mg of the specific antibody after affinity purification using a peptide column.

  15. Endogenous development. Theories and policies of territorial development

    OpenAIRE

    Vázquez Barquero , Antonio

    2007-01-01

    Endogenous development is an interpretation that includes different points of view which share the same theoretical and policy patterns. It is a territorial approach to development that refers to growth and capital accumulation processes of territories that have their own culture and institutions, upon which investment decisions are made. From this perspective, endogenous development policy is the local actors answer to the challenge of globalization. The paper argues that endogenous developm...

  16. Horizontalists, verticalists, and structuralists: The theory of endogenous money reassessed

    OpenAIRE

    Palley, Thomas I.

    2013-01-01

    This paper uses the occasion of the twenty-fifth anniversary of Basil Moore’s book, Horizontalists and Verticalists, to reassess the theory of endogenous money. The paper distinguishes between horizontalists, verticalists, and structuralists. It argues Moore’s horizontalist representation of endogenous money was an over-simplification that discarded important enduring insights from monetary theory. The structuralist approach to endogenous money retains the basic insight that the money supply ...

  17. Methylated DNA Immunoprecipitation Analysis of Mammalian Endogenous Retroviruses.

    Science.gov (United States)

    Rebollo, Rita; Mager, Dixie L

    2016-01-01

    Endogenous retroviruses are repetitive sequences found abundantly in mammalian genomes which are capable of modulating host gene expression. Nevertheless, most endogenous retrovirus copies are under tight epigenetic control via histone-repressive modifications and DNA methylation. Here we describe a common method used in our laboratory to detect, quantify, and compare mammalian endogenous retrovirus DNA methylation. More specifically we describe methylated DNA immunoprecipitation (MeDIP) followed by quantitative PCR.

  18. Are human endogenous retroviruses triggers of autoimmune diseases?

    DEFF Research Database (Denmark)

    Nexø, Bjørn A; Villesen, Palle; Nissen, Kari K

    2016-01-01

    factors. Viruses including human endogenous retroviruses have long been linked to the occurrence of autoimmunity, but never proven to be causative factors. Endogenous viruses are retroviral sequences embedded in the host germline DNA and transmitted vertically through successive generations in a Mendelian...... manner. In this study by means of genetic epidemiology, we have searched for the involvement of endogenous retroviruses in three selected autoimmune diseases: multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. We found that at least one human endogenous retroviral locus...

  19. Involvement of Endogenous Retroviruses in Prion Diseases

    Directory of Open Access Journals (Sweden)

    Yong-Sun Kim

    2013-08-01

    Full Text Available For millions of years, vertebrates have been continuously exposed to infection by retroviruses. Ancient retroviral infection of germline cells resulted in the formation and accumulation of inherited retrovirus sequences in host genomes. These inherited retroviruses are referred to as endogenous retroviruses (ERVs, and recent estimates have revealed that a significant portion of animal genomes is made up of ERVs. Although various host factors have suppressed ERV activation, both positive and negative functions have been reported for some ERVs in normal and abnormal physiological conditions, such as in disease states. Similar to other complex diseases, ERV activation has been observed in prion diseases, and this review will discuss the potential involvement of ERVs in prion diseases.

  20. Creatine: endogenous metabolite, dietary, and therapeutic supplement.

    Science.gov (United States)

    Brosnan, John T; Brosnan, Margaret E

    2007-01-01

    Creatine and phosphocreatine serve not only as an intracellular buffer for adenosine triphosphate, but also as an energy shuttle for the movement of high-energy phosphates from mitochondrial sites of production to cytoplasmic sites of utilization. The spontaneous loss of creatine and of phosphocreatine to creatinine requires that creatine be continuously replaced; this occurs by a combination of diet and endogenous synthesis. Vegetarians obtain almost no dietary creatine. Creatine synthesis makes major demands on the metabolism of glycine, arginine, and methionine. Large doses of creatine monohydrate are widely taken, particularly by athletes, as an ergogenic supplement; creatine supplements are also taken by patients suffering from gyrate atrophy, muscular dystrophy, and neurodegenerative diseases. Children with inborn errors of creatine synthesis or transport present with severe neurological symptoms and a profound depletion of brain creatine. It is evident that creatine plays a critical, though underappreciated, role in brain function.

  1. Changing Endogenous Development: the Territorial Capital

    Directory of Open Access Journals (Sweden)

    Balázs István Tóth

    2011-12-01

    Full Text Available The aim of this research is to analyze territorial capital as a new paradigm to make best use of endogenous assets. The study is dealing with the preconditions, meaning and possible theoretical taxonomies of territorial capital. In this study I emphasize that the cumulative effects of regional potentials are more important than economies of scale and location factors. I present different approaches and interpretations of territorial capital, then make an attempt to create an own model. I try to find answers for questions, such as why territorial capital shows a new perspective of urban and regional development; how cognitive elements of territorial capital provide increasing return; how territorial capital influences competitiveness and what kind of relation it has with cohesion.

  2. Endogenous Brucella endophthalmitis: A case report

    Directory of Open Access Journals (Sweden)

    Merih Oray

    2017-04-01

    Full Text Available Brucellosis may be associated with a wide range of ophthalmic manifestations including endophthalmitis, which is a sight-threatening condition that needs to be rapidly recognized and treated to avoid permanent visual loss. A 26-year-old female with a 6-month history of vision loss in the left eye was treated with high dose systemic corticosteroids and azathioprine with an initial misdiagnosis elsewhere. A dense vitreous haze with opacities at the posterior hyaloid and a wide area of retinochoroiditis led to the diagnosis of endogenous endophthalmitis at presentation to us. The vitreous sample and blood cultures demonstrated growth of Brucella melitensis. She received 6 months of systemic antibiotherapy, which resulted in resolution of inflammation; however, visual acuity remained poor due to irreversible damage. Infectious etiology, including brucellosis in endemic countries, has to be considered in the differential diagnosis before administering immunomodulatory therapy in patients with panuveitis of unknown origin.

  3. Endogenous methanol regulates mammalian gene activity.

    Science.gov (United States)

    Komarova, Tatiana V; Petrunia, Igor V; Shindyapina, Anastasia V; Silachev, Denis N; Sheshukova, Ekaterina V; Kiryanov, Gleb I; Dorokhov, Yuri L

    2014-01-01

    We recently showed that methanol emitted by wounded plants might function as a signaling molecule for plant-to-plant and plant-to-animal communications. In mammals, methanol is considered a poison because the enzyme alcohol dehydrogenase (ADH) converts methanol into toxic formaldehyde. However, the detection of methanol in the blood and exhaled air of healthy volunteers suggests that methanol may be a chemical with specific functions rather than a metabolic waste product. Using a genome-wide analysis of the mouse brain, we demonstrated that an increase in blood methanol concentration led to a change in the accumulation of mRNAs from genes primarily involved in detoxification processes and regulation of the alcohol/aldehyde dehydrogenases gene cluster. To test the role of ADH in the maintenance of low methanol concentration in the plasma, we used the specific ADH inhibitor 4-methylpyrazole (4-MP) and showed that intraperitoneal administration of 4-MP resulted in a significant increase in the plasma methanol, ethanol and formaldehyde concentrations. Removal of the intestine significantly decreased the rate of methanol addition to the plasma and suggested that the gut flora may be involved in the endogenous production of methanol. ADH in the liver was identified as the main enzyme for metabolizing methanol because an increase in the methanol and ethanol contents in the liver homogenate was observed after 4-MP administration into the portal vein. Liver mRNA quantification showed changes in the accumulation of mRNAs from genes involved in cell signalling and detoxification processes. We hypothesized that endogenous methanol acts as a regulator of homeostasis by controlling the mRNA synthesis.

  4. Dynamic option pricing with endogenous stochastic arbitrage

    Science.gov (United States)

    Contreras, Mauricio; Montalva, Rodrigo; Pellicer, Rely; Villena, Marcelo

    2010-09-01

    Only few efforts have been made in order to relax one of the key assumptions of the Black-Scholes model: the no-arbitrage assumption. This is despite the fact that arbitrage processes usually exist in the real world, even though they tend to be short-lived. The purpose of this paper is to develop an option pricing model with endogenous stochastic arbitrage, capable of modelling in a general fashion any future and underlying asset that deviate itself from its market equilibrium. Thus, this investigation calibrates empirically the arbitrage on the futures on the S&P 500 index using transaction data from September 1997 to June 2009, from here a specific type of arbitrage called “arbitrage bubble”, based on a t-step function, is identified and hence used in our model. The theoretical results obtained for Binary and European call options, for this kind of arbitrage, show that an investment strategy that takes advantage of the identified arbitrage possibility can be defined, whenever it is possible to anticipate in relative terms the amplitude and timespan of the process. Finally, the new trajectory of the stock price is analytically estimated for a specific case of arbitrage and some numerical illustrations are developed. We find that the consequences of a finite and small endogenous arbitrage not only change the trajectory of the asset price during the period when it started, but also after the arbitrage bubble has already gone. In this context, our model will allow us to calibrate the B-S model to that new trajectory even when the arbitrage already started.

  5. Endogenous Methanol Regulates Mammalian Gene Activity

    Science.gov (United States)

    Komarova, Tatiana V.; Petrunia, Igor V.; Shindyapina, Anastasia V.; Silachev, Denis N.; Sheshukova, Ekaterina V.; Kiryanov, Gleb I.; Dorokhov, Yuri L.

    2014-01-01

    We recently showed that methanol emitted by wounded plants might function as a signaling molecule for plant-to-plant and plant-to-animal communications. In mammals, methanol is considered a poison because the enzyme alcohol dehydrogenase (ADH) converts methanol into toxic formaldehyde. However, the detection of methanol in the blood and exhaled air of healthy volunteers suggests that methanol may be a chemical with specific functions rather than a metabolic waste product. Using a genome-wide analysis of the mouse brain, we demonstrated that an increase in blood methanol concentration led to a change in the accumulation of mRNAs from genes primarily involved in detoxification processes and regulation of the alcohol/aldehyde dehydrogenases gene cluster. To test the role of ADH in the maintenance of low methanol concentration in the plasma, we used the specific ADH inhibitor 4-methylpyrazole (4-MP) and showed that intraperitoneal administration of 4-MP resulted in a significant increase in the plasma methanol, ethanol and formaldehyde concentrations. Removal of the intestine significantly decreased the rate of methanol addition to the plasma and suggested that the gut flora may be involved in the endogenous production of methanol. ADH in the liver was identified as the main enzyme for metabolizing methanol because an increase in the methanol and ethanol contents in the liver homogenate was observed after 4-MP administration into the portal vein. Liver mRNA quantification showed changes in the accumulation of mRNAs from genes involved in cell signalling and detoxification processes. We hypothesized that endogenous methanol acts as a regulator of homeostasis by controlling the mRNA synthesis. PMID:24587296

  6. How Active Are Porcine Endogenous Retroviruses (PERVs?

    Directory of Open Access Journals (Sweden)

    Joachim Denner

    2016-08-01

    Full Text Available Porcine endogenous retroviruses (PERVs represent a risk factor if porcine cells, tissues, or organs were to be transplanted into human recipients to alleviate the shortage of human transplants; a procedure called xenotransplantation. In contrast to human endogenous retroviruses (HERVs, which are mostly defective and not replication-competent, PERVs are released from normal pig cells and are infectious. PERV-A and PERV-B are polytropic viruses infecting cells of several species, among them humans; whereas PERV-C is an ecotropic virus infecting only pig cells. Virus infection was shown in co-culture experiments, but also in vivo, in the pig, leading to de novo integration of proviruses in certain organs. This was shown by measurement of the copy number per cell, finding different numbers in different organs. In addition, recombinations between PERV-A and PERV-C were observed and the recombinant PERV-A/C were found to be integrated in cells of different organs, but not in the germ line of the animals. Here, the evidence for such in vivo activities of PERVs, including expression as mRNA, protein and virus particles, de novo infection and recombination, will be summarised. These activities make screening of pigs for provirus number and PERV expression level difficult, especially when only blood or ear biopsies are available for analysis. Highly sensitive methods to measure the copy number and the expression level will be required when selecting pigs with low copy number and low expression of PERV as well as when inactivating PERVs using the clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated nuclease (CRISPR/Cas technology.

  7. Ezetimibe Increases Endogenous Cholesterol Excretion in Humans.

    Science.gov (United States)

    Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Ostlund, Richard E

    2017-05-01

    Ezetimibe improves cardiovascular outcomes when added to optimum statin treatment. It lowers low-density lipoprotein cholesterol and percent intestinal cholesterol absorption, but the exact cardioprotective mechanism is unknown. We tested the hypothesis that the dominant effect of ezetimibe is to increase the reverse transport of cholesterol from rapidly mixing endogenous cholesterol pool into the stool. In a randomized, placebo-controlled, double-blind parallel trial in 24 healthy subjects with low-density lipoprotein cholesterol 100 to 200 mg/dL, we measured cholesterol metabolism before and after a 6-week treatment period with ezetimibe 10 mg/d or placebo. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d 7 in a lipid emulsion and dietary cholesterol with cholesterol-d 5 and sitostanol-d 4 solubilized in oil. Plasma and stool samples collected during a cholesterol- and phytosterol-controlled metabolic kitchen diet were analyzed by mass spectrometry. Ezetimibe reduced intestinal cholesterol absorption efficiency 30±4.3% (SE, P <0.0001) and low-density lipoprotein cholesterol 19.8±1.9% ( P =0.0001). Body cholesterol pool size was unchanged, but fecal endogenous cholesterol excretion increased 66.6±12.2% ( P <0.0001) and percent cholesterol excretion from body pools into the stool increased 74.7±14.3% ( P <0.0001), whereas plasma cholesterol turnover rose 26.2±3.6% ( P =0.0096). Fecal bile acids were unchanged. Ezetimibe increased the efficiency of reverse cholesterol transport from rapidly mixing plasma and tissue pools into the stool. Further work is needed to examine the potential relation of reverse cholesterol transport and whole body cholesterol metabolism to coronary events and the treatment of atherosclerosis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01603758. © 2017 American Heart Association, Inc.

  8. Antimicrobial Peptides (AMPs

    Directory of Open Access Journals (Sweden)

    Mehrzad Sadredinamin

    2016-04-01

    Full Text Available Antimicrobial peptides (AMPs are extensive group of molecules that produced by variety tissues of invertebrate, plants, and animal species which play an important role in their immunity response. AMPs have different classifications such as; biosynthetic machines, biological sources, biological functions, molecular properties, covalent bonding patterns, three dimensional structures, and molecular targets.These molecules have multidimensional properties including antimicrobial activity, antiviral activity, antifungal activity, anti-parasite activity, biofilm control, antitumor activity, mitogens activity and linking innate to adaptive immunity that making them promising agents for therapeutic drugs. In spite of this advantage of AMPs, their clinical developments have some limitation for commercial development. But some of AMPs are under clinical trials for the therapeutic purpose such as diabetic foot ulcers, different bacterial infections and tissue damage. In this review, we emphasized on the source, structure, multidimensional properties, limitation and therapeutic applications of various antimicrobial peptides.

  9. Recent trends in the analysis of bioactive peptides in milk and dairy products.

    Science.gov (United States)

    Capriotti, Anna Laura; Cavaliere, Chiara; Piovesana, Susy; Samperi, Roberto; Laganà, Aldo

    2016-04-01

    Food-derived constituents represent important sources of several classes of bioactive compounds. Among them peptides have gained great attention in the last two decades thanks to the scientific evidence of their beneficial effects on health in addition to their established nutritional value. Several functionalities for bioactive peptides have been described, including antioxidative, antihypertensive, anti-inflammatory, immunomodulatory, and antimicrobial activity. They are now considered as novel and potential dietary ingredients to promote human health, though in some cases they may also have detrimental effects on health. Bioactive peptides can be naturally occurring, produced in vitro by enzymatic hydrolysis, and formed in vivo during gastrointestinal digestion of proteins. Thus, the need to gain a better understanding of the positive health effects of food peptides has prompted the development of analytical strategies for their isolation, separation, and identification in complex food matrices. Dairy products and milk are potential sources of bioactive peptides: several of them possess extra-nutritional physiological functions that qualify them to be classified under the functional food label. In this trends article we briefly describe the state-of-the-art of peptidomics methods for the identification and discovery of bioactive peptides, also considering recent progress in their analysis and highlighting the difficulty in the analysis of short amino acid sequences and endogenous peptides.

  10. Proteolytic signatures define unique thrombin-derived peptides present in human wound fluid in vivo.

    Science.gov (United States)

    Saravanan, Rathi; Adav, Sunil S; Choong, Yeu Khai; van der Plas, Mariena J A; Petrlova, Jitka; Kjellström, Sven; Sze, Siu Kwan; Schmidtchen, Artur

    2017-10-13

    The disease burden of failing skin repair and non-healing ulcers is extensive. There is an unmet need for new diagnostic approaches to better predict healing activity and wound infection. Uncontrolled and excessive protease activity, of endogenous or bacterial origin, has been described as a major contributor to wound healing impairments. Proteolytic peptide patterns could therefore correlate and "report" healing activity and infection. This work describes a proof of principle delineating a strategy by which peptides from a selected protein, human thrombin, are detected and attributed to proteolytic actions. With a particular focus on thrombin-derived C-terminal peptides (TCP), we show that distinct peptide patterns are generated in vitro by the human S1 peptidases human neutrophil elastase and cathepsin G, and the bacterial M4 peptidases Pseudomonas aeruginosa elastase and Staphylococcus aureus aureolysin, respectively. Corresponding peptide sequences were identified in wound fluids from acute and non-healing ulcers, and notably, one peptide, FYT21 (FYTHVFRLKKWIQKVIDQFGE), was only present in wound fluid from non-healing ulcers colonized by P. aeruginosa and S. aureus. Our result is a proof of principle pointing at the possibility of defining peptide biomarkers reporting distinct proteolytic activities, of potential implication for improved diagnosis of wound healing and infection.

  11. Involvement of human endogenous retroviral syncytin-1 in human osteoclast fusion

    DEFF Research Database (Denmark)

    Søe, Kent; Andersen, Thomas Lykke; Hobolt-Pedersen, Anne-Sofie

    2011-01-01

    Generation of osteoclasts through fusion of mono-nucleated precursors is a key event of bone physiology and bone resorption is inefficient without osteoclast fusion. Several factors playing a critical role in the fusion process have already been recognized, but the factors involved in the actual...... fusion of the lipid bilayers of their cell membranes are still unknown. Syncytin-1 is a protein encoded by a human endogenous retroviral gene which was stably integrated into the human ancestor genome more than 24 million years ago. Upon activation, syncytin-1 is able to destabilize the lipid bilayer....... This was documented through Q-PCR, Western blot and immunofluorescence analyses. These in vitro findings were confirmed by immunohistochemical stainings in human iliac crest biopsies. A syncytin-1 inhibitory peptide reduced the number of nuclei per osteoclast by 30%, as well as TRACP activity. From a mechanistic...

  12. Sensitive method for precise measurement of endogenous angiotensins I, II and III in human plasma

    International Nuclear Information System (INIS)

    Kawamura, M.; Yoshida, K.; Akabane, S.

    1987-01-01

    We measured endogenous angiotensins (ANGs) I, IIandIII using a system of extraction by Sep-Pak column followed by high performance liquid chromatography (HPLC) combined with radioimmunoassay (RIA). An excellent separation of ANGs was obtained by HPLC. The recovery of ANGs I, IIandIII was 80-84%, when these authentic peptides were added to 6 ml of plasma. The coefficient of variation of the ANGs was 0.04-0.09 for intra-assay and 0.08-0.13 for inter-assay, thereby indicating a good reproducibility. Plasma ANGs I, IIandIII measured by this method in 5 normal volunteers were 51,4.5 and 1.2 pg/ml. In the presence of captopril, ANGs IIandIII decreased by 84% and 77%, respectively, while ANG I increased 5.1 times. This method is therefore useful to assess the precise levels of plasma ANGs

  13. THE PROCESSES OF ENDOGENIZING IN THE ENDOGENOUS GROWTH: THE CASE OF TURKEY

    Directory of Open Access Journals (Sweden)

    OSMAN DEMİR

    2013-06-01

    Full Text Available The aim of this study is to state how the main inputs of endogenous growth, i.e. knowledge, human capital and technological progress are made endogenous by education, R&D, university-industry cooperation, learning by doing and diffusion within the production process. Competitiveness of firms and countries would increase as educated people enter into workforce; as R&D produces new technologies which are used in the production process; as theoretical knowledge meets with practice by university-industry cooperation; and as workers have more experience by learning by doing. In empirical analysis for Turkey is made by using data of 1970-2001 term it was found that a positive relationship among labour and capital factors and GNP and a negative relationship among education expenditures and foreign trade volume and capital stock.

  14. Potential molecular mimicry between the human endogenous retrovirus W family envelope proteins and myelin proteins in multiple sclerosis.

    Science.gov (United States)

    Ramasamy, Ranjan; Joseph, Blessy; Whittall, Trevor

    2017-03-01

    Multiple sclerosis is an autoimmune disease caused by the destruction of the myelin sheath in the central nervous system. The major target molecules for the immune response are the myelin basic protein, myelin oligodendrocyte glycoprotein and proteolipid protein but the aetiology of the disease is as yet poorly understood. The HLA Class II allele DRB1*1501 in particular as well as DRB5*0101 and the expression of human endogenous retroviral envelope proteins have been linked to multiple sclerosis but the molecular mechanisms relating these remain to be elucidated. We hypothesised that cross-reactive peptide epitopes in retroviral envelope proteins and myelin proteins that can be presented by the two Class II DR molecules may play a role in initiating multiple sclerosis. Sequence homologies between retroviral envelope and myelin proteins and in silico predictions of peptides derived from them that are able to bind to the two Class II alleles were examined to test the hypothesis. The results support the hypothesis that molecular mimicry in peptide epitopes from envelope proteins of the HERV-W family of endogenous retroviruses and myelin proteins is possible and could potentially trigger multiple sclerosis. Mimicry between syncytin-1, a HERV-W envelope protein that is expressed during placentation, and myelin proteins may also explain the higher prevalence of multiple sclerosis in women. Experiments to test the ability of the identified peptide epitopes to activate T H cells are required to confirm the present findings. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  15. Radiolabelled peptides vs. nanoparticle-peptide complexes for medical applications

    International Nuclear Information System (INIS)

    Ferro F, G.

    2007-01-01

    Full text: The principle that peptide receptors can be used successfully for in vivo targeting of human cancers has been provided and the peptide-receptor radionuclide therapy for malignant tumors is a real treatment option. Targeted entry into cells is an increasingly important area of research. The diagnoses and treatment of disease by novel methods would be enhanced greatly by the efficient transport of materials to living cell nuclei. Membrane-trans locating peptides complexed to nanoparticles are small enough (30 nm) to cross the nuclear membrane and to enter the cell via receptor-mediated endocytosis, emerging as a new type of pharmaceuticals. Pharmacokinetic properties and molecular specificity of iron or gold nanoparticle-peptide complexes that do not induce biological toxicity is a topic of world interest in current and future medical investigations. Some perspectives and achievements on the preparation, pharmacokinetics and dosimetry of radiolabelled peptides versus nanoparticle-peptide complexes for medical applications are presented. (Author)

  16. An endogenous Taylor condition in an endogenous growth monetary policy model

    OpenAIRE

    Le, Mai Vo; Gillman, Max; Minford, Patrick

    2007-01-01

    The paper derives a Taylor condition as part of the agent's equilibrium behavior in an endogenous growth monetary economy. It shows the assumptions necessary to make it almost identical to the original Taylor rule, and that it can interchangably take a money supply growth rate form. From the money supply form, simple policy experiments are conducted. A full central bank policy model is derived that includes the Taylor condition along with equations comparable to the standard aggregate-demand/...

  17. Proteolytic signatures define unique thrombin-derived peptides present in human wound fluid in vivo

    DEFF Research Database (Denmark)

    Saravanan, Rathi; Adav, Sunil S; Choong, Yeu Khai

    2017-01-01

    The disease burden of failing skin repair and non-healing ulcers is extensive. There is an unmet need for new diagnostic approaches to better predict healing activity and wound infection. Uncontrolled and excessive protease activity, of endogenous or bacterial origin, has been described as a major...... of principle pointing at the possibility of defining peptide biomarkers reporting distinct proteolytic activities, of potential implication for improved diagnosis of wound healing and infection....

  18. Vitamin D, the Cutaneous Barrier, Antimicrobial Peptides and Allergies: Is There a Link?

    OpenAIRE

    Roider, Elisabeth; Ruzicka, Thomas; Schauber, J?rgen

    2013-01-01

    Atopic diseases such as atopic dermatitis (AD) are very common in industrialized countries. Up to 15%-30% of all children and 2%-10% of all adults suffer from AD. Already in early disease stages, a defective epidermal barrier is known to contribute to the pathogenesis of AD. Central elements in the epidermal barrier are antimicrobial peptides (AMPs), which are secreted by keratinocytes, sweat gland cells but also infiltrating immune cells. AMPs function as endogenous antibiotics and are able ...

  19. Identification and characterization of histidine-rich peptides from hard ticks Ixodes ricinus and Ixodes scapularis.

    OpenAIRE

    DORŇÁKOVÁ, Veronika

    2011-01-01

    Antimicrobial (cationic) proteins play an important role in innate imunity. Such proteins can possess antibacterial, antiendotoxic or fungicidal abilities. The rising resistence of microbes to common antibiotics evokes acute need of studying more endogenous proteins to reveal new potential antibiotics. Ticks, the blood-feeding ectoparasites with effectual defense system, present an endless source of newly described and unknown antimicrobial peptides/proteins with significant theurapeutic pote...

  20. Endogenous ghrelin-O-acyltransferase (GOAT) acylates local ghrelin in the hippocampus.

    Science.gov (United States)

    Murtuza, Mohammad I; Isokawa, Masako

    2018-01-01

    Ghrelin is an appetite-stimulating peptide. Serine 3 on ghrelin must be acylated by octanoate via the enzyme ghrelin-O-acyltransferase (GOAT) for the peptide to bind and activate the cognate receptor, growth hormone secretagogue receptor type 1a (GHSR1a). Interest in GHSR1a increased dramatically when GHSR1a mRNA was demonstrated to be widespread in the brain, including the cortex and hippocampus, indicating that it has multifaceted functions beyond the regulation of metabolism. However, the source of octanoylated ghrelin for GHSR1a in the brain, outside of the hypothalamus, is not well understood. Here, we report the presence of GOAT and its ability to acylate non-octanoylated ghrelin in the hippocampus. GOAT immunoreactivity is aggregated at the base of the dentate granule cell layer in the rat and wild-type mouse. This immunoreactivity was not affected by the pharmacological inhibition of GHSR1a or the metabolic state-dependent fluctuation of systemic ghrelin levels. However, it was absent in the GHSR1a knockout mouse hippocampus, pointing the possibility that the expression of GHSR1a may be a prerequisite for the production of GOAT. Application of fluorescein isothiocyanate (FITC)-conjugated non-octanoylated ghrelin in live hippocampal slice culture (but not in fixed culture or in the presence of GOAT inhibitors) mimicked the binding profile of FITC-conjugated octanoylated ghrelin, suggesting that extracellularly applied non-octanoylated ghrelin was acylated by endogenous GOAT in the live hippocampus while GOAT being mobilized out of neurons. Our results will advance the understanding for the role of endogenous GOAT in the hippocampus and facilitate the search for the source of ghrelin that is intrinsic to the brain. © 2017 International Society for Neurochemistry.

  1. Distinct Signaling Cascades Elicited by Different Formyl Peptide Receptor 2 (FPR2 Agonists

    Directory of Open Access Journals (Sweden)

    Fabio Cattaneo

    2013-04-01

    Full Text Available The formyl peptide receptor 2 (FPR2 is a remarkably versatile transmembrane protein belonging to the G-protein coupled receptor (GPCR family. FPR2 is activated by an array of ligands, which include structurally unrelated lipids and peptide/proteins agonists, resulting in different intracellular responses in a ligand-specific fashion. In addition to the anti-inflammatory lipid, lipoxin A4, several other endogenous agonists also bind FPR2, including serum amyloid A, glucocorticoid-induced annexin 1, urokinase and its receptor, suggesting that the activation of FPR2 may result in potent pro- or anti-inflammatory responses. Other endogenous ligands, also present in biological samples, include resolvins, amyloidogenic proteins, such as beta amyloid (Aβ-42 and prion protein (Prp106–126, the neuroprotective peptide, humanin, antibacterial peptides, annexin 1-derived peptides, chemokine variants, the neuropeptides, vasoactive intestinal peptide (VIP and pituitary adenylate cyclase activating polypeptide (PACAP-27, and mitochondrial peptides. Upon activation, intracellular domains of FPR2 mediate signaling to G-proteins, which trigger several agonist-dependent signal transduction pathways, including activation of phospholipase C (PLC, protein kinase C (PKC isoforms, the phosphoinositide 3-kinase (PI3K/protein kinase B (Akt pathway, the mitogen-activated protein kinase (MAPK pathway, p38MAPK, as well as the phosphorylation of cytosolic tyrosine kinases, tyrosine kinase receptor transactivation, phosphorylation and nuclear translocation of regulatory transcriptional factors, release of calcium and production of oxidants. FPR2 is an attractive therapeutic target, because of its involvement in a range of normal physiological processes and pathological diseases. Here, we review and discuss the most significant findings on the intracellular pathways and on the cross-communication between FPR2 and tyrosine kinase receptors triggered by different FPR2

  2. Peptide-enhanced oral delivery of therapeutic peptides and proteins

    DEFF Research Database (Denmark)

    Kristensen, Mie; Foged, Camilla; Berthelsen, Jens

    2013-01-01

    Systemic therapy upon oral delivery of biologics, such as peptide and protein drugs is limited due to their large molecular size, their low enzymatic stability and their inability to cross the intestinal epithelium. Ways to overcome the epithelial barrier include the use of peptide-based excipients...... throughout the gastrointestinal (GI) tract, chemical stability is an inherent challenge when employing amino acid-based excipients for oral delivery, and multiple approaches have been investigated to improve this. The exact mechanisms of transepithelial translocation are discussed, and it is believed...... for oral delivery of peptide and protein drugs highlighting recent studies and the most promising compounds from these classes of peptide excipients....

  3. On the Endogeneity of the Mean-Variance Efficient Frontier.

    Science.gov (United States)

    Somerville, R. A.; O'Connell, Paul G. J.

    2002-01-01

    Explains that the endogeneity of the efficient frontier in the mean-variance model of portfolio selection is commonly obscured in portfolio selection literature and in widely used textbooks. Demonstrates endogeneity and discusses the impact of parameter changes on the mean-variance efficient frontier and on the beta coefficients of individual…

  4. Endogene opioider og deres terapeutiske anvendelse i smertebehandling

    DEFF Research Database (Denmark)

    Juul, A; Pedersen, A T

    1990-01-01

    Cancer patients with chronic pain and obstetric patients have participated in clinical trials of the analgesic effects of endogenous opioids. It is possible to achieve adequate relief of pain in these patients following epidural or intrathecal administration of endogenous opioids. Further...

  5. Explaining Cigarette Smoking: An Endogenous-Exogenous Analysis.

    Science.gov (United States)

    McKillip, Jack

    Kruglanski's endogenous-exogenous partition, when applied to reasons given by smokers for smoking cigarettes, distinguishes two types of actions: (1) endogenous reasons implying that the behavior of consuming the cigarette is the goal of the action and the actor is positive toward the behavior, and (2) exogenous reasons implying that the behavior…

  6. The Endogenous-Exogenous Partition in Attribution Theory

    Science.gov (United States)

    Kruglanski, Arie W.

    1975-01-01

    Within lay explanation of actions, several significant inferences are assumed to follow from the partition between endogenous and exogenous attributions. An endogenous action is judged to constitute an end in itself; an exogenous action is judged to serve as a means to some further end. (Editor/RK)

  7. Endogene opioider og deres terapeutiske anvendelse i smertebehandling

    DEFF Research Database (Denmark)

    Juul, A; Pedersen, A T

    1990-01-01

    Cancer patients with chronic pain and obstetric patients have participated in clinical trials of the analgesic effects of endogenous opioids. It is possible to achieve adequate relief of pain in these patients following epidural or intrathecal administration of endogenous opioids. Further investi...

  8. Functional and mechanistic aspects of endogenous RNAi in C. elegans

    NARCIS (Netherlands)

    van Wolfswinkel, J.C.

    2009-01-01

    RNAi is widely used as a genetic tool in a range of model organisms, however still relatively little is known about the endogenous functions of RNAi. In this thesis we have studied several aspects of the endogenous role of RNAi in order to enhance our understanding of the capabilities of this

  9. Rising Trade Costs? Agglomeration and Trade with Endogenous Transaction Costs

    OpenAIRE

    Gilles Duranton; Michael Storper

    2005-01-01

    costs. In a model of industry location with endogenous transaction costs that seeks to replicate features from the machinery industry, we show how and under which conditions a decline in transport costs can lead to an increase in the total cost of trade. The subtle relationship between (endogenous) transport costs and the sensitivity of trade to distance is also explored.

  10. Role of endogenous substances in enhancing radioresistance background

    International Nuclear Information System (INIS)

    Goncharenko, E.N.; Gorskaya, T.G.; Graevskaya, E.Eh.; Kozlova, M.A.

    1979-01-01

    Presumable sources of endogenous were studied amines in radiosensitive tissues under the effect of radioprotective agents were studied. The data obtained support the idea that mast cells of rats, having large deposits of biogenous amines, might be one of the reserves contributing to mobilization of endogeneous protective resources of the organism treated with radioprotective agents

  11. Ileal recovery of endogenous amino acids in pigs

    NARCIS (Netherlands)

    Caine, W.

    1997-01-01

    Ileal recovery of endogenous amino acids is important for determining balanced homeostasis of protein metabolism in pigs and the true digestibility of dietary protein. In this context, the ileal recoveries of endogenous amino acids were determined in growing pigs fed guanidinated Nutrisoy protein

  12. Optimized endogenous post-stratification in forest inventories

    Science.gov (United States)

    Paul L. Patterson

    2012-01-01

    An example of endogenous post-stratification is the use of remote sensing data with a sample of ground data to build a logistic regression model to predict the probability that a plot is forested and using the predicted probabilities to form categories for post-stratification. An optimized endogenous post-stratified estimator of the proportion of forest has been...

  13. Do Endogenous and Exogenous Action Control Compete for Perception?

    Science.gov (United States)

    Pfister, Roland; Heinemann, Alexander; Kiesel, Andrea; Thomaschke, Roland; Janczyk, Markus

    2012-01-01

    Human actions are guided either by endogenous action plans or by external stimuli in the environment. These two types of action control seem to be mediated by neurophysiologically and functionally distinct systems that interfere if an endogenously planned action suddenly has to be performed in response to an exogenous stimulus. In this case, the…

  14. Testing R&D-Based Endogenous Growth Models

    DEFF Research Database (Denmark)

    Kruse-Andersen, Peter Kjær

    2017-01-01

    is estimated using cointegrated VAR models. The results provide evidence against the widely used fully endogenous variety and in favor of the semi-endogenous variety. Forecasts based on the empirical estimates suggest that the slowdown in US productivity growth will continue. Particularly, the annual long...

  15. The potential of endogenous learning approaches to gender and ...

    African Journals Online (AJOL)

    USER

    continents in the multiplicity of gender perspectives. Therefore, this study explores Rwanda's effort to integrate endogenous learning in gender and development studies in Rwanda's effort to define their socio-cultural, economic, political being. Archie Mafege also affirms the importance of endogeneity in African scholarship.

  16. Endogenous change : On cooperation and water in ancient history

    NARCIS (Netherlands)

    Pande, S.; Ertsen, M.W.

    2013-01-01

    We propose and test the theory of endogenous change based on historical reconstructions of two ancient civilizations, Indus and Hohokam, in two water scarce basins, the Indus basin in the Indian subcontinent and the Lower Colorado basin in Southwestern United States. The endogenous institutional

  17. Specific Immune Stimulation by Endogenous Bacteria in Honey Bees (Hymenoptera: Apidae).

    Science.gov (United States)

    Janashia, Irakli; Alaux, Cédric

    2016-04-10

    Honey bees are highly important pollinators in agroecosystems, but they are currently under growing environmental pressures (e.g., from pesticides, poor nutrition, and parasites). Due to the multiplicity of environmental stress factors, their protection requires diverse and integrative approaches. Among those is the development of immunomodulatory tools, as immunosuppression is often observed in stressed bees. Toward this goal, the use of exogenous bacteria with immunomodulatory potential has recently been investigated, but knowledge about the potential of honey bee endogenous bacteria is limited. We therefore tested the influence of single strains of five species of endogenous lactic acid bacteria strains on the bee immune system during the larval stage. We measured the expression level of seven immune-related genes and the gene encoding the storage protein Hexamerin 70b. Two of the strains induced an immune stimulation, but this was limited to the antimicrobial peptide Apidaecin1. Upregulation of Apidaecin1 was associated to the downregulation of Hexamerin 70b. Those results suggest that the bee response to endogenous bacteria is specific both at the species and immune levels. As immune responses are costly, this specificity may be adaptive for saving energy and avoiding any negative side effects on the host development or survival. Further screening of bacteria immunomodulatory potential is needed, but associated immune cost needs to be taken into account for improving honey bee resilience to environmental stress. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Delivery of bioactive peptides and proteins across oral (buccal) mucosa.

    Science.gov (United States)

    Senel, S; Kremer, M; Nagy, K; Squier, C

    2001-06-01

    The identification of an increasing array of highly potent, endogenous peptide and protein factors termed cytokines, that can be efficiently synthesized using recombinant DNA technology, offers exciting new approaches for drug therapy. However, the physico-chemical and biological properties of these agents impose limitations in formulation and development of optimum drug delivery systems as well as on the routes of delivery. Oral mucosa, including the lining of the cheek (buccal mucosa), floor of mouth and underside of tongue (sublingual mucosa) and gingival mucosa, has received much attention in the last decade because it offers excellent accessibility, is not easily traumatized and avoids degradation of proteins and peptides that occurs as a result of oral administration, gastrointestinal absorption and first-pass hepatic metabolism. Peptide absorption occurs across oral mucosa by passive diffusion and it is unlikely that there is a carrier-mediated transport mechanism. The principal pathway is probably via the intercellular route where the major permeability barrier is represented by organized array of neutral lipids in the superficial layers of the epithelium. The relative role of aqueous as opposed to the lipid pathway in drug transport is still under investigation; penetration is not necessarily enhanced by simply increasing lipophilicity, for other effects, such as charge and molecular size, also play an important role in absorption of peptide and protein drugs. Depending on the pharmacodynamics of the peptides, various oral mucosal delivery systems can be designed. Delivery of peptide/protein drugs by conventional means such as solutions has some limitations. The possibility of excluding a major part of drug from absorption by involuntary swallowing and the continuous dilution due to salivary flow limits a controlled release. However these limitations can be overcome by adhesive dosage forms such as gels, films, tablets, and patches. They can localize the

  19. Conjugation of 3, 4-benzpyrene and 1, 2-benzanthracene with plant peptides

    International Nuclear Information System (INIS)

    Durmishidze, A.S.V.; Chrikishvili, D.I.; Devdariani, T.A.

    1993-01-01

    It is known that one of the main pathways in the biotransformation of certain xenobiotics is their conjugation with endogenous compounds of the plant cell. This work presents the results on the establishment of pathway of conjugation of BP and BA with endogenous compounds of the cell. Ten-day corn and pea seedlings, grown under sterile conditions, were incubated in aqueous solutions of [7,10 14 C]-3,4-benzpyrene and [9 14 C]-1,2-benzanthracene. The specific radioactivity of aqueous solutions of [7,10 14 C]-BP and [9 14 C]-BA was 2112·10 4 and 2006·10 4 Bq/ml, respectively. Individual highly radioactive conversion products of BP and BA were subjected to acid hydrolysis and qualitative analysis of the radioactive and nonradioactive compounds of the hydrolysates. An analysis of the nonradioactive components showed that they are peptides with various amino acid compositions. Thus, the investigated conversion products are conjugation products of hydroxy derivatives of BP and BA with endogenous cell peptides. The conversion products of BP and BA were investigated to detect conjugates with endogenous carbohydrates. Despite careful searches, the conjugates of interest could not be detected

  20. Bioluminescent probe for detecting endogenous hypochlorite in living mice.

    Science.gov (United States)

    Tang, Chunchao; Gao, Yuqi; Liu, Tingting; Lin, Yuxing; Zhang, Xiaomeng; Zhang, Chaochao; Li, Xiang; Zhang, Tianchao; Du, Lupei; Li, Minyong

    2018-01-24

    As a kind of biologically important reactive oxygen species (ROS), hypochlorite (ClO - ) plays a crucial role in many physiological processes. As such, endogenous ClO - is a powerful antibacterial agent during pathogen invasion. Nonetheless, excessive endogenous ClO - could pose a health threat to mammalian animals including humans. However, the detection of endogenous ClO - by bioluminescence probes in vivo remains a considerable challenge. Herein, based on a caged strategy, we developed a turn-on bioluminescent probe 1 for the highly selective detection of ClO - in vitro and imaging endogenous ClO - in a mouse inflammation model. We anticipate that such a probe could help us understand the role of endogenous ClO - in a variety of physiological and pathological processes.

  1. Monocular channels have a functional role in endogenous orienting.

    Science.gov (United States)

    Saban, William; Sekely, Liora; Klein, Raymond M; Gabay, Shai

    2018-03-01

    The literature has long emphasized the role of higher cortical structures in endogenous orienting. Based on evolutionary explanation and previous data, we explored the possibility that lower monocular channels may also have a functional role in endogenous orienting of attention. Sensitive behavioral manipulation was used to probe the contribution of monocularly segregated regions in a simple cue - target detection task. A central spatially informative cue, and its ensuing target, were presented to the same or different eyes at varying cue-target intervals. Results indicated that the onset of endogenous orienting was apparent earlier when the cue and target were presented to the same eye. The data provides converging evidence for the notion that endogenous facilitation is modulated by monocular portions of the visual stream. This, in turn, suggests that higher cortical mechanisms are not exclusively responsible for endogenous orienting, and that a dynamic interaction between higher and lower neural levels, might be involved. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Endogenous retroviruses mobilized during friend murine leukemia virus infection.

    Science.gov (United States)

    Boi, Stefano; Rosenke, Kyle; Hansen, Ethan; Hendrick, Duncan; Malik, Frank; Evans, Leonard H

    2016-12-01

    We have demonstrated in a mouse model that infection with a retrovirus can lead not only to the generation of recombinants between exogenous and endogenous gammaretrovirus, but also to the mobilization of endogenous proviruses by pseudotyping entire polytropic proviral transcripts and facilitating their infectious spread to new cells. However, the frequency of this occurrence, the kinetics, and the identity of mobilized endogenous proviruses was unclear. Here we find that these mobilized transcripts are detected after only one day of infection. They predominate over recombinant polytropic viruses early in infection, persist throughout the course of disease and are comprised of multiple different polytropic proviruses. Other endogenous retroviral elements such as intracisternal A particles (IAPs) were not detected. The integration of the endogenous transcripts into new cells could result in loss of transcriptional control and elevated expression which may facilitate pathogenesis, perhaps by contributing to the generation of polytropic recombinant viruses. Published by Elsevier Inc.

  3. Peptide Signals Encode Protein Localization▿

    OpenAIRE

    Russell, Jay H.; Keiler, Kenneth C.

    2007-01-01

    Many bacterial proteins are localized to precise intracellular locations, but in most cases the mechanism for encoding localization information is not known. Screening libraries of peptides fused to green fluorescent protein identified sequences that directed the protein to helical structures or to midcell. These peptides indicate that protein localization can be encoded in 20-amino-acid peptides instead of complex protein-protein interactions and raise the possibility that the location of a ...

  4. The Equine PeptideAtlas

    DEFF Research Database (Denmark)

    Bundgaard, Louise; Jacobsen, Stine; Sorensen, Mette A.

    2014-01-01

    Equine PeptideAtlas encompassing high-resolution tandem MS analyses of 51 samples representing a selection of equine tissues and body fluids from healthy and diseased animals. The raw data were processed through the Trans-Proteomic Pipeline to yield high quality identification of proteins and peptides...... analyses, and emphasizes the value of the Equine PeptideAtlas as a resource for the design of targeted quantitative proteomic studies....

  5. Structural Characterization of Peptide Antibodies

    DEFF Research Database (Denmark)

    Chailyan, Anna; Marcatili, Paolo

    2015-01-01

    The role of proteins as very effective immunogens for the generation of antibodies is indisputable. Nevertheless, cases in which protein usage for antibody production is not feasible or convenient compelled the creation of a powerful alternative consisting of synthetic peptides. Synthetic peptides...... can be modified to obtain desired properties or conformation, tagged for purification, isotopically labeled for protein quantitation or conjugated to immunogens for antibody production. The antibodies that bind to these peptides represent an invaluable tool for biological research and discovery...

  6. One Hundred Years of Peptide Chemistry

    Indian Academy of Sciences (India)

    thus a chiral center. Today, 20 amino acids are known as genetically encoded as building blocks of peptides and proteins. Almost all of them present in peptides have L-configura- tion. D-amino acids have been found only in small peptides of bacterial cell walls, peptide antibiotics and peptides in South American frog skin.

  7. Peptide Level Turnover Measurements Enable the Study of Proteoform Dynamics.

    Science.gov (United States)

    Zecha, Jana; Meng, Chen; Zolg, Daniel Paul; Samaras, Patroklos; Wilhelm, Mathias; Kuster, Bernhard

    2018-05-01

    The coordination of protein synthesis and degradation regulating protein abundance is a fundamental process in cellular homeostasis. Today, mass spectrometry-based technologies allow determination of endogenous protein turnover on a proteome-wide scale. However, standard dynamic SILAC (Stable Isotope Labeling in Cell Culture) approaches can suffer from missing data across pulse time-points limiting the accuracy of such analysis. This issue is of particular relevance when studying protein stability at the level of proteoforms because often only single peptides distinguish between different protein products of the same gene. To address this shortcoming, we evaluated the merits of combining dynamic SILAC and tandem mass tag (TMT)-labeling of ten pulse time-points in a single experiment. Although the comparison to the standard dynamic SILAC method showed a high concordance of protein turnover rates, the pulsed SILAC-TMT approach yielded more comprehensive data (6000 proteins on average) without missing values. Replicate analysis further established that the same reproducibility of turnover rate determination can be obtained for peptides and proteins facilitating proteoform resolved investigation of protein stability. We provide several examples of differentially turned over splice variants and show that post-translational modifications can affect cellular protein half-lives. For example, N-terminally processed peptides exhibited both faster and slower turnover behavior compared with other peptides of the same protein. In addition, the suspected proteolytic processing of the fusion protein FAU was substantiated by measuring vastly different stabilities of the cleavage products. Furthermore, differential peptide turnover suggested a previously unknown mechanism of activity regulation by post-translational destabilization of cathepsin D as well as the DNA helicase BLM. Finally, our comprehensive data set facilitated a detailed evaluation of the impact of protein

  8. Role of endogenous thiols in protection

    Science.gov (United States)

    Vos, O.

    Aminothiols represent the most important group of radioprotective compounds. The most effective compounds administered at an optimal dose and time before irradiation are able to provide a protection in mice with a dose reduction factor (DRF) of about 2-2.5. The working mechanism can partly be explained as a scavenging process of radicals induced in water and partly as a chemical repair process of injured DNA. The endogenous aminothiol which has far-out the highest intracellular concentration is glutathione (GSH). The importance of intracellular GSH in determining cellular radiosensitivity has been shown by irradiating cells that had very low GSH levels. Such cells appear to have a high radiosensitivity, especially in hypoxic conditions. On the other hand, it has been demonstrated that induction of a high GSH level (100-200% above the normal level) provides only a small protection. In vitro experiments with DNA indicate that thiols with a high positive charge condense in the vicinity of DNA and are effective protectors, whereas thiols with a negative charge are kep away from it and are poor protectors. In comparison with the most effective exogenous aminothiols like cysteamine and WR1065, GSH is not an effective radioprotector. Putative explanations for this relatively poor protective ability of GSH are presented.

  9. Enterococcus faecalis Endogenous Endophthalmitis from Valvular Endocarditis

    Directory of Open Access Journals (Sweden)

    Sidnei Barge

    2013-01-01

    Full Text Available We report a case of a 74-year-old female, with a mitral heart valve, who presented with pain and blurred vision in the right eye for 2 days. Her visual acuity was light perception (LP in the right eye and 20/40 in the left eye. Slit lamp examination showed corneal edema and hypopyon, and a view of the right fundus was impossible. Echography showed vitreous condensation. One day after presentation, the patient developed acute lung edema requiring hospitalization, so she was not submitted to vitreous tap and intravitreal treatment. The cardiac and systemic evaluations revealed a mitral endocarditis secondary to Enterococcus faecalis. The patient improved systemically with treatment with gentamicin, vancomycin, and linezolid. Her visual acuity remained as no LP, and her intraocular pressure (IOP has been controlled with brimonidine bid despite developing a total cataract with 360° posterior synechia. A cardiac source for endogenous endophthalmitis should be considered in the presence of a prosthetic cardiac valve. The treatment and followup must be made in cooperation with a cardiologist specialist, but the ophthalmologist can play a key role in the diagnosis.

  10. Endogenous retroviral promoter exaptation in human cancer

    Directory of Open Access Journals (Sweden)

    Artem Babaian

    2016-12-01

    Full Text Available Abstract Cancer arises from a series of genetic and epigenetic changes, which result in abnormal expression or mutational activation of oncogenes, as well as suppression/inactivation of tumor suppressor genes. Aberrant expression of coding genes or long non-coding RNAs (lncRNAs with oncogenic properties can be caused by translocations, gene amplifications, point mutations or other less characterized mechanisms. One such mechanism is the inappropriate usage of normally dormant, tissue-restricted or cryptic enhancers or promoters that serve to drive oncogenic gene expression. Dispersed across the human genome, endogenous retroviruses (ERVs provide an enormous reservoir of autonomous gene regulatory modules, some of which have been co-opted by the host during evolution to play important roles in normal regulation of genes and gene networks. This review focuses on the “dark side” of such ERV regulatory capacity. Specifically, we discuss a growing number of examples of normally dormant or epigenetically repressed ERVs that have been harnessed to drive oncogenes in human cancer, a process we term onco-exaptation, and we propose potential mechanisms that may underlie this phenomenon.

  11. Endogenous Retroviruses: With Us and Against Us

    Science.gov (United States)

    Meyer, Thomas J.; Rosenkrantz, Jimi L.; Carbone, Lucia; Chavez, Shawn L.

    2017-04-01

    Mammalian genomes are scattered with thousands of copies of endogenous retroviruses (ERVs), mobile genetic elements that are relics of ancient retroviral infections. After inserting copies into the germ line of a host, most ERVs accumulate mutations that prevent the normal assembly of infectious viral particles, becoming trapped in host genomes and unable to leave to infect other cells. While most copies of ERVs are inactive, some are transcribed and encode the proteins needed to generate new insertions at novel loci. In some cases, old copies are removed via recombination and other mechanisms. This creates a shifting landscape of ERV copies within host genomes. New insertions can disrupt normal expression of nearby genes via directly inserting into key regulatory elements or by containing regulatory motifs within their sequences. Further, the transcriptional silencing of ERVs via epigenetic modification may result in changes to the epigenetic regulation of adjacent genes. In these ways, ERVs can be potent sources of regulatory disruption as well as genetic innovation. Here, we provide a brief review of the association between ERVs and gene expression, especially as observed in pre-implantation development and placentation. Moreover, we will describe the roles ERVs may play in somatic tissues, mostly in the context of human disease, including cancer, neurodegenerative disorders, and schizophrenia. Lastly, we discuss the recent discovery that some ERVs may have been pressed into the service of their host genomes to aid in the innate immune response to exogenous viral infections.

  12. Endogenous hepadnaviruses, bornaviruses and circoviruses in snakes.

    Science.gov (United States)

    Gilbert, C; Meik, J M; Dashevsky, D; Card, D C; Castoe, T A; Schaack, S

    2014-09-22

    We report the discovery of endogenous viral elements (EVEs) from Hepadnaviridae, Bornaviridae and Circoviridae in the speckled rattlesnake, Crotalus mitchellii, the first viperid snake for which a draft whole genome sequence assembly is available. Analysis of the draft assembly reveals genome fragments from the three virus families were inserted into the genome of this snake over the past 50 Myr. Cross-species PCR screening of orthologous loci and computational scanning of the python and king cobra genomes reveals that circoviruses integrated most recently (within the last approx. 10 Myr), whereas bornaviruses and hepadnaviruses integrated at least approximately 13 and approximately 50 Ma, respectively. This is, to our knowledge, the first report of circo-, borna- and hepadnaviruses in snakes and the first characterization of non-retroviral EVEs in non-avian reptiles. Our study provides a window into the historical dynamics of viruses in these host lineages and shows that their evolution involved multiple host-switches between mammals and reptiles. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  13. The Effect of Globalization in an Endogenous Growth Model with Heterogeneous Firms and Endogenous International Spillovers: Note

    OpenAIRE

    Katsufumi Fukuda

    2013-01-01

    This paper shows that globalization increases (decreases) the growth rate if and only if the beachhead cost for the domestic market is strictly higher (lower) than that for the foreign market in a endogenous growth model with firm heterogeneity, international trade, and endogenous international spillover under specified necessary and sufficient conditions for exporting firms being more productive than non-exporting firms.

  14. Biochemical and pharmacological characterization of three opioid-nociceptin hybrid peptide ligands reveals substantially differing modes of their actions.

    Science.gov (United States)

    Erdei, Anna I; Borbély, Adina; Magyar, Anna; Taricska, Nóra; Perczel, András; Zsíros, Ottó; Garab, Győző; Szűcs, Edina; Ötvös, Ferenc; Zádor, Ferenc; Balogh, Mihály; Al-Khrasani, Mahmoud; Benyhe, Sándor

    2018-01-01

    In an attempt to design opioid-nociceptin hybrid peptides, three novel bivalent ligands, H-YGGFGGGRYYRIK-NH 2 , H-YGGFRYYRIK-NH 2 and Ac-RYYRIKGGGYGGFL-OH were synthesized and studied by biochemical, pharmacological, biophysical and molecular modelling tools. These chimeric molecules consist of YGGF sequence, a crucial motif in the N-terminus of natural opioid peptides, and Ac-RYYRIK-NH 2, which was isolated from a combinatorial peptide library as an antagonist or partial agonist that inhibits the biological activity of the endogenously occurring heptadecapeptide nociceptin. Solution structures for the peptides were studied by analysing their circular dichroism spectra. Receptor binding affinities were measured by equilibrium competition experiments using four highly selective radioligands. G-protein activating properties of the multitarget peptides were estimated in [ 35 S]GTPγS binding tests. The three compounds were also measured in electrically stimulated mouse vas deferens (MVD) bioassay. H-YGGFGGGRYYRIK-NH 2 (BA55), carrying N-terminal opioid and C-terminal nociceptin-like sequences interconnected with GGG tripeptide spacer displayed a tendency of having either unordered or β-sheet structures, was moderately potent in MVD and possessed a NOP/KOP receptor preference. A similar peptide without spacer H-YGGFRYYRIK-NH 2 (BA62) exhibited the weakest effect in MVD, more α-helical periodicity was present in its structure and it exhibited the most efficacious agonist actions in the G-protein stimulation assays. The third hybrid peptide Ac-RYYRIKGGGYGGFL-OH (BA61) unexpectedly displayed opioid receptor affinities, because the opioid message motif is hidden within the C-terminus. The designed chimeric peptide ligands presented in this study accommodate well into a group of multitarget opioid compounds that include opioid-non-opioid peptide dimer analogues, dual non-peptide dimers and mixed peptide- non-peptide bifunctional ligands. Copyright © 2017 Elsevier Inc

  15. Fully automated multidimensional reversed-phase liquid chromatography with tandem anion/cation exchange columns for simultaneous global endogenous tyrosine nitration detection, integral membrane protein characterization, and quantitative proteomics mapping in cerebral infarcts.

    Science.gov (United States)

    Quan, Quan; Szeto, Samuel S W; Law, Henry C H; Zhang, Zaijun; Wang, Yuqiang; Chu, Ivan K

    2015-10-06

    Protein tyrosine nitration (PTN) is a signature hallmark of radical-induced nitrative stress in a wide range of pathophysiological conditions, with naturally occurring abundances at substoichiometric levels. In this present study, a fully automated four-dimensional platform, consisting of high-/low-pH reversed-phase dimensions with two additional complementary, strong anion (SAX) and cation exchange (SCX), chromatographic separation stages inserted in tandem, was implemented for the simultaneous mapping of endogenous nitrated tyrosine-containing peptides within the global proteomic context of a Macaca fascicularis cerebral ischemic stroke model. This integrated RP-SA(C)X-RP platform was initially benchmarked through proteomic analyses of Saccharomyces cerevisiae, revealing extended proteome and protein coverage. A total of 27 144 unique peptides from 3684 nonredundant proteins [1% global false discovery rate (FDR)] were identified from M. fascicularis cerebral cortex tissue. The inclusion of the S(A/C)X columns contributed to the increased detection of acidic, hydrophilic, and hydrophobic peptide populations; these separation features enabled the concomitant identification of 127 endogenous nitrated peptides and 137 transmembrane domain-containing peptides corresponding to integral membrane proteins, without the need for specific targeted enrichment strategies. The enhanced diversity of the peptide inventory obtained from the RP-SA(C)X-RP platform also improved analytical confidence in isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analyses.

  16. Determination of nitrogen absorption and endogenous nitrogen secretion in the digestive tract of pigs fed with nitrogen-15-labelled dried whey

    International Nuclear Information System (INIS)

    Gebhardt, G.; Souffrant, W.; Koehler, R.; Zebrowska, T.

    1977-01-01

    Two fistulated pigs weighing between 15kg and 54kg were given experimental diets containing 15 N-labelled dried whey. The labelled experimental diets were given once only. Samples of the digesta were taken from the duodenum and terminal ileum at various intervals of time up to 48h after feeding the labelled protein feed. The digesta were separated into the four following fractions: Residue on centrifugation, proteins, peptides and free amino acids. The secretion of endogenous nitrogen in the duodenum was 12.5g/24h in pigs having a live weight of 50kg. The endogenous nitrogen was found to be relatively uniformly distributed among the four fractions. The rate of secretion of endogenous nitrogen showed a continuous decrease during 24h. The secretion of endogenous nitrogen in the terminal ileum was 54 to 60mg of nitrogen per kilogram live weight. After passage through the small intestine the greater part of the free amino acids in digesta was of exogenous origin. In the protein fraction most came from endogenous proteins. A true absorption of 17% of nitrogen was determined in the duodenum. The amount of nitrogen absorbed in the terminal part of the small intestine was, on average, 90% relative to the nitrogen intake. The true digestibility calculated with the amount of 15 N in food and faeces was 98%. (author)

  17. A simple in chemico method for testing skin sensitizing potential of chemicals using small endogenous molecules.

    Science.gov (United States)

    Nepal, Mahesh Raj; Shakya, Rajina; Kang, Mi Jeong; Jeong, Tae Cheon

    2018-06-01

    Among many of the validated methods for testing skin sensitization, direct peptide reactivity assay (DPRA) employs no cells or animals. Although no immune cells are involved in this assay, it reliably predicts the skin sensitization potential of a chemical in chemico. Herein, a new method was developed using endogenous small-molecular-weight compounds, cysteamine and glutathione, rather than synthetic peptides, to differentiate skin sensitizers from non-sensitizers with an accuracy as high as DPRA. The percent depletion of cysteamine and glutathione by test chemicals was measured by an HPLC equipped with a PDA detector. To detect small-size molecules, such as cysteamine and glutathione, a derivatization by 4-(4-dimethylaminophenylazo) benzenesulfonyl chloride (DABS-Cl) was employed prior to the HPLC analysis. Following test method optimization, a cut-off criterion of 7.14% depletion was applied to differentiate skin sensitizers from non-sensitizers in combination of the ratio of 1:25 for cysteamine:test chemical with 1:50 for glutathione:test chemical for the best predictivity among various single or combination conditions. Although overlapping HPLC peaks could not be fully resolved for some test chemicals, high levels of sensitivity (100.0%), specificity (81.8%), and accuracy (93.3%) were obtained for 30 chemicals tested, which were comparable or better than those achieved with DPRA. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Endogenous vasopressin and the central control of heart rate during dynamic exercise

    Directory of Open Access Journals (Sweden)

    L.C. Michelini

    1998-09-01

    Full Text Available The present article contains a brief review on the role of vasopressinergic projections to the nucleus tractus solitarii in the genesis of reflex bradycardia and in the modulation of heart rate control during exercise. The effects of vasopressin on exercise tachycardia are discussed on the basis of both the endogenous peptide content changes and the heart rate response changes observed during running in sedentary and trained rats. Dynamic exercise caused a specific vasopressin content increase in dorsal and ventral brainstem areas. In accordance, rats pretreated with the peptide or the V1 blocker into the nucleus tractus solitarii showed a significant potentiation or a marked blunting of the exercise tachycardia, respectively, without any change in the pressure response to exercise. It is proposed that the long-descending vasopressinergic pathway to the nucleus tractus solitarii serves as one link between the two main neural controllers of circulation, i.e., the central command and feedback control mechanisms driven by the peripheral receptors. Therefore, vasopressinergic input could contribute to the adjustment of heart rate response (and cardiac output to the circulatory demand during exercise.

  19. Peptide Vaccines for Cancer

    Directory of Open Access Journals (Sweden)

    Kono K

    2013-10-01

    Full Text Available Background: In general, the preferable characteristic of the target molecules for development of cancer vaccines are high immunogenicity, very common expression in cancer cells, specific expression in cancer cells and essential molecules for cell survival (to avoid loss of expression. We previously reported that three novel HLA-A24-restricted immunodominant peptides, which were derived from three different oncoantigens, TTK, LY6K, and IMP-3,were promising targets for cancer vaccination for esophageal squamous cell carcinoma (ESCCpatients. Then, we had performed a phase I clinical trial using three HLA-A24-binding peptides and the results had been shown to be promising for ESCC. Therefore, we further performed a multicenter, non-randomized phase II clinical trial. Patients and Methods: Sixty ESCC patients were enrolled to evaluate OS, PFS, immunological response employing ELISPOT and pentamer assays. Each of the three peptides was administered with IFA weekly. All patients received the vaccination without knowing an HLA-A type, and the HLA types were key-opened at the analysis point. Hence, the endpoints were set to evaluate differences between HLA-A*2402-positive (24(+ and -negative (24(- groups. Results: The OS in the 24 (+ group (n=35 tended to be better than that in the 24(- group (n=25 (MST 4.6 vs. 2.6 month, respectively, p = 0.121, although the difference was not statistically significant. However, the PFS in the 24(+ group was significantly better than that in the 24(- group (p = 0.032. In the 24(+ group, ELISPOT assay indicated that the LY6K-, TTK-, and IMP3-specific CTL responses were observed after the vaccination in 63%, 45%, and 60% of the 24(+ group, respectively. The patients having LY6K-, TTK-, and IMP3-specific CTL responses revealed the better OS than those not having CTL induction, respectively. The patients showing the CTL induction for multiple peptides have better clinical responses. Conclusion: The immune response induced

  20. The endogenous preproglucagon system is not essential for gut growth homeostasis in mice.

    Science.gov (United States)

    Wismann, Pernille; Barkholt, Pernille; Secher, Thomas; Vrang, Niels; Hansen, Henrik B; Jeppesen, Palle Bekker; Baggio, Laurie L; Koehler, Jacqueline A; Drucker, Daniel J; Sandoval, Darleen A; Jelsing, Jacob

    2017-07-01

    The prevalence of obesity and related co-morbidities is reaching pandemic proportions. Today, the most effective obesity treatments are glucagon-like peptide 1 (GLP-1) analogs and bariatric surgery. Interestingly, both intervention paradigms have been associated with adaptive growth responses in the gut; however, intestinotrophic mechanisms associated with or secondary to medical or surgical obesity therapies are poorly understood. Therefore, the objective of this study was to assess the local basal endogenous and pharmacological intestinotrophic effects of glucagon-like peptides and bariatric surgery in mice. We used in situ hybridization to provide a detailed and comparative anatomical map of the local distribution of GLP-1 receptor ( Glp1r ), GLP-2 receptor ( Glp2r ), and preproglucagon ( Gcg ) mRNA expression throughout the mouse gastrointestinal tract. Gut development in GLP-1R-, GLP-2R-, or GCG-deficient mice was compared to their corresponding wild-type controls, and intestinotrophic effects of GLP-1 and GLP-2 analogs were assessed in wild-type mice. Lastly, gut volume was determined in a mouse model of vertical sleeve gastrectomy (VSG). Comparison of Glp1r , Glp2r , and Gcg mRNA expression indicated a widespread, but distinct, distribution of these three transcripts throughout all compartments of the mouse gastrointestinal tract. While mice null for Glp1r or Gcg showed normal intestinal morphology, Glp2r -/- mice exhibited a slight reduction in small intestinal mucosa volume. Pharmacological treatment with GLP-1 and GLP-2 analogs significantly increased gut volume. In contrast, VSG surgery had no effect on intestinal morphology. The present study indicates that the endogenous preproglucagon system, exemplified by the entire GCG gene and the receptors for GLP-1 and GLP-2, does not play a major role in normal gut development in the mouse. Furthermore, elevation in local intestinal and circulating levels of GLP-1 and GLP-2 achieved after VSG has limited impact

  1. Peptide aptamers expressed in the secretory pathway interfere with cellular PrPSc formation.

    Science.gov (United States)

    Gilch, Sabine; Kehler, Claudia; Schätzl, Hermann M

    2007-08-10

    Prion diseases are rare and obligatory fatal neurodegenerative disorders caused by the accumulation of a misfolded isoform (PrPSc) of the host-encoded prion protein (PrPc). Prophylactic and therapeutic regimens against prion diseases are very limited. To extend such strategies we selected peptide aptamers binding to PrP from a combinatorial peptide library presented on the Escherichia coli thioredoxin A (trxA) protein as a scaffold. In a yeast two-hybrid screen employing full-length murine PrP (aa 23-231) as a bait we identified three peptide aptamers that reproducibly bind to PrP. Treatment of prion-infected cells with recombinantly expressed aptamers added to the culture medium abolished PrPSc conversion with an IC50 between 350 and 700 nM. For expression in eukaryotic cells, peptide aptamers were fused to an N-terminal signal peptide for entry of the secretory pathway. The C terminus was modified by a glycosyl-phosphatidyl-inositol-(GPI) anchoring signal, a KDEL retention motif and the transmembrane and cytosolic domain of LAMP-I, respectively. These peptide aptamers retained their binding properties to PrPc and, depending on peptide sequence and C-terminal modification, interfered with endogenous PrPSc conversion upon expression in prion-infected cells. Notably, infection of cell cultures could be prevented by expression of KDEL peptide aptamers. For the first time, we show that trxA-based peptide aptamers can be targeted to the secretory pathway, thereby not losing the affinity for their target protein. Beside their inhibitory effect on prion conversion, these molecules could be used as fundament for rational drug design.

  2. Localization of receptors for bombesin-like peptides in the rat brain

    International Nuclear Information System (INIS)

    Moody, T.W.; Getz, R.; O'Donohue, T.L.; Rosenstein, J.M.

    1988-01-01

    BN-like peptides and receptors are present in discrete areas of the mammalian brain. By radioimmunoassay, endogenous BN/GRP, neuromedin B, and ranatensin-like peptides are present in the rat brain. High-to-moderate concentrations of BN/GRP are present in the rat hypothalamus and thalamus, whereas moderate-to-high densities of neuromedin B and ranatensin-like peptides are present in the olfactory bulb and hippocampus, as well as in the hypothalamus and thalamus. While the distribution of neuromedin B and ranatensin-like peptides appears similar, it is distinct from that of BN/GRP. When released from CNS neurons, these peptides may interact with receptors for BN-like peptides. BN, GRP, ranatensin, and neuromedin B inhibit specific [ 125 I-Tyr4]BN binding with high affinity. By use of in vitro autoradiographic techniques to detect binding of [ 125 I-Tyr4]BN to receptors for BN-like peptides, high grain densities were found in the olfactory bulb and tubercle, the nucleus accumbens, the suprachiasmatic and paraventricular nucleus of the hypothalamus, the central medial and paraventricular thalamic nuclei, the hippocampus, the dentate gyrus, and the amygdala of the rat brain. Some of these receptors may be biologically active and mediate the biological effects of BN-like peptides. For example, when BN is directly injected into the nucleus accumbens, pronounced grooming results and the effects caused by BN are reversed by spantide and [D-Phe12]BN. Thus, the putative BN receptor antagonists may serve as useful agents to investigate the biological significance of BN-like peptides in the CNS

  3. Natriuretic peptides in cardiometabolic regulation and disease

    DEFF Research Database (Denmark)

    Zois, Nora E; Bartels, Emil D; Hunter, Ingrid

    2014-01-01

    these conditions can coexist and potentially lead to heart failure, a syndrome associated with a functional natriuretic peptide deficiency despite high circulating concentrations of immunoreactive peptides. Therefore, dysregulation of the natriuretic peptide system, a 'natriuretic handicap', might be an important...

  4. Radiolabeling of methionine containing proteins and peptides

    International Nuclear Information System (INIS)

    Garlick, R.K.; Jirousek, L.

    1986-01-01

    A process for radiolabeling methionine-containing peptides and proteins is disclosed. The process comprises the steps of oxidizing the protein or peptide, radiolabeling and reducing the radiolabeled protein or peptide. (author)

  5. Endogenous synthesis of corticosteroids in the hippocampus.

    Directory of Open Access Journals (Sweden)

    Shimpei Higo

    Full Text Available BACKGROUND: Brain synthesis of steroids including sex-steroids is attracting much attention. The endogenous synthesis of corticosteroids in the hippocampus, however, has been doubted because of the inability to detect deoxycorticosterone (DOC synthase, cytochrome P450(c21. METHODOLOGY/PRINCIPAL FINDINGS: The expression of P450(c21 was demonstrated using mRNA analysis and immmunogold electron microscopic analysis in the adult male rat hippocampus. DOC production from progesterone (PROG was demonstrated by metabolism analysis of (3H-steroids. All the enzymes required for corticosteroid synthesis including P450(c21, P450(2D4, P450(11β1 and 3β-hydroxysteroid dehydrogenase (3β-HSD were localized in the hippocampal principal neurons as shown via in situ hybridization and immunoelectron microscopic analysis. Accurate corticosteroid concentrations in rat hippocampus were determined by liquid chromatography-tandem mass spectrometry. In adrenalectomized rats, net hippocampus-synthesized corticosterone (CORT and DOC were determined to 6.9 and 5.8 nM, respectively. Enhanced spinogenesis was observed in the hippocampus following application of low nanomolar (10 nM doses of CORT for 1 h. CONCLUSIONS/SIGNIFICANCE: These results imply the complete pathway of corticosteroid synthesis of 'pregnenolone →PROG→DOC→CORT' in the hippocampal neurons. Both P450(c21 and P450(2D4 can catalyze conversion of PROG to DOC. The low nanomolar level of CORT synthesized in hippocampal neurons may play a role in modulation of synaptic plasticity, in contrast to the stress effects by micromolar CORT from adrenal glands.

  6. Manager's effort and endogenous economic discrimination

    Directory of Open Access Journals (Sweden)

    Jaime Orrillo

    2004-09-01

    Full Text Available Assume a labor supply consisting of two types of workers, 1 and 2. Both workers are equally productive and exhibit supply functions with the same elasticity. We consider a firm (entrepreneur or shareholders that is competitive in the output market and monopsonistic in input markets. The firm uses the services of a manager who has a high human capital and whose wage is given by the market. It is supposed that the manager does not like to work with one type of worker, say type 1. If we allow the manager's effort to be an additional input without any extra (in addition to his salary cost for the firm, then the firm's pricing decision will be different for both workers. That is, there will be a wage differential and therefore endogenous economic discrimination2 in the labor markets.Vamos assumir que a oferta de trabalho consiste de dois tipos de trabalhadores, 1 e 2. Ambos os trabalhadores são igualmente produtivos e exibem funções de oferta com a mesma elasticidade. Consideramos uma firma (empresário ou acionistas, a qual é competitiva no mercado de produtos e monopsonista nos mercados de insumos. A firma usa os serviços de um gerente quem tem um alto capital humano e cujo salário é dado pelo mercado. Suponhamos que o gerente não gosta de trabalhar com um tipo de trabalhador, digamos o tipo 1. Se permitirmos que o esforço do gerente seja um insumo adicional sem nenhum custo extra (além de seu salário, a decisão de salários será diferente para ambos os trabalhadores. Isto é, haverá um diferencial de salários e, em conseqüência, uma discriminação econômica1 endógena nos mercados de trabalho.

  7. Mitochondrial respiratory function induces endogenous hypoxia.

    Science.gov (United States)

    Prior, Sara; Kim, Ara; Yoshihara, Toshitada; Tobita, Seiji; Takeuchi, Toshiyuki; Higuchi, Masahiro

    2014-01-01

    Hypoxia influences many key biological functions. In cancer, it is generally believed that hypoxic condition is generated deep inside the tumor because of the lack of oxygen supply. However, consumption of oxygen by cancer should be one of the key means of regulating oxygen concentration to induce hypoxia but has not been well studied. Here, we provide direct evidence of the mitochondrial role in the induction of intracellular hypoxia. We used Acetylacetonatobis [2-(2'-benzothienyl) pyridinato-kN, kC3'] iridium (III) (BTP), a novel oxygen sensor, to detect intracellular hypoxia in living cells via microscopy. The well-differentiated cancer cell lines, LNCaP and MCF-7, showed intracellular hypoxia without exogenous hypoxia in an open environment. This may be caused by high oxygen consumption, low oxygen diffusion in water, and low oxygen incorporation to the cells. In contrast, the poorly-differentiated cancer cell lines: PC-3 and MDAMB231 exhibited intracellular normoxia by low oxygen consumption. The specific complex I inhibitor, rotenone, and the reduction of mitochondrial DNA (mtDNA) content reduced intracellular hypoxia, indicating that intracellular oxygen concentration is regulated by the consumption of oxygen by mitochondria. HIF-1α was activated in endogenously hypoxic LNCaP and the activation was dependent on mitochondrial respiratory function. Intracellular hypoxic status is regulated by glucose by parabolic dose response. The low concentration of glucose (0.045 mg/ml) induced strongest intracellular hypoxia possibly because of the Crabtree effect. Addition of FCS to the media induced intracellular hypoxia in LNCaP, and this effect was partially mimicked by an androgen analog, R1881, and inhibited by the anti-androgen, flutamide. These results indicate that mitochondrial respiratory function determines intracellular hypoxic status and may regulate oxygen-dependent biological functions.

  8. Mitochondrial respiratory function induces endogenous hypoxia.

    Directory of Open Access Journals (Sweden)

    Sara Prior

    Full Text Available Hypoxia influences many key biological functions. In cancer, it is generally believed that hypoxic condition is generated deep inside the tumor because of the lack of oxygen supply. However, consumption of oxygen by cancer should be one of the key means of regulating oxygen concentration to induce hypoxia but has not been well studied. Here, we provide direct evidence of the mitochondrial role in the induction of intracellular hypoxia. We used Acetylacetonatobis [2-(2'-benzothienyl pyridinato-kN, kC3'] iridium (III (BTP, a novel oxygen sensor, to detect intracellular hypoxia in living cells via microscopy. The well-differentiated cancer cell lines, LNCaP and MCF-7, showed intracellular hypoxia without exogenous hypoxia in an open environment. This may be caused by high oxygen consumption, low oxygen diffusion in water, and low oxygen incorporation to the cells. In contrast, the poorly-differentiated cancer cell lines: PC-3 and MDAMB231 exhibited intracellular normoxia by low oxygen consumption. The specific complex I inhibitor, rotenone, and the reduction of mitochondrial DNA (mtDNA content reduced intracellular hypoxia, indicating that intracellular oxygen concentration is regulated by the consumption of oxygen by mitochondria. HIF-1α was activated in endogenously hypoxic LNCaP and the activation was dependent on mitochondrial respiratory function. Intracellular hypoxic status is regulated by glucose by parabolic dose response. The low concentration of glucose (0.045 mg/ml induced strongest intracellular hypoxia possibly because of the Crabtree effect. Addition of FCS to the media induced intracellular hypoxia in LNCaP, and this effect was partially mimicked by an androgen analog, R1881, and inhibited by the anti-androgen, flutamide. These results indicate that mitochondrial respiratory function determines intracellular hypoxic status and may regulate oxygen-dependent biological functions.

  9. Lacto-ghrestatin, a novel bovine milk-derived peptide, suppresses ghrelin secretion.

    Science.gov (United States)

    Aoki, Hayato; Nakato, Junya; Mizushige, Takafumi; Iwakura, Hiroshi; Sato, Masaru; Suzuki, Hideyuki; Kanamoto, Ryuhei; Ohinata, Kousaku

    2017-07-01

    Ghrelin, an endogenous peptide isolated from the stomach, is known to stimulate food intake after peripheral administration. We found that the enzymatic digest of β-lactoglobulin decreases ghrelin secretion from the ghrelin-producing cell line MGN3-1. The peptides present in the digest were comprehensively analyzed using the nanoLC-OrbitrapMS. Among them, we identified that the nonapeptide LIVTQTMKG, corresponding to β-lactoglobulin(1-9), suppresses ghrelin secretion from MGN3-1 cells. We named LIVTQTMKG 'lacto-ghrestatin'. We found that lacto-ghrestatin decreases intracellular cAMP levels and mRNA expression levels of ghrelin production-related genes in MGN3-1 cells. Orally administered lacto-ghrestatin decreases plasma ghrelin levels and food intake in fasted mice. Lacto-ghrestatin is the first food-derived peptide to suppress ghrelin secretion in vitro and in vivo. © 2017 Federation of European Biochemical Societies.

  10. The vasorelaxant effect of adrenomedullin, proadrenomedullin N-terminal 20 peptide and amylin in human skin

    DEFF Research Database (Denmark)

    Hasbak, Philip; Eskesen, Karen; Lind, Peter Henrik

    2006-01-01

    ) and substance P and to examine the mRNA expression of calcitonin receptor-like receptor (CL-R) and receptor-activity modifying proteins, RAMP1, RAMP 2 and RAMP3 in human subcutaneous arteries. Changes in skin blood flow of the forearm were measured using a Laser Doppler Imager after intradermal injection......In this study we aimed to assess in vivo, the vasodilator effects of adrenomedullin, proadrenomedullin N-terminal 20 peptide (PAMP) and amylin in human skin vasculature and compare the responses to the effects mediated by the endogenous neuropeptides calcitonin gene-related peptide (CGRP...... of the peptides. The mRNA expression was assessed by real-time reverse transcriptase-polymerase chain reaction (real-time PCR). CGRP, adrenomedullin and amylin induced concentration-dependent, long-lasting increases in skin blood flow. The response to PAMP was shorter in duration appearing similar...

  11. Peptide radiopharmaceuticals in nuclear medicine

    International Nuclear Information System (INIS)

    Blok, D.; Vermeij, P.; Feitsma, R.I.J.; Pauwels, E.J.K.

    1999-01-01

    This article reviews the labelling of peptides that are recognised to be of interest for nuclear medicine or are the subject of ongoing nuclear medicine research. Applications and approaches to the labelling of peptide radiopharmaceuticals are discussed, and drawbacks in their development considered. (orig.)

  12. Antimicrobial peptides in the airway.

    Science.gov (United States)

    Laube, D M; Yim, S; Ryan, L K; Kisich, K O; Diamond, G

    2006-01-01

    The airway provides numerous defense mechanisms to prevent microbial colonization by the large numbers of bacteria and viruses present in ambient air. An important component of this defense is the antimicrobial peptides and proteins present in the airway surface fluid (ASF), the mucin-rich fluid covering the respiratory epithelium. These include larger proteins such as lysozyme and lactoferrin, as well as the cationic defensin and cathelicidin peptides. While some of these peptides, such as human beta-defensin (hBD)-1, are present constitutively, others, including hBD2 and -3 are inducible in response to bacterial recognition by Toll-like receptor-mediated pathways. These peptides can act as microbicides in the ASF, but also exhibit other activities, including potent chemotactic activity for cells of the innate and adaptive immune systems, suggesting they play a complex role in the host defense of the airway. Inhibition of antimicrobial peptide activity or gene expression can result in increased susceptibility to infections. This has been observed with cystic fibrosis (CF), where the CF phenotype leads to reduced antimicrobial capacity of peptides in the airway. Pathogenic virulence factors can inhibit defensin gene expression, as can environmental factors such as air pollution. Such an interference can result in infections by airway-specific pathogens including Bordetella bronchiseptica, Mycobacterium tuberculosis, and influenza virus. Research into the modulation of peptide gene expression in animal models, as well as the optimization of peptide-based therapeutics shows promise for the treatment and prevention of airway infectious diseases.

  13. Peptide-LNA oligonucleotide conjugates

    DEFF Research Database (Denmark)

    Astakhova, I Kira; Hansen, Lykke Haastrup; Vester, Birte

    2013-01-01

    properties, peptides were introduced into oligonucleotides via a 2'-alkyne-2'-amino-LNA scaffold. Derivatives of methionine- and leucine-enkephalins were chosen as model peptides of mixed amino acid content, which were singly and doubly incorporated into LNA/DNA strands using highly efficient copper...

  14. Chemical Synthesis of Antimicrobial Peptides.

    Science.gov (United States)

    Münzker, Lena; Oddo, Alberto; Hansen, Paul R

    2017-01-01

    Solid-phase peptide synthesis (SPPS) is the method of choice for chemical synthesis of peptides. In this nonspecialist review, we describe commonly used resins, linkers, protecting groups, and coupling reagents in 9-fluorenylmethyloxycarbonyl (Fmoc) SPPS. Finally, a detailed protocol for manual Fmoc SPPS is presented.

  15. Synthetic peptides for antibody production

    NARCIS (Netherlands)

    N.D. Zegers (Netty)

    1995-01-01

    textabstractSynthetic peptides are useful tools for the generation of antibodies. The use of antibodies as specific reagents in inununochemical assays is widely applied. In this chapter, the application of synthetic peptides for the generation of antibodies is described. The different steps

  16. Synthetic peptides for antibody production

    NARCIS (Netherlands)

    Zegers, N.D.

    1995-01-01

    Synthetic peptides are useful tools for the generation of antibodies. The use of antibodies as specific reagents in inununochemical assays is widely applied. In this chapter, the application of synthetic peptides for the generation of antibodies is described. The different steps that lead to the

  17. Urinary Peptides in Rett Syndrome.

    Science.gov (United States)

    Solaas, K. M.; Skjeldal, O.; Gardner, M. L. G.; Kase, B. F.; Reichelt, K. L.

    2002-01-01

    A study found a significantly higher level of peptides in the urine of 53 girls with Rett syndrome compared with controls. The elevation was similar to that in 35 girls with infantile autism. Levels of peptides were lower in girls with classic Rett syndrome than those with congenital Rett syndrome. (Contains references.) (Author/CR)

  18. Solid-phase peptide synthesis

    DEFF Research Database (Denmark)

    Jensen, Knud Jørgen

    2013-01-01

    This chapter provides an introduction to and overview of peptide chemistry with a focus on solid-phase peptide synthesis. The background, the most common reagents, and some mechanisms are presented. This chapter also points to the different chapters and puts them into perspective....

  19. Demonstration of endogenous imipramine like material in rat brain

    International Nuclear Information System (INIS)

    Rehavi, M.; Ventura, I.; Sarne, Y.

    1985-01-01

    The extraction and partial purification of an endogenous imipramine-like material from rat brain is described. The endogenous factor obtained after gel filtration and silica chromatography inhibits [ 3 H] imipramine specific binding and mimics the inhibitory effect of imipramine on [ 3 H] serotonin uptake in both brain and platelet preparations. The effects of the endogenous material are dose-dependent and it inhibits [ 3 H] imipramine binding in a competitive fashion. The factor is unevenly distributed in the brain with high concentration in the hypothalamus and low concentration in the cerebellum

  20. Amplification and chromosomal dispersion of human endogenous retroviral sequences

    Energy Technology Data Exchange (ETDEWEB)

    Steele, P.E.; Martin, M.A.; Rabson, A.B.; Bryan, T.; O' Brien, S.J.

    1986-09-01

    Endogenous retroviral sequences have undergone amplification events involving both viral and flanking cellular sequences. The authors cloned members of an amplified family of full-length endogenous retroviral sequences. Genomic blotting, employing a flanking cellular DNA probe derived from a member of this family, revealed a similar array of reactive bands in both humans and chimpanzees, indicating that an amplification event involving retroviral and associated cellular DNA sequences occurred before the evolutionary separation of these two primates. Southern analyses of restricted somatic cell hybrid DNA preparations suggested that endogenous retroviral segments are widely dispersed in the human genome and that amplification and dispersion events may be linked.

  1. Amplification and chromosomal dispersion of human endogenous retroviral sequences

    International Nuclear Information System (INIS)

    Steele, P.E.; Martin, M.A.; Rabson, A.B.; Bryan, T.; O'Brien, S.J.

    1986-01-01

    Endogenous retroviral sequences have undergone amplification events involving both viral and flanking cellular sequences. The authors cloned members of an amplified family of full-length endogenous retroviral sequences. Genomic blotting, employing a flanking cellular DNA probe derived from a member of this family, revealed a similar array of reactive bands in both humans and chimpanzees, indicating that an amplification event involving retroviral and associated cellular DNA sequences occurred before the evolutionary separation of these two primates. Southern analyses of restricted somatic cell hybrid DNA preparations suggested that endogenous retroviral segments are widely dispersed in the human genome and that amplification and dispersion events may be linked

  2. Strategies for the photo-control of endogenous protein activity.

    Science.gov (United States)

    Brechun, Katherine E; Arndt, Katja M; Woolley, G Andrew

    2017-08-01

    Photo-controlled or 'optogenetic' effectors interfacing with endogenous protein machinery allow the roles of endogenous proteins to be probed. There are two main approaches being used to develop optogenetic effectors: (i) caging strategies using photo-controlled conformational changes, and (ii) protein relocalization strategies using photo-controlled protein-protein interactions. Numerous specific examples of these approaches have been reported and efforts to develop general methods for photo-control of endogenous proteins are a current focus. The development of improved screening and selection methods for photo-switchable proteins would advance the field. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Maize Bioactive Peptides against Cancer

    Science.gov (United States)

    Díaz-Gómez, Jorge L.; Castorena-Torres, Fabiola; Preciado-Ortiz, Ricardo E.; García-Lara, Silverio

    2017-06-01

    Cancer is one of the main chronic degenerative diseases worldwide. In recent years, consumption of whole-grain cereals and their derived food products has been associated with reduction risks of various types of cancer. Cereals main biomolecules includes proteins, peptides, and amino acids present in different quantities within the grain. The nutraceutical properties associated with peptides exerts biological functions that promote health and prevent this disease. In this review, we report the current status and advances on maize peptides regarding bioactive properties that have been reported such as antioxidant, antihypertensive, hepatoprotective, and anti-tumour activities. We also highlighted its biological potential through which maize bioactive peptides exert anti-cancer activity. Finally, we analyse and emphasize the possible areas of application for maize peptides.

  4. A simple endogenous growth model with endogenous fertility: indeterminacy and uniqueness.

    Science.gov (United States)

    Yip, C K; Zhang, J

    1997-01-01

    Considerable literature exists upon the effect of population growth upon per capita income growth. Among the reported studies, Brander and Dowrick (1994) try to explain the large variation across countries in per capita income growth. The authors explore the possibility that even with little differences in fertility rates, different countries may experience disparate growth performances solely due to the emergence of indeterminate equilibria, which could push them into different equilibrium trajectories. The equilibrium dynamics and indeterminacy of equilibria in an endogenous growth model with endogenous fertility choice are studied. The authors characterize the conditions which give rise to a unique equilibrium as well as multiple equilibria. When a unique equilibrium exists, it will be globally determinate, and when multiple equilibria arise, indeterminacy occurs. Two equilibria were found to occur, one associated with high fertility and low growth and the other with low fertility and high growth. A parameterized example is presented to assess the empirical feasibility of results. The validity of the neo-Malthusian relation between fertility and growth is then re-examined. The authors also explore the relationship between growth and welfare, and compare different balanced growth equilibria in terms of their lifetime attained utility.

  5. Hyperthermic responses to central injections of some peptide and non-peptide opioids in the guinea-pig

    Science.gov (United States)

    Kandasamy, S. B.; Williams, B. A.

    1983-01-01

    The intracerebroventricular administration of prototype nonpeptide opioid receptor (mu, kappa, and sigma) agonists, morphine, ketocyclazocine, and N-allyl normetazocine and an agonist at both kappa and sigma receptors, pentazocine, was found to induce hyperthermia in guinea pigs. The similar administration of peptide opioids like beta endorphin, methionine endkephalin, leucine endkephaline, and several of their synthetic analogues was also found to cause hyperthermia. Only the liver-like transport system of the three anion transport systems (iodide, hippurate, and liver-like) present in the choroid plexus was determined to be important to the central inactivation of beta-endorphin and two synthetic analogues. Prostaglandins and norepinephrine (NE) as well as cAMP were not involved in peptide and nonpeptide opioid-induced hyperthermia. Naloxone-sensitive receptors were found to be involved in the induction of hyperthermia by morphine and beta-endorphin, while hyperthermic responses to ketocyclazocine, N-allyl normetazocine, pentazocine, Met-enkephalin, Leu-enkephalin, and two of the synthetic analogues were not antagonized by nalozone. The lack of antagonism of naloxone on pyrogen, arachidonic acid, PGE2, dibutyryl cAMP, and NE-induced hyperthermia shows that endogenous opioid peptides are not likely to be central mediators of the hyperthermia induced by these agents.

  6. Neural tissue engineering: Bioresponsive nanoscaffolds using engineered self-assembling peptides.

    Science.gov (United States)

    Koss, K M; Unsworth, L D

    2016-10-15

    Rescuing or repairing neural tissues is of utmost importance to the patient's quality of life after an injury. To remedy this, many novel biomaterials are being developed that are, ideally, non-invasive and directly facilitate neural wound healing. As such, this review surveys the recent approaches and applications of self-assembling peptides and peptide amphiphiles, for building multi-faceted nanoscaffolds for direct application to neural injury. Specifically, methods enabling cellular interactions with the nanoscaffold and controlling the release of bioactive molecules from the nanoscaffold for the express purpose of directing endogenous cells in damaged or diseased neural tissues is presented. An extensive overview of recently derived self-assembling peptide-based materials and their use as neural nanoscaffolds is presented. In addition, an overview of potential bioactive peptides and ligands that could be used to direct behaviour of endogenous cells are categorized with their biological effects. Finally, a number of neurotrophic and anti-inflammatory drugs are described and discussed. Smaller therapeutic molecules are emphasized, as they are thought to be able to have less potential effect on the overall peptide self-assembly mechanism. Options for potential nanoscaffolds and drug delivery systems are suggested. Self-assembling nanoscaffolds have many inherent properties making them amenable to tissue engineering applications: ease of synthesis, ease of customization with bioactive moieties, and amenable for in situ nanoscaffold formation. The combination of the existing knowledge on bioactive motifs for neural engineering and the self-assembling propensity of peptides is discussed in specific reference to neural tissue engineering. Copyright © 2016. Published by Elsevier Ltd.

  7. Cathepsin-Mediated Cleavage of Peptides from Peptide Amphiphiles Leads to Enhanced Intracellular Peptide Accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Acar, Handan [Institute; Department; Samaeekia, Ravand [Institute; Department; Schnorenberg, Mathew R. [Institute; Department; Medical; Sasmal, Dibyendu K. [Institute; Huang, Jun [Institute; Tirrell, Matthew V. [Institute; Institute; LaBelle, James L. [Department

    2017-08-24

    Peptides synthesized in the likeness of their native interaction domain(s) are natural choices to target protein protein interactions (PPIs) due to their fidelity of orthostatic contact points between binding partners. Despite therapeutic promise, intracellular delivery of biofunctional peptides at concentrations necessary for efficacy remains a formidable challenge. Peptide amphiphiles (PAs) provide a facile method of intracellular delivery and stabilization of bioactive peptides. PAs consisting of biofunctional peptide headgroups linked to hydrophobic alkyl lipid-like tails prevent peptide hydrolysis and proteolysis in circulation, and PA monomers are internalized via endocytosis. However, endocytotic sequestration and steric hindrance from the lipid tail are two major mechanisms that limit PA efficacy to target intracellular PPIs. To address these problems, we have constructed a PA platform consisting of cathepsin-B cleavable PAs in which a selective p53-based inhibitory peptide is cleaved from its lipid tail within endosomes, allowing for intracellular peptide accumulation and extracellular recycling of the lipid moiety. We monitor for cleavage and follow individual PA components in real time using a resonance energy transfer (FRET)-based tracking system. Using this platform, components in real time using a Forster we provide a better understanding and quantification of cellular internalization, trafficking, and endosomal cleavage of PAs and of the ultimate fates of each component.

  8. Purification and use of E. coli peptide deformylase for peptide deprotection in chemoenzymatic peptide synthesis

    NARCIS (Netherlands)

    Di Toma, Claudia; Sonke, Theo; Quaedflieg, Peter J.; Janssen, Dick B.

    Peptide deformylases (PDFs) catalyze the removal of the formyl group from the N-terminal methionine residue in nascent polypeptide chains in prokaryotes. Its deformylation activity makes PDF an attractive candidate for the biocatalytic deprotection of formylated peptides that are used in

  9. Detection and distribution of endogenous steroids in human stratum corneum

    Directory of Open Access Journals (Sweden)

    Shu-Ping Tseng

    2014-03-01

    Conclusion: The results demonstrate that, with the achievable sensitivity of current analytical technology, physiological concentrations of endogenous steroids, such as hydrocortisone and cortisone, can be found in the SC of some individuals.

  10. Quantitative regularities of development of endogenous infection in irradiated organism

    International Nuclear Information System (INIS)

    Mal'tsev, V.N.

    1979-01-01

    A statistical analysis of data from the literature and the author's own experimental results are reviewed to show the functional relationships between the radiation dose and the development of endogenous infection in irradiated organisms. A direct linear dependence was found between the dose of radiation and the severity of endogenous infection at doses causing death from the ''bone marrow'' syndrome in acute radiation sickness. In case of death from the ''intestinal'' syndrome, an inverse linear dependence can be observed between the radiation dose and the culture yield of microbes from internal organs. In this case, the pathological effect on the organism is due to bacterial endotoxins formed during the disintegration of microbial cells in the organism. Endogenous infection and endotoxinaemia essentially aggravate the progress of acute radiation disease. The importance of endogenous infection for the death of the organism is minimized in irradiation at doses causing death ''under the ray''. (author)

  11. Endogenous vehicle-type choices in a monocentric city

    DEFF Research Database (Denmark)

    Kim, Jinwon

    2012-01-01

    Motivated by several empirical studies showing a positive relationship between residential density and vehicle fuel efficiency chosen by the residents, this paper presents a modified monocentric city model with endogenous vehicle-typechoices. Consumers are assumed to explicitly consider driving...

  12. Importance of Endogenous Fibrinolysis in Platelet Thrombus Formation.

    Science.gov (United States)

    Gue, Ying X; Gorog, Diana A

    2017-08-25

    The processes of thrombosis and coagulation are finely regulated by endogenous fibrinolysis maintaining healthy equilibrium. When the balance is altered in favour of platelet activation and/or coagulation, or if endogenous fibrinolysis becomes less efficient, pathological thrombosis can occur. Arterial thrombosis remains a major cause of morbidity and mortality in the world despite advances in medical therapies. The role endogenous fibrinolysis in the pathogenesis of arterial thrombosis has gained increasing attention in recent years as it presents novel ways to prevent and treat existing diseases. In this review article, we discuss the role of endogenous fibrinolysis in platelet thrombus formation, methods of measurement of fibrinolytic activity, its role in predicting cardiovascular diseases and clinical outcomes and future directions.

  13. Isolating Exogenous and Endogenous Modes of Temporal Attention

    Science.gov (United States)

    Lawrence, Michael A.; Klein, Raymond M.

    2013-01-01

    The differential allocation of information processing resources over time, here termed "temporal attention," may be achieved by relatively automatic "exogenous" or controlled "endogenous" mechanisms. Over 100 years of research has confounded these theoretically distinct dimensions of temporal attention. The current…

  14. Sucessfull management of bilateral presumed Candida endogenous endophtalmitis following pancreatitis

    OpenAIRE

    Aragão, Ricardo Evangelista Marrocos de; Barreira, Ieda Maria Alexandre; Oliveira Neto, Francisco Holanda; Beserra, Felipe de Freitas; Araujo, Cesar Pereira de; Nascimento, Carine Soares Ramos do

    2016-01-01

    ABSTRACT Endogenous endophthalmitis is a rare, and frequently devastating, ophthalmic disease. It occurs mostly in immunocompromised patients, or those with diabetes mellitus, cancer or intravenous drugs users. Candida infection is the most common cause of endogenous endophthalmitis. Ocular candidiasis develops within days to weeks of fungemia. The association of treatment for pancreatitis with endophthalmitis is unusual. Treatment with broad-spectrum antibiotics and total parenteral nutritio...

  15. A General Outlook to the Endogenous Money Theory

    OpenAIRE

    ÖZGÜR, Gökçer

    2008-01-01

    The purpose of this study is to shed light on theorigins of the endogenous money theory and analyze the currentdebates on this topic. Endogenous money approach depends on a fundamental postulate: As banks meet the credit needs ofnon-financial businesses, new deposits emerge in the banking sector. Similarly,as the necessary reserves found for these new deposits the broad money expandsas well. Even though the central bank can intervene into this process it cannotfully control it. There...

  16. Invasive fungal infections in endogenous Cushing’s syndrome

    Directory of Open Access Journals (Sweden)

    Rafael Selbach Scheffel

    2010-06-01

    Full Text Available Cushing’s syndrome is a condition characterized by elevated cortisol levels that can result from either augmented endogenous production or exogenous administration of corticosteroids. The predisposition to fungal infections among patients with hypercortisolemia has been noted since Cushing’s original description of the disease. We describe here a patient with endo-genous Cushing’s syndrome secondary to an adrenocortical carcinoma, who developed concomitant disseminated cryptococcosis and candidiasis in the course of his disease.

  17. A generalized endogenous grid method for discrete-continuous choice

    OpenAIRE

    John Rust; Bertel Schjerning; Fedor Iskhakov

    2012-01-01

    This paper extends Carroll's endogenous grid method (2006 "The method of endogenous gridpoints for solving dynamic stochastic optimization problems", Economic Letters) for models with sequential discrete and continuous choice. Unlike existing generalizations, we propose solution algorithm that inherits both advantages of the original method, namely it avoids all root finding operations, and also efficiently deals with restrictions on the continuous decision variable. To further speed up the s...

  18. A Reformulation of Normative Economics for Models with Endogenous Preferences

    OpenAIRE

    Vipul Bhatt; Masao Ogaki; Yuichi Yaguchi

    2014-01-01

    This paper proposes a framework to balance considerations of welfarism and virtue ethics in the normative analysis of economic models with endogenous preferences. We introduce the moral evaluation function (MEF), which ranks alternatives based purely on virtue ethics, and define the social objective function (SOF), which combines the Social Welfare Function (SWF) and the MEF. In a model of intergenerational altruism with endogenous time preference, using numerical simulations we show that max...

  19. A Reformulation of Normative Economics for Models with Endogenous

    OpenAIRE

    Bhatt, Vipul; Ogaki, Masao; Yaguchi, Yuichi

    2015-01-01

    This paper proposes a framework to balance considerations of welfarism and virtue ethics in the normative analysis of economic models with endogenous preferences. We introduce the moral evaluation function (MEF), which ranks alternatives based purely on virtue ethics, and define the social objective function (SOF), which combines the Social Welfare Function (SWF) and the MEF. In a model of intergenerational altruism with endogenous time preference, using numerical simulations we show that max...

  20. Gut Microbial Glycerol Metabolism as an Endogenous Acrolein Source

    OpenAIRE

    Zhang, Jianbo; Sturla, Shana; Lacroix, Christophe; Schwab, Clarissa

    2018-01-01

    ABSTRACT Acrolein is a highly reactive electrophile causing toxic effects, such as DNA and protein adduction, oxidative stress, endoplasmic reticulum stress, immune dysfunction, and membrane damage. This Opinion/Hypothesis provides an overview of endogenous and exogenous acrolein sources, acrolein’s mode of action, and its metabolic fate. Recent reports underpin the finding that gut microbial glycerol metabolism leading to the formation of reuterin is an additional source of endogenous acrole...

  1. EXOGENOUS OR ENDOGENOUS MONEY SUPPLY: EVIDENCE FROM AUSTRALIA

    OpenAIRE

    ZATUL E. BADARUDIN; AHMED M. KHALID; MOHAMED ARIFF

    2012-01-01

    This paper investigates the nature of money supply in Australia over two separate monetary policy regimes: monetary and inflation targeting. The post-Keynesian theory on endogenous money was tested with the aim of investigating whether endogenous money supply, if it did exist, followed the accomodationist, structuralist or liquidity preference viewpoints. Data used are quarterly series from 1977 to 2007 and we used vector error-correction model for long-run and short-run causality tests. We f...

  2. Policy Endogeneity and the Effects of Trade on the Environment

    OpenAIRE

    Copeland, Brian R.

    2005-01-01

    This paper reviews recent work on the implications of endogenous policy for the effects of trade on the environment and the sustainability of renewable resource stocks. A recognition that pollution policy is endogenous has had a major impact on the trade and environment literature and has reversed some of the previously established empirical findings. Work on pollution has proceeded faster than work on renewable resources. I suggest some directions for future work in this area.

  3. Therapeutic targeting strategies using endogenous cells and proteins.

    Science.gov (United States)

    Parayath, Neha N; Amiji, Mansoor M

    2017-07-28

    Targeted drug delivery has become extremely important in enhancing efficacy and reducing the toxicity of therapeutics in the treatment of various disease conditions. Current approaches include passive targeting, which relies on naturally occurring differences between healthy and diseased tissues, and active targeting, which utilizes various ligands that can recognize targets expressed preferentially at the diseased site. Clinical translation of these mechanisms faces many challenges including the immunogenic and toxic effects of these non-natural systems. Thus, use of endogenous targeting systems is increasingly gaining momentum. This review is focused on strategies for employing endogenous moieties, which could serve as safe and efficient carriers for targeted drug delivery. The first part of the review involves cells and cellular components as endogenous carriers for therapeutics in multiple disease states, while the second part discusses the use of endogenous plasma components as endogenous carriers. Further understanding of the biological tropism with cells and proteins and the newer generation of delivery strategies that exploits these endogenous approaches promises to provide better solutions for site-specific delivery and could further facilitate clinical translations. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. In situ tissue regeneration: chemoattractants for endogenous stem cell recruitment.

    Science.gov (United States)

    Vanden Berg-Foels, Wendy S

    2014-02-01

    Tissue engineering uses cells, signaling molecules, and/or biomaterials to regenerate injured or diseased tissues. Ex vivo expanded mesenchymal stem cells (MSC) have long been a cornerstone of regeneration therapies; however, drawbacks that include altered signaling responses and reduced homing capacity have prompted investigation of regeneration based on endogenous MSC recruitment. Recent successful proof-of-concept studies have further motivated endogenous MSC recruitment-based approaches. Stem cell migration is required for morphogenesis and organogenesis during development and for tissue maintenance and injury repair in adults. A biomimetic approach to in situ tissue regeneration by endogenous MSC requires the orchestration of three main stages: MSC recruitment, MSC differentiation, and neotissue maturation. The first stage must result in recruitment of a sufficient number of MSC, capable of effecting regeneration, to the injured or diseased tissue. One of the challenges for engineering endogenous MSC recruitment is the selection of effective chemoattractant(s). The objective of this review is to synthesize and evaluate evidence of recruitment efficacy by reported chemoattractants, including growth factors, chemokines, and other more recently appreciated MSC chemoattractants. The influence of MSC tissue sources, cell culture methods, and the in vitro and in vivo environments is discussed. This growing body of knowledge will serve as a basis for the rational design of regenerative therapies based on endogenous MSC recruitment. Successful endogenous MSC recruitment is the first step of successful tissue regeneration.

  5. Delivery systems for antimicrobial peptides

    DEFF Research Database (Denmark)

    Nordström, Randi; Malmsten, Martin

    2017-01-01

    on the identification such peptides, as well as on their optimization to reach potent antimicrobial and anti-inflammatory effects at simultaneously low toxicity against human cells. In comparison, delivery systems for antimicrobial peptides have attracted considerably less interest. However, such delivery systems......, or through achieving co-localization with intracellular pathogens. Here, an overview is provided of the current understanding of delivery systems for antimicrobial peptides, with special focus on AMP-carrier interactions, as well as consequences of these interactions for antimicrobial and related biological...

  6. Anorexigenic Lipopeptides Ameliorate Central Insulin Signaling and Attenuate Tau Phosphorylation in Hippocampi of Mice with Monosodium Glutamate-Induced Obesity

    Czech Academy of Sciences Publication Activity Database

    Špolcová, Andrea; Mikulášková, Barbora; Holubová, Martina; Nagelová, Veronika; Pirník, Zdenko; Zemenová, Jana; Haluzík, M.; Železná, Blanka; Galas, M. C.; Maletínská, Lenka

    2015-01-01

    Roč. 45, č. 3 (2015), s. 823-835 ISSN 1387-2877 R&D Projects: GA ČR GAP303/12/0576 Institutional support: RVO:61388963 Keywords : Alzheimer's disease * insulin signaling * liraglutide * monosodium glutamate-obese mice * obesity * pre- diabetes * prolactin-releasing peptide Subject RIV: CE - Biochemistry Impact factor: 3.920, year: 2015

  7. Enhanced induction of human WT1-specific cytotoxic T lymphocytes with a 9-mer WT1 peptide modified at HLA-A*2402-binding residues.

    Science.gov (United States)

    Tsuboi, Akihiro; Oka, Yoshihiro; Udaka, Keiko; Murakami, Masaki; Masuda, Tomoki; Nakano, Akiko; Nakajima, Hiroko; Yasukawa, Masaki; Hiraki, Akio; Oji, Yusuke; Kawakami, Manabu; Hosen, Naoki; Fujioka, Tatsuya; Wu, Fei; Taniguchi, Yuki; Nishida, Sumiyuki; Asada, Momotaro; Ogawa, Hiroyasu; Kawase, Ichiro; Sugiyama, Haruo

    2002-12-01

    The Wilms' tumor gene WT1 is overexpressed in most types of leukemias and various kinds of solid tumors, including lung and breast cancer, and participates in leukemogenesis and tumorigenesis. WT1 protein has been reported to be a promising tumor antigen in mouse and human. In the present study, a single amino-acid substitution, M-->Y, was introduced into the first anchor motif at position 2 of the natural immunogenic HLA-A*2402-restricted 9-mer WT1 peptide (CMTWNQMNL; a.a. 235-243). This substitution increased the binding affinity of the 9-mer WT1 peptide to HLA-A*2402 molecules from 1.82 x 10(-5) to 6.40 x 10(-7) M. As expected from the increased binding affinity, the modified 9-mer WT1 peptide (CYTWNQMNL) elicited WT1-specific cytotoxic T lymphocytes (CTL) more effectively than the natural 9-mer WT1 peptide from peripheral blood mononuclear cells (PBMC) of HLA-A*2402-positive healthy volunteers. CTL induced by the modified 9-mer WT1 peptide killed the natural 9-mer WT1 peptide-pulsed CIR-A*2402 cells, primary leukemia cells with endogenous WT1 expression and lung cancer cell lines in a WT1-specific HLA-A*2402-restricted manner. These results showed that this modified 9-mer WT1 peptide was more immunogenic for the induction of WT1-specific CTL than the natural 9-mer WT1 peptide, and that CTL induced by the modified 9-mer WT1 peptide could effectively recognize and kill tumor cells with endogenous WT1 expression. Therefore, cancer immunotherapy using this modified 9-mer WT1 peptide should provide efficacious treatment for HLA-A*2402-positive patients with leukemias and solid tumors.

  8. Novel peptides with tyrosinase inhibitory activity

    NARCIS (Netherlands)

    Schurink, M.; Berkel, van W.J.H.; Wichers, H.J.; Boeriu, C.G.

    2007-01-01

    Tyrosinase inhibition by peptides may find its application in food, cosmetics or medicine. In order to identify novel tyrosinase inhibitory peptides, protein-based peptide libraries made by SPOT synthesis were used to screen for peptides that show direct interaction with tyrosinase. One of the

  9. Characterization of Synthetic Peptides by Mass Spectrometry.

    Science.gov (United States)

    Prabhala, Bala K; Mirza, Osman; Højrup, Peter; Hansen, Paul R

    2015-01-01

    Mass spectrometry (MS) is well suited for analysis of the identity and purity of synthetic peptides. The sequence of a synthetic peptide is most often known, so the analysis is mainly used to confirm the identity and purity of the peptide. Here, simple procedures are described for MALDI-TOF-MS and LC-MS of synthetic peptides.

  10. Neoglycolipidation for modulating peptide properties

    DEFF Research Database (Denmark)

    van Witteloostuijn, Søren Blok

    regulation of appetite, food intake, and glucose homeostasis, and many of these peptides display a signicant potential for treatment of obesity and/or type 2 diabetes. This Ph.D. thesis describes three novel approaches for utilizing gut peptides as the starting point for developing obesity and diabetes drugs....... Subsequent stereological analyses of the pancreata showed that chronic treatment with GUB06-046 led to increased cell mass in db/db mice. The results of projects I and II clearly illustrate how chemical modications can improve the pharmacological properties of native peptides. Collectively, the ndings...... of this thesis contribute to emphasize the tremendous therapeutic potential of gut peptides for treatment of obesity and diabetes....

  11. New vasoactive peptides in cirrhosis

    DEFF Research Database (Denmark)

    Kimer, Nina; Goetze, Jens Peter; Bendtsen, Flemming

    2014-01-01

    BACKGROUND: Patients with cirrhosis have substantial circulatory imbalance between vasoconstrictive and vasodilating forces. The study of circulatory vasoactive peptides may provide important pathophysiological information. This study aimed to assess concentrations, organ extraction and relations...

  12. Moonlighting peptides with emerging function.

    Directory of Open Access Journals (Sweden)

    Jonathan G Rodríguez Plaza

    Full Text Available Hunter-killer peptides combine two activities in a single polypeptide that work in an independent fashion like many other multi-functional, multi-domain proteins. We hypothesize that emergent functions may result from the combination of two or more activities in a single protein domain and that could be a mechanism selected in nature to form moonlighting proteins. We designed moonlighting peptides using the two mechanisms proposed to be involved in the evolution of such molecules (i.e., to mutate non-functional residues and the use of natively unfolded peptides. We observed that our moonlighting peptides exhibited two activities that together rendered a new function that induces cell death in yeast. Thus, we propose that moonlighting in proteins promotes emergent properties providing a further level of complexity in living organisms so far unappreciated.

  13. Impact of human milk pasteurization on the kinetics of peptide release during in vitro dynamic term newborn digestion.

    Science.gov (United States)

    Deglaire, Amélie; De Oliveira, Samira C; Jardin, Julien; Briard-Bion, Valérie; Emily, Mathieu; Ménard, Olivia; Bourlieu, Claire; Dupont, Didier

    2016-07-01

    Holder pasteurization (62.5°C, 30 min) ensures sanitary quality of donor's human milk but also denatures beneficial proteins. Understanding whether this further impacts the kinetics of peptide release during gastrointestinal digestion of human milk was the aim of the present paper. Mature raw (RHM) or pasteurized (PHM) human milk were digested (RHM, n = 2; PHM, n = 3) by an in vitro dynamic system (term stage). Label-free quantitative peptidomics was performed on milk and digesta (ten time points). Ascending hierarchical clustering was conducted on "Pasteurization × Digestion time" interaction coefficients. Preproteolysis occurred in human milk (159 unique peptides; RHM: 91, PHM: 151), mostly on β-casein (88% of the endogenous peptides). The predicted cleavage number increased with pasteurization, potentially through plasmin activation (plasmin cleavages: RHM, 53; PHM, 76). During digestion, eight clusters resumed 1054 peptides from RHM and PHM, originating for 49% of them from β-casein. For seven clusters (57% of peptides), the kinetics of peptide release differed between RHM and PHM. The parent protein was significantly linked to the clustering (p-value = 1.4 E-09), with β-casein and lactoferrin associated to clusters in an opposite manner. Pasteurization impacted selectively gastric and intestinal kinetics of peptide release in term newborns, which may have further nutritional consequences. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Matrix-assisted peptide synthesis on nanoparticles.

    Science.gov (United States)

    Khandadash, Raz; Machtey, Victoria; Weiss, Aryeh; Byk, Gerardo

    2014-09-01

    We report a new method for multistep peptide synthesis on polymeric nanoparticles of differing sizes. Polymeric nanoparticles were functionalized via their temporary embedment into a magnetic inorganic matrix that allows multistep peptide synthesis. The matrix is removed at the end of the process for obtaining nanoparticles functionalized with peptides. The matrix-assisted synthesis on nanoparticles was proved by generating various biologically relevant peptides. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.

  15. Chemoselective synthesis and analysis of naturally occurring phosphorylated cysteine peptides

    Science.gov (United States)

    Bertran-Vicente, Jordi; Penkert, Martin; Nieto-Garcia, Olaia; Jeckelmann, Jean-Marc; Schmieder, Peter; Krause, Eberhard; Hackenberger, Christian P. R.

    2016-09-01

    In contrast to protein O-phosphorylation, studying the function of the less frequent N- and S-phosphorylation events have lagged behind because they have chemical features that prevent their manipulation through standard synthetic and analytical methods. Here we report on the development of a chemoselective synthetic method to phosphorylate Cys side-chains in unprotected peptides. This approach makes use of a reaction between nucleophilic phosphites and electrophilic disulfides accessible by standard methods. We achieve the stereochemically defined phosphorylation of a Cys residue and verify the modification using electron-transfer higher-energy dissociation (EThcD) mass spectrometry. To demonstrate the use of the approach in resolving biological questions, we identify an endogenous Cys phosphorylation site in IICBGlc, which is known to be involved in the carbohydrate uptake from the bacterial phosphotransferase system (PTS). This new chemical and analytical approach finally allows further investigating the functions and significance of Cys phosphorylation in a wide range of crucial cellular processes.

  16. Material Binding Peptides for Nanotechnology

    Directory of Open Access Journals (Sweden)

    Urartu Ozgur Safak Seker

    2011-02-01

    Full Text Available Remarkable progress has been made to date in the discovery of material binding peptides and their utilization in nanotechnology, which has brought new challenges and opportunities. Nowadays phage display is a versatile tool, important for the selection of ligands for proteins and peptides. This combinatorial approach has also been adapted over the past decade to select material-specific peptides. Screening and selection of such phage displayed material binding peptides has attracted great interest, in particular because of their use in nanotechnology. Phage display selected peptides are either synthesized independently or expressed on phage coat protein. Selected phage particles are subsequently utilized in the synthesis of nanoparticles, in the assembly of nanostructures on inorganic surfaces, and oriented protein immobilization as fusion partners of proteins. In this paper, we present an overview on the research conducted on this area. In this review we not only focus on the selection process, but also on molecular binding characterization and utilization of peptides as molecular linkers, molecular assemblers and material synthesizers.

  17. Role of Endogenous Opioid System in Ischemic-Induced Late Preconditioning.

    Directory of Open Access Journals (Sweden)

    Jan Fraessdorf

    Full Text Available Opioid receptors (OR are involved in myocardial late preconditioning (LPC induced by morphine and δ1-opioid receptor (δ1-OR agonists. The role of OR in ischemic-induced LPC is unknown. We investigated whether 1 OR are involved in the trigger and/or mediation phase of LPC and 2 a time course effect on the expression of different opioid receptors and their endogenous ligands exists.Male Wistar rats were randomly allocated to four groups (each group n = 8. Awake animals were ischemic preconditioned by a 5 minutes coronary occlusion. 24 hours later, anesthetized animals underwent 25 minutes coronary occlusion followed by 2 hours of reperfusion. The role of OR was investigated by treatment with intraperitoneal naloxone (Nal 10 minutes prior to LPC (Nal-LPC; trigger phase or 10 min prior to sustained ischemia (LPC-Nal; mediation phase.LPC reduced infarct size from 61±10% in controls to 25±9% (P<0.001. Naloxone during trigger or mediation phase completely abolished LPC-induced cardioprotection (59±9% and 62±9%; P<0.001 vs. LPC. 8, 12 and 24 hours after the ischemic stimulus, expression of δ-OR in the heart was increased, whereas μ-opioid receptor (μ-OR and κ-opioid receptor (κ-OR were not. Plasma concentrations of β-endorphin and leu-enkephalin but not dynorphin were increased by LPC.Ischemic LPC is triggererd and mediated by OR. Expression of δ-OR and plasma levels of endogenous opioid peptides are increased after ischemic LPC.

  18. Endogenous dynorphin protects against neurotoxin-elicited nigrostriatal dopaminergic neuron damage and motor deficits in mice

    Directory of Open Access Journals (Sweden)

    Wang Qingshan

    2012-06-01

    Full Text Available Abstract Background The striato-nigral projecting pathway contains the highest concentrations of dynorphin in the brain. The functional role of this opioid peptide in the regulation of mesencephalic dopaminergic (DAergic neurons is not clear. We reported previously that exogenous dynorphin exerts potent neuroprotective effects against inflammation-induced dopaminergic neurodegeneration in vitro. The present study was performed to investigate whether endogenous dynorphin has neuroprotective roles in vivo. Methods 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP and methamphetamine (MA, two commonly used neurotoxins in rodent models of Parkinson’s disease, were administered to wild-type (Dyn+/+ and prodynorphin-deficient mice (Dyn−/−. We examined dopaminergic neurotoxicity by using an automated video tracking system, HPLC, immunocytochemistry, and reverse transcription and polymerase chain reaction (RT-PCR. Results Treatment with MPTP resulted in behavioral impairments in both strains. However, these impairments were more pronounced in Dyn-l- than in Dyn+/+. Dyn−/− showed more severe MPTP-induced dopaminergic neuronal loss in the substantia nigra and striatum than Dyn+/+. Similarly, the levels of dopamine and its metabolites in the striatum were depleted to a greater extent in Dyn−/− than in Dyn+/+. Additional mechanistic studies revealed that MPTP treatment caused a higher degree of microglial activation and M1 phenotype differentiation in Dyn−/− than in Dyn+/+. Consistent with these observations, prodynorphin deficiency also exacerbated neurotoxic effects induced by MA, although this effect was less pronounced than that of MPTP. Conclusions The in vivo results presented here extend our previous in vitro findings and further indicate that endogenous dynorphin plays a critical role in protecting dopaminergic neurons through its anti-inflammatory effects.

  19. Endogenous adaptation to low oxygen modulates T-cell regulatory pathways in EAE.

    Science.gov (United States)

    Esen, Nilufer; Katyshev, Vladimir; Serkin, Zakhar; Katysheva, Svetlana; Dore-Duffy, Paula

    2016-01-19

    In the brain, chronic inflammatory activity may lead to compromised delivery of oxygen and glucose suggesting that therapeutic approaches aimed at restoring metabolic balance may be useful. In vivo exposure to chronic mild normobaric hypoxia (10 % oxygen) leads to a number of endogenous adaptations that includes vascular remodeling (angioplasticity). Angioplasticity promotes tissue survival. We have previously shown that induction of adaptive angioplasticity modulates the disease pattern in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). In the present study, we define mechanisms by which adaptation to low oxygen functionally ameliorates the signs and symptoms of EAE and for the first time show that tissue hypoxia may fundamentally alter neurodegenerative disease. C57BL/6 mice were immunized with MOG, and some of them were kept in the hypoxia chambers (day 0) and exposed to 10 % oxygen for 3 weeks, while the others were kept at normoxic environment. Sham-immunized controls were included in both hypoxic and normoxic groups. Animals were sacrificed at pre-clinical and peak disease periods for tissue collection and analysis. Exposure to mild hypoxia decreased histological evidence of inflammation. Decreased numbers of cluster of differentiation (CD)4+ T cells were found in the hypoxic spinal cords associated with a delayed Th17-specific cytokine response. Hypoxia-induced changes did not alter the sensitization of peripheral T cells to the MOG peptide. Exposure to mild hypoxia induced significant increases in anti-inflammatory IL-10 levels and an increase in the number of spinal cord CD25+FoxP3+ T-regulatory cells. Acclimatization to mild hypoxia incites a number of endogenous adaptations that induces an anti-inflammatory milieu. Further understanding of these mechanisms system may pinpoint possible new therapeutic targets to treat neurodegenerative disease.

  20. Deep brain stimulation of the periaqueductal gray releases endogenous opioids in humans.

    Science.gov (United States)

    Sims-Williams, Hugh; Matthews, Julian C; Talbot, Peter S; Love-Jones, Sarah; Brooks, Jonathan Cw; Patel, Nikunj K; Pickering, Anthony E

    2017-02-01

    Deep brain stimulation (DBS) of the periaqueductal gray (PAG) is used in the treatment of severe refractory neuropathic pain. We tested the hypothesis that DBS releases endogenous opioids to exert its analgesic effect using [ 11 C]diprenorphine (DPN) positron emission tomography (PET). Patients with de-afferentation pain (phantom limb pain or Anaesthesia Dolorosa (n=5)) who obtained long-lasting analgesic benefit from DBS were recruited. [ 11 C]DPN and [ 15 O]water PET scanning was performed in consecutive sessions; first without, and then with PAG stimulation. The regional cerebral tracer distribution and kinetics were quantified for the whole brain and brainstem. Analysis was performed on a voxel-wise basis using statistical parametric mapping (SPM) and also within brainstem regions of interest and correlated to the DBS-induced improvement in pain score and mood. Brain-wide analysis identified a single cluster of reduced [ 11 C]DPN binding (15.5% reduction) in the caudal, dorsal PAG following DBS from effective electrodes located in rostral dorsal/lateral PAG. There was no evidence for an accompanying focal change in blood flow within the PAG. No correlation was found between the change in PAG [ 11 C]DPN binding and the analgesic effect or the effect on mood (POMS SV ) of DBS. The analgesic effect of DBS in these subjects was not altered by systemic administration of the opioid antagonist naloxone (400ug). These findings indicate that DBS of the PAG does indeed release endogenous opioid peptides focally within the midbrain of these neuropathic pain patients but we are unable to further resolve the question of whether this release is responsible for the observed analgesic benefit. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Endogenous leptin contributes to baroreflex suppression within the solitary tract nucleus of aged rats.

    Science.gov (United States)

    Arnold, Amy C; Diz, Debra I

    2014-12-01

    The decline in cardiovagal baroreflex function that occurs with aging is accompanied by an increase in circulating leptin levels. Our previous studies showed that exogenous leptin impairs the baroreflex sensitivity for control of heart rate in younger rats, but the contribution of this hormone to baroreflex dysfunction during aging is unknown. Thus we assessed the effect of bilateral leptin microinjection (500 fmol/60 nl) within the solitary tract nucleus (NTS) on the baroreflex sensitivity in older (66 ± 2 wk of age) urethane/chloralose anesthetized Sprague-Dawley rats with elevated circulating leptin levels. In contrast to the 63% reduction observed in younger rats, leptin did not alter the baroreflex sensitivity for bradycardia evoked by phenylephrine in older rats (0.76 ± 0.19 baseline vs. 0.71 ± 0.15 ms/mmHg after leptin; P = 0.806). We hypothesized that this loss of sensitivity reflected endogenous suppression of the baroreflex by elevated leptin, rather than cardiovascular resistance to the peptide. Indeed, NTS administration of a leptin receptor antagonist (75 pmol/120 nl) improved the baroreflex sensitivity for bradycardia in older rats (0.73 ± 0.13 baseline vs. 1.19 ± 0.26 at 10 min vs. 1.87 ± 0.32 at 60 min vs. 1.22 ± 0.54 ms/mmHg at 120 min; P = 0.002), with no effect in younger rats. There was no effect of the leptin antagonist on the baroreflex sensitivity for tachycardia, responses to cardiac vagal chemosensitive fiber activation, or resting hemodynamics in older rats. These findings suggest that the actions of endogenous leptin within the NTS, either produced locally or derived from the circulation, contribute to baroreflex suppression during aging. Copyright © 2014 the American Physiological Society.

  2. Characterization of Macrophage Endogenous S-Nitrosoproteome Using a Cysteine-Specific Phosphonate Adaptable Tag in Combination with TiO2Chromatography.

    Science.gov (United States)

    Ibáñez-Vea, María; Huang, Honggang; Martínez de Morentin, Xabier; Pérez, Estela; Gato, Maria; Zuazo, Miren; Arasanz, Hugo; Fernández-Irigoyen, Joaquin; Santamaría, Enrique; Fernandez-Hinojal, Gonzalo; Larsen, Martin R; Escors, David; Kochan, Grazyna

    2018-03-02

    Protein S-nitrosylation is a cysteine post-translational modification mediated by nitric oxide. An increasing number of studies highlight S-nitrosylation as an important regulator of signaling involved in numerous cellular processes. Despite the significant progress in the development of redox proteomic methods, identification and quantification of endogeneous S-nitrosylation using high-throughput mass-spectrometry-based methods is a technical challenge because this modification is highly labile. To overcome this drawback, most methods induce S-nitrosylation chemically in proteins using nitrosylating compounds before analysis, with the risk of introducing nonphysiological S-nitrosylation. Here we present a novel method to efficiently identify endogenous S-nitrosopeptides in the macrophage total proteome. Our approach is based on the labeling of S-nitrosopeptides reduced by ascorbate with a cysteine specific phosphonate adaptable tag (CysPAT), followed by titanium dioxide (TiO 2 ) chromatography enrichment prior to nLC-MS/MS analysis. To test our procedure, we performed a large-scale analysis of this low-abundant modification in a murine macrophage cell line. We identified 569 endogeneous S-nitrosylated proteins compared with 795 following exogenous chemically induced S-nitrosylation. Importantly, we discovered 579 novel S-nitrosylation sites. The large number of identified endogenous S-nitrosylated peptides allowed the definition of two S-nitrosylation consensus sites, highlighting protein translation and redox processes as key S-nitrosylation targets in macrophages.

  3. Endogenous versus exogenous growth factor regulation of articular chondrocytes.

    Science.gov (United States)

    Shi, Shuiliang; Chan, Albert G; Mercer, Scott; Eckert, George J; Trippel, Stephen B

    2014-01-01

    Anabolic growth factors that regulate the function of articular chondrocytes are candidates for articular cartilage repair. Such factors may be delivered by pharmacotherapy in the form of exogenous proteins, or by gene therapy as endogenous proteins. It is unknown whether delivery method influences growth factor effectiveness in regulating articular chondrocyte reparative functions. We treated adult bovine articular chondrocytes with exogenous recombinant insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1), or with the genes encoding these growth factors for endogenous production. Treatment effects were measured as change in chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression. We found that IGF-I stimulated chondrocyte biosynthesis similarly when delivered by either exogenous or endogenous means. In contrast, exogenous TGF-β1 stimulated these reparative functions, while endogenous TGF-β1 had little effect. Endogenous TGF-β1 became more bioactive following activation of the transgene protein product. These data indicate that effective mechanisms of growth factor delivery for articular cartilage repair may differ for different growth factors. In the case of IGF-I, gene therapy or protein therapy appear to be viable options. In contrast, TGF-β1 gene therapy may be constrained by a limited ability of chondrocytes to convert latent complexes to an active form. Published 2013 by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. This article is a U.S. Government work and is in the public domain in the USA.

  4. Biopsychosocial Factors Associated with Prurigo Nodularis in Endogenous Eczema.

    Science.gov (United States)

    Oh, Choon Chiat; Li, Huihua; Lee, Wellington; Tey, Hong Liang

    2015-01-01

    Prurigo nodularis is a dermatological manifestation secondary to chronic scratching or picking on focal areas of the skin. Its pathogenesis remains poorly understood, and limited data has indicated its association with psychological factors. To determine the biological, psychological and social factors associated with the occurrence of prurigo nodularis in patients with underlying endogenous eczema. A prospective case-control questionnaire -based study on patients with endogenous eczema, with and without prurigo nodules, was performed. The Impact of Skin Disease on Daily Life questionnaire was used to assess dimensions of physical functioning, including extent and severity of skin disease, itch, pain, fatigue and scratching, as well as dimensions of psychological and social functioning, including mood, illness cognition, disease-related impact, stigmatization and social support. Thirty-six cases and 47 controls were recruited. Patients with endogenous eczema and prurigo nodules indicated a higher itch score on the visual analog scale over the previous 4 weeks compared to those without prurigo nodules (p=0.0292). There were no significant differences between the 2 groups in the scores reflecting the other parameters of physical, psychological and social functioning. In patients with endogenous eczema, those with prurigo nodules experience a greater itch intensity compared to those without prurigo nodules. There were no other physical, psychological and social factors that were found to be associated with the occurrence of prurigo nodules in endogenous eczema.

  5. Staphylococcal endogenous endophthalmitis in association with pyogenic vertebral osteomyelitis.

    Science.gov (United States)

    Steeples, L R; Jones, N P

    2016-01-01

    PURPOSE To describe pyogenic vertebral osteomyelitis as a rare infection associated with endogenous endophthalmitis.METHODS A retrospective review of three patients with endogenous endophthalmitis and sepsis due to underlying Staphylococcal vertebral osteomyelitis presenting during a 21-month time period. The ophthalmic and systemic features and management and outcomes are presented.RESULTS One patient developed unilateral endophthalmitis with cervical spine osteomyelitis, Staphylococcus aureus being isolated from blood cultures. The second presented with bilateral endophthalmitis with disseminated Methicillin-resistant S. aureus (MRSA) infection, with thoracic and lumbar discitis and para-spinal abscesses. MRSA was cultured from vitreous, blood, and synovial fluid. Both patients received prolonged courses of intravenous antibiotics. Intravitreal antibiotic therapy was used in the second patient. Excellent visual and systemic outcomes were achieved in both cases with no ocular complications. The third patient developed lumbar osteomyelitis following spinal surgery and presented with disseminated S. aureus sepsis including unilateral endogenous endophthalmitis. Despite systemic antibiotics and intensive care the patient died.CONCLUSIONS Endogenous endophthalmitis should be suspected in septic patients developing eye symptoms. Endogenous endophthalmitis with staphylococcal bone infection is a rare but serious condition. Osteomyelitis should be considered as an infective source in any such patient reporting bone pain or reduced spinal mobility. Prompt investigation and treatment can achieve favourable visual and systemic outcomes.

  6. Endogenous Cartilage Repair by Recruitment of Stem Cells.

    Science.gov (United States)

    Im, Gun-Il

    2016-04-01

    Articular cartilage has a very limited capacity for repair after injury. The adult body has a pool of stem cells that are mobilized during injury or disease. These cells exist inside niches in bone marrow, muscle, adipose tissue, synovium, and other connective tissues. A method that mobilizes this endogenous pool of stem cells will provide a less costly and less invasive alternative if these cells successfully regenerate defective cartilage. Traditional microfracture procedures employ the concept of bone marrow stimulation to regenerate cartilage. However, the regenerated tissue usually is fibrous cartilage, which has very poor mechanical properties compared to those of normal hyaline cartilage. A method that directs the migration of a large number of autologous mesenchymal stem cells toward injury sites, retains these cells around the defects, and induces chondrogenic differentiation that would enhance success of endogenous cartilage repair. This review briefly summarizes chemokines and growth factors that induce recruitment, proliferation, and differentiation of endogenous progenitor cells, endogenous cell sources for regenerating cartilage, scaffolds for delivery of bioactive factors, and bioadhesive materials that are necessary to bring about endogenous cartilage repair.

  7. Tissue-specific tagging of endogenous loci in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Kate Koles

    2016-01-01

    Full Text Available Fluorescent protein tags have revolutionized cell and developmental biology, and in combination with binary expression systems they enable diverse tissue-specific studies of protein function. However these binary expression systems often do not recapitulate endogenous protein expression levels, localization, binding partners and/or developmental windows of gene expression. To address these limitations, we have developed a method called T-STEP (tissue-specific tagging of endogenous proteins that allows endogenous loci to be tagged in a tissue specific manner. T-STEP uses a combination of efficient CRISPR/Cas9-enhanced gene targeting and tissue-specific recombinase-mediated tag swapping to temporally and spatially label endogenous proteins. We have employed this method to GFP tag OCRL (a phosphoinositide-5-phosphatase in the endocytic pathway and Vps35 (a Parkinson's disease-implicated component of the endosomal retromer complex in diverse Drosophila tissues including neurons, glia, muscles and hemocytes. Selective tagging of endogenous proteins allows, for the first time, cell type-specific live imaging and proteomics in complex tissues.

  8. PptAB Exports Rgg Quorum-Sensing Peptides in Streptococcus.

    Directory of Open Access Journals (Sweden)

    Jennifer C Chang

    Full Text Available A transposon mutagenesis screen designed to identify mutants that were defective in peptide-pheromone signaling of the Rgg2/Rgg3 pathway in Streptococcus pyogenes generated insertions in sixteen loci displaying diminished reporter activity. Fourteen unique transposon insertions were mapped to pptAB, an ABC-type transporter recently described to export sex pheromones of Enterococcus faecalis. Consistent with an idea that PptAB exports signaling peptides, the pheromones known as SHPs (short hydrophobic peptides were no longer detected in cell-free culture supernatants in a generated deletion mutant of pptAB. PptAB exporters are conserved among the Firmicutes, but their function and substrates remain unclear. Therefore, we tested a pptAB mutant generated in Streptococcus mutans and found that while secretion of heterologously expressed SHP peptides required PptAB, secretion of the S. mutans endogenous pheromone XIP (sigX inducing peptide was only partially disrupted, indicating that a secondary secretion pathway for XIP exists.

  9. PptAB Exports Rgg Quorum-Sensing Peptides in Streptococcus.

    Science.gov (United States)

    Chang, Jennifer C; Federle, Michael J

    2016-01-01

    A transposon mutagenesis screen designed to identify mutants that were defective in peptide-pheromone signaling of the Rgg2/Rgg3 pathway in Streptococcus pyogenes generated insertions in sixteen loci displaying diminished reporter activity. Fourteen unique transposon insertions were mapped to pptAB, an ABC-type transporter recently described to export sex pheromones of Enterococcus faecalis. Consistent with an idea that PptAB exports signaling peptides, the pheromones known as SHPs (short hydrophobic peptides) were no longer detected in cell-free culture supernatants in a generated deletion mutant of pptAB. PptAB exporters are conserved among the Firmicutes, but their function and substrates remain unclear. Therefore, we tested a pptAB mutant generated in Streptococcus mutans and found that while secretion of heterologously expressed SHP peptides required PptAB, secretion of the S. mutans endogenous pheromone XIP (sigX inducing peptide) was only partially disrupted, indicating that a secondary secretion pathway for XIP exists.

  10. Is chronic fatigue syndrome an autoimmune disorder of endogenous neuropeptides, exogenous infection and molecular mimicry?

    Science.gov (United States)

    Staines, Donald R

    2004-01-01

    Chronic fatigue syndrome is a disorder characterised by prolonged fatigue and debility and is mostly associated with post-infection sequelae although ongoing infection is unproven. Immunological aberration is likely and this may prove to be associated with an expanding group of vasoactive neuropeptides in the context of molecular mimicry and inappropriate immunological memory. Vasoactive neuropeptides including vasoactive intestinal peptide (VIP) and pituitary adenylate activating polypeptide (PACAP) belong to the secretin/glucagon superfamily and act as hormones, neurotransmitters, immune modulators and neurotrophes. They are readily catalysed to smaller peptide fragments by antibody hydrolysis. They and their binding sites are immunogenic and are known to be associated with a range of autoimmune conditions. Vasoactive neuropeptides are widely distributed in the body particularly in the central, autonomic and peripheral nervous systems and have been identified in the gut, adrenal gland, reproductive organs, vasculature, blood cells and other tissues. They have a vital role in maintaining vascular flow in organs, and in thermoregulation, memory and concentration. They are co-transmitters for acetylcholine, nitric oxide, endogenous opioids and insulin, are potent immune regulators with primarily anti-inflammatory activity, and have a significant role in protection of the nervous system to toxic assault, promotion of neural development and the maintenance of homeostasis. This paper describes a biologically plausible mechanism for the development of CFS based on loss of immunological tolerance to the vasoactive neuropeptides following infection, significant physical exercise or de novo. It is proposed that release of these substances is accompanied by a loss of tolerance either to them or their receptor binding sites in CFS. Such an occurrence would have predictably serious consequences resulting from compromised function of the key roles these substances perform. All

  11. A rapid and clean synthetic approach to cyclic peptides via micro-flow peptide chain elongation and photochemical cyclization: synthesis of a cyclic RGD peptide.

    Science.gov (United States)

    Mifune, Yuto; Nakamura, Hiroyuki; Fuse, Shinichiro

    2016-11-29

    A cyclic RGD peptide was efficiently synthesized based on micro-flow, triphosgene-mediated peptide chain elongation and micro-flow photochemical macrolactamization. Our approach enabled a rapid (amidation for peptide chain elongation peptide.

  12. Automated solid-phase peptide synthesis to obtain therapeutic peptides

    Directory of Open Access Journals (Sweden)

    Veronika Mäde

    2014-05-01

    Full Text Available The great versatility and the inherent high affinities of peptides for their respective targets have led to tremendous progress for therapeutic applications in the last years. In order to increase the drugability of these frequently unstable and rapidly cleared molecules, chemical modifications are of great interest. Automated solid-phase peptide synthesis (SPPS offers a suitable technology to produce chemically engineered peptides. This review concentrates on the application of SPPS by Fmoc/t-Bu protecting-group strategy, which is most commonly used. Critical issues and suggestions for the synthesis are covered. The development of automated methods from conventional to essentially improved microwave-assisted instruments is discussed. In order to improve pharmacokinetic properties of peptides, lipidation and PEGylation are described as covalent conjugation methods, which can be applied by a combination of automated and manual synthesis approaches. The synthesis and application of SPPS is described for neuropeptide Y receptor analogs as an example for bioactive hormones. The applied strategies represent innovative and potent methods for the development of novel peptide drug candidates that can be manufactured with optimized automated synthesis technologies.

  13. A small peptide with potential ability to promote wound healing.

    Directory of Open Access Journals (Sweden)

    Jing Tang

    Full Text Available Wound-healing represents a major health burden, such as diabetes-induced skin ulcers and burning. Many works are being tried to find ideal clinical wound-healing biomaterials. Especially, small molecules with low cost and function to promote production of endogenous wound healing agents (i.e. transforming growth factor beta, TGF-β are excellent candidates. In this study, a small peptide (tiger17, c[WCKPKPKPRCH-NH2] containing only 11 amino acid residues was designed and proved to be a potent wound healer. It showed strong wound healing-promoting activity in a murine model of full thickness dermal wound. Tiger17 exerted significant effects on three stages of wound healing progresses including (1 the induction of macrophages recruitment to wound site at inflammatory reaction stage; (2 the promotion of the migration and proliferation both keratinocytes and fibroblasts, leading to reepithelialization and granulation tissue formation; and (3 tissue remodeling phase, by promoting the release of transforming TGF-β1 and interleukin 6 (IL-6 in murine macrophages and activating mitogen-activated protein kinases (MAPK signaling pathways. Considering its easy production, store and transfer and function to promote production of endogenous wound healing agents (TGF-β, tiger17 might be an exciting biomaterial or template for the development of novel wound-healing agents.

  14. Peptides and Food Intake

    Directory of Open Access Journals (Sweden)

    Carmen Sobrino Crespo

    2014-04-01

    Full Text Available Nutrients created by the digestion of food are proposed to active G protein coupled receptors on the luminal side of enteroendocrine cells e.g. the L-cell. This stimulates the release of gut hormones. Hormones released from the gut and adipose tissue play an important rol in the regulation of food intake and energy expenditure (1.Many circulating signals, including gut hormones, can influence the activity of the arcuate nucleus (ARC neurons directly, after passing across the median eminence. The ARC is adjacent to the median eminence, a circumventricular organ with fenestrated capillaries and hence an incomplete blood-brain barrier (2. The ARC of the hypothalamus is believed to play a crucial role in the regulation of food intake and energy homeostasis. The ARC contains two populations of neurons with opposing effect on food intake (3. Medially located orexigenic neurons (i.e those stimulating appetite express neuropeptide Y (NPY and agouti-related protein (AgRP (4-5. Anorexigenic neurons (i.e. those inhibiting appetite in the lateral ARC express alpha-melanocyte stimulating hormone (α-MSH derived from pro-opiomelanocortin (POMC and cocaine and amphetamine-regulated transcript (CART (6. The balance between activities of these neuronal circuits is critical to body weight regulation.In contrast, other peripheral signals influence the hypothalamus indirectly via afferent neuronal pathway and brainstem circuits. In this context gastrointestinal’s vagal afferents are activated by mechanoreceptors and chemoreceptors, and converge in the nucleus of the tractus solitaries (NTS of the brainstem. Neuronal projections from the NTS, in turn, carry signals to the hypotalamus (1, 7. Gut hormones also alter the activity of the ascending vagal pathway from the gut to the brainstem. In the cases of ghrelin and Peptide tyrosine tyrosine (PYY, there are evidences for both to have a direct action on the arcuate nucleus and an action via the vagus nerve a

  15. Neuronal Rat Brain Damage Caused by Endogenous and Exogenous Hyperthermia

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    Mustafa Aydın

    2012-03-01

    Full Text Available OBJECTIVE: Hyperthermia may induce pathologic alterations within body systems and organs including brain. In this study, neuronal effects of endogenous and exogenous hyperthermia (41°C were studied in rats. METHODS: The endogenous hyperthermia (41°C was induced by lipopolysaccharide and the exogenous by an (electric heater. Possible neuronal damage was evaluated by examining healthy, apoptotic and necrotic cells, and heat shock proteins (HSP 27, HSP 70 in the cerebral cortex, cerebellum and hypothalamus RESULTS: At cellular level, when all neuronal tissues are taken into account; (i a significant increase in the necrotic cells was observed in the both groups (p0.05. CONCLUSION: The neural tissue of brain can show different degree of response to hyperthermia. But we can conclude that endogenous hyperthermia is more harmful to central nervous system than exogenous hyperthermia

  16. Endogenous infection and hospital's civil liability - a case study.

    Science.gov (United States)

    Wąsik, D; Wąsik, N; Sygit, B; Dubiel, M

    2014-01-01

    The subject matter of this publication is the legal assessment of endogenous infection - the specific type of hospital infections. The main aim of the publication is to answer the question of whether medical and legal grounds exist for civil liability for endogenous infections and for treating those infections as cases of medical malpractice or medical events. The research method adopted is a case study. The authors have analysed a civil lawsuit for compensation instituted by an infected patient against a Polish hospital, adjudicated in 2013. The main conclusion of the publication is to postulate distinguishing medical malpractice from complications resulting from the reactions of the human body to treatment. The authors argue that endogenous infections should be treated as the latter-mentioned of these two cases.

  17. Endogenous induced technical change and the costs of Kyoto

    International Nuclear Information System (INIS)

    Buonanno, Paolo; Carraro, Carlo; Galeotti, Marzio

    2003-01-01

    We present a model for climate change policy analysis which accounts for the possibility that technology evolves endogenously and that technical change can be induced by environmental policy measures. Both the output production technology and the emission-output ratio depend upon a stock of knowledge, which accumulates through R and D activities. Two versions of this model are studied, one with endogenous technical change but exogenous environmental technical change and the other with both endogenous and induced technical change. A third version also captures technological spillover effects. As an application, the model is simulated allowing for trade of pollution permits as specified in the Kyoto Protocol and assessing the implications in terms of cost efficiency, economic growth and R and D efforts of the three different specifications of technical change

  18. The value of reliability with endogenous meeting time

    DEFF Research Database (Denmark)

    Abegaz, Dereje Fentie; Fosgerau, Mogens

    that the model takes scheduling choices merely as an individual matter. Since scheduling choices could affect and be affected by the distribution of travel times, the assumption of exogenous scheduling preferences is unreasonable. Fosgerau & Small (2010) examined how these preferences could arise endogenously...... is the strategic interaction between individuals in the choice of optimal departure time. This interaction causes individual scheduling preferences to be endogenous. They find that whether an improvement in the reliability of travel times for either person benefits both individuals depends on how their travel...... distribution on an urban road. Transportation Research Part C: Emerging Technologies, 24(0), 83–101. Fosgerau, Mogens, & Karlström, Anders. 2010. The value of reliability. Transportation Research Part B: Methodological, 44(1), 38–49. Fosgerau, Mogens, & Small, Kenneth. 2010. Endogenous scheduling preferences...

  19. Residential water demand with endogenous pricing: The Canadian Case

    Science.gov (United States)

    Reynaud, Arnaud; Renzetti, Steven; Villeneuve, Michel

    2005-11-01

    In this paper, we show that the rate structure endogeneity may result in a misspecification of the residential water demand function. We propose to solve this endogeneity problem by estimating a probabilistic model describing how water rates are chosen by local communities. This model is estimated on a sample of Canadian local communities. We first show that the pricing structure choice reflects efficiency considerations, equity concerns, and, in some cases, a strategy of price discrimination across consumers by Canadian communities. Hence estimating the residential water demand without taking into account the pricing structures' endogeneity leads to a biased estimation of price and income elasticities. We also demonstrate that the pricing structure per se plays a significant role in influencing price responsiveness of Canadian residential consumers.

  20. Public procurement of innovation; endogenous institutions in user producer interaction

    DEFF Research Database (Denmark)

    Hjaltadóttir, Rannveig Edda

    2013-01-01

    possible institutional barriers and what can be done to fence against them. The article addresses the question: How do endogenous institutions in the context of user-producer interaction affect performance in public procurement of innovation? Innovation is an interactive learning process...... and the participants in this interaction need a common code of communication to efficiently work together. The institutions that govern user-producer interaction have therefore been seen as a possible explanation for success or failure in public procurement of innovation. Endogenous institutions were found......This article sets out to explore endogenous institutions as the rules that govern the interaction between users and producers in public procurement of innovation in a regional context. It further aims to study how this interaction influences the results of the procurement process by investigating...