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Sample records for abundance vasoactive peptides

  1. Vasoactive intestinal peptide stimulates tracheal submucosal gland secretion in ferret

    SciTech Connect

    Peatfield, A.C.; Barnes, P.J.; Bratcher, C.

    1983-07-01

    We studied the effect of vasoactive intestinal peptide (VIP) on the output of 35S-labeled macromolecules from ferret tracheal explants either placed in beakers or suspended in modified Ussing chambers. In Ussing chamber experiments, the radiolabel precursor, sodium (35S)sulfate, and all drugs were placed on the submucosal side of the tissue. Washings were collected at 30-min intervals from the luminal side and were dialyzed to remove unbound 35S, leaving radiolabeled macromolecules. Vasoactive intestinal peptide at 3 X 10(-7) M stimulated bound 35S output by a mean of + 252.6% (n . 14). The VIP response was dose-dependent with a near maximalmore » response and a half maximal response at approximately 10(-6) M and 10(-8), M, respectively. The VIP effect was not inhibited by a mixture of tetrodotoxin, atropine, I-propranolol, and phentolamine. Vasoactive intestinal peptide had no effect on the electrical properties of the of the tissues. We conclude that VIP stimulates output of sulfated-macromolecules from ferret tracheal submucosal glands without stimulating ion transport. Our studies also suggest that VIP acts on submucosal glands via specific VIP receptors. Vasoactive intestinal peptide has been shown to increase intracellular levels of cyclic AMP, and we suggest that this may be the mechanism for its effect on the output of macromolecules. This mechanism may be important in the neural regulation of submucosal gland secretion.« less

  2. Vasoactive intestinal peptide and electrical activity influence neuronal survival

    SciTech Connect

    Brenneman, D.E.; Eiden, L.E.

    1986-02-01

    Blockage of electrical activity in dissociated spinal cord cultures results in a significant loss of neurons during a critical period in development. Decreases in neuronal cell numbers and SVI-labeled tetanus toxin fixation produced by electrical blockage with tetrodotoxin (TTX) were prevented by addition of vasoactive intestinal peptide (VIP) to the nutrient medium. The most effective concentration of VIP was 0.1 nM. At higher concentrations, the survival-enhancing effect of VIP on TTX-treated cultures was attenuated. Addition of the peptide alone had no significant effect on neuronal cell counts or tetanus toxin fixation. With the same experimental conditions, two closely related peptides,more » PHI-27 (peptide, histidyl-isoleucine amide) and secretin, were found not to increase the number of neurons in TTX-treated cultures. Interference with VIP action by VIP antiserum resulted in neuronal losses that were not significantly different from those observed after TTX treatment. These data indicate that under conditions of electrical blockade a neurotrophic action of VIP on neuronal survival can be demonstrated.« less

  3. Characterization of autoantibodies to vasoactive intestinal peptide in asthma.

    PubMed

    Paul, S; Said, S I; Thompson, A B; Volle, D J; Agrawal, D K; Foda, H; de la Rocha, S

    1989-07-01

    Vasoactive intestinal peptide (VIP) is a potent relaxant of the airway smooth muscle. In this study, VIP-binding autoantibodies were observed in the plasma of 18% asthma patients and 16% healthy subjects. Immunoprecipitation studies and chromatography on DEAE-cellulose and immobilized protein G indicated that the plasma VIP-binding activity was largely due to IgG antibodies. Saturation analysis of VIP binding by the plasmas suggested the presence of one or two classes of autoantibodies, distinguished by their apparent equilibrium affinity constants (Ka). The autoantibodies from asthma patients exhibited a larger VIP-binding affinity compared to those from healthy subjects (Ka 7.8 x 10(9) M-1 and 0.13 x 10(9) M-1, respectively; P less than 0.005). The antibodies were specific for VIP, judged by their poor reaction with peptides bearing partial sequence homology with VIP (peptide histidine isoleucine, growth hormone releasing factor and secretin). IgG prepared from the plasma of an antibody-positive asthma patient inhibited the saturable binding of 125I-VIP by receptors in guinea pig lung membranes (by 39-59%; P less than 0.001). These observations are consistent with a role for the VIP autoantibodies in the airway hyperresponsiveness of asthma.

  4. Infection-Mediated Vasoactive Peptides Modulate Cochlear Uptake of Fluorescent Gentamicin

    PubMed Central

    Koo, Ja-Won; Wang, Qi; Steyger, Peter S.

    2011-01-01

    Inflammatory mediators released during bacterial infection include vasoactive peptides such as histamine and serotonin, and their serum levels are frequently elevated. These peptides also modulate the vascular permeability of endothelial cells lining the blood-brain and blood-labyrinth barriers (BLB). These peptides may also modulate the permeability of the BLB to ototoxic aminoglycoside antibiotics prescribed to resolve bacterial sepsis. To test this hypothesis, we compared the effect of histamine and serotonin on the cochlear distribution of fluorescently conjugated gentamicin (GTTR) in control animals at 0.5, 1 and 3 h after injection of GTTR. The intensity of GTTR fluorescence was attenuated at 1 h in the histamine group compared to control mice, and more intense 3 h after injection (p < 0.05). In the serotonin group, the intensity of GTTR fluorescence was attenuated at 0.5 and 1 h (p < 0.05) and was increased at 3 h compared to control animals, where GTTR intensities peaked at 1 h and then plateaued or was slightly decreased at 3 h. This biphasic pattern of modulation was statistically significant in the apical turn of the cochlea. No difference in the intensity of GTTR fluorescence was observed in kidney proximal tubules. Systemic increases in serum levels of vasoactive peptides can modulate cochlear uptake of gentamicin, likely via permeability changes in the BLB. Conditions that influence serum levels of vasoactive peptides may potentiate aminoglycoside ototoxicity. PMID:21196726

  5. Modulation of inflammation by vasoactive intestinal peptide and bombesin: lack of effects on neutrophil apoptosis.

    PubMed

    Djanani, Angela M; Kähler, Ch M

    2002-01-01

    Inhibition of neutrophil apoptosis has been identified as a prominent feature in chronic inflammation, parenchymal damage, and unresolved organ dysfunction. Lung injury animal models suggest that the neuropeptides vasoactive intestinal peptide and bombesin are protective. Therefore, in vitro effects of VIP and bombesin on apoptosis of normal human neutrophils were tested. For measuring effects on cell survival and apoptosis, trypan dye exclusion, colorimetric MTT assay to assess cell survival, and caspase-3 assay and annexin-V binding for analysing apoptosis rates were used. Foetal calf serum, Fas ligand, and tumour necrosis factor-alpha served as modulatory control agents; survival-promoting and apoptosis-inducing activities of the respective agents were confirmed. Vasoactive intestinal peptide and bombesin, however, failed to significantly affect cell death in neutrophils. Data suggest that direct regulation of neutrophil apoptosis is unlikely to be among the mechanisms of lung-protective actions of VIP and bombesin.

  6. Vasoactive Intestinal Peptide Inhibits Human Small-Cell Lung Cancer Proliferation in vitro and in vivo

    NASA Astrophysics Data System (ADS)

    Maruno, Kaname; Absood, Afaf; Said, Sami I.

    1998-11-01

    Small-cell lung carcinoma (SCLC) is an aggressive, rapidly growing and metastasizing, and highly fatal neoplasm. We report that vasoactive intestinal peptide inhibits the proliferation of SCLC cells in culture and dramatically suppresses the growth of SCLC tumor-cell implants in athymic nude mice. In both cases, the inhibition was mediated apparently by a cAMP-dependent mechanism, because the inhibition was enhanced by the adenylate cyclase activator forskolin and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine in proportion to increases in intracellular cAMP levels, and the inhibition was abolished by selective inhibition of cAMP-dependent protein kinase. If confirmed in clinical trials, this antiproliferative action of vasoactive intestinal peptide may offer a new and promising means of suppressing SCLC in human subjects, without the toxic side effects of chemotherapeutic agents.

  7. Deficient Vasoactive Intestinal Peptide Innervation in the Sweat Glands of Cystic Fibrosis Patients

    NASA Astrophysics Data System (ADS)

    Heinz-Erian, Peter; Dey, Richard D.; Flux, Marinus; Said, Sami I.

    1985-09-01

    The innervation of acini and ducts of eccrine sweat glands by immunoreactive, vasoactive intestinal peptide--containing nerve fibers was sharply reduced in seven patients with cystic fibrosis compared to eight normal subjects. The decrease in innervation by this neuropeptide, which has been shown to promote blood flow and the movement of water and chloride across epithelial surfaces in other systems, may be a basic mechanism for the decreased water content and relative impermeability of the epithelium to chloride and other ions that characterize cystic fibrosis.

  8. Effects of vasoactive intestinal peptide and pancreatic polypeptide in rabbit intestine.

    PubMed Central

    Camilleri, M; Cooper, B T; Adrian, T E; Bloom, S R; Chadwick, V S

    1981-01-01

    The effects of porcine vasoactive intestinal peptide (VIP) and bovine pancreatic polypeptide (PP) on jejunal, ileal, and colonic fluid transport were studied in the rabbit. VIP produced secretion in the small intestine (jejunum greater than ileum) but did not affect absorption in the colon. PP had no secretory effects in jejunum, ileum, or colon. The small intestinal secretion induced by VIP was not associated with raised cAMP concentrations in the mucosa; this suggests that the secretory effects of VIP in vivo are mediated by a mechanism other than stimulation of adenylate cyclase. PMID:6257593

  9. The CGTCA sequence motif is essential for biological activity of the vasoactive intestinal peptide gene cAMP-regulated enhancer.

    PubMed Central

    Fink, J S; Verhave, M; Kasper, S; Tsukada, T; Mandel, G; Goodman, R H

    1988-01-01

    cAMP-regulated transcription of the human vasoactive intestinal peptide gene is dependent upon a 17-base-pair DNA element located 70 base pairs upstream from the transcriptional initiation site. This element is similar to sequences in other genes known to be regulated by cAMP and to sequences in several viral enhancers. We have demonstrated that the vasoactive intestinal peptide regulatory element is an enhancer that depends upon the integrity of two CGTCA sequence motifs for biological activity. Mutations in either of the CGTCA motifs diminish the ability of the element to respond to cAMP. Enhancers containing the CGTCA motif from the somatostatin and adenovirus genes compete for binding of nuclear proteins from C6 glioma and PC12 cells to the vasoactive intestinal peptide enhancer, suggesting that CGTCA-containing enhancers interact with similar transacting factors. Images PMID:2842787

  10. Ventilatory effects of substance P, vasoactive intestinal peptide, and nitroprusside in humans.

    PubMed

    Maxwell, D L; Fuller, R W; Dixon, C M; Cuss, F M; Barnes, P J

    1990-01-01

    Animal studies suggest that the neuropeptides, substance P and vasoactive intestinal peptide (VIP), may influence carotid body chemoreceptor activity and that substance P may take part in the carotid body response to hypoxia. The effects of these peptides on resting ventilation and on ventilatory responses to hypoxia and to hypercapnia have been investigated in six normal humans. Infusions of substance P (1 pmol.kg-1.min-1) and of VIP (6 pmol.kg-1.min-1) were compared with placebo and with nitroprusside (5 micrograms.kg-1.min-1) as a control for the hypotensive action of the peptides. Both peptides caused significantly less hypotension than nitroprusside. Substance P and nitroprusside caused significantly greater increases in ventilation and in the hypoxic ventilatory response than VIP. No changes were seen in hypercapnic sensitivity. The stimulation of ventilation and the differential effects on ventilatory chemosensitivity that accompanied hypotension are consistent either with stimulation of carotid body chemoreceptor activity or with an interaction with peripheral chemoreceptor input to the respiratory center, as is seen in animals. The similar cardiovascular but different ventilatory effects of the peptides suggest that substance P may also stimulate the carotid body in a manner independent of the effect of hypotension. This is consistent with a role of substance P in the hypoxic ventilatory response in humans.

  11. Pharmacological potential of exercise and RAS vasoactive peptides for prevention of diseases.

    PubMed

    Petriz, Bernardo de Assis; de Almeida, Jeeser Alves; Migliolo, Ludovico; Franco, Octavio Luiz

    2013-09-01

    The Renin-Angiotensin-System (RAS) molecular network has been widely studied, especially with attention to angiotensin II, the main effector peptide among RAS. The relation of Ang II to hypertension pathogenesis has led to research being extended to other molecules from the RAS, such as angiotensin III and IV, angiotensin (1-5), and angiotensin (1-9). Moreover, great pharmacologic advances have been made in hypertension treatment by inhibiting renin and angiotensin converting enzymes and blocking the bonding of angiotensin II to its receptor AT1. Thus, RAS molecular signaling and its effect on blood pressure as well as its relationship to renal function and cardiovascular disease are still being investigated. It is a great challenge to fully cover and understand all molecules from the RAS, especially those that interfere with or have vasoactive properties. Some of these targets respond to exercise, stimulating nitric oxide synthesis and endothelial vasodilation. The activation of these specific molecules via exercise is a systematic way of controlling high blood pressure without pharmacological treatment. Angiotensin (1-7) has been focused due to its vasodilation properties and its responses to exercise, improving vascular function. Thus, stimulation of the ACE2/Ang (1-7)/Mas axis has been gaining ground as a prospective clinical means to attenuate cardiovascular diseases such as hypertension by modulating RAS activity. This review focuses on the vasoactive peptides from the RAS, their responses to exercise and possible trends for pharmacological development. In several cases where exercise training is not achievable, cardiovascular drug therapy with vasodilator peptides may possibly be an option.

  12. ACE2 and vasoactive peptides: novel players in cardiovascular/renal remodeling and hypertension.

    PubMed

    Mendoza-Torres, Evelyn; Oyarzún, Alejandra; Mondaca-Ruff, David; Azocar, Andrés; Castro, Pablo F; Jalil, Jorge E; Chiong, Mario; Lavandero, Sergio; Ocaranza, María Paz

    2015-08-01

    The renin-angiotensin system (RAS) is a key component of cardiovascular physiology and homeostasis due to its influence on the regulation of electrolyte balance, blood pressure, vascular tone and cardiovascular remodeling. Deregulation of this system contributes significantly to the pathophysiology of cardiovascular and renal diseases. Numerous studies have generated new perspectives about a noncanonical and protective RAS pathway that counteracts the proliferative and hypertensive effects of the classical angiotensin-converting enzyme (ACE)/angiotensin (Ang) II/angiotensin type 1 receptor (AT1R) axis. The key components of this pathway are ACE2 and its products, Ang-(1-7) and Ang-(1-9). These two vasoactive peptides act through the Mas receptor (MasR) and AT2R, respectively. The ACE2/Ang-(1-7)/MasR and ACE2/Ang-(1-9)/AT2R axes have opposite effects to those of the ACE/Ang II/AT1R axis, such as decreased proliferation and cardiovascular remodeling, increased production of nitric oxide and vasodilation. A novel peptide from the noncanonical pathway, alamandine, was recently identified in rats, mice and humans. This heptapeptide is generated by catalytic action of ACE2 on Ang A or through a decarboxylation reaction on Ang-(1-7). Alamandine produces the same effects as Ang-(1-7), such as vasodilation and prevention of fibrosis, by interacting with Mas-related GPCR, member D (MrgD). In this article, we review the key roles of ACE2 and the vasoactive peptides Ang-(1-7), Ang-(1-9) and alamandine as counter-regulators of the ACE-Ang II axis as well as the biological properties that allow them to regulate blood pressure and cardiovascular and renal remodeling. © The Author(s), 2015.

  13. TUNING IMMUNE TOLERANCE WITH VASOACTIVE INTESTINAL PEPTIDE: A NEW THERAPEUTIC APPROACH FOR IMMUNE DISORDERS

    PubMed Central

    POZO, DAVID; GONZALEZ-REY, ELENA; CHORNY, ALEJO; ANDERSON, PER; VARELA, NIEVES; DELGADO, MARIO

    2007-01-01

    The induction of immune tolerance is essential for the maintenance of immune homeostasis and to limit the occurrence of exacerbated inflammatory and autoimmune conditions. Multiple mechanisms act together to ensure self-tolerance, including central clonal deletion, cytokine deviation and induction of regulatory T cells. Identifying the factors that regulate these processes is crucial for the development of new therapies of autoimmune diseases and transplantation. The vasoactive intestinal peptide (VIP) is a well-characterized endogenous anti-inflammatory neuropeptide with therapeutic potential for a variety of immune disorders. Here we examine the latest research findings, which indicate that VIP participates in maintaining immune tolerance in two distinct ways: by regulating the balance between pro-inflammatory and anti-inflammatory factors, and by inducing the emergence of regulatory T cells with suppressive activity against autoreactive T-cell effectors. PMID:17521775

  14. Clostridium difficile suppresses colonic vasoactive intestinal peptide associated with altered motility

    PubMed Central

    Nassif, A.; Sexe, R.; Stratton, M.; Standeven, J.; Vernava, A. M.; Kaminski, D. L.

    1995-01-01

    We investigated whether Clostridium difficile toxin alters colonic tissue levels of vasoactive intestinal peptide (VIP) at the expense of changes in colonic motility in the isolated perfused rabbit left colon. Colonic inflammation was induced by the intracolonic administration of 10−8 M C. difflcile toxin. Strain gauge transducers were sewn onto the serosal surface of the colon to evaluate colonic motility. C. difflcile administration produced histologic changes consistent with epithelial damage. This was associated with an increased production of prostaglandin E2 and thromboxane B2. Tissue levels of VIP but not substance P were significantly reduced. This was associated with an increased number of contractions per minute and an average force of each colonic contraction. These results suggest that tissue levels of VIP are suppressed by C. difflcile and may participate in colonic dysmotility during active inflammation. PMID:18475679

  15. Clostridium difficile suppresses colonic vasoactive intestinal peptide associated with altered motility.

    PubMed

    Nassif, A; Longo, W E; Sexe, R; Stratton, M; Standeven, J; Vernava, A M; Kaminski, D L

    1995-01-01

    We investigated whether Clostridium difficile toxin alters colonic tissue levels of vasoactive intestinal peptide (VIP) at the expense of changes in colonic motility in the isolated perfused rabbit left colon. Colonic inflammation was induced by the intracolonic administration of 10(-8) M C. difflcile toxin. Strain gauge transducers were sewn onto the serosal surface of the colon to evaluate colonic motility. C. difflcile administration produced histologic changes consistent with epithelial damage. This was associated with an increased production of prostaglandin E(2) and thromboxane B(2). Tissue levels of VIP but not substance P were significantly reduced. This was associated with an increased number of contractions per minute and an average force of each colonic contraction. These results suggest that tissue levels of VIP are suppressed by C. difflcile and may participate in colonic dysmotility during active inflammation.

  16. Vasoactive intestinal peptide prevents lung injury due to xanthine/xanthine oxidase.

    PubMed

    Berisha, H; Foda, H; Sakakibara, H; Trotz, M; Pakbaz, H; Said, S I

    1990-08-01

    Reactive oxygen species mediate injury and inflammation in many tissues. The addition of xanthine and xanthine oxidase to perfused rat lungs led to increases in peak airway pressure and perfusion pressure, pulmonary edema, and increased protein content in bronchoalveolar lavage fluid. Treatment with 1-10 micrograms.kg-1.min-1 of vasoactive intestinal peptide (VIP), a widely distributed neuropeptide, markedly reduced or totally prevented all signs of injury. Simultaneously, VIP also diminished or abolished the associated generation of arachidonate products. Similar protection was provided by catalase (100 micrograms/ml) but not by the VIP-related peptides secretin or glucagon. The pulmonary vasodilator papaverine (0.15 mg/ml) was also ineffective. Injured lungs that were not treated with VIP released large amounts of this peptide in the perfusate. The results indicate that VIP has potent protective activity against injury triggered by xanthine/xanthine oxidase and may be a physiological modulator of inflammatory tissue damage associated with toxic oxygen metabolites.

  17. Depot formulation of vasoactive intestinal peptide by protamine-based biodegradable nanoparticles.

    PubMed

    Wernig, Karin; Griesbacher, Martin; Andreae, Fritz; Hajos, Franz; Wagner, Julian; Mosgoeller, Wilhelm; Zimmer, Andreas

    2008-09-10

    Drug delivery of protein and peptide-based drugs, which represent a growing and important therapeutic class, is hampered by these drugs' very short half-lives. High susceptibility towards enzymatic degradation necessitates frequent drug administration followed by poor adherence to therapy. Among these drugs is vasoactive intestinal peptide (VIP), a potent systemic and pulmonary vasodilator, which is a promising drug for the treatment of idiopathic pulmonary arterial hypertension (IPAH). Encapsulation of VIP into the nanoparticle matrix of biodegradable protamine-oligonucleotide nanoparticles (proticles) protects the peptide against rapid enzymatic degradation. Additionally, the nanoparticle matrix will be able to sustain drug release. Proticles consist of 18mer non-sense oligonucleotides and protamine, a polycationic arginine-rich peptide. VIP encapsulation occurs during self-assembly of the components. Within the present study, we evaluate nanoparticle size (hydrodynamic diameter) and zeta potential of VIP-loaded proticles as well as encapsulation efficiency and VIP release. Further, the pharmacological VIP response of "encapsulated VIP" is investigated using an ex vivo lung arterial model system. We found satisfying encapsulation efficiency (up to 80%), VIP release (77-87%), and an appropriate nanoparticle size (177-251 nm). Investigations on rat pulmonary arteries showed a modified VIP response of proticle-associated VIP. We noted differences in the profile of artery relaxation where VIP proticles lead to a 20-30% lower relaxation maximum than aqueous VIP solutions followed by prolonged vasodilatation. Our data indicate that proticles could be a feasible drug delivery system for a pulmonary VIP depot formulation.

  18. Synergistic airway gland mucus secretion in response to vasoactive intestinal peptide and carbachol is lost in cystic fibrosis

    PubMed Central

    Choi, Jae Young; Joo, Nam Soo; Krouse, Mauri E.; Wu, Jin V.; Robbins, Robert C.; Ianowski, Juan P.; Hanrahan, John W.; Wine, Jeffrey J.

    2007-01-01

    Cystic fibrosis (CF) is caused by dysfunction of the CF transmembrane conductance regulator (CFTR), an anion channel whose dysfunction leads to chronic bacterial and fungal airway infections via a pathophysiological cascade that is incompletely understood. Airway glands, which produce most airway mucus, do so in response to both acetylcholine (ACh) and vasoactive intestinal peptide (VIP). CF glands fail to secrete mucus in response to VIP, but do so in response to ACh. Because vagal cholinergic pathways still elicit strong gland mucus secretion in CF subjects, it is unclear whether VIP-stimulated, CFTR-dependent gland secretion participates in innate defense. It was recently hypothesized that airway intrinsic neurons, which express abundant VIP and ACh, are normally active and stimulate low-level gland mucus secretion that is a component of innate mucosal defenses. Here we show that low levels of VIP and ACh produced significant mucus secretion in human glands via strong synergistic interactions; synergy was lost in glands of CF patients. VIP/ACh synergy also existed in pig glands, where it was CFTR dependent, mediated by both Cl– and HCO3–, and clotrimazole sensitive. Loss of “housekeeping” gland mucus secretion in CF, in combination with demonstrated defects in surface epithelia, may play a role in the vulnerability of CF airways to bacterial infections. PMID:17853942

  19. Vasoactive Intestinal Peptide Nanomedicine for the Management of Inflammatory Bowel Disease.

    PubMed

    Jayawardena, Dulari; Anbazhagan, Arivarasu N; Guzman, Grace; Dudeja, Pradeep K; Onyuksel, Hayat

    2017-11-06

    Inflammatory bowel disease (IBD) is a chronic relapsing disorder of the intestine, with increasing incidence worldwide. At present, the management of IBD is an unmet medical need due to the ineffectiveness of currently available drugs in treating all patients, and there is strong demand for novel therapeutics. In this regard, vasoactive intestinal peptide, a potent anti-inflammatory endogenous hormone, has shown promise in managing multiple immune disorders in animal models. However, when administered in the free form, VIP undergoes rapid degradation in vivo, and with continuous infusion, it causes severe dose limiting side effects. To overcome these barriers, we have developed a superior mode to deliver VIP in its native form, using sterically stabilized micelles (VIP-SSM). Our previous studies demonstrated that, VIP, when administered in SSM, prevented joint damage and inflammation in a mouse model of rheumatoid arthritis at a significantly lower dose than the free peptide, completely abrogating the serious side effect of hypotension associated with VIP. In the current study, we demonstrate the therapeutic benefit of VIP-SSM over free peptide in reversing severe colitis associated with IBD. First, we conducted preliminary studies with dextran sulfate sodium (DSS) induced colitis in mice, to determine the effectiveness of VIP administered on alternate days in reducing disease severity. Thereafter, a single intra peritoneal injection of VIP-SSM or the free peptide was used to determine its therapeutic effect on the reversal of colitis and associated diarrhea. The results demonstrated that when administered on alternate days, both VIP-SSM and VIP were capable of alleviating DSS colitis in mice. However, when administered as a single dose, in a therapeutic setting, VIP-SSM showed superior benefits compared to the free peptide in ameliorating colitis phenotype. Namely, the loss of solid fecal pellets and increased fluid accumulation in colon resulting from DSS insult

  20. Substance P and vasoactive intestinal peptide degradation by mast cell tryptase and chymase.

    PubMed

    Caughey, G H; Leidig, F; Viro, N F; Nadel, J A

    1988-01-01

    The peptides substance P (SP) and vasoactive intestinal peptide (VIP) released from peptidergic neurons have potent effects on gland secretion and on smooth muscle tone. Because mast cells release proteases during degranulation, and are located in many of the same tissue microenvironments into which SP and VIP are released, we wished to examine whether mast cell proteases, by cleaving and thus inactivating these peptides, could modulate their effects. We used active site-titrated preparations of the two major neutral proteases of mast cell granules, tryptase and chymase, to determine the sites and rates of cleavage of SP and VIP. The proteases were purified from dog mastocytomas. Tryptase cleaved VIP rapidly at two sites with a kcat/Km of 2.2 X 10(5) sec-1 M-1, but had no effect on SP. Chymase cleaved both SP and VIP at primarily a single site with kcat/Km of 3.9 X 10(4) and 5.4 X 10(4) sec-1 M-1, respectively. Thus, these data show that mast cell proteases degrade SP and VIP. The differences in peptidase activity between tryptase and chymase suggest that the consequences of protease release could vary according to mast cell protease phenotype and location in various tissues and species. Tryptase, by cleaving the bronchodilator VIP but not the bronchoconstrictor SP, might promote bronchial hyper-responsiveness in asthma by decreasing the nonadrenergic neural inhibitory influence mediated by VIP. In skin and other tissues, chymase might interrupt axon reflex-mediated neurogenic inflammation by cleaving SP.

  1. Vinpocetine and Vasoactive Intestinal Peptide Attenuate Manganese-Induced Toxicity in NE-4C Cells.

    PubMed

    Bora, Saylav; Erdogan, Mumin Alper; Armagan, Güliz; Sevgili, Elvin; Dagcı, Taner

    2016-12-01

    Increased concentration of manganese (Mn) in the brain is known to be associated with excitotoxicity and neuroinflammation. Vinpocetine, an alkaloid derived from the plant Vinca minor L., basically shows its effect via phosphodiesterase inhibition and voltage-dependent Na + channels. Vasoactive intestinal peptide (VIP) has gastrointestinal, vasomotor, muscular, and neuroprotective effects. The aim of this study was to examine the potential protective effects of vinpocetine and VIP against Mn toxicity in NE-4C neural stem cells (NSCs). VIP treatment at 1 μM and vinpocetine treatment at 2 μM concentrations were sufficient to yield maximum protection, and these concentrations were adopted in the following experiments. In this study, Mn treatment significantly increased lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) production, and triggered cell death in NE-4C cultures. However, significant reduction in LDH release was observed following vinpocetine or VIP treatments when compared with control. Similar to these findings, vinpocetine or VIP treatments significantly reduced membrane degradation induced by Mn (p < 0.001). Moreover, vinpocetine attenuated Mn-induced decrease of mitochondrial membrane potential. Similarly, proapoptotic protein bax and ROS production significantly decreased in cells after incubation with vinpocetine (p = 0.01) or VIP in the presence of Mn (p < 0.001). Our study provides the evidence that both vinpocetine and VIP may exert protective effects via modulating oxidative stress and apoptosis in Mn-induced neurodegeneration in NE-4C cells.

  2. Effects of vasoactive intestinal peptide on vascular conductance are unaffected by anesthesia

    SciTech Connect

    Bouder, T.G.; Huffman, L.J.; Hedge, G.A.

    1988-12-01

    In rats anesthetized with ketamine and pentobarbital (KET/PB), vasoactive intestinal peptide (VIP) increases vascular conductance (VC) in the salivary gland, pancreas, and thyroid gland, whereas no changes in VC are observed in a number of other organs. Because anesthesia may alter the responsiveness of physiological systems, we compared the effects of VIP on organ VC in conscious or anesthetized rats. Chronically catheterized rats were studied in the conscious state or 30 min after induction of anesthesia with KET/PB, isoflurane, or Inactin. Blood flows were measured by the reference sample version of the radioactive microsphere (MS) technique using two MS injectionsmore » ({sup 141}Ce-MS/{sup 85}Sr-MS). Mean arterial blood pressure was monitored and used in the calculation of VC. Organ VCs were similar under basal conditions in conscious and anesthetized rats. VIP infusion caused systemic hypotension and increased VCs in the salivary gland, pancreas, and thyroid gland, and these responses were largely unaffected by anesthesia. These results indicate that the anesthetics used do not alter basal VC or the responsiveness of the vasculature to exogenous VIP.« less

  3. Association of vasoactive intestinal peptide with polymer-grafted liposomes: structural aspects for pulmonary delivery.

    PubMed

    Stark, Brigitte; Debbage, Paul; Andreae, Fritz; Mosgoeller, Wilhelm; Prassl, Ruth

    2007-03-01

    A polymer-grafted liposomal formulation that has the potential to be developed for aerosolic pulmonary delivery of vasoactive intestinal peptide (VIP), a potent vasodilatory neuropeptide, is described. As VIP is prone to rapid proteolytic degradation in the microenvironment of the lung a proper delivery system is required to increase the half-life and bioavailability of the peptide. Here we investigate structural parameters of unilamellar liposomes composed of palmitoyl-oleoyl-phosphatidylcholine, lyso-stearyl-phosphatidylglycerol and distearyl-phosphatidyl-ethanolamine covalently linked to polyethylene glycol 2000, and report on VIP-lipid interaction mechanisms. We found that the cationic VIP is efficiently entrapped by the negatively charged spherical liposomes and becomes converted to an amphipathic alpha-helix. By fluorescence spectroscopy using single Trp-modified VIP we could show that VIP is closely associated to the membrane. Our data suggest that the N-terminal random-coiled domain is embedded in the interfacial headgroup region of the phospholipid bilayer. By doing so, neither the bilayer thickness of the lipid membrane nor the mobility of the phospholipid acyl chains are affected as shown by small angle X-ray scattering and electron spin resonance spectroscopy. Finally, in an ex vivo lung arterial model system we found that liposomal-associated VIP is recognized by its receptors to induce vasodilatory effects with comparable high relaxation efficiency as free VIP but with a significantly retarded dilatation kinetics. In conclusion, we have designed and characterized a liposomal formulation that is qualified to entrap biologically active VIP and displays structural features to be considered for delivery of VIP to the lung.

  4. Mast cell number, substance P and vasoactive intestinal peptide in irritable bowel syndrome with diarrhea.

    PubMed

    Sohn, Won; Lee, Oh Young; Lee, Sang Pyo; Lee, Kang Nyeong; Jun, Dae Won; Lee, Hang Lak; Yoon, Byung Chul; Choi, Ho Soon; Sim, Jongmin; Jang, Ki-Seok

    2014-01-01

    Recent studies have shown that mast cells play an important role in irritable bowel syndrome (IBS). We investigated the relationship between mast cells and the gut hormones substance P and vasoactive intestinal peptide (VIP) in irritable bowel syndrome with diarrhea (IBS-D). Colonoscopic biopsies were performed on the rectal mucosa of 43 subjects (IBS-D patients: 22, healthy volunteers: 21) diagnosed according to the Rome III criteria. Mast cells, and substance P & VIP were evaluated by quantitative immunohistology and image analysis. Mast cells were counted as tryptase-positive cells in the lamina propria, and substance P and VIP levels were expressed as percentages of total areas of staining. Mast cell counts were higher in IBS-D patients than healthy volunteers (9.6 ± 3.3 vs. 5.7 ± 2.5/high power field (HPF), p < 0.01). Substance P was also elevated (0.11 ± 0.08% vs. 0.03 ± 0.02 %, p < 0.01) while VIP was only high in women with IBS-D. Mast cell counts were positively correlated with levels of substance P & VIP in women but not men (women: r = 0.625, p < 0.01 for substance P and r = 0.651, p < 0.01 for VIP). However, mast cell counts were not correlated with IBS symptoms including abdominal pain. Mast cells are activated leading to the raised levels of substance P & VIP in IBS-D patients. However, the correlation between mast cells and levels of substance P & VIP differs according to gender.

  5. Peptidase modulation of vasoactive intestinal peptide pulmonary relaxation in tracheal superfused guinea pig lungs.

    PubMed Central

    Lilly, C M; Martins, M A; Drazen, J M

    1993-01-01

    The effects of enzyme inhibitors on vasoactive intestinal peptide (VIP)-induced decreases in airway opening pressure (PaO) and VIP-like immunoreactivity (VIP-LI) recovery were studied in isolated tracheal superfused guinea pig lungs. In the absence of inhibitors, VIP 0.38 (95% CI 0.33-0.54) nmol/kg animal, resulted in a 50% decrease in PaO and 33% of a 1 nmol/kg VIP dose was recovered as intact VIP. In the presence of two combinations of enzyme inhibitors, SCH 32615 (S, 10 microM) and aprotinin (A, 500 tyrpsin inhibitor units [TIU]/kg) or S and soybean trypsin inhibitor (T, 500 TIU/kg), VIP caused a significantly greater decrease in PaO and greater quantities of VIP were recovered from lung effluent (both P < 0.001). The addition of captopril, (3 microM), leupeptin (4 microM), or bestatin (1 microM) failed to further increase pulmonary relaxation or recovery of VIP-LI. When given singly, A, T, and S did not augment the effects or recovery of VIP. The efficacy of S (a specific inhibitor of neutral endopeptidase [NEP]) and A and T (serine protease inhibitors) thus implicated NEP and at least one serine protease as primary modulators of VIP activity in the guinea pig lung. We sought to corroborate this finding by characterizing the predominant amino acid sites at which VIP is hydrolized in the lung. When [mono(125I)iodo-Tyr10]VIP was offered to the lung, in the presence and absence of the active inhibitors, cleavage products consistent with activity by NEP and a tryptic enzyme were recovered. These data demonstrate that NEP and a peptidase with an inhibitor profile and cleavage pattern compatible with a tryptic enzyme inactivate VIP in a physiologically competitive manner. PMID:7678603

  6. 123I-labelled vasoactive intestinal peptide receptor scintigraphy in patients with colorectal cancer.

    PubMed Central

    Raderer, M.; Kurtaran, A.; Hejna, M.; Vorbeck, F.; Angelberger, P.; Scheithauer, W.; Virgolini, I.

    1998-01-01

    Recent studies have shown that various gastrointestinal tumours express substantial amounts of vasoactive intestinal peptide (VIP) receptors. Based on these observations, we have developed a receptor scintigraphy using [123I]VIP as a radioligand. An initial series performed at our institution showed promising potential for visualization of various gastrointestinal adenocarcinomas by means of [123I]VIP. In this article, we now report the results obtained in 80 consecutive patients with colorectal adenocarcinoma. Eighty consecutive patients with histologically verified colorectal cancer underwent scanning by means of [123I]VIP (1 microg, approximately 150 MBq). Thirteen patients were free of tumour after complete resection of Dukes' C cancer, eight patients presented with primary and 14 with locally recurrent tumours but were free of metastases. Ten patients had locally recurrent disease and liver, lung or lymph node metastases. Disease confined to organ metastases (i.e. liver, lung or lymph nodes) was present in 35 patients. The size of the primary or recurrent tumours ranged between 3 and 6 cm, and the size of metastases was between 1 and 13 cm in diameter. Scan results were evaluated independently by two nuclear medicine physicians in a blinded way, and results were then compared with computerized tomography (CT)scans not older than 4 weeks. Seven out of eight primary (87%) and 21 out of 24 (82%) locally relapsing cancers were imaged with [123I]VIP. Negative VIP scans were obtained in all 13 patients in whom the cancers had been curatively resected. All patients with lymph node metastases showed positive VIP scans (four out of four), and positive scans were obtained in 25 out of 28 (89%) patients with liver metastases and in two out of three cases with lung metastases. In four patients with relapsing cancer, the VIP scan indicated the presence of disease before CT, and in two patients the diagnosis of scar tissue instead of a local recurrence of rectal cancer as

  7. [Substance P and vasoactive intestinal peptide in patients with progressive scleroderma. Determination of plasma level before and after autogenic training].

    PubMed

    Haustein, U F; Weber, B; Seikowski, K

    1995-02-01

    In 12 patients suffering from systemic sclerosis (SSc) the influence of autogenic training on the plasma level of the neuropeptides substance P and vasoactive intestinal peptide (VIP) was studied. Compared with healthy controls the SSc patients exhibited significantly elevated levels of substance P (mean +/- SD: 7.1 +/- 3.2 pmol/l vs 1.6 +/- 1.6 pmol/l). Apart from variations the VIP plasma concentration did not significantly differ from that in healthy controls (mean +/- SD 10.7 +/- 7.1 pmol/l versus 12.0 +/- 5.3 pmol/l). Autogenic training did not bring about any significant changes in the plasma levels of neuropeptides.

  8. Vasoactive intestinal peptide is a local mediator in a gut-brain neural axis activating intestinal gluconeogenesis.

    PubMed

    De Vadder, F; Plessier, F; Gautier-Stein, A; Mithieux, G

    2015-03-01

    Intestinal gluconeogenesis (IGN) promotes metabolic benefits through activation of a gut-brain neural axis. However, the local mediator activating gluconeogenic genes in the enterocytes remains unknown. We show that (i) vasoactive intestinal peptide (VIP) signaling through VPAC1 receptor activates the intestinal glucose-6-phosphatase gene in vivo, (ii) the activation of IGN by propionate is counteracted by VPAC1 antagonism, and (iii) VIP-positive intrinsic neurons in the submucosal plexus are increased under the action of propionate. These data support the role of VIP as a local neuromodulator released by intrinsic enteric neurons and responsible for the induction of IGN through a VPAC1 receptor-dependent mechanism in enterocytes. © 2015 John Wiley & Sons Ltd.

  9. Vasoactive intestinal peptide-null mice demonstrate enhanced sweet taste preference, dysglycemia, and reduced taste bud leptin receptor expression.

    PubMed

    Martin, Bronwen; Shin, Yu-Kyong; White, Caitlin M; Ji, Sunggoan; Kim, Wook; Carlson, Olga D; Napora, Joshua K; Chadwick, Wayne; Chapter, Megan; Waschek, James A; Mattson, Mark P; Maudsley, Stuart; Egan, Josephine M

    2010-05-01

    It is becoming apparent that there is a strong link between taste perception and energy homeostasis. Recent evidence implicates gut-related hormones in taste perception, including glucagon-like peptide 1 and vasoactive intestinal peptide (VIP). We used VIP knockout mice to investigate VIP's specific role in taste perception and connection to energy regulation. Body weight, food intake, and plasma levels of multiple energy-regulating hormones were measured and pancreatic morphology was determined. In addition, the immunocytochemical profile of taste cells and gustatory behavior were examined in wild-type and VIP knockout mice. VIP knockout mice demonstrate elevated plasma glucose, insulin, and leptin levels, with no islet beta-cell number/topography alteration. VIP and its receptors (VPAC1, VPAC2) were identified in type II taste cells of the taste bud, and VIP knockout mice exhibit enhanced taste preference to sweet tastants. VIP knockout mouse taste cells show a significant decrease in leptin receptor expression and elevated expression of glucagon-like peptide 1, which may explain sweet taste preference of VIP knockout mice. This study suggests that the tongue can play a direct role in modulating energy intake to correct peripheral glycemic imbalances. In this way, we could view the tongue as a sensory mechanism that is bidirectionally regulated and thus forms a bridge between available foodstuffs and the intricate hormonal balance in the animal itself.

  10. Effects of endopeptidase inhibition on the relaxation response of isolated human penile erectile tissue to vasoactive peptides.

    PubMed

    Rahardjo, H E; Reichelt, K; Sonnenberg, J E; Sohn, M; Kuczyk, M A; Ückert, S

    2016-12-01

    Peptides, such as CNP, CGRP and VIP, are involved in the function of male penile erectile tissue. Tissue levels of said peptides are controlled by the endopeptidase enzymes. Theoretically, the inhibition of the degradation of CNP, CGRP and/or VIP should result in an enhancement in penile smooth muscle relaxation. The effects were investigated of CNP or VIP (0.1 nm-1 μm), without and following pre-exposure of the tissue to a threshold concentration of the endopeptidase inhibitor KC 12615 (10 μm, for 20 min), on the reversion of tension induced by means of electrical field stimulation. Drug effects on the production of cyclic AMP/GMP were also evaluated. Neither KC 12615, CNP and VIP nor the combination of CNP plus KC 12615 or VIP plus KC 12615 increased the response of the tissue to EFS. While no effects were observed of a pre-exposure of the tissue to KC 12615 on the production of cyclic AMP in the presence of VIP, an enhancement was registered in the accumulation of cyclic AMP in the presence of CNP plus KC 12615. Further studies are indicated to investigate whether endopeptidase inhibitors might tend to be more effective in tissues affected by a decreased local production of vasoactive peptides. © 2016 Blackwell Verlag GmbH.

  11. Effects of neutral endopeptidase (neprilysin) inhibition on the response to other vasoactive peptides in small human resistance arteries: studies with thiorphan and omapatrilat.

    PubMed

    Dalzell, Jonathan R; Seed, Alison; Berry, Colin; Whelan, Carol J; Petrie, Mark C; Padmanabhan, Neal; Clarke, Amanda; Biggerstaff, Fiona; Hillier, Christopher; McMurray, John J V

    2014-02-01

    New compounds with neprilysin or neutral endopeptidase (NEP) inhibiting activity are under clinical investigation in heart failure and hypertension. We investigated the effect of NEP inhibition on the functional vasomotor responses to a range of vasoactive peptides in human blood vessels. Small human resistance arteries from patients with coronary artery disease and preserved left ventricular systolic function were studied. Thiorphan (a NEP inhibitor) was compared with captopril (an ACE inhibitor) and omapatrilat (a dual NEP-ACE inhibitor) with regard to their effects on the response of human arteries to key vasoactive peptides. As expected, both captopril and omapatrilat (but not thiorphan) inhibited the vasoconstrictor effect of angiotensin I (maximal response [SEM]: 27 ± 8% vehicle, 6 ± 2% captopril, 39 ± 10% thiorphan, 8 ± 7% omapatrilat, P < 0.05). Thiorphan, captopril, and omapatrilat all enhanced the vasodilator response to bradykinin (all P < 0.01). Omapatrilat markedly augmented the vasodilator action of adrenomedullin (P < 0.05), whilst thiorphan and captopril did not. None of the three inhibitors studied affected the vasodilator action of c-type natriuretic peptide, calcitonin gene-related peptide, vasoactive intestinal polypeptide or substance P. NEP inhibition with thiorphan modestly augmented the vasodilator action of bradykinin, but did not potentiate the response to adrenomedullin; dual ACE and NEP inhibition with omapatrilat, as expected, markedly augmented the response to bradykinin and also potentiated the effect of adrenomedullin. Thiorphan weakly enhanced the vasoconstrictor response to angiotensin I. Neither omapatrilat nor thiorphan had any effect on the action of a range of other vasoactive peptides including CNP. © 2013 John Wiley & Sons Ltd.

  12. Immunohistochemical study of vasoactive intestinal peptide (VIP) enteric neurons in diabetic rats supplemented with L-glutamine.

    PubMed

    Alves, Eder Paulo Belato; Alves, Angela Maria Pereira; Pereira, Renata Virginia Fernandes; de Miranda Neto, Marcílio Hubner; Zanoni, Jacqueline Nelisis

    2010-02-01

    The purpose of this work was to study the area of the varicosities of nerve fibers of myenteric neurons immunoreactive to vasoactive intestinal peptide (VIP-IR) and of the cell bodies of VIP-IR submucosal neurons of the jejunum of diabetic rats supplemented with 2% L-glutamine. Twenty male rats were divided into the following groups: normoglycemic (N), normoglycemic supplemented with L-glutamine (NG), diabetic (D) and diabetic supplemented with L-glutamine (DG). Whole-mounts of the muscle tunica and the submucosal layer were subjected to the immunohistochemical technique for neurotransmitter VIP identification. Morphometric analyses were carried out in 500 VIP-IR cell bodies of submucosal neurons and 2000 VIP-IR varicosities from each group. L-Glutamine supplementation to the normoglycemic animals caused an increase in the areas of the cell bodies (8.49%) and varicosities (21.3%) relative to the controls (P < 0.05). On the other hand, there was a decrease in the areas of the cell bodies (4.55%) and varicosities (28.9%) of group DG compared to those of group D (P < 0.05). It is concluded that L-glutamine supplementation was positive both to normoglycemic and diabetic animals.

  13. Protective effects of poly (butyl) cyanoacrylate nanoparticles containing vasoactive intestinal peptide against 6-hydroxydopamine-induced neurotoxicity in vitro.

    PubMed

    Xu, Zhi-Ran; Wang, Wu-Fang; Liang, Xin-Fang; Liu, Ze-Hua; Liu, Yu; Lin, Liang; Zhu, Xuan

    2015-04-01

    The present study investigated brain delivery system of vasoactive intestinal peptide (VIP) adsorbed on poly (butyl cyanoacrylate) nanoparticles coated with polysorbate 80 (P80-poly (butyl) cyanoacrylate (PBCA)-nanoparticles (NPs)) and the neuroprotective effects on the formulation in the model of 6-hydroxydopamine (6-OHDA)-induced Parkinsonian dysfunction in the human neuroblastoma cell line SH-SY5Y. Drug-loaded nanoparticles were prepared by emulsion polymerization method using VIP and PBCA and then stirring with polysorbate 80. The resulting nanoparticles possessed high entrapment efficiency and favorable stability against CaCl2 or fetal bovine serum (FBS)-induced aggregation. Use of fluorescein isothiocyanate (FITC)-conjugated polysorbate 80-PBCA nanoparticles in confocal microscopy revealed that nanoparticles are located inside, while the FITC solution could not penetrate into the cells. The blank nanoparticles showed no significant effects on cell viability, indicating that they had no role in protection; however, polysorbate 80-modified VIP-loading PBCA nanoparticles showed enhanced cell viability compared to free VIP in 6-OHDA-mimic cellular model of Parkinson's disease. In addition, the nanoparticles strikingly increased the anti-apoptosis activity and restored the loss of mitochondrial membrane potential (MMP) significantly after the treatment of 6-OHDA. These results demonstrated that the activity of VIP was enhanced by polysorbate 80-PBCA nanoparticles compared to control solutions, suggesting that PBCA nanoparticles coated with polysorbate 80 could be an effective carrier system for VIP.

  14. Phorbol esters alter adenylate cyclase responses to vasoactive intestinal peptide and forskolin in the GH cell line

    SciTech Connect

    Summers, S.; Florio, T.; Cronin, M.

    1986-05-01

    Activation of protein kinase C with phorbol ester modifies cyclic AMP production in several anterior pituitary cell systems. In the GH cell line from a rat pituitary tumor, exposure to phorbol 12-myristate 13-acetate (PMA: 100 nM) for 30 minutes significantly reduces vasoactive intestinal peptide (VIP: 100 nM) stimulated adenylate cyclase (AC) activity in subsequent membrane preparations to 62 + 4% of control (n = 6 independent studies). In contrast, these same membrane preparations respond to forskolin (1 ..mu..M) with significantly more activity, 130 +/- 6% of controls (n = 6 independent studies). Finally, phorbol ester does not block an inhibitorymore » hormone input into the AC system; somatostatin (100 nM) reduction of VIP-stimulated AC activity is not significantly different in membrane preparations from PMA treated and control cells (n = 3 independent studies). These other findings lead the authors to propose that protein kinase C can modify several sites in the AC complex in anterior pituitary cells.« less

  15. Distribution of vasotocin- and vasoactive intestinal peptide-like immunoreactivity in the brain of blue tit (Cyanistes coeruleus)

    PubMed Central

    Montagnese, Catherine M.; Székely, Tamás; Csillag, András; Zachar, Gergely

    2015-01-01

    Blue tits (Cyanistes coeruleus) are songbirds, used as model animals in numerous studies covering a wide field of research. Nevertheless, the distribution of neuropeptides in the brain of this avian species remains largely unknown. Here we present some of the first results on distribution of Vasotocine (AVT) and Vasoactive intestinal peptide (VIP) in the brain of males and females of this songbird species, using immunohistochemistry mapping. The bulk of AVT-like cells are found in the hypothalamic supraoptic, paraventricular and suprachiasmatic nuclei, bed nucleus of the stria terminalis, and along the lateral forebrain bundle. Most AVT-like fibers course toward the median eminence, some reaching the arcopallium, and lateral septum. Further terminal fields occur in the dorsal thalamus, ventral tegmental area and pretectal area. Most VIP-like cells are in the lateral septal organ and arcuate nucleus. VIP-like fibers are distributed extensively in the hypothalamus, preoptic area, lateral septum, diagonal band of Broca. They are also found in the bed nucleus of the stria terminalis, amygdaloid nucleus of taenia, robust nucleus of the arcopallium, caudo-ventral hyperpallium, nucleus accumbens and the brainstem. Taken together, these results suggest that both AVT and VIP immunoreactive structures show similar distribution to other avian species, emphasizing evolutionary conservatism in the history of vertebrates. The current study may enable future investigation into the localization of AVT and VIP, in relation to behavioral and ecological traits in the brain of tit species. PMID:26236200

  16. Effects of epithelium removal on relaxation of airway smooth muscle induced by vasoactive intestinal peptide and electrical field stimulation.

    PubMed Central

    Farmer, S. G.; Togo, J.

    1990-01-01

    1. We have studied the effect of epithelium removal on relaxation of guinea-pig isolated tracheal smooth muscle induced by vasoactive intestinal peptide (VIP) or stimulation of non-adrenergic, non-cholinergic (NANC) inhibitory nerves. Also examined were the effects of inhibitors of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE). 2. Epithelium removal produced a 3.6 +/- 0.4 fold leftward shift in the VIP concentration-response curve. The supersensitivity to VIP, following epithelium removal was abolished by phosphoramidon or thiorphan (NEP inhibitors), but unaffected by captopril (an ACE inhibitor). In intact trachea, the NEP inhibitors produced leftward shifts in the VIP curves similar to those produced by epithelium removal. 3. In contrast to responses to exogenous VIP, neurogenic NANC inhibitory responses to electrical field stimulation were affected neither by epithelial denudation nor by the peptidase inhibitors. 4. As in previous studies, epithelium removal increased tracheal sensitivity to isoprenaline. This was not altered by pretreatment with a cocktail of peptidase inhibitors. Thus, the effect of the NEP inhibitors on responses to VIP appears to be relatively specific. 5. These data indicate that exogenous VIP is a substrate for airway NEP, since inhibition of the enzyme potentiates the peptide. This is further evidence that the airway epithelium provides a source for the metabolism of mediators. 6. In guinea-pig trachea the NEP responsible for cleaving VIP may be located largely in the epithelial layer, since NEP inhibition was without effect on sensitivity to VIP in epithelium-denuded preparations. If VIP is a NANC inhibitory neurotransmitter in this tissue its degradation endogenously does not appear to involve epithelial NEP. PMID:2196967

  17. Covariation of Peptide Abundances Accurately Reflects Protein Concentration Differences*

    PubMed Central

    Pirmoradian, Mohammad

    2017-01-01

    Most implementations of mass spectrometry-based proteomics involve enzymatic digestion of proteins, expanding the analysis to multiple proteolytic peptides for each protein. Currently, there is no consensus of how to summarize peptides' abundances to protein concentrations, and such efforts are complicated by the fact that error control normally is applied to the identification process, and do not directly control errors linking peptide abundance measures to protein concentration. Peptides resulting from suboptimal digestion or being partially modified are not representative of the protein concentration. Without a mechanism to remove such unrepresentative peptides, their abundance adversely impacts the estimation of their protein's concentration. Here, we present a relative quantification approach, Diffacto, that applies factor analysis to extract the covariation of peptides' abundances. The method enables a weighted geometrical average summarization and automatic elimination of incoherent peptides. We demonstrate, based on a set of controlled label-free experiments using standard mixtures of proteins, that the covariation structure extracted by the factor analysis accurately reflects protein concentrations. In the 1% peptide-spectrum match-level FDR data set, as many as 11% of the peptides have abundance differences incoherent with the other peptides attributed to the same protein. If not controlled, such contradicting peptide abundance have a severe impact on protein quantifications. When adding the quantities of each protein's three most abundant peptides, we note as many as 14% of the proteins being estimated as having a negative correlation with their actual concentration differences between samples. Diffacto reduced the amount of such obviously incorrectly quantified proteins to 1.6%. Furthermore, by analyzing clinical data sets from two breast cancer studies, our method revealed the persistent proteomic signatures linked to three subtypes of breast cancer

  18. VIPhyb, an antagonist of vasoactive intestinal peptide receptor, enhances cellular antiviral immunity in murine cytomegalovirus infected mice.

    PubMed

    Li, Jian-Ming; Darlak, Kasia A; Southerland, Lauren; Hossain, Mohammad S; Jaye, David L; Josephson, Cassandra D; Rosenthal, Hilary; Waller, Edmund K

    2013-01-01

    Vasoactive intestinal peptide (VIP) is a neuropeptide hormone that suppresses Th1-mediated cellular immunity. We previously reported that VIP-knockout (VIP-KO) mice have enhanced cellular immune responses and increased survival following murine cytomegalovirus (mCMV) infection in C57BL/6 mice. In this study, we tested whether treatment with a VIP receptor antagonistic peptide protects C57BL/6 and BALB/c mice from mCMV-infection. One week of daily subcutaneous injections of VIPhyb was non-toxic and did not alter frequencies of immune cell subsets in non-infected mice. VIPhyb administration to mCMV-infected C57BL/6 and BALB/c mice markedly enhanced survival, viral clearance, and reduced liver and lung pathology compared with saline-treated controls. The numbers of effector/memory CD8+ T-cells and mature NK cells were increased in VIPhyb-treated mice compared with PBS-treated groups. Pharmacological blockade of VIP-receptor binding or genetic blockade of VIP-signaling prevented the up-regulation of PD-L1 and PD-1 expression on DC and activated CD8+ T-cells, respectively, in mCMV-infected mice, and enhanced CD80, CD86, and MHC-II expression on conventional and plasmacytoid DC. VIPhyb-treatment increased type-I IFN synthesis, numbers of IFN-γ- and TNF-α-expressing NK cells and T-cells, and the numbers of mCMV-M45 epitope-peptide-MHC-I tetramer CD8+ T-cells following mCMV infection. VIP-treatment lowered the percentage of Treg cells in spleens compared with PBS-treated WT mice following mCMV infection, while significantly decreasing levels of serum VEGF induced by mCMV-infection. The mice in all treated groups exhibited similar levels of anti-mCMV antibody titers. Short-term administration of a VIP-receptor antagonist represents a novel approach to enhance innate and adaptive cellular immunity in a murine model of CMV infection.

  19. Early postnatal development of vasoactive intestinal polypeptide- and peptide histidine isoleucine-immunoreactive structures in the cat visual cortex.

    PubMed

    Wahle, P; Meyer, G

    1989-04-08

    The early postnatal development of neurons containing vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) has been analyzed in visual areas 17 and 18 of cats aged from postnatal day (P) 0 to adulthood. Neuronal types are established mainly by axonal criteria. Both peptides occur in the same neuronal types and display the same postnatal chronology of appearance. Several cell types are transient, which means that they are present in the cortex only for a limited period of development. According to their chronology of appearance the VIP/PHI-immunoreactive (ir) cell types are grouped into three neuronal populations. The first population comprises six cell types which appear early in postnatal life. The pseudohorsetail cells of layer I possess a vertically descending axon which initially gives rise to recurrent collaterals, then forms a bundle passing layers III to V, and finally, horizontal terminal fibers in layer VI. The neurons differentiate at P 4 and disappear by degeneration around P 30. The neurons with columnar dendritic fields of layers IV/V are characterized by a vertical arrangement of long dendrites ascending or descending parallel to each other, thus forming an up to 600 microns long dendritic column. Their axons always descend and terminate in broad fields in layer VI. The neurons appear at P 7 and are present until P 20. The multipolar neurons of layer VI occur in isolated positions and have broad axonal territories. The neurons differentiate at P 7 and persist into adulthood. Bitufted to multipolar neurons of layers II/III have axons descending as a single fiber to layer VI, where they terminate. The neurons appear at P 12 and persist into adulthood. The four cell types described above issue a vertically oriented fiber architecture in layers II-V and a horizontal terminal plexus in layer VI which is dense during the second, third and fourth week. Concurrent with the disappearance of the two transient types the number of

  20. The effect of active immunization against vasoactive intestinal peptide (VIP) and inhibin on reproductive performance of aging White Leghorn roosters.

    PubMed

    Avital-Cohen, N; Heiblum, R; Argov, N; Rosenstrauch, A; Chaiseha, Y; Mobarkey, N; Rozenboim, I

    2012-01-01

    Decreasing fertility in aging domestic roosters is a well-known phenomenon. Aging is manifested by a decrease in plasma testosterone level, testis function, and spermatogenesis, resulting in a low level of fertility. The roles of vasoactive intestinal peptide (VIP) and testicular inhibin in this aging process are not clear. The effects of active immunization against VIP, inhibin, or the combination of both hormones on the reproduction of aging White Leghorn (WL) roosters were assayed. In experiment 1a, 60 White Leghorn roosters (67 wk of age) were divided into 4 groups (n = 15/group). The first group was actively immunized against VIP, the second against inhibin, the third against VIP and inhibin, and the fourth served as a control. Active immunization against VIP decreased semen quality parameters, plasma steroid levels, and gene expression of gonadotropin-releasing hormone-I (GnRH-I), follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH receptor, VIP, and prolactin (Prl). Immunization against inhibin increased some of the semen quality parameters and FSH mRNA gene expression but decreased inhibin gene expression. In experiment 1b, at 94 wk of age, we took the actively immunized against VIP group and the control group and divided them into 2 subgroups (n = 7 or 8): the first group was injected with 1 mg of ovine Prl (oPrl) daily for 7 d, and the second group served as a control. Administration of oPrl to previously VIP-immunized birds significantly elevated semen quality parameters. We suggest that VIP, Prl, and inhibin have an important effect on the reproductive axis in aging roosters. Active immunization against VIP-depressed reproductive activity and Prl administration restored their reproduction, indicating that both VIP and Prl are essential for reproduction in aging roosters. Immunization against inhibin improved FSH mRNA gene expression, suggesting a negative role of inhibin on FSH secretion in aging roosters. Not all semen quality parameters

  1. Vasoactive intestinal peptide test

    MedlinePlus

    ... found in cells in the nervous system and gut. VIP has many functions, including relaxing certain muscles, triggering release of hormones from the pancreas, gut, and hypothalamus, and increasing the amount of water ...

  2. Watery diarrhea syndrome in an adult with ganglioneuroma-pheochromocytoma: identification of vasoactive intestinal peptide, calcitonin, and catecholamines and assessment of their biologic activity.

    PubMed

    Trump, D L; Livingston, J N; Baylin, S B

    1977-10-01

    A case of adult ganglioneuroma-pheochromocytoma with an associated watery diarrhea syndrome is reported. High levels of vasoactive intestinal peptide (VIP) were found in preoperative serum and in tumor tissue. The serum VIP levels fell to normal, and the watery diarrhae syndrome completely ceased following removal of the tumor. In addition to containing VIP, the tumor was rich in catecholamines, and calcitonin. Peptide hormone-containing extracts and catecholamine extracts from the tumor both activated the adenyl cyclase system and increased lipolytic activity in a preparation of isolated rat fat cells. The findings in this patient further link VIP with neural crest tissues, and suggest the importance of determining catecholamine levels in patients with the watery diarrhea syndrome.

  3. Amelioration of Cardiac Function and Activation of Anti-Inflammatory Vasoactive Peptides Expression in the Rat Myocardium by Low Level Laser Therapy

    PubMed Central

    Manchini, Martha Trindade; Serra, Andrey Jorge; Feliciano, Regiane dos Santos; Santana, Eduardo Tadeu; Antônio, Ednei Luis; de Tarso Camillo de Carvalho, Paulo; Montemor, Jairo; Crajoinas, Renato Oliveira; Girardi, Adriana Castello Costa; Tucci, Paulo José Ferreira; Silva, José Antônio

    2014-01-01

    Low-level laser therapy (LLLT) has been used as an anti-inflammatory treatment in several disease conditions, even when inflammation is a secondary consequence, such as in myocardial infarction (MI). However, the mechanism by which LLLT is able to protect the remaining myocardium remains unclear. The present study tested the hypothesis that LLLT reduces inflammation after acute MI in female rats and ameliorates cardiac function. The potential participation of the Renin-Angiotensin System (RAS) and Kallikrein-Kinin System (KKS) vasoactive peptides was also evaluated. LLLT treatment effectively reduced MI size, attenuated the systolic dysfunction after MI, and decreased the myocardial mRNA expression of interleukin-1 beta and interleukin-6 in comparison to the non-irradiated rat tissue. In addition, LLLT treatment increased protein and mRNA levels of the Mas receptor, the mRNA expression of kinin B2 receptors and the circulating levels of plasma kallikrein compared to non-treated post-MI rats. On the other hand, the kinin B1 receptor mRNA expression decreased after LLLT. No significant changes were found in the expression of vascular endothelial growth factor (VEGF) in the myocardial remote area between laser-irradiated and non-irradiated post-MI rats. Capillaries density also remained similar between these two experimental groups. The mRNA expression of the inducible nitric oxide synthase (iNOS) was increased three days after MI, however, this effect was blunted by LLLT. Moreover, endothelial NOS mRNA content increased after LLLT. Plasma nitric oxide metabolites (NOx) concentration was increased three days after MI in non-treated rats and increased even further by LLLT treatment. Our data suggest that LLLT diminishes the acute inflammation in the myocardium, reduces infarct size and attenuates left ventricle dysfunction post-MI and increases vasoactive peptides expression and nitric oxide (NO) generation. PMID:24991808

  4. Recent Advances in the Gastric Mucosal Protection Against Stress-induced Gastric Lesions. Importance of Renin-angiotensin Vasoactive Metabolites, Gaseous Mediators and Appetite Peptides.

    PubMed

    Brzozowski, Tomasz; Magierowska, Katarzyna; Magierowski, Marcin; Ptak-Belowska, Agata; Pajdo, Robert; Kwiecien, Slawomir; Olszanecki, Rafal; Korbut, Ryszard

    2017-01-01

    Stress is known to cause severe adverse effects in the human gastrointestinal tract including mucosal microbleedings and erosions or even gastric ulceration but the mechanism of these complications has not been fully elucidated. The pathogenesis of stress-induced gastric damage involves the fall in Gastric Blood Flow (GBF), an increase in gastric acid secretion and gastric motility, enhanced adrenergic and cholinergic nerve activity and the rise in gastric mucosal generation of reactive oxygen species. The gastric mucosal defense mechanisms against the deleterious effect of stress include the activation of the hypothalamic-pituitary-adrenal axis which has been linked with glucocorticoids release capable of counteracting of stress-induced gastric lesions. Here we summarize the novel gastroprotective mechanisms against stress damage exhibited by angiotensin-(1-7), the newly discovered metabolite of Renin-Angiotensin System (RAS), the gaseous mediators such as nitric oxide (NO), hydrogen sulfide (H2S) or Carbon Monoxide (CO), and the food intake controlling peptides ghrelin, nesfatin- 1 and apelin possibly acting via brain-gut axis. These bioactive molecules such as RAS vasoactive metabolite angiotensin-(1-7) and appetite peptides have been shown to afford gastroprotective effect against stressinduced gastric lesions mainly mediated by an increase in gastric microcirculation. Gaseous mediators protect the gastric mucosa against stress lesions by mechanism involving the activation of PG/COX and CO/HO-1 biosynthetic pathways, and their anti-inflammatory and anti-oxidizing properties. Thus, these new components add new mechanistic aspects to the common cooperation of NO/NO-synthase, PG/COX systems and vasoactive sensory neuropeptides including CGRP but their gastroprotective efficacy against experimental stress ulcerogenesis requires the confirmation in human clinical trials. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Inhibition of CD26/DPP IV attenuates ischemia/reperfusion injury in orthotopic mouse lung transplants: the pivotal role of vasoactive intestinal peptide.

    PubMed

    Jungraithmayr, Wolfgang; De Meester, Ingrid; Matheeussen, Veerle; Inci, Ilhan; Augustyns, Koen; Scharpé, Simon; Weder, Walter; Korom, Stephan

    2010-04-01

    The T cell activation Ag CD26/dipeptidylpeptidase IV (DPP IV) combines co-stimulatory and enzymatic properties. Catalytically, it functions as an exopeptidase, modulating biological activity of key chemokines and peptides. Here we investigated the effect of organ-specific inhibition of DPP IV catalytic activity on ischemia/reperfusion injury after extended ischemia in the mouse model of orthotopic single lung transplantation. C57BL/6 mice were syngeneically, transplanted, grafts were perfused and stored in Perfadex with (treated) or without (control) a DPP IV enzymatic activity inhibitor (AB192). Transplantation was performed after 18h cold ischemia time; following 2-h reperfusion, grafts were analyzed for oxygenation, thiobarbituric acid-reactive substances, histomorphology, and immunohistochemistry was performed for leukocyte Ag 6, myeloperoxidase, hemoxygenase 1, vasoactive intestinal protein (VIP), and real-time PCR for VIP. Treatment with the DPP IV inhibitor AB192 resulted in significant improvement of gas exchange, less lipid oxidation, preservation of parenchymal ultrastructure, reduced neutrophil infiltration, reduced myeloperoxidase expression, increased hemoxygenase 1 expression, pronounced expression of VIP in alveolar macrophages and increased mRNA expression of VIP. Inhibition of intragraft DPP IV catalytic activity with AB192 strikingly ameliorates ischemia/reperfusion injury after extended ischemia. Furthermore, preservation of endogenous intragraft VIP levels correlate with maintaining lung function and structural integrity. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  6. Peripheral nerve reconstruction with epsilon-caprolactone conduits seeded with vasoactive intestinal peptide gene-transfected mesenchymal stem cells in a rat model

    NASA Astrophysics Data System (ADS)

    Hernández-Cortés, P.; Toledo-Romero, M. A.; Delgado, M.; Sánchez-González, C. E.; Martin, F.; Galindo-Moreno, P.; O'Valle, F.

    2014-08-01

    Objective. Attempts have been made to improve nerve conduits in peripheral nerve reconstruction. We investigated the potential therapeutic effect of a vasoactive intestinal peptide (VIP), a neuropeptide with neuroprotective, trophic and developmental regulatory actions, in peripheral nerve regeneration in a severe model of nerve injury that was repaired with nerve conduits. Approach. The sciatic nerve of each male Wistar rat was transected unilaterally at 10 mm and then repaired with Dl-lactic-ɛ-caprolactone conduits. The rats were treated locally with saline, with the VIP, with adipose-derived mesenchymal stem cells (ASCs) or with ASCs that were transduced with the VIP-expressing lentivirus. The rats with the transected nerve, with no repairs, were used as untreated controls. At 12 weeks post-surgery, we assessed their limb function by measuring the ankle stance angle and the percentage of their muscle mass reduction, and we evaluated the histopathology, immunohistochemistry and morphometry of the myelinated fibers. Main results. The rats that received a single injection of VIP-expressing ASCs showed a significant functional recovery in the ankle stance angle (p = 0.049) and a higher number of myelinated fibers in the middle and distal segments of the operated nerve versus the other groups (p = 0.046). Significance. These results suggest that utilization of a cellular substrate, plus a VIP source, is a promising method for enhancing nerve regeneration using Dl-lactic-ɛ-caprolactone conduits and that this method represents a potential useful clinical approach to repairing peripheral nerve damage.

  7. Signaling Pathways Involved in Renal Oxidative Injury: Role of the Vasoactive Peptides and the Renal Dopaminergic System

    PubMed Central

    Rukavina Mikusic, N. L.; Kravetz, M. C.; Kouyoumdzian, N. M.; Della Penna, S. L.; Rosón, M. I.; Fernández, B. E.; Choi, M. R.

    2014-01-01

    The physiological hydroelectrolytic balance and the redox steady state in the kidney are accomplished by an intricate interaction between signals from extrarenal and intrarenal sources and between antinatriuretic and natriuretic factors. Angiotensin II, atrial natriuretic peptide and intrarenal dopamine play a pivotal role in this interactive network. The balance between endogenous antioxidant agents like the renal dopaminergic system and atrial natriuretic peptide, by one side, and the prooxidant effect of the renin angiotensin system, by the other side, contributes to ensuring the normal function of the kidney. Different pathological scenarios, as nephrotic syndrome and hypertension, where renal sodium excretion is altered, are associated with an impaired interaction between two natriuretic systems as the renal dopaminergic system and atrial natriuretic peptide that may be involved in the pathogenesis of renal diseases. The aim of this review is to update and comment the most recent evidences about the intracellular pathways involved in the relationship between endogenous antioxidant agents like the renal dopaminergic system and atrial natriuretic peptide and the prooxidant effect of the renin angiotensin system in the pathogenesis of renal inflammation. PMID:25436148

  8. Signaling pathways involved in renal oxidative injury: role of the vasoactive peptides and the renal dopaminergic system.

    PubMed

    Rukavina Mikusic, N L; Kravetz, M C; Kouyoumdzian, N M; Della Penna, S L; Rosón, M I; Fernández, B E; Choi, M R

    2014-01-01

    The physiological hydroelectrolytic balance and the redox steady state in the kidney are accomplished by an intricate interaction between signals from extrarenal and intrarenal sources and between antinatriuretic and natriuretic factors. Angiotensin II, atrial natriuretic peptide and intrarenal dopamine play a pivotal role in this interactive network. The balance between endogenous antioxidant agents like the renal dopaminergic system and atrial natriuretic peptide, by one side, and the prooxidant effect of the renin angiotensin system, by the other side, contributes to ensuring the normal function of the kidney. Different pathological scenarios, as nephrotic syndrome and hypertension, where renal sodium excretion is altered, are associated with an impaired interaction between two natriuretic systems as the renal dopaminergic system and atrial natriuretic peptide that may be involved in the pathogenesis of renal diseases. The aim of this review is to update and comment the most recent evidences about the intracellular pathways involved in the relationship between endogenous antioxidant agents like the renal dopaminergic system and atrial natriuretic peptide and the prooxidant effect of the renin angiotensin system in the pathogenesis of renal inflammation.

  9. Effects of vasoactive intestinal peptide, helodermin and galanin on responses of guinea-pig lung parenchyma to histamine, acetylcholine and leukotriene D4.

    PubMed Central

    Conroy, D. M.; Samhoun, M. N.; Piper, P. J.

    1991-01-01

    1. The effect of vasoactive intestinal peptide (VIP) was studied on the contractile response of guinea-pig lung parenchymal strips (GPP) induced by bronchoconstrictor agonists, such as leukotriene D4 (LTD4), histamine and acetylcholine (ACh). This effect of VIP was compared with helodermin, a peptide that is structurally related to VIP, and galanin, another neuropeptide that is thought to co-exist with VIP. 2. VIP (10 nM) induced a potent and reversible inhibition of the contractions of GPP induced by LTD4 (1-30 pmol) but did not affect those due to ACh (1-100 nmol) or histamine (1-30 nmol). A ten fold higher concentration of VIP (100 nM) did not further inhibit LTD4-induced responses or reduce those induced by histamine or ACh. 3. Helodermin (10 nM) had a similar inhibitory effect on contractions of GPP induced by LTD4 (3-30 pmol) but did not affect contractions induced by histamine (1-10 nmol). 4. Indomethacin (2.8 microM) and salbutamol (10 nM) significantly reduced responses elicited by LTD4 and histamine but not those due to ACh. A ten fold higher concentration of salbutamol (100 nM) further inhibited the contractions due to LTD4 and histamine and at this concentration responses induced by ACh were inhibited. 5. VIP (10 nM) and helodermin (10 nM) significantly reduced the LTD4-induced release of thromboxane A2 (TXA2), measured as TxB2 by radioimmunoassay, from GPP. The smaller release of TxA2 induced by histamine was not significantly reduced in the presence of VIP. 6. In comparative studies, galanin (10-100 nM) did not affect contractions of GPP induced by either LTD4, histamine or ACh.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1725762

  10. Modulation of circulating vasoactive peptides and extracellular matrix proteins are two novel mechanisms in the cardioprotective action of acarbose.

    PubMed

    Rudovich, Natalia; Pivovarova, Olga; Bernigau, Wolfgang; Sparwasser, Andrea; Tacke, Christopher; Murahovshi, Veronica; Mertes, Gabriele; Birkenfeld, Andreas L; Bergmann, Andreas; Weickert, Martin O; Pfeiffer, Andreas F

    2016-12-01

    Acarbose, an alpha-glucosidase inhibitor, unexpectedly reduced the incidence of hypertension and cardiovascular endpoints in the STOP-NIDDM study. Based on the growing evidence of a link between vasoregulatory peptides and metabolic traits, we hypothesized that changes of the Glycemic Index by acarbose may modulate vasoregulatory peptide levels via regulation of postprandial metabolism. Subjects with type 2 diabetes and with metabolic syndrome were treated with acarbose (12 weeks, 300mg/d) in a double-blind, placebo-controlled, cross-over intervention. Changes in fasting and postprandial levels of midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-endothelin-1 (CT-proET-1) and midregional pro-adrenomedullin (MR-proADM), WNT1 Inducible Signaling Pathway Protein 1 (WISP1) as well as fasting and postprandial glucose/insulin levels in the liquid meal test were assessed. Acarbose strongly decreased postprandial insulin concentrations in subjects with metabolic syndrome (P=0.004), and postprandial glucose excursions in both groups. Postprandial MR-proANP and CT-proET-1 levels increased after acarbose treatment (P<0.01 and P<0.05, respectively) in subjects with metabolic syndrome only. No effect of acarbose treatment on MR-prADM was observed in both groups. All three peptides were correlated with each over, but neither with insulin sensitivity in euglycemic clamps, nor with adiponectin levels. WISP1 decreased after acarbose treatment in subjects with metabolic syndrome. Plasma MR- proANP and CT-proET-1 concentrations, but not MR-prADM concentrations, were affected by treatment with acarbose over 12 weeks. Our findings provide new possible mechanisms of acarbose action in diabetes and metabolic syndrome.

  11. Nitric oxide and vasoactive intestinal peptide as co-transmitters of airway smooth-muscle relaxation: analysis in neuronal nitric oxide synthase knockout mice.

    PubMed

    Hasaneen, Nadia A; Foda, Hussein D; Said, Sami I

    2003-09-01

    Both vasoactive intestinal peptide (VIP) and nitric oxide (NO) relax airway smooth muscle and are potential co-transmitters of neurogenic airway relaxation. The availability of neuronal NO synthase (nNOS) knockout mice (nNOS-/-) provides a unique opportunity for evaluating NO. To evaluate the relative importance of NO, especially that generated by nNOS, and VIP as transmitters of the inhibitory nonadrenergic, noncholinergic (NANC) system. In this study, we compared the neurogenic (tetrodotoxin-sensitive) NANC relaxation of tracheal segments from nNOS-/- mice and control wild-type mice (nNOS(+/+)), induced by electrical field stimulation (EFS). We also examined the tracheal contractile response to methacholine and its relaxant response to VIP. EFS (at 60 V for 2 ms, at 10, 15, or 20 Hz) dose-dependently reduced tracheal tension, and the relaxations were consistently smaller (approximately 40%) in trachea from nNOS-/- mice than from control wild-type mice (p < 0.001). VIP (10(- 8) to 10(-6) mol/L) induced concentration-dependent relaxations that were approximately 50% smaller in nNOS-/- tracheas than in control tracheas. Methacholine induced concentration-dependent contractions that were consistently higher in the nNOS-/- tracheas relative to wild-type mice tracheas (p > 0.05). Our data suggest that, in mouse trachea, NO is probably responsible for mediating a large (approximately 60%) component of neurogenic NANC relaxation, and a similar (approximately 50%) component of the relaxant effect of VIP. The results imply that NO contributes significantly to neurogenic relaxation of mouse airway smooth muscle, whether due to neurogenic stimulation or to the neuropeptide VIP.

  12. Increasing proportions of tyrosine hydroxylase-immunoreactive interneurons colocalize with choline acetyltransferase or vasoactive intestinal peptide in the developing rat cerebral cortex

    PubMed Central

    Asmus, Stephen E.; Cocanougher, Benjamin T.; Allen, Donald L.; Boone, John B.; Brooks, Elizabeth A.; Hawkins, Sarah M.; Hench, Laura A.; Ijaz, Talha; Mayfield, Meredith N.

    2011-01-01

    Cortical interneurons are critical for information processing, and their dysfunction has been implicated in neurological disorders. One subset of this diverse cell population expresses tyrosine hydroxylase (TH) during postnatal rat development. Cortical TH-immunoreactive neurons appear at postnatal day (P) 16. The number of TH cells sharply increases between P16 and P20 and subsequently decreases to adult values. The absence of apoptotic markers in these cells suggests that the reduction in cell number is not due to cell death but is due to a decline in TH production. Cortical TH cells lack all additional catecholaminergic enzymes, and many coexpress GABA and calretinin, but little else is known about their phenotype or function. Because interneurons containing choline acetyltransferase (ChAT) or vasoactive intestinal peptide (VIP) share characteristics with cortical TH neurons, the coexpression of TH with ChAT or VIP was examined throughout the neocortex at P16, P20, and P30. The proportions of TH cell profiles double-labeled for ChAT or VIP significantly increased between P16 and P30. Based on their proximity to blood vessels, intrinsic cholinergic and VIPergic cells have been hypothesized to regulate cortical microcirculation. Labeling with the gliovascular marker aquaporin-4 revealed that at least half of the TH cells were apposed to microvessels at these ages, and many of these cells contained ChAT or VIP. Cortical TH neurons did not coproduce nitric oxide synthase. These results suggest that increasing proportions of cortical TH neurons express ChAT or VIP developmentally and that a subset of these TH neurons may regulate local blood flow. PMID:21295554

  13. The mechanism of gentisic acid-induced relaxation of the guinea pig isolated trachea: the role of potassium channels and vasoactive intestinal peptide receptors.

    PubMed

    Cunha, J F; Campestrini, F D; Calixto, J B; Scremin, A; Paulino, N

    2001-03-01

    We examined some of the mechanisms by which the aspirin metabolite and the naturally occurring metabolite gentisic acid induced relaxation of the guinea pig trachea in vitro. In preparations with or without epithelium and contracted by histamine, gentisic acid caused concentration-dependent and reproducible relaxation, with mean EC(50) values of 18 microM and E(max) of 100% (N = 10) or 20 microM and E(max) of 92% (N = 10), respectively. The relaxation caused by gentisic acid was of slow onset in comparison to that caused by norepinephrine, theophylline or vasoactive intestinal peptide (VIP). The relative rank order of potency was: salbutamol 7.9 > VIP 7.0 > gentisic acid 4.7 > theophylline 3.7. Gentisic acid-induced relaxation was markedly reduced (24 +/- 7.0, 43 +/- 3.9 and 78 +/- 5.6%) in preparations with elevated potassium concentration in the medium (20, 40 or 80 mM, respectively). Tetraethylammonium (100 microM), a nonselective blocker of the potassium channels, partially inhibited the relaxation response to gentisic acid, while 4-AP (10 microM), a blocker of the voltage potassium channel, inhibited gentisic acid-induced relaxation by 41 +/- 12%. Glibenclamide (1 or 3 microM), at a concentration which markedly inhibited the relaxation induced by the opener of ATP-sensitive K(+) channels, levcromakalim, had no effect on the relaxation induced by gentisic acid. Charybdotoxin (0.1 or 0.3 microM), a selective blocker of the large-conductance Ca(2+)-activated K(+) channels, caused rightward shifts (6- and 7-fold) of the gentisic acid concentration-relaxation curve. L-N(G)-nitroarginine (100 microM), a NO synthase inhibitor, had no effect on the relaxant effect of gentisic acid, and caused a slight displacement to the right in the relaxant effect of the gentisic acid curve at 300 microM, while methylene blue (10 or 30 microM) or ODQ (1 microM), the inhibitors of soluble guanylate cyclase, all failed to affect gentisic acid-induced relaxation. D-(P)-Cl-Phe(6),Leu(17

  14. Seasonal plasticity in the peptide neuronal systems: potential roles of gonadotrophin-releasing hormone, gonadotrophin-inhibiting hormone, neuropeptide Y and vasoactive intestinal peptide in the regulation of the reproductive axis in subtropical Indian weaver birds.

    PubMed

    Surbhi; Rastogi, A; Rani, S; Kumar, V

    2015-05-01

    Two experiments examined the expression of gonadotrophin-releasing and inhibiting hormones (GnRH-I, GnRH-II and GnIH), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) in subtropical Indian weaver birds, which demonstrate relative photorefractoriness. Experiment 1 measured peptide expression levels in the form of immunoreactive (-IR) cells, percentage cell area and cell optical density in the preoptic area (GnRH-I), midbrain (GnRH-II), paraventricular nucleus (GnIH), mediobasal hypothalamus [dorsomedial hypothalamus (DMH), infundibular complex (INc), NPY and VIP] and lateral septal organ (VIP) during the progressive, breeding, regressive and nonbreeding phases of the annual reproductive cycle. GnRH-I was decreased in the nonbreeding and VIP was increased in INc in the breeding and regressive states. GnRH-II and NPY levels did not differ between the testicular phases. Double-labelled immunohistochemistry (IHC) revealed a close association between the GnRH/GnIH, GnRH/NPY, GnRH/VIP and GnIH/NPY peptide systems, implicating them interacting and playing roles in the reproductive regulation in weaver birds. Experiment 2 further measured these peptide levels in the middle of day and night in weaver birds that were maintained under short days (8 : 16 h light /dark cycle; photosensitive), exposed to ten long days (16 : 8 h light /dark cycle; photostimulated) or maintained for approximately 2 years on a 16 : 8 h light /dark cycle (photorefractory). Reproductively immature testes in these groups precluded the possible effect of an enhanced gonadal feedback on the hypothalamic peptide expression. There were group differences in the GnRH-I (not GnRH-II), GnIH, NPY and VIP immunoreactivity, albeit with variations in immunoreactivity measures in the present study. These results, which are consistent with those reported in birds with relative photorefractoriness, show the distribution and possibly a complex interaction of key neuropeptides in the regulation of the

  15. Regulation of NANC neural bronchoconstriction in vivo in the guinea-pig: involvement of nitric oxide, vasoactive intestinal peptide and soluble guanylyl cyclase.

    PubMed

    Lei, Y H; Barnes, P J; Rogers, D F

    1993-01-01

    .v.). SNP significantly (P <0.05) reduced by 65% the bronchoconstriction induced by nerve stimulation at 10 Hz. Methylene blue did not effect baseline PIP in sham-stimulated controls. The airway effects of methylene blue and SNP were not associated with their cardiovascular effects. 6. a-Chymotrypsin (2 units kg-', i.v.) significantly potentiated vagally-induced bronchoconstriction by a further 63% at 2.5 Hz, by a further 95.6% at 5 Hz but did not potentiate the increase in PIP at 10 Hz. alpha-Chymotrypsin also potentiated (by 116%) capsaicin-induced bronchoconstriction. Vasoactive intestinal peptide (VIP, 10 ig kg-' i.v. infused over min) significantly reduced by 70% the increase in PIP induced by NKA (0.1 .Lmol kg-' i.v., infused over 30 s). 7. The combination of a-chymotrypsin (2 units kg-', i.v.) and L-NAME (5 mg kg-', i.v.) significantly potentiated NANC bronchoconstriction by a further 304% at 2.5 Hz, an increase in PIP which was greater than that induced by either a-chymotrypsin or L-NAME alone (P <0.05). 8. We conclude that endogenous NO and a bronchodilator peptide, possibly VIP, released in association with nerve stimulation, as well as activation of soluble guanylyl cyclase, regulate the magnitude of NANC neurogenic bronchoconstriction in guinea-pigs in vivo.

  16. Excitotoxicity in the Lung: N-Methyl-D-Aspartate-Induced, Nitric Oxide-Dependent, Pulmonary Edema is Attenuated by Vasoactive Intestinal Peptide and by Inhibitors of Poly(ADP-Ribose) Polymerase

    NASA Astrophysics Data System (ADS)

    Said, Sami I.; Berisha, Hasan I.; Pakbaz, Hedayatollah

    1996-05-01

    Excitatory amino acid toxicity, resulting from overactivation of N-methyl-D-aspartate (NMDA) glutamate receptors, is a major mechanism of neuronal cell death in acute and chronic neurological diseases. We have investigated whether excitotoxicity may occur in peripheral organs, causing tissue injury, and report that NMDA receptor activation in perfused, ventilated rat lungs triggered acute injury, marked by increased pressures needed to ventilate and perfuse the lung, and by high-permeability edema. The injury was prevented by competitive NMDA receptor antagonists or by channel-blocker MK-801, and was reduced in the presence of Mg2+. As with NMDA toxicity to central neurons, the lung injury was nitric oxide (NO) dependent: it required L-arginine, was associated with increased production of NO, and was attenuated by either of two NO synthase inhibitors. The neuropeptide vasoactive intestinal peptide and inhibitors of poly(ADP-ribose) polymerase also prevented this injury, but without inhibiting NO synthesis, both acting by inhibiting a toxic action of NO that is critical to tissue injury. The findings indicate that: (i) NMDA receptors exist in the lung (and probably elsewhere outside the central nervous system), (ii) excessive activation of these receptors may provoke acute edematous lung injury as seen in the ``adult respiratory distress syndrome,'' and (iii) this injury can be modulated by blockade of one of three critical steps: NMDA receptor binding, inhibition of NO synthesis, or activation of poly(ADP-ribose) polymerase.

  17. Collision-Induced Dissociation of Deprotonated Peptides. Relative Abundance of Side-Chain Neutral Losses, Residue-Specific Product Ions, and Comparison with Protonated Peptides

    NASA Astrophysics Data System (ADS)

    Liang, Yuxue; Neta, Pedatsur; Yang, Xiaoyu; Stein, Stephen E.

    2018-03-01

    High-accuracy MS/MS spectra of deprotonated ions of 390 dipeptides and 137 peptides with three to six residues are studied. Many amino acid residues undergo neutral losses from their side chains. The most abundant is the loss of acetaldehyde from threonine. The abundance of losses from the side chains of other amino acids is estimated relative to that of threonine. While some amino acids lose the whole side chain, others lose only part of it, and some exhibit two or more different losses. Side-chain neutral losses are less abundant in the spectra of protonated peptides, being significant mainly for methionine and arginine. In addition to the neutral losses, many amino acid residues in deprotonated peptides produce specific negative ions after peptide bond cleavage. An expanded list of fragment ions from protonated peptides is also presented and compared with those of deprotonated peptides. Fragment ions are mostly different for these two cases. These lists of fragments are used to annotate peptide mass spectral libraries and to aid in the confirmation of specific amino acids in peptides. [Figure not available: see fulltext.

  18. Collision-Induced Dissociation of Deprotonated Peptides. Relative Abundance of Side-Chain Neutral Losses, Residue-Specific Product Ions, and Comparison with Protonated Peptides.

    PubMed

    Liang, Yuxue; Neta, Pedatsur; Yang, Xiaoyu; Stein, Stephen E

    2018-03-01

    High-accuracy MS/MS spectra of deprotonated ions of 390 dipeptides and 137 peptides with three to six residues are studied. Many amino acid residues undergo neutral losses from their side chains. The most abundant is the loss of acetaldehyde from threonine. The abundance of losses from the side chains of other amino acids is estimated relative to that of threonine. While some amino acids lose the whole side chain, others lose only part of it, and some exhibit two or more different losses. Side-chain neutral losses are less abundant in the spectra of protonated peptides, being significant mainly for methionine and arginine. In addition to the neutral losses, many amino acid residues in deprotonated peptides produce specific negative ions after peptide bond cleavage. An expanded list of fragment ions from protonated peptides is also presented and compared with those of deprotonated peptides. Fragment ions are mostly different for these two cases. These lists of fragments are used to annotate peptide mass spectral libraries and to aid in the confirmation of specific amino acids in peptides. Graphical Abstract ᅟ.

  19. The effects of vasoactive peptide urocortin 2 on hemodynamics in spontaneous hypertensive rat and the role of L-type calcium channel and CRFR2.

    PubMed

    Liu, Chunna; Liu, Xinyu; Yang, Jing; Duan, Yan; Yao, Hongyue; Li, Fenghua; Zhang, Xia

    2015-04-01

    Urocortin (UCN) is a newly identified vascular-active peptide that has been shown to reverse cardiovascular remodeling and improve left ventricular (LV) function. The effects and mechanism of urocortin 2 (UCN2) in vivo on the electrical remodeling of left ventricle and the hemodynamics of hypertensive objectives have not been investigated. UCN2 (1 μg/kg/d, 3.5 μg/kg/d or 7 μg/kg/d) was intravenously injected for 2 weeks and its effects on hemodynamics in spontaneously hypertensive rats (SHRs) observed. The whole-cell patch clamp technique was used to explore the effects of UCN2 on the electrical remodeling of left ventricular cardiomyocytes. The flow cytometry method was used to determine the content of fluorescence calcium in myocardium. UCN2 improved the systolic and diastolic function of SHRs as demonstrated by decreased left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), increased +dp/dtmax and -dp/dtmax and decreased cAMP level. UCN2 inhibited the opening of L-type calcium channel and decreased the calcium channel current of cardiomyocytes. In addition, UCN2 also decreased the contents of fluorescence calcium in SHR myocardium. However, astressin2-B (AST-2B), the antagonist of corticotropin-releasing factor receptor 2 (CRFR2), could reverse the inhibitory effects of UCN2 on calcium channel. UCN2 can modulate electrical remodeling of the myocardium and hemodynamics in an experimental model of SHR via inhibition of L-type calcium channel and CRFR2 in cardiomyocytes. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  20. Abundant pyroglutamate-modified ABri and ADan peptides in extracellular and vascular amyloid deposits in familial British and Danish dementias.

    PubMed

    Saul, Anika; Lashley, Tammaryn; Revesz, Tamas; Holton, Janice; Ghiso, Jorge A; Coomaraswamy, Janaky; Wirths, Oliver

    2013-05-01

    Familial British and familial Danish dementia (FDD) are progressive neurodegenerative disorders characterized by cerebral deposition of the amyloidogenic peptides ABri and ADan, respectively. These amyloid peptides start with an N-terminal glutamate residue, which can be posttranslationally converted into a pyroglutamate (pGlu) modified form, a mechanism which has been extensively described to be relevant for amyloid-beta (Aβ) peptides in Alzheimer's disease. Like pGlu-Aβ peptides, pGlu-ABri peptides have an increased aggregation propensity and show higher toxicity on human neuroblastoma cells as their nonmodified counterparts. We have generated novel N-terminal specific antibodies detecting the pGlu-modified forms of ABri and ADan peptides. With these antibodies we were able to identify abundant extracellular amyloid plaques, vascular, and parenchymal deposits in human familial British dementia and FDD brain tissue, and in a mouse model for FDD. Double-stainings using C-terminal specific antibodies in human samples revealed that highly aggregated pGlu-ABri and pGlu-ADan peptides are mainly present in plaque cores and central vascular deposits, leading to the assumption that these peptides have seeding properties. Furthermore, in an FDD-mouse model ADan peptides were detected in presynaptic terminals of the hippocampus where they might contribute to impaired synaptic transmission. These similarities of ABri and ADan to Aβ in Alzheimer's disease suggest that the posttranslational pGlu-modification of amyloid peptides might represent a general pathological mechanism leading to increased aggregation and toxicity in these forms of degenerative dementias. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Abundant pyroglutamate-modified ABri and ADan peptides in extracellular and vascular amyloid deposits in familial British and Danish dementias

    PubMed Central

    Saul, Anika; Lashley, Tammaryn; Revesz, Tamas; Holton, Janice; Ghiso, Jorge A.; Coomaraswamy, Janaky; Wirths, Oliver

    2013-01-01

    Familial British (FBD) and familial Danish dementia (FDD) are progressive neurodegenerative disorders characterized by cerebral deposition of the amyloidogenic peptides ABri and ADan. These amyloid peptides start with an N-terminal glutamate residue, which can be posttranslationally converted into a pyroglutamate (pGlu-) modified form, a mechanism which has been extensively described to be relevant for Aβ peptides in Alzheimer’s disease (AD). Like pGlu-Aβ peptides, pGlu-ABri peptides have an increased aggregation propensity and show higher toxicity on human neuroblastoma cells as their non-modified counterparts. We have generated novel N-terminal specific antibodies detecting the pGlu-modified forms of ABri and ADan peptides. With these antibodies we were able to identify abundant extracellular amyloid plaques, vascular and parenchymal deposits in human FBD and FDD brain tissue, as well as in a mouse model for FDD. Double-stainings using C-terminal specific antibodies in human samples revealed that highly aggregated pGlu-ABri and pGlu-ADan peptides are mainly present in plaque cores and central vascular deposits, leading to the assumption that these peptides have seeding properties. Furthermore, in an FDD-mouse model ADan peptides were detected in pre-synaptic terminals of the hippocampus where they might contribute to impaired synaptic transmission. These similarities of ABri and ADan to Aβ in AD suggest that the posttranslational pGlu-modification of amyloid peptides might represent a general pathological mechanism leading to increased aggregation and toxicity in these forms of degenerative dementias. PMID:23261769

  2. Immune challenge differentially affects transcript abundance of three antimicrobial peptides in hemocytes from the moth Pseudoplusia includens.

    PubMed

    Lavine, M D; Chen, G; Strand, M R

    2005-12-01

    Inducible expression of antimicrobial peptides and other humoral immune factors by the insect fat body is well documented. Hemocytes comprise the second essential arm of the insect immune system but it is unclear whether antimicrobial peptide genes are expressed by all or only some types of hemocytes. Here we report the cloning of cecropin A (Pi-cecA), lebocin (Pi-leb) and lysozyme (Pi-lys) homologs from the moth Pseudoplusia includens. Relative-quantitative real-time PCR (rq-rtPCR) indicated that transcript abundance for each antimicrobial gene increased in fat body and hemocytes following immune challenge with the Gram-negative bacterium Escherichia coli. Relative transcript abundance of Pi-cecA was much higher in fat body than hemocytes. In contrast, transcript levels of Pi-leb were three-fold lower in hemocytes than fat body while transcript levels of Pi-lys were three-fold higher. Estimates for the overall contribution of the fat body and hemocytes to antimicrobial peptide expression suggested that hemocytes contribute significantly to Pi-lys transcript levels in larvae but produce much smaller amounts of Pi-cecA and Pi-leb compared to the fat body. Each antimicrobial peptide was also inducibly expressed in hemocytes following challenge with the Gram-positive bacterium Micrococcus luteus or when hemocytes formed capsules around chromatography beads. Analysis of hemocyte types indicated that granulocytes and plasmatocytes expressed all three antimicrobial peptides, whereas spherule cells and oenocytoids expressed only lysozyme. Transcriptional profiles of these antimicrobial genes were similar in granulocytes and plasmatocytes in vivo but were very different in vitro.

  3. Second generation multiple reaction monitoring assays for enhanced detection of ultra-low abundance Mycobacterium tuberculosis peptides in human serum.

    PubMed

    Mehaffy, Carolina; Dobos, Karen M; Nahid, Payam; Kruh-Garcia, Nicole A

    2017-01-01

    Mycobacterium tuberculosis (Mtb) is the causative agent of Tuberculosis (TB), the number one cause of death due to an infectious disease. TB diagnosis is performed by microscopy, culture or PCR amplification of bacterial DNA, all of which require patient sputum or the biopsy of infected tissue. Detection of mycobacterial products in serum, as biomarkers of diagnosis or disease status would provide an improvement over current methods. Due to the low-abundance of mycobacterial products in serum, we have explored exosome enrichment to improve sensitivity. Mtb resides intracellularly where its secreted proteins have been shown to be packaged into host exosomes and released into the bloodstream. Exosomes can be readily purified assuring an enrichment of mycobacterial analytes from the complex mix of host serum proteins. Multiple reaction monitoring assays were optimized for the enhanced detection of 41 Mtb peptides in exosomes purified from the serum of individuals with TB. Exosomes isolated from the serum of healthy individuals was used to create and validate a unique data analysis algorithm and identify filters to reduce the rate of false positives, attributed to host m / z interference. The final optimized method was tested in 40 exosome samples from TB positive patients. Our enhanced methods provide limit of detection and quantification averaging in the low femtomolar range for detection of mycobacterial products in serum. At least one mycobacterial peptide was identified in 92.5% of the TB positive patients. Four peptides from the Mtb proteins, Cfp2, Mpt32, Mpt64 and BfrB, show normalized total peak areas significantly higher in individuals with active TB as compared to healthy controls; three of the peptides from these proteins have not previously been associated with serum exosomes from individuals with active TB disease. Some of the detected peptides were significantly associated with specific geographical locations, highlighting potential markers that can be

  4. Absolute quantitation of low abundance plasma APL1β peptides at sub-fmol/mL Level by SRM/MRM without immunoaffinity enrichment.

    PubMed

    Sano, Shozo; Tagami, Shinji; Hashimoto, Yuuki; Yoshizawa-Kumagaye, Kumiko; Tsunemi, Masahiko; Okochi, Masayasu; Tomonaga, Takeshi

    2014-02-07

    Selected/multiple reaction monitoring (SRM/MRM) has been widely used for the quantification of specific proteins/peptides, although it is still challenging to quantitate low abundant proteins/peptides in complex samples such as plasma/serum. To overcome this problem, enrichment of target proteins/peptides is needed, such as immunoprecipitation; however, this is labor-intense and generation of antibodies is highly expensive. In this study, we attempted to quantify plasma low abundant APLP1-derived Aβ-like peptides (APL1β), a surrogate marker for Alzheimer's disease, by SRM/MRM using stable isotope-labeled reference peptides without immunoaffinity enrichment. A combination of Cibacron Blue dye mediated albumin removal and acetonitrile extraction followed by C18-strong cation exchange multi-StageTip purification was used to deplete plasma proteins and unnecessary peptides. Optimal and validated precursor ions to fragment ion transitions of APL1β were developed on a triple quadruple mass spectrometer, and the nanoliquid chromatography gradient for peptide separation was optimized to minimize the biological interference of plasma. Using the stable isotope-labeled (SI) peptide as an internal control, absolute concentrations of plasma APL1β peptide could be quantified as several hundred amol/mL. To our knowledge, this is the lowest detection level of endogenous plasma peptide quantified by SRM/MRM.

  5. Characterization of low-abundance species in the active pharmaceutical ingredient of CIGB-300: A clinical-grade anticancer synthetic peptide.

    PubMed

    Garay, Hilda; Espinosa, Luis Ariel; Perera, Yasser; Sánchez, Aniel; Diago, David; Perea, Silvio E; Besada, Vladimir; Reyes, Osvaldo; González, Luis Javier

    2018-04-20

    CIGB-300 is a first-in-class synthetic peptide-based drug of 25 amino acids currently undergoing clinical trials in cancer patients. It contains an amidated disulfide cyclic undecapeptide fused to the TAT cell-penetrating peptide through a beta-alanine spacer. CIGB-300 inhibits the CK2-mediated phosphorylation leading to apoptosis of tumor cells in vitro, and in vivo in cancer patients. Despite the clinical development of CIGB-300, the characterization of peptide-related impurities present in the active pharmaceutical ingredient has not been reported earlier. In the decision tree of ICHQ3A(R2) guidelines, the daily doses intake, the abundance, and the identity of the peptide-related species are pivotal nodes that define actions to be taken (reporting, identification, and qualification). For this, purity was first assessed by reverse-phase chromatography (>97%) and low-abundance impurities (≤0.27%) were collected and identified by mass spectrometry. Most of the impurities were generated during peptide synthesis, the spontaneous air oxidation of the reduced peptide, and the lyophilization step. The most abundant impurity, with no biological activity, was the full-length peptide containing Met 17 transformed into a sulfoxide residue. Interestingly, parallel and antiparallel dimers of CIGB-300 linked by 2 intermolecular disulfide bonds exhibited a higher antiproliferative activity than the CIGB-300 monomer. Likewise, very low abundance trimers and tetramers of CIGB-300 linked by disulfide bonds (≤0.01%) were also detected. Here we describe for the first time the presence of active dimeric species whose feasibility as novel CIGB-300 derived entities merits further investigation. Copyright © 2018 European Peptide Society and John Wiley & Sons, Ltd.

  6. Vasoactive intestinal polypeptide microinjections into the oral pontine tegmentum enhance rapid eye movement sleep in the rat.

    PubMed

    Bourgin, P; Lebrand, C; Escourrou, P; Gaultier, C; Franc, B; Hamon, M; Adrien, J

    1997-03-01

    Rapid eye movement sleep can be elicited in the rat by microinjection of the cholinergic agonist carbachol into the oral pontine reticular nucleus. Intracerebroventricular administration, during the light period, of vasoactive intestinal peptide enhances rapid eye movement sleep in several species. Since this peptide is co-localized with acetylcholine in many neurons in the central nervous system, it was assumed that the oral pontine tegmentum could also be one target for vasoactive intestinal peptide to induce rapid eye movement sleep. This hypothesis was tested by recording the sleep-wakefulness cycle in freely-moving rats injected with vasoactive intestinal peptide or its fragments (1-12 and 10-28) directly into the oral pontine reticular nucleus. when administered into the posterior part of this nucleus, vasoactive intestinal peptide at 1 and 10 ng (in 0.1 microliter of saline), but not its fragments, induced a 2-fold enhancement of rapid eye movement sleep during 4 h, at the expense of wakefulness. At the dose of 10 ng, a significant increase in rapid eye movement sleep persisted for up to 8 h. Moreover, when the peptide was injected into the centre of the positive zone, rapid eye movement sleep was enhanced during three to eight consecutive days. These data provide the first evidence that rapid eye movement sleep can be elicited at both short- and long-term by a single intracerebral microinjection of vasoactive intestinal peptide. Peptidergic mechanisms, possibly in association with cholinergic mechanisms, within the caudal part of the oral pontine reticular nucleus may play a critical role in the long-term regulation of rapid eye movement sleep in rats.

  7. Baroreflex buffering and susceptibility to vasoactive drugs

    NASA Technical Reports Server (NTRS)

    Jordan, Jens; Tank, Jens; Shannon, John R.; Diedrich, Andre; Lipp, Axel; Schroder, Christoph; Arnold, Guy; Sharma, Arya M.; Biaggioni, Italo; Robertson, David; hide

    2002-01-01

    BACKGROUND: The overall effect of vasoactive drugs on blood pressure is determined by a combination of the direct effect on vascular tone and an indirect baroreflex-mediated effect, a baroreflex buffering of blood pressure. Differences in baroreflex function affect the responsiveness to vasoactive medications, particularly baroreflex buffering of blood pressure; however, the magnitude is not known. METHODS AND RESULTS: We characterized baroreflex function and responses to vasoactive drugs in patients with idiopathic orthostatic intolerance, patients with essential hypertension, patients with monogenic hypertension and brachydactyly, patients with multiple system atrophy, and control subjects. We used phenylephrine sensitivity during ganglionic blockade as a measure of baroreflex buffering. Phenylephrine (25 microg) increased systolic blood pressure 6+/-1.6 mm Hg in control subjects, 6+/-1.1 mm Hg in orthostatic intolerance patients, 18+/-3.9 mm Hg in patients with essential hypertension, 31+/-3.4 mm Hg in patients with monogenic hypertension, and 25+/-3.4 mm Hg in patients with multiple system atrophy. Similar differences in sensitivities between groups were observed with nitroprusside. The sensitivity to vasoactive drugs was highly correlated with baroreflex buffering function and to a lesser degree with baroreflex control of heart rate. In control subjects, sensitivities to nitroprusside and phenylephrine infusions were correlated with baroreflex heart rate control and sympathetic nerve traffic. CONCLUSIONS: Our findings are consistent with an important effect of baroreflex blood pressure buffering on the sensitivity to vasoactive drugs. They suggest that even moderate changes in baroreflex function may have a substantial effect on the sensitivity to vasoactive medications.

  8. Isolation and amino acid sequences of opossum vasoactive intestinal polypeptide and cholecystokinin octapeptide.

    PubMed Central

    Eng, J; Yu, J; Rattan, S; Yalow, R S

    1992-01-01

    Evolutionary history suggests that the marsupials entered South America from North America about 75 million years ago and subsequently dispersed into Australia before the separation between South America and Antarctica-Australia. A question of interest is whether marsupial peptides resemble the corresponding peptides of Old or New World mammals. Previous studies had shown that "little" gastrin of the North American marsupial, the opossum, is identical in length to that of the New World mammals, the guinea pig and chinchilla. In this report, we demonstrate that opossum cholecystokinin octapeptide, like that of the Australian marsupials, the Eastern quoll and the Tamar wallaby, is identical to the cholecystokinin octapeptide of Old World mammals and differs from that of the guinea pig and chinchilla. However, opossum vasoactive intestinal polypeptide differs from the usual Old World mammalian vasoactive intestinal polypeptide in five sites: [sequence; see text]. PMID:1542675

  9. Protocol for Standardizing High-to-Moderate Abundance Protein Biomarker Assessments Through an MRM-with-Standard-Peptides Quantitative Approach.

    PubMed

    Percy, Andrew J; Yang, Juncong; Chambers, Andrew G; Mohammed, Yassene; Miliotis, Tasso; Borchers, Christoph H

    2016-01-01

    Quantitative mass spectrometry (MS)-based approaches are emerging as a core technology for addressing health-related queries in systems biology and in the biomedical and clinical fields. In several 'omics disciplines (proteomics included), an approach centered on selected or multiple reaction monitoring (SRM or MRM)-MS with stable isotope-labeled standards (SIS), at the protein or peptide level, has emerged as the most precise technique for quantifying and screening putative analytes in biological samples. To enable the widespread use of MRM-based protein quantitation for disease biomarker assessment studies and its ultimate acceptance for clinical analysis, the technique must be standardized to facilitate precise and accurate protein quantitation. To that end, we have developed a number of kits for assessing method/platform performance, as well as for screening proposed candidate protein biomarkers in various human biofluids. Collectively, these kits utilize a bottom-up LC-MS methodology with SIS peptides as internal standards and quantify proteins using regression analysis of standard curves. This chapter details the methodology used to quantify 192 plasma proteins of high-to-moderate abundance (covers a 6 order of magnitude range from 31 mg/mL for albumin to 18 ng/mL for peroxidredoxin-2), and a 21-protein subset thereof. We also describe the application of this method to patient samples for biomarker discovery and verification studies. Additionally, we introduce our recently developed Qualis-SIS software, which is used to expedite the analysis and assessment of protein quantitation data in control and patient samples.

  10. Identification of low-abundance cancer biomarker candidate TIMP1 from serum with lectin fractionation and peptide affinity enrichment by ultrahigh-resolution mass spectrometry.

    PubMed

    Ahn, Yeong Hee; Kim, Kwang Hoe; Shin, Park Min; Ji, Eun Sun; Kim, Hoguen; Yoo, Jong Shin

    2012-02-07

    As investigating a proteolytic target peptide originating from the tissue inhibitor of metalloproteinase 1 (TIMP1) known to be aberrantly glycosylated in patients with colorectal cancer (CRC), we first confirmed that TIMP1 is to be a CRC biomarker candidate in human serum. For this, we utilized matrix-assisted laser desorption/ionization (MALDI) Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) showing ultrahigh-resolution and high mass accuracy. This investigation used phytohemagglutinin-L(4) (L-PHA) lectin, which shows binding affinity to the β-1,6-N-acetylglucosamine moiety of N-linked glycan on a protein, to compare fractionated aberrant protein glycoforms from both noncancerous control and CRC serum. Each lectin-captured fraction containing aberrant glycoforms of TIMP1 was digested by trypsin, resulting in the tryptic target peptide, representative of the serum glycoprotein TIMP1. The resulting target peptide was enriched using a stable isotope standard and capture by the antipeptide antibody (SISCAPA) technique and analyzed by a 15 T MALDI FTICR mass spectrometer with high mass accuracy (Δ < 0.5 ppm to the theoretical mass value of the target peptide). Since exact measurement of multiplex isotopic peaks of the target peptide could be accomplished by virtue of high mass resolution (Rs > 400,000), robust identification of the target peptide is only achievable with 15 T FTICR MS. Also, MALDI data obtained in this study showed that the L-PHA-captured glycoforms of TIMP1 were measured in the pooled CRC serum with about 5 times higher abundance than that in the noncancerous serum, and were further proved by MRM mass analysis. These results confirm that TIMP1 in human serum is a potent CRC biomarker candidate, demonstrating that ultrahigh-resolution MS can be a powerful tool toward identifying and verifying potential protein biomarker candidates. © 2011 American Chemical Society

  11. Safety of peripheral intravenous administration of vasoactive medication.

    PubMed

    Cardenas-Garcia, Jose; Schaub, Karen F; Belchikov, Yuly G; Narasimhan, Mangala; Koenig, Seth J; Mayo, Paul H

    2015-09-01

    Central venous access is commonly performed to administer vasoactive medication. The administration of vasoactive medication via peripheral intravenous access is a potential method of reducing the need for central venous access. The aim of this study was to evaluate the safety of vasoactive medication administered through peripheral intravenous access. Over a 20-month period starting in September 2012, we monitored the use of vasoactive medication via peripheral intravenous access in an 18-bed medical intensive care unit. Norepinephrine, dopamine, and phenylephrine were all approved for use through peripheral intravenous access. A total of 734 patients (age 72 ± 15 years, male/female 398/336, SAPS II score 75 ± 15) received vasoactive medication via peripheral intravenous access 783 times. Vasoactive medication used was norepinephrine (n = 506), dopamine (n = 101), and phenylephrine (n = 176). The duration of vasoactive medication via peripheral intravenous access was 49 ± 22 hours. Extravasation of the peripheral intravenous access during administration of vasoactive medication occurred in 19 patients (2%) without any tissue injury following treatment, with local phentolamine injection and application of local nitroglycerin paste. There were 95 patients (13%) receiving vasoactive medication through peripheral intravenous access who eventually required central intravenous access. Administration of norepinephrine, dopamine, or phenylephrine by peripheral intravenous access was feasible and safe in this single-center medical intensive care unit. Extravasation from the peripheral intravenous line was uncommon, and phentolamine with nitroglycerin paste were effective in preventing local ischemic injury. Clinicians should not regard the use of vasoactive medication is an automatic indication for central venous access. © 2015 Society of Hospital Medicine.

  12. Validation of the Vasoactive-Inotropic Score in Pediatric Sepsis*

    PubMed Central

    Tong, Suhong; Deakyne, Sara J.; Davidson, Jesse A.; Scott, Halden F.

    2017-01-01

    Objectives: To assess the validity of Vasoactive-Inotropic Score as a scoring system for cardiovascular support and surrogate outcome in pediatric sepsis. Design: Secondary retrospective analysis of a single-center sepsis registry. Setting: Freestanding children’s hospital and tertiary referral center. Patients: Children greater than 60 days and less than 18 years with sepsis identified in the emergency department between January 2012 and June 2015 treated with at least one vasoactive medication within 48 hours of admission to the PICU. Interventions: None. Measurements and Main Results: Vasoactive-Inotropic Score was abstracted at 6, 12, 24, and 48 hours post ICU admission. Primary outcomes were ventilator days and ICU length of stay. The secondary outcome was a composite outcome of cardiac arrest/extracorporeal membrane oxygenation/in-hospital mortality. One hundred thirty-eight patients met inclusion criteria. Most common infectious sources were pneumonia (32%) and bacteremia (23%). Thirty-three percent were intubated and mortality was 6%. Of the time points assessed, Vasoactive-Inotropic Score at 48 hours showed the strongest correlation with ICU length of stay (r = 0.53; p < 0.0001) and ventilator days (r = 0.52; p < 0.0001). On multivariable analysis, Vasoactive-Inotropic Score at 48 hours was a strong independent predictor of primary outcomes and intubation. For every unit increase in Vasoactive-Inotropic Score at 48 hours, there was a 13% increase in ICU length of stay (p < 0.001) and 8% increase in ventilator days (p < 0.01). For every unit increase in Vasoactive-Inotropic Score at 12 hours, there was a 14% increase in odds of having the composite outcome (p < 0.01). Conclusions: Vasoactive-Inotropic Score in pediatric sepsis patients is independently associated with important clinically relevant outcomes including ICU length of stay, ventilator days, and cardiac arrest/extracorporeal membrane oxygenation/mortality. Vasoactive-Inotropic Score may be a

  13. Validation of the Vasoactive-Inotropic Score in Pediatric Sepsis.

    PubMed

    McIntosh, Amanda M; Tong, Suhong; Deakyne, Sara J; Davidson, Jesse A; Scott, Halden F

    2017-08-01

    To assess the validity of Vasoactive-Inotropic Score as a scoring system for cardiovascular support and surrogate outcome in pediatric sepsis. Secondary retrospective analysis of a single-center sepsis registry. Freestanding children's hospital and tertiary referral center. Children greater than 60 days and less than 18 years with sepsis identified in the emergency department between January 2012 and June 2015 treated with at least one vasoactive medication within 48 hours of admission to the PICU. None. Vasoactive-Inotropic Score was abstracted at 6, 12, 24, and 48 hours post ICU admission. Primary outcomes were ventilator days and ICU length of stay. The secondary outcome was a composite outcome of cardiac arrest/extracorporeal membrane oxygenation/in-hospital mortality. One hundred thirty-eight patients met inclusion criteria. Most common infectious sources were pneumonia (32%) and bacteremia (23%). Thirty-three percent were intubated and mortality was 6%. Of the time points assessed, Vasoactive-Inotropic Score at 48 hours showed the strongest correlation with ICU length of stay (r = 0.53; p < 0.0001) and ventilator days (r = 0.52; p < 0.0001). On multivariable analysis, Vasoactive-Inotropic Score at 48 hours was a strong independent predictor of primary outcomes and intubation. For every unit increase in Vasoactive-Inotropic Score at 48 hours, there was a 13% increase in ICU length of stay (p < 0.001) and 8% increase in ventilator days (p < 0.01). For every unit increase in Vasoactive-Inotropic Score at 12 hours, there was a 14% increase in odds of having the composite outcome (p < 0.01). Vasoactive-Inotropic Score in pediatric sepsis patients is independently associated with important clinically relevant outcomes including ICU length of stay, ventilator days, and cardiac arrest/extracorporeal membrane oxygenation/mortality. Vasoactive-Inotropic Score may be a useful surrogate outcome in pediatric sepsis.

  14. Intramural distribution of regulatory peptides in the human stomach and duodenum.

    PubMed

    Ferri, G L; Adrian, T E; Ghatei, M A; Soimero, L; Rebecchi, L; Biliotti, G; Polak, J M; Bloom, S R

    1987-04-01

    The distribution of regulatory peptides was studied by radioimmunoassay in the separated mucosa, submucosa and muscularis externa of the human oxyntic stomach, antrum and duodenum. Immunoreactive gastrin, secretin, gastric inhibitory polypeptide and motilin were virtually confined to the mucosa and duodenal submucosa, where endocrine cells are present. Only minor amounts of motilin and gastrin (3.2 +/- 0.5% and 4.3 +/- 0.8% of their total content, means + SEM, respectively) were found in the separated duodenal muscle. Somatostatin-, vasoactive intestinal polypeptide-, substance P-, and mammalian bombesin-like peptides showed distinct differential distributions in all layers. Substance P was low in the stomach and markedly increased in the duodenum, especially in the mucosa (fundus 0.8 +/- 0.2 pmol/g, duodenum 66 +/- 12). Vasoactive intestinal polypeptide and somatostatin, although well represented in the stomach, also increased in the duodenum in all layers of the wall (whole fundus 281 +/- 33 and 334 +/- 46 pmol/g, antrum 124 +/- 18 and 426 +/- 59, duodenum 507 +/- 99 and 1816 +/- 149, respectively). Mammalian bombesin immunoreactivity was comparatively abundant in the oxyntic stomach (mucosa 34 +/- 4.5 pmol/g, muscularis externa 29 +/- 4.8), less so in the antrum (6.3 +/- 1.5 and 11 +/- 3.2 pmol/g, respectively). Low concentrations of this peptide were measured in the duodenum, practically confined to the muscle (this layer 5.1 +/- 1.5 pmol/g, or 83 +/- 5.6% of the total content).

  15. The Na+/K+-ATPase and the amyloid-beta peptide aβ1-40 control the cellular distribution, abundance and activity of TRPC6 channels.

    PubMed

    Chauvet, Sylvain; Boonen, Marielle; Chevallet, Mireille; Jarvis, Louis; Abebe, Addis; Benharouga, Mohamed; Faller, Peter; Jadot, Michel; Bouron, Alexandre

    2015-11-01

    The Na(+)/K(+)-ATPase interacts with the non-selective cation channels TRPC6 but the functional consequences of this association are unknown. Experiments performed with HEK cells over-expressing TRPC6 channels showed that inhibiting the activity of the Na(+)/K(+)-ATPase with ouabain reduced the amount of TRPC6 proteins and depressed Ca(2+) entry through TRPC6. This effect, not mimicked by membrane depolarization with KCl, was abolished by sucrose and bafilomycin-A, and was partially sensitive to the intracellular Ca(2+) chelator BAPTA/AM. Biotinylation and subcellular fractionation experiments showed that ouabain caused a multifaceted redistribution of TRPC6 to the plasma membrane and to an endo/lysosomal compartment where they were degraded. The amyloid beta peptide Aβ(1-40), another inhibitor of the Na(+)/K(+)-ATPase, but not the shorter peptide Aβ1-16, reduced TRPC6 protein levels and depressed TRPC6-mediated responses. In cortical neurons from embryonic mice, ouabain, veratridine (an opener of voltage-gated Na(+) channel), and Aβ(1-40) reduced TRPC6-mediated Ca(2+) responses whereas Aβ(1-16) was ineffective. Furthermore, when Aβ(1-40) was co-added together with zinc acetate it could no longer control TRPC6 activity. Altogether, this work shows the existence of a functional coupling between the Na(+)/K(+)-ATPase and TRPC6. It also suggests that the abundance, distribution and activity of TRPC6 can be regulated by cardiotonic steroids like ouabain and the naturally occurring peptide Aβ(1-40) which underlines the pathophysiological significance of these processes. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Regulatory peptide distribution in separated layers of the human jejunum.

    PubMed

    Ferri, G L; Adrian, T E; Soimero, L; McGregor, G P; Ghatei, M A; Morreale, R A; Rebecchi, L; Tonelli, L; Polak, J M; Bloom, S R

    1987-01-01

    The distribution of regulatory peptides was studied in the separated epithelium, lamina propria, submucosa and muscularis externa of the human jejunum. Gastrin, secretin, gastric inhibitory polypeptide, enteroglucagon and neurotensin immunoreactivity were almost confined to the endocrine cell-containing mucosal epithelium (greater than 98% of the total content), only minor amounts of motilin being detected in non-epithelial layers (3.6 +/- 0.7%, mean +/- SEM, n = 7). Conversely, vasoactive intestinal polypeptide, substance P and mammalian bombesin were virtually limited to non-epithelial layers (greater than 99%). Only somatostatin was found in all layers (44 +/- 6.7% in the epithelium, 34 +/- 5.2% in the lamina propria, 13 +/- 2.9% in the submucosa, and 7.9 +/- 2.8% in the muscularis). Substance P was found in higher concentrations in the mucosa, compared to submucosa and muscle (56 +/- 10, 30 +/- 4.0 and 29 +/- 4.0 pmol/g, respectively), while vasoactive intestinal polypeptide was more abundant in the muscle (411 +/- 52 pmol/g) compared to mucosa and submucosa (228 +/- 64 and 219 +/- 31 pmol/g, respectively). Only low levels of mammalian bombesin were measured, mainly in the muscle (6.9 +/- 1.5 pmol/g, or 89 +/- 3.6% of total content).

  17. Vasoactive receptors in abdominal blood vessels of the dogfish shark, Squalus acanthias.

    PubMed

    Evans, D H

    2001-01-01

    Previous studies have demonstrated that the ventral aorta of the dogfish shark, Squalus acanthias, responds to a variety of cell-signaling agents. To investigate the generality of vasoactive receptors in the shark vasculature, in particular a conductance artery (anterior mesenteric) and vein (posterior intestinal), I measured the effect of acetylcholine, endothelin, nitric oxide, natriuretic peptides, and prostaglandins on tension in isolated rings from these vessels. Both vessels responded to these agents, and responses to receptor-specific ligands for endothelin and natriuretic peptide receptors suggest that B-type endothelin receptors are expressed in both vessels and that the artery expresses both A- and B-type natriuretic peptide receptors; however, the vein (like the ventral aorta) expresses only the B-type natriuretic peptide receptor. My data suggest that a suite of signaling systems is ubiquitous in both arteries and veins in at least this elasmobranch species. Their role in hemodynamics and osmoregulation (perfusion of gill and rectal gland) remains to be determined.

  18. Isoelectric focusing of proteins and peptides

    NASA Technical Reports Server (NTRS)

    Egen, N.

    1979-01-01

    Egg-white solution was chosen as the reference solution in order to assess the effects of operational parameters (voltage, flow rate, ampholine pH range and concentration, and protein concentration) of the RIEF apparatus on protein resolution. Topics of discussion include: (1) comparison of RIEF apparatus to conventional IEF techniques (column and PAG) with respect to resolution and throughput; (2) peptide and protein separation (AHF, Thymosin - Fraction 5, vasoactive peptide, L-asparaginase and ACP); and (3) detection of peptides - dansyl derivatives of amino acids and peptides, post-focusing fluorescent labeling of amino acids, peptides and proteins, and ampholine extraction from focused gels.

  19. Frog secretions and hunting magic in the upper Amazon: identification of a peptide that interacts with an adenosine receptor.

    PubMed Central

    Daly, J W; Caceres, J; Moni, R W; Gusovsky, F; Moos, M; Seamon, K B; Milton, K; Myers, C W

    1992-01-01

    A frog used for "hunting magic" by several groups of Panoan-speaking Indians in the borderline between Brazil and Peru is identified as Phyllomedusa bicolor. This frog's skin secretion, which the Indians introduce into the body through fresh burns, is rich in peptides. These include vasoactive peptides, opioid peptides, and a peptide that we have named adenoregulin, with the sequence GLWSKIKEVGKEAAKAAAKAAGKAALGAVSEAV as determined from mass spectrometry and Edman degradation. The natural peptide may contain a D amino acid residue, since it is not identical in chromatographic properties to the synthetic peptide. Adenoregulin enhances binding of agonists to A1 adenosine receptors; it is accompanied in the skin secretion by peptides that inhibit binding. The vasoactive peptide sauvagine, the opioid peptides, and adenoregulin and related peptides affect behavior in mice and presumably contribute to the behavioral sequelae observed in humans. Images PMID:1438301

  20. Frog secretions and hunting magic in the upper Amazon: identification of a peptide that interacts with an adenosine receptor.

    PubMed

    Daly, J W; Caceres, J; Moni, R W; Gusovsky, F; Moos, M; Seamon, K B; Milton, K; Myers, C W

    1992-11-15

    A frog used for "hunting magic" by several groups of Panoan-speaking Indians in the borderline between Brazil and Peru is identified as Phyllomedusa bicolor. This frog's skin secretion, which the Indians introduce into the body through fresh burns, is rich in peptides. These include vasoactive peptides, opioid peptides, and a peptide that we have named adenoregulin, with the sequence GLWSKIKEVGKEAAKAAAKAAGKAALGAVSEAV as determined from mass spectrometry and Edman degradation. The natural peptide may contain a D amino acid residue, since it is not identical in chromatographic properties to the synthetic peptide. Adenoregulin enhances binding of agonists to A1 adenosine receptors; it is accompanied in the skin secretion by peptides that inhibit binding. The vasoactive peptide sauvagine, the opioid peptides, and adenoregulin and related peptides affect behavior in mice and presumably contribute to the behavioral sequelae observed in humans.

  1. A Novel Vasoactive Proline-Rich Oligopeptide from the Skin Secretion of the Frog Brachycephalus ephippium.

    PubMed

    Arcanjo, Daniel Dias Rufino; Vasconcelos, Andreanne Gomes; Comerma-Steffensen, Simón Gabriel; Jesus, Joilson Ramos; Silva, Luciano Paulino; Pires Júnior, Osmindo Rodrigues; Costa-Neto, Claudio Miguel; Oliveira, Eduardo Brandt; Migliolo, Ludovico; Franco, Octávio Luiz; Restini, Carolina Baraldi Araújo; Paulo, Michele; Bendhack, Lusiane Maria; Bemquerer, Marcelo Porto; Oliveira, Aldeidia Pereira; Simonsen, Ulf; Leite, José Roberto de Souza de Almeida

    2015-01-01

    Proline-rich oligopeptides (PROs) are a large family which comprises the bradykinin-potentiating peptides (BPPs). They inhibit the activity of the angiotensin I-converting enzyme (ACE) and have a typical pyroglutamyl (Pyr)/proline-rich structure at the N- and C-terminus, respectively. Furthermore, PROs decrease blood pressure in animals. In the present study, the isolation and biological characterization of a novel vasoactive BPP isolated from the skin secretion of the frog Brachycephalus ephippium is described. This new PRO, termed BPP-Brachy, has the primary structure WPPPKVSP and the amidated form termed BPP-BrachyNH2 inhibits efficiently ACE in rat serum. In silico molecular modeling and docking studies suggest that BPP-BrachyNH2 is capable of forming a hydrogen bond network as well as multiple van der Waals interactions with the rat ACE, which blocks the access of the substrate to the C-domain active site. Moreover, in rat thoracic aorta BPP-BrachyNH2 induces potent endothelium-dependent vasodilatation with similar magnitude as captopril. In DAF-FM DA-loaded aortic cross sections examined by confocal microscopy, BPP-BrachyNH2 was found to increase the release of nitric oxide (NO). Moreover, BPP-BrachyNH2 was devoid of toxicity in endothelial and smooth muscle cell cultures. In conclusion, the peptide BPP-BrachyNH2 has a novel sequence being the first BPP isolated from the skin secretion of the Brachycephalidae family. This opens for exploring amphibians as a source of new biomolecules. The BPP-BrachyNH2 is devoid of cytotoxicity and elicits endothelium-dependent vasodilatation mediated by NO. These findings open for the possibility of potential application of these peptides in the treatment of endothelial dysfunction and cardiovascular diseases.

  2. A Novel Vasoactive Proline-Rich Oligopeptide from the Skin Secretion of the Frog Brachycephalus ephippium

    PubMed Central

    Arcanjo, Daniel Dias Rufino; Vasconcelos, Andreanne Gomes; Comerma-Steffensen, Simón Gabriel; Jesus, Joilson Ramos; Silva, Luciano Paulino; Pires, Osmindo Rodrigues; Costa-Neto, Claudio Miguel; Oliveira, Eduardo Brandt; Migliolo, Ludovico; Franco, Octávio Luiz; Restini, Carolina Baraldi Araújo; Paulo, Michele; Bendhack, Lusiane Maria; Bemquerer, Marcelo Porto; Oliveira, Aldeidia Pereira; Simonsen, Ulf; Leite, José Roberto de Souza de Almeida

    2015-01-01

    Proline-rich oligopeptides (PROs) are a large family which comprises the bradykinin-potentiating peptides (BPPs). They inhibit the activity of the angiotensin I-converting enzyme (ACE) and have a typical pyroglutamyl (Pyr)/proline-rich structure at the N- and C-terminus, respectively. Furthermore, PROs decrease blood pressure in animals. In the present study, the isolation and biological characterization of a novel vasoactive BPP isolated from the skin secretion of the frog Brachycephalus ephippium is described. This new PRO, termed BPP-Brachy, has the primary structure WPPPKVSP and the amidated form termed BPP-BrachyNH2 inhibits efficiently ACE in rat serum. In silico molecular modeling and docking studies suggest that BPP-BrachyNH2 is capable of forming a hydrogen bond network as well as multiple van der Waals interactions with the rat ACE, which blocks the access of the substrate to the C-domain active site. Moreover, in rat thoracic aorta BPP-BrachyNH2 induces potent endothelium-dependent vasodilatation with similar magnitude as captopril. In DAF-FM DA-loaded aortic cross sections examined by confocal microscopy, BPP-BrachyNH2 was found to increase the release of nitric oxide (NO). Moreover, BPP-BrachyNH2 was devoid of toxicity in endothelial and smooth muscle cell cultures. In conclusion, the peptide BPP-BrachyNH2 has a novel sequence being the first BPP isolated from the skin secretion of the Brachycephalidae family. This opens for exploring amphibians as a source of new biomolecules. The BPP-BrachyNH2 is devoid of cytotoxicity and elicits endothelium-dependent vasodilatation mediated by NO. These findings open for the possibility of potential application of these peptides in the treatment of endothelial dysfunction and cardiovascular diseases. PMID:26661890

  3. Vasoactive exposures during pregnancy and risk of microtia.

    PubMed

    Van Bennekom, Carla M; Mitchell, Allen A; Moore, Cynthia A; Werler, Martha M

    2013-01-01

    Little is known about the etiology of nonsyndromic microtia. This study investigated the hypothesis that microtia is caused by vascular disruption. The study analyzed data from the population-based National Birth Defects Prevention Study (NBDPS) for deliveries between 1997 and 2005. Four hundred eleven nonsyndromic cases of microtia, with or without additional defects, were compared to 6560 nonmalformed infants with respect to maternal exposures to vasoactive medications and smoking during the periconceptional period and conditions that have previously been associated with vascular events (multiple gestation, maternal history of type 1, type 2, or gestational diabetes, and hypertension). Odds ratios (ORs) were estimated with multivariable models, controlling for the effects of race/ethnicity, education, periconceptional folic acid use, and study center. Risk estimates for vasoactive medications and smoking were not meaningfully increased. Maternal type 1/2 diabetes was diagnosed before or during the index pregnancy in 4% and 1% of cases, respectively, compared to 1% and 0.05% of controls; the adjusted OR for these two groups combined was 7.2 (95% confidence interval [CI], 3.9-13.1). Gestational diabetes was observed for 9% of cases and 6% of controls; the OR was moderately elevated (OR, 1.4; 95% CI, 0.9-2.0). ORs were also increased for multiple gestations (OR, 2.5; 95% CI, 1.5-4.2) and pre-existing hypertension (OR, 1.6; 95% CI, 1.0-2.5). Because ORs were only elevated for diabetes and not for vasoactive exposures or other potential vascular events, findings suggest that some microtia occurrences may be part of the diabetic embryopathy rather than manifestations of vascular disruption. Birth Defects Research (Part A), 2013. © 2012 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc.

  4. Vasoactive drugs and the gut: is there anything new?

    PubMed

    Woolsey, Cheryl A; Coopersmith, Craig M

    2006-04-01

    Systemic changes in blood pressure and cardiac output induced by pressors and inotropes do not always correlate to improvements in regional perfusion. Since the gut is often referred to as the 'motor' of the systemic inflammatory response syndrome, the impact of vasoactive agents on splanchnic perfusion has theoretical importance. This review will highlight recent studies examining secondary effects of vasoactive agents on intestinal perfusion, metabolism, and barrier function. Norepinephrine has minimal impact on mesenteric blood flow although the combination of norepinephrine and dobutamine increases splanchnic blood flow in sepsis. Dopamine also increases mesenteric blood flow although this may be associated with negative hepatic energy balance at high does. Vasopressin and epinephrine both have negative effects on splanchnic blood flow. Newer inodilators levosimendan and olprinone preferentially improve mesenteric perfusion in animal models. Secondary effects of norepinephrine and dopamine on splanchnic perfusion are minor compared with their systemic effects. While vasopressin usage is increasing in the intensive care unit, caution should be used because of its adverse effects on gut perfusion. Experimental agents for the treatment of heart failure have beneficial gut-specific effects although the clinical significance of this is currently limited by their availability.

  5. A high-throughput in vitro ring assay for vasoactivity using magnetic 3D bioprinting

    PubMed Central

    Tseng, Hubert; Gage, Jacob A.; Haisler, William L.; Neeley, Shane K.; Shen, Tsaiwei; Hebel, Chris; Barthlow, Herbert G.; Wagoner, Matthew; Souza, Glauco R.

    2016-01-01

    Vasoactive liabilities are typically assayed using wire myography, which is limited by its high cost and low throughput. To meet the demand for higher throughput in vitro alternatives, this study introduces a magnetic 3D bioprinting-based vasoactivity assay. The principle behind this assay is the magnetic printing of vascular smooth muscle cells into 3D rings that functionally represent blood vessel segments, whose contraction can be altered by vasodilators and vasoconstrictors. A cost-effective imaging modality employing a mobile device is used to capture contraction with high throughput. The goal of this study was to validate ring contraction as a measure of vasoactivity, using a small panel of known vasoactive drugs. In vitro responses of the rings matched outcomes predicted by in vivo pharmacology, and were supported by immunohistochemistry. Altogether, this ring assay robustly models vasoactivity, which could meet the need for higher throughput in vitro alternatives. PMID:27477945

  6. Morphology and vasoactive hormone profiles from endothelial cells derived from stem cells of different sources.

    PubMed

    Reed, Daniel M; Foldes, Gabor; Kirkby, Nicholas S; Ahmetaj-Shala, Blerina; Mataragka, Stefania; Mohamed, Nura A; Francis, Catherine; Gara, Edit; Harding, Sian E; Mitchell, Jane A

    2014-12-12

    Endothelial cells form a highly specialised lining of all blood vessels where they provide an anti-thrombotic surface on the luminal side and protect the underlying vascular smooth muscle on the abluminal side. Specialised functions of endothelial cells include their unique ability to release vasoactive hormones and to morphologically adapt to complex shear stress. Stem cell derived-endothelial cells have a growing number of applications and will be critical in any organ regeneration programme. Generally endothelial cells are identified in stem cell studies by well-recognised markers such as CD31. However, the ability of stem cell-derived endothelial cells to release vasoactive hormones and align with shear stress has not been studied extensively. With this in mind, we have compared directly the ability of endothelial cells derived from a range of stem cell sources, including embryonic stem cells (hESC-EC) and adult progenitors in blood (blood out growth endothelial cells, BOEC) with those cultured from mature vessels, to release the vasoconstrictor peptide endothelin (ET)-1, the cardioprotective hormone prostacyclin, and to respond morphologically to conditions of complex shear stress. All endothelial cell types, except hESC-EC, released high and comparable levels of ET-1 and prostacyclin. Under static culture conditions all endothelial cell types, except for hESC-EC, had the typical cobblestone morphology whilst hESC-EC had an elongated phenotype. When cells were grown under shear stress endothelial cells from vessels (human aorta) or BOEC elongated and aligned in the direction of shear. By contrast hESC-EC did not align in the direction of shear stress. These observations show key differences in endothelial cells derived from embryonic stem cells versus those from blood progenitor cells, and that BOEC are more similar than hESC-EC to endothelial cells from vessels. This may be advantageous in some settings particularly where an in vitro test bed is required

  7. Hippocampal asymmetry in exploratory behavior to vasoactive intestinal polypeptide.

    PubMed

    Ivanova, Margarita; Ternianov, Alexandar; Belcheva, Stiliana; Tashev, Roman; Negrev, Negrin; Belcheva, Iren

    2008-06-01

    The effects of vasoactive intestinal polypeptide (VIP) microinjected uni- or bilaterally into the CA1 hippocampal area of male Wistar rats at a dose of 10, 50 and 100 ng on exploratory behavior were examined. VIP microinjected bilaterally at a high dose (100 ng) significantly decreased the horizontal movements, while at low doses (10 and 50 ng) had no effect on the exploratory activity. Microinjections of VIP into the left hippocampal CA1 area at doses 50 and 100 ng suppressed the exploratory activity, while right-side VIP administration at a dose 100 ng significantly increased horizontal movements compared to the respective controls. Vertical activity was stimulated only by VIP administered into the right hippocampal CA1 area at the three doses used. Neither bilateral nor left injections of VIP induced changes in the vertical movements. The main finding was the presence of hippocampal asymmetry in exploratory behavior to unilateral microinjections of VIP depending on the dose and the microinjected hemisphere.

  8. The effects of delivery route and anesthesia type on early postnatal weight loss in newborns: the role of vasoactive hormones.

    PubMed

    Okumus, Nurullah; Atalay, Yildiz; Onal, Eray E; Turkyilmaz, Canan; Senel, Saliha; Gunaydin, Berrin; Pasaoglu, Hatice; Koc, Esin; Ergenekon, Ebru; Unal, Suna

    2011-01-01

    To investigate the effects of delivery route and maternal anesthesia type and the roles of vasoactive hormones on early postnatal weight loss in term newborns. Ninety-four term infants delivered vaginally (group 1, n=31), cesarean section (C/S) with general anesthesia (GA) (group 2, n=29), and C/S with epidural anesthesia (EA) (group 3, n=34) were included in this study. All infants were weighed at birth and on the second day of life and intravenous (IV) fluid infused to the mothers for the last 6 h prior to delivery was recorded. Serum electrolytes, osmolality, N-terminal proANP (NT-proANP), brain natriuretic peptide (BNP), aldosterone and plasma antidiuretic hormone (ADH) concentrations were measured at cord blood and on the second day of life. Our research showed that postnatal weight loss of infants was higher in C/S than vaginal deliveries (5.7% vs. 1.3%) (p < 0.0001) and in EA group than GA group (6.8% vs. 4.3%) (p < 0.0001). Postnatal weight losses were correlated with IV fluid volume infused to the mothers for the last 6 h prior to delivery (R = 0.814, p = 0.000) and with serum NT-proANP (R = 0.418, p = 0.000), BNP (R = 0.454, p = 0.000), and ADH (R = 0.509, p = 0.000) but not with aldosterone concentrations (p > 0.05). Large amounts of IV fluid given to the mothers who were applied EA prior to the delivery affect their offsprings' postnatal weight loss via certain vasoactive hormones.

  9. Effect of two oral contraceptives with different ethinyl estradiol and levonorgestrel concentrations on the urinary excretion of biochemical vasoactive markers.

    PubMed

    Mueck, A O; Seeger, H; Petersen, G; Schulte-Wintrop, E; Wallwiener, D

    2001-12-01

    In the present study the effect on the urinary excretion of vasoactive markers of two oral contraceptives (OCs), i.e., Leios, containing 0.02 mg ethinyl estradiol and 0.1 mg levonorgestrel, and Stediril 30, containing 0.03 mg ethinyl estradiol and 0.15 mg levonorgestrel, was investigated. cGMP, prostacyclin and its antagonist thromboxane, serotonin, and urodilatin, a natriuretic and diuretic peptide formed in the kidney, were measured as markers. In a comparative, double-blind, randomized, parallel group study, 34 women received Leios and 33 women Stediril 30. Nocturnal urine was collected before treatment and during cyclic treatment after 3 and 12 cycles. Both contraceptives significantly enhanced cGMP excretion after 12 cycles. The prostacyclin metabolite remained unchanged for both formulations, but the excretion of the thromboxane metabolite was significantly decreased after 12 cycles. Thus, the ratio of prostacyclin to thromboxane, crucial for the resulting effect on vascular tone, increased significantly. For the serotonin metabolite, no changes were observed for both contraceptives. The excretion of urodilatin significantly increased for both preparations after 12 cycles compared to the pretreatment values. These results indicate that the low-dose OCs Leios and Stediril 30 may stimulate the production of some vasoactive markers, at least after 12 cycles of treatment. The positive influence of these contraceptives on the various markers investigated may improve vascular tone, impede development of atherosclerosis and arterial thrombosis, and improve water and electrolyte homeostasis. These effects most likely can be attributed to the estrogenic component. Levonorgestrel may elicit no impact on these estrogen-induced changes that, however, seem only to be manifested after a longer treatment period.

  10. Learning to manage vasoactive drugs-A qualitative interview study with critical care nurses.

    PubMed

    Häggström, Marie; Bergsman, Ann-Christin; Månsson, Ulrika; Holmström, Malin Rising

    2017-04-01

    Being a nurse in an intensive care unit entails caring for seriously ill patients. Vasoactive drugs are one of the tools that are used to restore adequate circulation. Critical care nurses often manage and administer these potent drugs after medical advice from physicians. To describe the experiences of critical care nurses learning to manage vasoactive drugs, and to highlight the competence required to manage vasoactive drugs. Twelve critical care nurses from three hospitals in Sweden were interviewed. Qualitative content analysis was applied. The theme "becoming proficient requires accuracy, practice and precaution" illustrated how critical care nurses learn to manage vasoactive drugs. Learning included developing cognitive, psychomotor, and effective skills. Sources for knowledge refers to specialist education combined with practical exercises, collegial support, and accessible routine documents. The competence required to manage vasoactive drugs encompassed well-developed safety thinking that included being careful, in control, and communicating failures. Specific skills were required such as titrating doses, being able to analyse and evaluate the technological assessments, adapting to the situation, and staying calm. Learning to manage vasoactive drugs requires a supportive introduction for novices, collegial support, lifelong learning, and a culture of safety. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Vasoactive intestinal polypeptide (VIP) innervation of the human eyelid glands.

    PubMed

    Seifert, P; Spitznas, M

    1999-06-01

    This study was conducted to obtain morphological proof of innervating nerve fibres in the glands of the human eyelid (accessory lacrimal glands of Wolfring, meibomian glands, goblet cells, glands of Zeis, glands of Moll, sweat glands, glands of lanugo hair follicles) and identification of the secretomotorically active neuropeptide vasoactive intestinal polypeptide (VIP) as a common transmitter. Epoxy-embedded ultrathin sections of tissue samples from human eyelids were studied using electron microscopy. Paraffin sections fixed in Bouin-Hollande solution were immunostained with rabbit antiserum against VIP. With the electron microscope we were able to identify nerves in the glandular stroma of all the glands examined with the exception of goblet cells. Intraepithelial single axons were only seen in the parenchyma of Wolfring glands. The morphological findings corresponded with the immunological finding of VIP-positive, nerve-like structures in the same locations, with the exception of lanugo hair follicle glands, and goblet cells. Our findings indicate that the glands of the eyelids and main lacrimal gland represent a functional unit with VIP as a possible common stimulating factor. Copyright 1999 Academic Press.

  12. Vasoactive intestinal polypeptide provokes acetylcholine release from the myenteric plexus

    SciTech Connect

    Kusunoki, M.; Tsai, L.H.; Taniyama, K.

    1986-07-01

    Effects of vasoactive intestinal polypeptide (VIP) on the release of acetylcholine (ACh) from longitudinal muscle strips with myenteric plexus (LM) preparations were examined in the guinea pig small intestine. VIP (10 to 10 W M) induced a concentration-dependent contraction of LM preparation. The VIP-induced contractions seem to be related to three components, the scopolamine-sensitive, the scopolamine-insensitive, the tetrodotoxin-sensitive, and the tetrodotoxin-insensitive contractions. VIP (10 to 10 W M) induced a concentration-dependent increase in the release of (TH)ACh from LM preparations preloaded with (TH)choline. The VIP-evoked (TH)ACh release was inhibited by removal of CaS from the perfusion medium and by treatmentmore » with tetrodotoxin but not by scopolamine and hexamethonium. The spontaneous and VIP-evoked (TH)ACh release was not affected by phentolamine, propranolol, methysergide, diphenhydramine, cimetidine, bicuculline, or (D-ProS, D-Trp/sup 7,9/)substance P. The result demonstrates that VIP induces contractions of longitudinal smooth muscle directly and indirectly by the stimulation of both cholinergic neurons and noncholinergic excitatory neurons.« less

  13. The role of vasoactive intestinal peptide in neuroprotection: Professor Illana Gozes is interviewed by Emma Quigley.

    PubMed

    Gozes, Illana

    2007-06-01

    Professor Illana Gozes was interviewed by Emma Quigley (Senior Editor, Expert Opinion) on 17(th) April 2007. Professor Illana Gozes BSc, PhD holds the titles of Professor of Clinical Biochemistry; The Lily and Avraham Gildor Chair for the Investigation of Growth Factors; Director of Adams Super Center for Brain Studies and Levi-Edersheim-Gitter fMRI Institute; Head of the Dr Diana and Zelman Elton (Elbaum) Laboratory for Molecular Neuroendocrinology, Tel Aviv University and Chief Scientific Officer, Allon Therapeutics, Inc., Vancouver BC, Canada. Professor Gozes has served as a member (or chair) of several faculty, university or national and international committees and she currently serves on the Board of Directors of Allon Therapeutics, the Scientific Review Board of the ISOA, and is the Editor-in-Chief of the Journal of Molecular Neuroscience. Professor Gozes has received a number of scientific awards for her work including the Landau Award for an excellent PhD dissertation, the Juludan Prize and the Teva Founders Prize for exceptional scientific studies that may lead to biotechnology developments as well as the Bergmann Prize and the Neufeld award for outstanding/leading US-Israel BSF grant proposals, and has published extensively in the fields of molecular neuroscience and neuroprotection (> 200 scientific manuscripts). She is co-inventor of > 15 patents and applications, including the composition of matter patent on AL-108 and AL-208, Allon's lead compounds. Professor Gozes received a BSc from Tel Aviv University, a PhD from The Weizmann Institute of Science and was a Weizmann Postdoctoral Fellow at Massachusetts Institute of Technology, Research Associate/Visiting Scientist at the Salk Institute and the Scripps Clinic and Research Foundation, a Senior Scientist/Associate Professor at the Weizmann Institute and a Fogarty-Scholar-in-Residence at the National Institutes of Health (USA). Professor Gozes directs a very active research laboratory at Tel Aviv University and is mentoring and has mentored directly approximately 50 graduate students toward their MSc or PhD degrees.

  14. Analysis of expressed sequence tags (ESTs) from avocado seed (Persea americana var. drymifolia) reveals abundant expression of the gene encoding the antimicrobial peptide snakin.

    PubMed

    Guzmán-Rodríguez, Jaquelina J; Ibarra-Laclette, Enrique; Herrera-Estrella, Luis; Ochoa-Zarzosa, Alejandra; Suárez-Rodríguez, Luis María; Rodríguez-Zapata, Luis C; Salgado-Garciglia, Rafael; Jimenez-Moraila, Beatriz; López-Meza, Joel E; López-Gómez, Rodolfo

    2013-09-01

    Avocado is one of the most important fruits in the world. Avocado "native mexicano" (Persea americana var. drymifolia) seeds are widely used in the propagation of this plant and are the primary source of rootstocks globally for a variety of avocado cultivars, such as the Hass avocado. Here, we report the isolation of 5005 ESTs from the 5' ends of P. americana var. drymifolia seed cDNA clones representing 1584 possible unigenes. These avocado seed ESTs were compared with the avocado flower EST library, and we detected several genes that are expressed either in both tissues or only in the seed. The snakin gene, which encodes an element of the innate immune response in plants, was one of those most frequently found among the seed ESTs, and this suggests that it is abundantly expressed in the avocado seed. We expressed the snakin gene in a heterologous system, namely the bovine endothelial cell line BVE-E6E7. Conditioned media from transfected BVE-E6E7 cells showed antimicrobial activity against strains of Escherichia coli and Staphylococcus aureus. This is the first study of the function of the snakin gene in plant seed tissue, and our observations suggest that this gene might play a protective role in the avocado seed. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  15. Regional differences in concentrations of regulatory peptides in human colon mucosal biopsy.

    PubMed

    Calam, J; Ghatei, M A; Domin, J; Adrian, T E; Myszor, M; Gupta, S; Tait, C; Bloom, S R

    1989-08-01

    The study was undertaken to examine regional differences in the concentrations of five regulatory peptides in the human colonic mucosa. Biopsies were obtained during routine colonoscopy from 33 patients whose colonic mucosa was macroscopically and histologically normal. Regulatory peptides were extracted, and measured by specific radioimmunoassays. Concentrations of three peptides that are present predominantly in endocrine cells within colonic mucosa increased significantly towards the rectum: Mean concentrations of peptide YY, enteroglucagon, and somatostatin were about three times greater in the rectum than in the cecum. However, concentrations of two peptides that are present in mucosal nerve fibers diminished significantly towards the rectum: Mean rectal concentrations of vasoactive intestinal peptide and peptide histidine methionine were both about 0.6 of mean cecal concentrations. Concentrations of all five peptides were lower in biopsies taken from colonic polyps than in normal colonic mucosa. Regional differences in colonic mucosal concentrations of regulatory peptides probably reflect differences in the physiological functions of different parts of the colon.

  16. Characterization of three peptides derived from prosomatostatin [prosomatostatin-(1-63)-, -(65-76)- and -(79-92)-peptides] in a human pancreatic tumour.

    PubMed

    Conlon, J M; Eriksson, B; Grimelius, L; Oberg, K; Thim, L

    1987-11-15

    By using only reverse-phase h.p.l.c., three fragments of prosomatostatin were isolated from an extract of a human pancreatic neuroendocrine tumour that produced somatostatin, vasoactive intestinal polypeptide and gastrin-releasing peptide. The amino acid composition of the peptides indicated that they represented prosomatostatin-(1-63)-peptide, prosomatostain-(65-76)-peptide and prosomatostatin-(79-92)-peptide (somatostatin-14). The identity of prosomatostatin-(1-63)-peptide was confirmed by characterization of the products of digestion with Armillaria mellea (honey fungus) proteinase. Partial micro-sequencing of prosomatostatin-(1-63)-peptide showed that the Gly24-Ala25 bond of preprosomatostatin was the site of cleavage of the signal peptide. Thus human prosomatostatin is a protein of 92 amino acid residues that is proteolytically cleaved in a pancreatic tumour at the site of a dibasic-residue (arginine-lysine) processing site and at a single-monobasic-residue (arginine) processing site.

  17. Mast cell chymase reduces the toxicity of Gila monster venom, scorpion venom, and vasoactive intestinal polypeptide in mice

    PubMed Central

    Akahoshi, Mitsuteru; Song, Chang Ho; Piliponsky, Adrian M.; Metz, Martin; Guzzetta, Andrew; Åbrink, Magnus; Schlenner, Susan M.; Feyerabend, Thorsten B.; Rodewald, Hans-Reimer; Pejler, Gunnar; Tsai, Mindy; Galli, Stephen J.

    2011-01-01

    Mast cell degranulation is important in the pathogenesis of anaphylaxis and allergic disorders. Many animal venoms contain components that can induce mast cell degranulation, and this has been thought to contribute to the pathology and mortality caused by envenomation. However, we recently reported evidence that mast cells can enhance the resistance of mice to the venoms of certain snakes and that mouse mast cell–derived carboxypeptidase A3 (CPA3) can contribute to this effect. Here, we investigated whether mast cells can enhance resistance to the venom of the Gila monster, a toxic component of that venom (helodermin), and the structurally similar mammalian peptide, vasoactive intestinal polypeptide (VIP). Using 2 types of mast cell–deficient mice, as well as mice selectively lacking CPA3 activity or the chymase mouse mast cell protease-4 (MCPT4), we found that mast cells and MCPT4, which can degrade helodermin, can enhance host resistance to the toxicity of Gila monster venom. Mast cells and MCPT4 also can limit the toxicity associated with high concentrations of VIP and can reduce the morbidity and mortality induced by venoms from 2 species of scorpions. Our findings support the notion that mast cells can enhance innate defense by degradation of diverse animal toxins and that release of MCPT4, in addition to CPA3, can contribute to this mast cell function. PMID:21926462

  18. Estimating abundance

    USGS Publications Warehouse

    Sutherland, Chris; Royle, Andy

    2016-01-01

    This chapter provides a non-technical overview of ‘closed population capture–recapture’ models, a class of well-established models that are widely applied in ecology, such as removal sampling, covariate models, and distance sampling. These methods are regularly adopted for studies of reptiles, in order to estimate abundance from counts of marked individuals while accounting for imperfect detection. Thus, the chapter describes some classic closed population models for estimating abundance, with considerations for some recent extensions that provide a spatial context for the estimation of abundance, and therefore density. Finally, the chapter suggests some software for use in data analysis, such as the Windows-based program MARK, and provides an example of estimating abundance and density of reptiles using an artificial cover object survey of Slow Worms (Anguis fragilis).

  19. Vasoactive intestinal polypeptide in the suprachiasmatic nucleus of the mink (Mustela vison) could play a key role in photic induction.

    PubMed

    Martinet, L; Bonnefond, C; Peytevin, J; Monnerie, R; Marcilloux, J C

    1995-01-01

    The present study was conducted to visualize neuropeptides in the SCN of a mustelid, the American mink in which seasonal cycles of reproduction rely totally on the annual changes in day length. At this time, data in mustelids are lacking. Results were obtained with in situ hybridization (ISH) using synthetic oligonucleotide vasopressin (AVP) and somatostatin (SOM) and with single and dual immunohistochemistry (IHC) performed with antisera against AVP, SOM, vasoactive intestinal polypeptide (VIP), gastrin releasing peptide (GRP) and met-enkephalin (Met-ENK) in untreated (AVP and VIP) or colchicine (SOM, Met-ENK and GRP) treated adult male and female mink. The most striking result, evidenced by ISH as well as IHC was the lack of AVP, SOM and Met-ENK immunoreactive (ir)-neurons in the SCN. In contrast, strongly VIP ir-perikarya were widely distributed within the SCN and gave rise to a dense network of fibres extending within the periventricular (peVA) and subparaventricular (subPVA) areas. Weakly GRP ir-perikarya were also observed in the median part of the SCN. Dual IHC revealed that the magnocellular neurons located just dorsal to the SCN, in the peVA and subPVA co-stored AVP with VIP, SOM or Met-ENK. The lack of SCN AVP and SOM ir-neurons, reported for the first time in a mammalian species, raises the question of their implication in the functions of the circadian pacemaker and its entrainment by the light/dark cycle in other species. The significance of the large neurons co-storing peptides in the terminal field of VIPergic fibres originating in the SCN has also to be determined. These results suggest that VIP could be of major importance in processing photic information mediating circadian entrainment and consequently annual rhythms.

  20. [Plant signaling peptides. Cysteine-rich peptides].

    PubMed

    Ostrowski, Maciej; Kowalczyk, Stanisław

    2015-01-01

    Recent bioinformatic and genetic analyses of several model plant genomes have revealed the existence of a highly abundant group of signaling peptides that are defined as cysteine-rich peptides (CRPs). CRPs are usually in size between 50 and 90 amino acid residues, they are positively charged, and they contain 4-16 cysteine residues that are important for the correct conformational folding. Despite the structural differences among CRP classes, members from each class have striking similarities in their molecular properties and function. The present review presents the recent progress in research on signaling peptides from several families including: EPF/EPFL, SP11/SCR, PrsS, RALF, LURE, and some other peptides belonging to CRP group. There is convincing evidence indicating multiple roles for these CRPs as signaling molecules during the plant life cycle, ranging from stomata development and patterning, self-incompatibility, pollen tube growth and guidance, reproductive processes, and nodule formation.

  1. Effect of grazing seedhead-suppressed tall fescue pasture on the vasoactivity of serotonin receptors

    USDA-ARS?s Scientific Manuscript database

    Previous research has demonstrated that exposure to ergot alkaloids reduces vasoactivity of serotonin (5HT) receptors. Chemical suppression of tall fescue seedhead production is a tool to reduce the level of exposure to ergot alkaloids by a grazing animal. Therefore, the objective was to evaluate co...

  2. 3D 14N/1H Double Quantum/1H Single Quantum Correlation Solid-State NMR for Probing Parallel and Anti-Parallel Beta-Sheet Arrangement of Oligo-Peptides at Natural Abundance.

    PubMed

    Hong, You-Lee; Asakura, Tetsuo; Nishiyama, Yusuke

    2018-05-08

    β-sheet structure of oligo- and poly-peptides can be formed in anti-parallel (AP)- and parallel (P)-structure, which is the important feature to understand the structures. In principle, P- and AP-β-sheet structures can be identified by the presence (AP) and absence (P) of the interstrand 1HNH/1HNH correlations on a diagonal in 2D 1H double quantum (DQ)/1H single quantum (SQ) spectrum due to the different interstrand 1HNH/1HNH distances between these two arrangements. However, the 1HNH/1HNH peaks overlap to the 1HNH3+/1HNH3+ peaks, which always give cross peaks regardless of the β-sheet arrangement. The 1HNH3+/1HNH3+ peaks disturb the observation of the presence/absence of 1HNH/1HNH correlations and the assignment of 1HNH and 1HNH3+ is not always available. Here, 3D 14N/1H DQ/1H SQ correlation solid-state NMR experiments at fast magic angle spinning (70 kHz) are introduced to distinguish AP and P β-sheet structure. The 14N dimension allows the separate observation of 1HNH/1HNH peaks from 1HNH3+/1HNH3+ peaks with clear assignment of 1HNH and 1HNH3+. In addition, the high natural abundance of 1H and 14N enables 3D 14N/1H DQ/1H SQ experiments of oligo-alanines (Ala3-6) in four hours without any isotope labelling. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. [Blood oxygen transport, prooxidant -- antioxidant status, and vasoactive characteristics of vascular endothelium in rats treated with endotoxin and taurine].

    PubMed

    Milosh, T S; Maksimovich, N E

    2014-01-01

    Experiments on a group of 74 pregnant rats upon intramuscular introduction of E. coli lipopolysaccharides during pregnancy revealed the correction effect of taurine on the blood oxygen transport function, prooxidant - antioxidant status, and vasoactive characteristics of vascular endothelium.

  4. Peptides as modifiers of Na+-induced pinocytosis in starved Amoeba proteus.

    PubMed

    Josefsson, J O; Johansson, P

    1985-01-01

    Low concentrations of six peptide hormones; glucagon, vasoactive intestinal peptide, substance P, angiotensin II, lysine-vasopressin, arginine-vasopressin, and the chemotactic peptide fMet-Leu-Phe, activated the capacity for pinocytosis in starved Amoeba proteus. Competitive inhibitors of the chemotactic peptide in leucocytes inhibited activation by fMet-Leu-Phe, suggesting that its action in the amoeba is mediated by specific receptors. The opioid peptides, beta-endorphin, dynorphin (1-13) and leu-enkephalin abolished through a naloxone-sensitive mechanism activation by hormones and several other activating agents. Also, low concentrations of beef and pork insulin inhibited activation by peptide hormones. An insulin analogue of low potency in mammalian cells was inactive in the amoeba. These results support the hypothesis that besides opioid receptors, there may be insulin receptors and possibly receptors for several other peptide hormones in Amoeba proteus.

  5. Effect of single dose of omeprazole on the gastrointestinal peptide response to food.

    PubMed

    Allen, J M; Adrian, T E; Webster, J; Howe, A; Bloom, S R

    1984-02-01

    The gastrointestinal peptide response to food was assessed in 6 healthy subjects following oral administration of 40 mg omeprazole. There was a small but statistically significant increase in basal plasma gastrin six hours after the dose of omeprazole, but the post-prandial plasma gastrin was not significantly increased. There was no significant effect on basal or post-prandial levels of somatostatin, insulin, pancreatic glucagon, enteroglucagon, gastric inhibitory polypeptide, pancreatic polypeptide, motilin, neurotensin, cholecystokinin, secretin, vasoactive intestinal peptide and gastrin-releasing peptide or blood glucose concentration.

  6. A Peptide Filtering Relation Quantifies MHC Class I Peptide Optimization

    PubMed Central

    Goldstein, Leonard D.; Howarth, Mark; Cardelli, Luca; Emmott, Stephen; Elliott, Tim; Werner, Joern M.

    2011-01-01

    Major Histocompatibility Complex (MHC) class I molecules enable cytotoxic T lymphocytes to destroy virus-infected or cancerous cells, thereby preventing disease progression. MHC class I molecules provide a snapshot of the contents of a cell by binding to protein fragments arising from intracellular protein turnover and presenting these fragments at the cell surface. Competing fragments (peptides) are selected for cell-surface presentation on the basis of their ability to form a stable complex with MHC class I, by a process known as peptide optimization. A better understanding of the optimization process is important for our understanding of immunodominance, the predominance of some T lymphocyte specificities over others, which can determine the efficacy of an immune response, the danger of immune evasion, and the success of vaccination strategies. In this paper we present a dynamical systems model of peptide optimization by MHC class I. We incorporate the chaperone molecule tapasin, which has been shown to enhance peptide optimization to different extents for different MHC class I alleles. Using a combination of published and novel experimental data to parameterize the model, we arrive at a relation of peptide filtering, which quantifies peptide optimization as a function of peptide supply and peptide unbinding rates. From this relation, we find that tapasin enhances peptide unbinding to improve peptide optimization without significantly delaying the transit of MHC to the cell surface, and differences in peptide optimization across MHC class I alleles can be explained by allele-specific differences in peptide binding. Importantly, our filtering relation may be used to dynamically predict the cell surface abundance of any number of competing peptides by MHC class I alleles, providing a quantitative basis to investigate viral infection or disease at the cellular level. We exemplify this by simulating optimization of the distribution of peptides derived from Human

  7. [Comparison of efficacy of different neurometabolic and vasoactive medicines in ischemic stroke patients's rehabilitation].

    PubMed

    Galkin, A S; Koval'chuk, V V; Gusev, A O

    2011-01-01

    The aim of present investigation is research of influence of vasoactive and neurometabolic medicines in stroke patients's rehabilitation. We had analysed 280 stroke patients. The degree of rehabilitation had been defined with the help of Barthel and Lindmark scales. The degree of cognitive functions's rehabilitation had been defined with the help of MMSE scale. For every medicine coefficients of efficiency were calculated. As the result of the present investigation the medicine's efficiency was found out. The most efficient medicines in ischaemic stroke patients's rehabilitation among the investigated ones are the medicines which activate the neuronal metabolism, first of all,--ceraxon (citicoline).

  8. Exploration of the immunoreactivity of the Traditional Chinese medicine Shenrouyangzhentang to vasoactive intestinal polypeptide

    PubMed Central

    Gu, Yu-Chun; Chen, De-Zhen

    1997-01-01

    AIM: To study the immunoreactivity of the Chinese medicine Shenrouyangzhentang to vasoactive intestinal polypeptide (VIP) and its therapeutic mechanism. METHODS: The immunoreactivity of the Chinese medicine Shenrouyangzhentang to VIP was detected in the plasma of 20 normal people and 20 patients with Piyinxu (Spleen Yin deficiency) using the radioimmunoassay (RIA) method. RESULTS: The maximum binding rate B0/T was 53.29%, the non-specific binding rate N0/T was 1.170%, and the VIP standard curve was Y = 0.81983 + 0.44319X - 0.28927X2, R2 = 0.990. The VIP content in Shenrouyangzhentang was 106.6 ng/L ± 20 ng/L), while it was 90.16 ng/L ± 15 ng/L in normal human plasma and 63.25 ng/L ± 11 ng/L in the plasma of Pixinxu patients. The difference between normal plasma and Pixinxu patient plasma was statistically significant (P < 0.05). CONCLUSION: The Chinese medicine Shenrouyangzhentang demonstrated VIP immunoreactivity similar to that of normal plasma. The (vasoactive intestinal polypeptide) VIP content in Pixinxu patient plasma was lower than that in healthy subjects (P < 0.05). PMID:27041949

  9. Robust linear parameter-varying control of blood pressure using vasoactive drugs

    NASA Astrophysics Data System (ADS)

    Luspay, Tamas; Grigoriadis, Karolos

    2015-10-01

    Resuscitation of emergency care patients requires fast restoration of blood pressure to a target value to achieve hemodynamic stability and vital organ perfusion. A robust control design methodology is presented in this paper for regulating the blood pressure of hypotensive patients by means of the closed-loop administration of vasoactive drugs. To this end, a dynamic first-order delay model is utilised to describe the vasoactive drug response with varying parameters that represent intra-patient and inter-patient variability. The proposed framework consists of two components: first, an online model parameter estimation is carried out using a multiple-model extended Kalman-filter. Second, the estimated model parameters are used for continuously scheduling a robust linear parameter-varying (LPV) controller. The closed-loop behaviour is characterised by parameter-varying dynamic weights designed to regulate the mean arterial pressure to a target value. Experimental data of blood pressure response of anesthetised pigs to phenylephrine injection are used for validating the LPV blood pressure models. Simulation studies are provided to validate the online model estimation and the LPV blood pressure control using phenylephrine drug injection models representing patients showing sensitive, nominal and insensitive response to the drug.

  10. Neural vasodilator control in the rectum of the cat and its possible mediation by vasoactive intestinal polypeptide.

    PubMed Central

    Andersson, P O; Bloom, S R; Edwards, A V; Järhult, J; Mellander, S

    1983-01-01

    Vascular and motor responses in the rectum to pelvic nerve stimulation are described in the anaesthetized cat and compared with corresponding effects observed in the colon. The responses comprise a cholinergic and a non-cholinergic component, and an attempt has been made to elucidate the latter. Pelvic nerve stimulation evoked a pronounced and well maintained vasodilator response in the rectum whereas that in the colon was transient. Maximal vasodilatation occurred at much lower stimulus frequencies in the rectum (2-4 Hz) than it did in the colon (8-16 Hz) and maximal blood flow under these conditions was also greater in the rectum (greater than 200 ml 100 g-1 min-1) than the colon (less than 150 ml 100 g-1 min-1). Muscarinic blockade further curtailed the colonic vasodilator response to pelvic nerve stimulation, whereas the rectal dilatation was only slightly reduced in the presence of atropine. Pelvic nerve stimulation caused a substantial release of vasoactive intestinal polypeptide (VIP) from the rectum, which was related both in magnitude and duration to the vasodilatation. Intra-arterial infusions of VIP, which reproduced this rise in rectal venous VIP concentration, caused a rectal vasodilator response which closely resembled that during pelvic nerve stimulation after cholinergic blockade. The rectal vasculature was estimated to be 50-100 times more sensitive to VIP than the colonic vasculature. VIP therefore seems to be the most likely putative neurotransmitter responsible for non-cholinergic rectal vasodilatation. Stimulation of the pelvic nerves also caused rapid contractile motor responses before, and more gradual motor responses after, muscarinic blockade in both the colon and rectum, in the latter preceded by a non-cholinergic relaxation. These patterns of motor activity largely confirm previous results. Infusions of substance P effectively mimicked the non-cholinergic contractile motor responses but failed to demonstrate significant release of this

  11. Extracts of Crataegus oxyacantha and Rosmarinus officinalis Attenuate Ischemic Myocardial Damage by Decreasing Oxidative Stress and Regulating the Production of Cardiac Vasoactive Agents.

    PubMed

    Cuevas-Durán, Raúl Enrique; Medrano-Rodríguez, Juan Carlos; Sánchez-Aguilar, María; Soria-Castro, Elizabeth; Rubio-Ruíz, María Esther; Del Valle-Mondragón, Leonardo; Sánchez-Mendoza, Alicia; Torres-Narvaéz, Juan Carlos; Pastelín-Hernández, Gustavo; Ibarra-Lara, Luz

    2017-11-14

    Numerous studies have supported a role for oxidative stress in the development of ischemic damage and endothelial dysfunction. Crataegus oxyacantha ( Co ) and Rosmarinus officinalis ( Ro ) extracts are polyphenolic-rich compounds that have proven to be efficient in the treatment of cardiovascular diseases. We studied the effect of extracts from Co and Ro on the myocardial damage associated with the oxidative status and to the production of different vasoactive agents. Rats were assigned to the following groups: (a) sham; (b) vehicle-treated myocardial infarction (MI) (MI-V); (c) Ro extract-treated myocardial infarction (MI- Ro ); (d) Co extract-treated myocardial infarction (MI- Co ); or (e) Ro+Co -treated myocardial infarction (MI- Ro+Co ). Ro and Co treatments increased total antioxidant capacity, the expression of superoxide dismutase (SOD)-Cu 2+ /Zn 2+ , SOD-Mn 2+ , and catalase, with the subsequent decline of malondialdehyde and 8-hydroxy-2'-deoxyguanosine levels. The extracts diminished vasoconstrictor peptide levels (angiotensin II and endothelin-1), increased vasodilators agents (angiotensin 1-7 and bradikinin) and improved nitric oxide metabolism. Polyphenol treatment restored the left intraventricular pressure and cardiac mechanical work. We conclude that Ro and Co treatment attenuate morphological and functional ischemic-related changes by both an oxidant load reduction and improvement of the balance between vasoconstrictors and vasodilators.

  12. Extracts of Crataegus oxyacantha and Rosmarinus officinalis Attenuate Ischemic Myocardial Damage by Decreasing Oxidative Stress and Regulating the Production of Cardiac Vasoactive Agents

    PubMed Central

    Cuevas-Durán, Raúl Enrique; Medrano-Rodríguez, Juan Carlos; Sánchez-Aguilar, María; Soria-Castro, Elizabeth; Del Valle-Mondragón, Leonardo; Sánchez-Mendoza, Alicia; Torres-Narvaéz, Juan Carlos; Pastelín-Hernández, Gustavo; Ibarra-Lara, Luz

    2017-01-01

    Numerous studies have supported a role for oxidative stress in the development of ischemic damage and endothelial dysfunction. Crataegus oxyacantha (Co) and Rosmarinus officinalis (Ro) extracts are polyphenolic-rich compounds that have proven to be efficient in the treatment of cardiovascular diseases. We studied the effect of extracts from Co and Ro on the myocardial damage associated with the oxidative status and to the production of different vasoactive agents. Rats were assigned to the following groups: (a) sham; (b) vehicle-treated myocardial infarction (MI) (MI-V); (c) Ro extract-treated myocardial infarction (MI-Ro); (d) Co extract-treated myocardial infarction (MI-Co); or (e) Ro+Co-treated myocardial infarction (MI-Ro+Co). Ro and Co treatments increased total antioxidant capacity, the expression of superoxide dismutase (SOD)-Cu2+/Zn2+, SOD-Mn2+, and catalase, with the subsequent decline of malondialdehyde and 8-hydroxy-2′-deoxyguanosine levels. The extracts diminished vasoconstrictor peptide levels (angiotensin II and endothelin-1), increased vasodilators agents (angiotensin 1–7 and bradikinin) and improved nitric oxide metabolism. Polyphenol treatment restored the left intraventricular pressure and cardiac mechanical work. We conclude that Ro and Co treatment attenuate morphological and functional ischemic-related changes by both an oxidant load reduction and improvement of the balance between vasoconstrictors and vasodilators. PMID:29135932

  13. Expression and GTP sensitivity of peptide histidine isoleucine high-affinity-binding sites in rat.

    PubMed

    Debaigt, Colin; Meunier, Annie-Claire; Goursaud, Stephanie; Montoni, Alicia; Pineau, Nicolas; Couvineau, Alain; Laburthe, Marc; Muller, Jean-Marc; Janet, Thierry

    2006-07-01

    High-affinity-binding sites for the vasoactive intestinal peptide (VIP) analogs peptide histidine/isoleucine-amide (PHI)/carboxyterminal methionine instead of isoleucine (PHM) are expressed in numerous tissues in the body but the nature of their receptors remains to be elucidated. The data presented indicate that PHI discriminated a high-affinity guanosine 5'-triphosphate (GTP)-insensitive-binding subtype that represented the totality of the PHI-binding sites in newborn rat tissues but was differentially expressed in adult animals. The GTP-insensitive PHI/PHM-binding sites were also observed in CHO cells over expressing the VPAC2 but not the VPAC1 VIP receptor.

  14. Responses of python gastrointestinal regulatory peptides to feeding

    PubMed Central

    Secor, Stephen M.; Fehsenfeld, Drew; Diamond, Jared; Adrian, Thomas E.

    2001-01-01

    In the Burmese python (Python molurus), the rapid up-regulation of gastrointestinal (GI) function and morphology after feeding, and subsequent down-regulation on completing digestion, are expected to be mediated by GI hormones and neuropeptides. Hence, we examined postfeeding changes in plasma and tissue concentrations of 11 GI hormones and neuropeptides in the python. Circulating levels of cholecystokinin (CCK), glucose-dependent insulinotropic peptide (GIP), glucagon, and neurotensin increase by respective factors of 25-, 6-, 6-, and 3.3-fold within 24 h after feeding. In digesting pythons, the regulatory peptides neurotensin, somatostatin, motilin, and vasoactive intestinal peptide occur largely in the stomach, GIP and glucagon in the pancreas, and CCK and substance P in the small intestine. Tissue concentrations of CCK, GIP, and neurotensin decline with feeding. Tissue distributions and molecular forms (as determined by gel-permeation chromatography) of many python GI peptides are similar or identical to those of their mammalian counterparts. The postfeeding release of GI peptides from tissues, and their concurrent rise in plasma concentrations, suggests that they play a role in regulating python-digestive responses. These large postfeeding responses, and similarities of peptide structure with mammals, make pythons an attractive model for studying GI peptides. PMID:11707600

  15. Oligonucleotide DNA microarray profiling of lung adenocarcinoma revealed significant downregulation and deletions of vasoactive intestinal peptide receptor 1.

    PubMed

    Mlakar, Vid; Strazisar, Mojca; Sok, Mihael; Glavac, Damjan

    2010-06-01

    The purpose of this study was to find novel gene(s) involved in the development of lung adenocarcinoma (AD). Using DNA microarrays, we identified 31 up-regulated and 8 downregulated genes in 12 AD. Real time PCR was used to measure expression of VIPR1 and SPP1 mRNA and possible losses or gains of genes in 32 AD. We describe significant upregulation of the SPP1 gene, downregulation of VIPR1, and losses of the VIPR1 gene. Our findings complement a proposed VIPR1 tumor suppressor role, in which deletions in the 3p22 chromosome region are an important mechanism leading to loss of the VIPR1 gene.

  16. Expression of vasoactive proteins in gastric antral mucosa reflects vascular dysfunction in patients with cirrhosis and portal hypertension.

    PubMed

    Trebicka, Jonel; Wix, Cyrus; von Heydebrand, Matthias; Hittatiya, Kanishka; Reiberger, Thomas; Klein, Sabine; Schierwagen, Robert; Kristiansen, Glen; Peck-Radosavljevic, Markus; Fischer, Hans-Peter; Møller, Søren; Bendtsen, Flemming; Krag, Aleksander; Sauerbruch, Tilman

    2015-04-01

    Patients with cirrhosis display hypocontractility of splanchnic vessels because of dysregulation of vasoactive proteins, such as decreased effect of RhoA/ROCK and increased activity of β-Arrestin-2 and eNOS. However, it is unknown whether the dysregulation of vasoactive proteins is displayed in other vessels. We investigated whether expression of vasoactive proteins can be evaluated in gastric mucosa vessels. Biopsies from the gastric mucosa of 111 patients with cirrhosis were collected at three different centres and from 13 controls. Forty-nine patients had received TIPS. Portal pressure gradient was measured in 49 patients with TIPS and in 16 patients without TIPS. Biopsies from the antrum were conserved in formaldehyde for immunohistochemistry or shock-frozen for PCR and Western blot. The mucosal transcription of vascular markers (αSMA, CD31) was higher in cirrhotic patients than controls, which was confirmed by immunohistochemistry. On average, relative mucosal levels of RhoA and ROCK were lower, while β-Arrestin-2 levels were higher in cirrhotic patients compared to controls. Transcriptional levels of eNOS increased with presence of ascites and grade of oesophageal varices. Patients with TIPS showed less pronounced markers of vascular dysfunction in gastric mucosa. This is the first evidence that the expression of vasoactive proteins in mucosa from the gastric antrum of patients with cirrhosis reflects their vascular dysfunction and possibly changes after therapeutic interventions. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Sacubitril/valsartan: beyond natriuretic peptides.

    PubMed

    Singh, Jagdeep S S; Burrell, Louise M; Cherif, Myriam; Squire, Iain B; Clark, Andrew L; Lang, Chim C

    2017-10-01

    Natriuretic peptides, especially B-type natriuretic peptide (BNP), have primarily been regarded as biomarkers in heart failure (HF). However, they are also possible therapeutic agents due to their potentially beneficial physiological effects. The angiotensin receptor-neprilysin inhibitor, sacubitril/valsartan, simultaneously augments the natriuretic peptide system (NPS) by inhibiting the enzyme neprilysin (NEP) and inhibits the renin-angiotensin-aldosterone system (RAAS) by blocking the angiotensin II receptor. It has been shown to improve mortality and hospitalisation outcomes in patients with HF due to left ventricular systolic dysfunction. The key advantage of sacubitril/valsartan has been perceived to be its ability to augment BNP, while its other effects have largely been overlooked. This review highlights the important effects of sacubitril/valsartan, beyond just the augmentation of BNP. First we discuss how NPS physiology differs between healthy individuals and those with HF by looking at mechanisms like the overwhelming effects of RAAS on the NPS, natriuretic peptide receptor desensitisation and absolute natriuretic deficiency. Second, this review explores other hormones that are augmented by sacubitril/valsartan such as bradykinin, substance P and adrenomedullin that may contribute to the efficacy of sacubitril/valsartan in HF. We also discuss concerns that sacubitril/valsartan may interfere with amyloid-β homeostasis with potential implications on Alzheimer's disease and macular degeneration. Finally, we explore the concept of 'autoinhibition' which is a recently described observation that humans have innate NEP inhibitory capability when natriuretic peptide levels rise above a threshold. There is speculation that autoinhibition may provide a surge of natriuretic and other vasoactive peptides to rapidly reverse decompensation. We contend that by pre-emptively inhibiting NEP, sacubitril/valsartan is inducing this surge earlier during decompensation

  18. Purification and structural characterization of vasoactive intestinal polypeptide from the trout and bowfin.

    PubMed

    Wang, Y; Conlon, J M

    1995-04-01

    Vasoactive intestinal polypeptide (VIP) was purified from extracts of the stomachs of the rainbow trout, Oncorhynchus mykiss, and the bowfin, Amia calva. The primary structure of VIP from both species was the same: His-Ser-Asp-Ala-Ile-Phe-Thr-Asp-Asn-Tyr10- Ser-Arg-Phe-Arg-Lys-Gln-Met-Ala-Val-Lys20-Lys-Tyr-Leu-Asn-Ser-Val- Leu-Thr. This amino acid sequence shows only one amino acid substitution (Val5-->Ile) compared with the common sequence of VIP from the chicken, alligator, and European green frog. The structural identity of VIP from the trout and bowfin is consistent with the close phylogenetic relationship between the Salmoniformes and the Amiiformes and the data indicate that pressure to conserve the complete primary structure of VIP during vertebrate evolution has been very strong.

  19. Clinicopathological study of pancreatic and ganglioneuroblastoma tumours secreting vasoactive intestinal polypeptide (vipomas).

    PubMed

    Long, R G; Bryant, M G; Mitchell, S J; Adrian, T E; Polak, J M; Bloom, S R

    1981-05-30

    During a six-year period (1973-9) 52 patients with pancreatic tumours and 10 with ganglioneuroblastomas were found to have raised plasma vasoactive intestinal polypeptide (VIP) concentrations. All the patients had severe secretory diarrhoea, weight loss, dehydration, hypokalaemic acidosis, and a raised plasma urea concentration. Reduced gastric acid secretion was seen in 72% of patients. Plasma VIP concentrations were not raised in patients with diarrhoea due to other types of tumour or disease or in hormone-secreting tumours not associated with diarrhoea. Plasma VIP measurement may therefore give clinical guidance in a patient with persistent watery diarrhoea and hypokalaemic acidosis. Surgical excision was clearly the treatment of choice, but metastatic pancreatic tumours usually responded to streptozotocin.

  20. Clinicopathological study of pancreatic and ganglioneuroblastoma tumours secreting vasoactive intestinal polypeptide (vipomas).

    PubMed Central

    Long, R G; Bryant, M G; Mitchell, S J; Adrian, T E; Polak, J M; Bloom, S R

    1981-01-01

    During a six-year period (1973-9) 52 patients with pancreatic tumours and 10 with ganglioneuroblastomas were found to have raised plasma vasoactive intestinal polypeptide (VIP) concentrations. All the patients had severe secretory diarrhoea, weight loss, dehydration, hypokalaemic acidosis, and a raised plasma urea concentration. Reduced gastric acid secretion was seen in 72% of patients. Plasma VIP concentrations were not raised in patients with diarrhoea due to other types of tumour or disease or in hormone-secreting tumours not associated with diarrhoea. Plasma VIP measurement may therefore give clinical guidance in a patient with persistent watery diarrhoea and hypokalaemic acidosis. Surgical excision was clearly the treatment of choice, but metastatic pancreatic tumours usually responded to streptozotocin. PMID:6786616

  1. Endosomolytic Nano-Polyplex Platform Technology for Cytosolic Peptide Delivery To Inhibit Pathological Vasoconstriction.

    PubMed

    Evans, Brian C; Hocking, Kyle M; Kilchrist, Kameron V; Wise, Eric S; Brophy, Colleen M; Duvall, Craig L

    2015-06-23

    A platform technology has been developed and tested for delivery of intracellular-acting peptides through electrostatically complexed nanoparticles, or nano-polyplexes, formulated from an anionic endosomolytic polymer and cationic therapeutic peptides. This delivery platform has been initially tested and optimized for delivery of two unique vasoactive peptides, a phosphomimetic of heat shock protein 20 and an inhibitor of MAPKAP kinase II, to prevent pathological vasoconstriction (i.e., vasospasm) in human vascular tissue. These peptides inhibit vasoconstriction and promote vasorelaxation by modulating actin dynamics in vascular smooth muscle cells. Formulating these peptides into nano-polyplexes significantly enhances peptide uptake and retention, facilitates cytosolic delivery through a pH-dependent endosomal escape mechanism, and enhances peptide bioactivity in vitro as measured by inhibition of F-actin stress fiber formation. In comparison to treatment with the free peptides, which were endowed with cell-penetrating sequences, the nano-polyplexes significantly increased vasorelaxation, inhibited vasoconstriction, and decreased F-actin formation in the human saphenous vein ex vivo. These results suggest that these formulations have significant potential for treatment of conditions such as cerebral vasospasm following subarachnoid hemorrhage. Furthermore, because many therapeutic peptides include cationic cell-penetrating segments, this simple and modular platform technology may have broad applicability as a cost-effective approach for enhancing the efficacy of cytosolically active peptides.

  2. Peptide identification

    DOEpatents

    Jarman, Kristin H [Richland, WA; Cannon, William R [Richland, WA; Jarman, Kenneth D [Richland, WA; Heredia-Langner, Alejandro [Richland, WA

    2011-07-12

    Peptides are identified from a list of candidates using collision-induced dissociation tandem mass spectrometry data. A probabilistic model for the occurrence of spectral peaks corresponding to frequently observed partial peptide fragment ions is applied. As part of the identification procedure, a probability score is produced that indicates the likelihood of any given candidate being the correct match. The statistical significance of the score is known without necessarily having reference to the actual identity of the peptide. In one form of the invention, a genetic algorithm is applied to candidate peptides using an objective function that takes into account the number of shifted peaks appearing in the candidate spectrum relative to the test spectrum.

  3. Effect of peptide histidine valine on cardiovascular and respiratory function in normal subjects.

    PubMed Central

    Chilvers, E R; Dixon, C M; Yiangou, Y; Bloom, S R; Ind, P W

    1988-01-01

    Non-adrenergic inhibitory nerves may have an important role in regulating airway calibre. A recently discovered peptide, peptide histidine valine, is a potent relaxer of airway smooth muscle in vitro and has been proposed as a possible neurotransmitter in this tissue. The cardiovascular and respiratory effects of graded infusions of this peptide (2.5-10 pmol kg-1 min-1) have been examined in six normal subjects in a placebo controlled, randomised double blind study. The mean (SEM) peak plasma concentration of peptide histidine valine during the highest infusion rate was 2392 (170) pmol/l, representing a 29 fold increase above the basal concentration. This was accompanied by flushing, a significant increase in heart rate of 28 (3.7) beats/min and skin temperature of 1.8 degrees (0.16 degrees) C, but no effect on systolic or diastolic blood pressure. Despite these high plasma concentrations of the peptide and the substantial tachycardia and increase in skin blood flow, there was no change in partial expiratory flow at 40% of vital capacity (Vp40) or in the airway response to inhaled histamine (geometric PD40 9.37 and 9.73 mumol during saline and peptide histidine valine infusion respectively). Although these findings provide no support for a physiological role of peptide histidine valine in controlling airway function in healthy subjects, important effects of locally released peptides in the vasoactive intestinal peptide family cannot be excluded. PMID:3206383

  4. Effect of peptide histidine valine on cardiovascular and respiratory function in normal subjects.

    PubMed

    Chilvers, E R; Dixon, C M; Yiangou, Y; Bloom, S R; Ind, P W

    1988-10-01

    Non-adrenergic inhibitory nerves may have an important role in regulating airway calibre. A recently discovered peptide, peptide histidine valine, is a potent relaxer of airway smooth muscle in vitro and has been proposed as a possible neurotransmitter in this tissue. The cardiovascular and respiratory effects of graded infusions of this peptide (2.5-10 pmol kg-1 min-1) have been examined in six normal subjects in a placebo controlled, randomised double blind study. The mean (SEM) peak plasma concentration of peptide histidine valine during the highest infusion rate was 2392 (170) pmol/l, representing a 29 fold increase above the basal concentration. This was accompanied by flushing, a significant increase in heart rate of 28 (3.7) beats/min and skin temperature of 1.8 degrees (0.16 degrees) C, but no effect on systolic or diastolic blood pressure. Despite these high plasma concentrations of the peptide and the substantial tachycardia and increase in skin blood flow, there was no change in partial expiratory flow at 40% of vital capacity (Vp40) or in the airway response to inhaled histamine (geometric PD40 9.37 and 9.73 mumol during saline and peptide histidine valine infusion respectively). Although these findings provide no support for a physiological role of peptide histidine valine in controlling airway function in healthy subjects, important effects of locally released peptides in the vasoactive intestinal peptide family cannot be excluded.

  5. Inflammatory and Vasoactive Effects of Serum Following Inhalation of Varied Complex Mixtures.

    PubMed

    Aragon, Mario J; Chrobak, Izabela; Brower, Jeremy; Roldan, Luis; Fredenburgh, Laura E; McDonald, Jacob D; Campen, Matthew J

    2016-04-01

    Chronic cardiovascular disease is associated with air pollution exposure in epidemiology and toxicology studies. Inhaled toxicants can induce changes in serum bioactivity that impact endothelial inflammatory gene expression in vitro and impair vasorelaxation ex vivo, which are common precursors to atherosclerosis. Comparisons between single pollutants and common combustion mixtures, in terms of driving such serum inflammatory and vasoactive effects, have not been characterized. Healthy C57BL/6 mice were exposed to a single 6-h period of contrasting pollutant atmospheres: road dust, mixed vehicle emissions (MVE; a combination of gasoline and diesel engine emissions) particulate matter, mixed vehicle emissions gases, road dust plus ozone, road dust plus MVE, and hardwood smoke. Serum obtained from mice 24 h after these exposures was used as a stimulus to assess inflammatory potential in two assays: incubated with primary murine cerebrovascular endothelial cells for 4 h to measure inflammatory gene expression or applied to naïve aortic rings in an ex vivo myographic preparation. Road dust and wood smoke exposures were most potent at inducing inflammatory gene expression, while MVE atmospheres and wood smoke were most potent at impairing vasorelaxation to acetylcholine. Responses are consistent with recent reports on MVE toxicity, but reveal novel serum bioactivity related to wood smoke and road dust. These studies suggest that the compositional changes in serum and resultant bioactivity following inhalation exposure to pollutants may be highly dependent on the composition of mixtures.

  6. Mediation of the vasoactive properties of diadenosine tetraphosphate via various purinoceptors.

    PubMed

    van der Giet, M; Jankowski, J; Schlüter, H; Zidek, W; Tepel, M

    1998-12-01

    The vasoactive properties of P1,P4-diadenosine tetraphosphate (Ap4A) were studied by measuring the effects of perfusion pressure of a rat isolated perfused kidney. The vasoconstrictive response to Ap4A was mediated to a large extent to a P2X receptor which could be shown by inhibition with pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid tetrasodium. The remaining vasoconstriction of Ap4A could be blocked by a 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective A1 receptor antagonist In raised tone preparation Ap4A evoked vasodilation when P2 receptors were blocked by suramin. The dilation was not mediated by a P2Y receptor as the effect could not be blocked by suramin. Ap4A induces vasoconstriction via A1 and P2X receptors and vasodilatation via an unidentified receptor which is not a P2Y receptor. Ap4A may play an important role in kidney perfusion and, thus, in blood-pressure control.

  7. ATP: a vasoactive signal in the pericyte-containing microvasculature of the rat retina

    PubMed Central

    Kawamura, Hajime; Sugiyama, Tetsuya; Wu, David M; Kobayashi, Masato; Yamanishi, Shigeki; Katsumura, Kozo; Puro, Donald G

    2003-01-01

    In this study we tested the hypothesis that extracellular ATP regulates the function of the pericyte-containing retinal microvessels. Pericytes, which are more numerous in the retina than in any other tissue, are abluminally located cells that may adjust capillary perfusion by contracting and relaxing. At present, knowledge of the vasoactive molecules that regulate pericyte function is limited. Here, we focused on the actions of extracellular ATP because this nucleotide is a putative glial-to-vascular signal, as well as being a substance released by activated platelets and injured cells. In microvessels freshly isolated from the adult rat retina, we monitored ionic currents via perforated-patch pipettes, measured intracellular calcium levels with the use of fura-2, and visualized microvascular contractions with the aid of time-lapse photography. We found that ATP induced depolarizing changes in the ionic currents, increased calcium levels and caused pericytes to contract. P2X7 receptors and UTP-activated receptors mediated these effects. Consistent with ATP serving as a vasoconstrictor for the pericyte-containing microvasculature of the retina, the microvascular lumen narrowed when an adjacent pericyte contracted. In addition, the sustained activation of P2X7 receptors inhibited cell-to-cell electrotonic transmission within the microvascular networks. Thus, ATP not only affects the contractility of individual pericytes, but also appears to regulate the spatial and temporal dynamics of the vasomotor response. PMID:12876212

  8. The interaction of vasoactive substances during exercise modulates platelet aggregation in hypertension and coronary artery disease

    PubMed Central

    Petidis, Konstantinos; Douma, Stella; Doumas, Michael; Basagiannis, Ilias; Vogiatzis, Konstantinos; Zamboulis, Chrysanthos

    2008-01-01

    Background Acute vigorous exercise, associated with increased release of plasma catecholamines, transiently increases the risk of primary cardiac arrest. We tested the effect of acute submaximal exercise on vasoactive substances and their combined result on platelet function. Methods Healthy volunteers, hypertensive patients and patients with coronary artery disease (CAD) performed a modified treadmill exercise test. We determined plasma catecholamines, thromboxane A2, prostacyclin, endothelin-1 and platelet aggregation induced by adenosine diphosphate (ADP) and collagen at rest and during exercise. Results Our results during exercise showed a) platelet activation (increased thromboxane B2, TXB2), b) increased prostacyclin release from endothelium and c) decreased platelet aggregation in all groups, significantly more in healthy volunteers than in patients with CAD (with hypertensives lying in between these two groups). Conclusion Despite the pronounced activation of Sympathetic Nervous System (SNS) and increased TXB2 levels during acute exercise platelet aggregation decreases, possibly to counterbalance the prothrombotic state. Since this effect seems to be mediated by the normal endothelium (through prostacyclin and nitric oxide), in conditions characterized by endothelial dysfunction (hypertension, CAD) reduced platelet aggregation is attenuated, thus posing such patients in increased risk for thrombotic complications. PMID:18505546

  9. HBOC vasoactivity: interplay between nitric oxide scavenging and capacity to generate bioactive nitric oxide species.

    PubMed

    Cabrales, Pedro; Friedman, Joel M

    2013-06-10

    Despite many advances in blood substitute research, the development of materials that are effective in maintaining blood volume and oxygen delivery remains a priority for emergency care and trauma. Clinical trials on hemoglobin (Hb)-based oxygen carriers (HBOCs) have not provided information on the mechanism of toxicity, although all commercial formulations have safety concerns. Specifically, it is important to reconcile the different hypotheses of Hb toxicity, such as nitric oxide (NO) depletion and oxidative reactions, to provide a coherent molecular basis for designing a safe HBOC. HBOCs with different sizes often exhibit differences in the degree of HBOC-induced vasoactivity. This has been attributed to differences in the degree of NO scavenging and in the extent of Hb extravasation. Additionally, it is appears that Hb can undergo reactions that compensate for NO scavenging by generating bioactive forms of NO. Engineering modifications to enhance bioactive NO production can result in diminished oxygen delivery by virtue of increased oxygen affinity. This strategy can prevent the HBOC from fulfilling the intended goal on preserving oxygenation; however, the NO production effects will increase perfusion and oxygen transport. Hb modifications influence NO scavenging and the capacity of certain HBOCs to compensate for NO scavenging through nitrite-mediated reactions that generate bioactive NO. Based on the current understanding of these NO-related factors, possible synthetic strategies are presented that address how HBOC formulations can be prepared that: (i) effectively deliver oxygen, (ii) maintain tissue perfusion, and (iii) limit/reverse underlying inflammation within the vasculature.

  10. Role of pulmonary diseases and physical condition in the regulation of vasoactive hormones.

    PubMed

    Hietanen, E; Marniemi, J; Liippo, K; Seppänen, A; Hartiala, J; Viinamäki, O

    1988-12-01

    Lungs have many non-respiratory metabolic functions, of which some take place in the capillary endothelium, while others are in parenchymal lung tissue. We have studied the role of the lungs in the metabolism of vasoactive and some other hormones by comparing patients who have undergone lung resection to those having various obstructive or fibrotic lung diseases. We have also compared these groups with persons in good physical health. The data suggested that lung resection patients had low angiotensin II levels in plasma but the response of angiotensin II to exercise was normal. Also adrenalin concentration was low in the lung resection group while dopamine did not show any significant difference between the groups. When hormone levels were correlated to the exercise data, renin levels were especially related to physical condition. Serum post-exercise renin values were inversely related to the uneven distribution of lung perfusion, possibly thus reflecting the diminished pulmonary vascularization. A negative association was found between angiotensin II and diffusion capacity. Thus, the angiotensin II levels may preferably be controlled by the non-circulatory functions of the lungs.

  11. pH-driven colloidal transformations based on the vasoactive drug nicergoline.

    PubMed

    Salentinig, Stefan; Tangso, Kristian J; Hawley, Adrian; Boyd, Ben J

    2014-12-16

    The structure of colloidal self-assembled drug delivery systems can be influenced by intermolecular interactions between drug and amphiphilic molecules, and is important to understand in the context of designing improved delivery systems. Controlling these structures can enable controlled or targeted release systems for poorly water-soluble drugs. Here we present the interaction of the hydrophobic vasoactive drug nicergoline with the internal structure of nanostructured emulsion particles based on the monoglyceride-water system. Addition of this drug leads to modification of the internal bicontinuous cubic structure to generate highly pH-responsive systems. The colloidal structures were characterized with small-angle X-ray scattering and visualized using cryogenic transmission electron microscopy. Reversible transformations to inverse micelles at high pH, vesicles at low pH, and the modification of the spacing of the bicontinuous cubic structure at intermediate pH were observed, and enabled the in situ determination of an apparent pKa for the drug in this system--a difficult task using solution-based approaches. The characterization of this phase behavior is also highly interesting for the design of pH-responsive controlled release systems for poorly water-soluble drug molecules.

  12. Active immunization against vasoactive intestinal polypeptide decreases neuronal recruitment and inhibits reproduction in zebra finches.

    PubMed

    Vistoropsky, Yulia; Heiblum, Rachel; Smorodinsky, Nechama-Ina; Barnea, Anat

    2016-08-15

    Neurogenesis and neuronal recruitment occur in adult brains of many vertebrates, and the hypothesis is that these phenomena contribute to the brain plasticity that enables organisms to adjust to environmental changes. In mammals, vasoactive intestinal polypeptide (VIP) is known to have many neuroprotective properties, but in the avian brain, although widely distributed, its role in neuronal recruitment is not yet understood. In the present study we actively immunized adult zebra finches against VIP conjugated to KLH and compared neuronal recruitment in their brains, with brains of control birds, which were immunized against KLH. We looked at two forebrain regions: the nidopallium caudale (NC), which plays a role in vocal communication, and the hippocampus (HC), which is involved in the processing of spatial information. Our data demonstrate that active immunization against VIP reduces neuronal recruitment, inhibits reproduction, and induces molting, with no change in plasma prolactin levels. Thus, our observations suggest that VIP has a direct positive role in neuronal recruitment and reproduction in birds. J. Comp. Neurol. 524:2516-2528, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Pathophysiology, prognostic significance and clinical utility of B-type natriuretic peptide in acute coronary syndromes.

    PubMed

    Wiviott, Stephen D; de Lemos, James A; Morrow, David A

    2004-08-16

    The natriuretic hormones are a family of vasoactive peptides that can be measured circulating in the blood. Because they serve as markers of hemodynamic stress, the major focus of the use of natriuretic peptide levels [predominantly B-type natriuretic peptide (BNP) and N-terminal (NT)-pro-BNP] has been as an aid to the clinical diagnosis and management of congestive heart failure (CHF). Recently, however, the measurement of natriuretic peptides in the acute coronary syndromes (ACS) has been shown to provide information complementary to traditional biomarkers (of necrosis) such as cardiac troponins and creatine kinase (CK). Studies in several types of acute coronary syndromes [ST-segment elevation myocardial infarction (STEMI), non-ST elevation MI (NSTEMI) and unstable angina (UA)] have shown that elevated levels of natriuretic peptides are independently associated with adverse outcomes, particularly mortality. Additional information is obtained from the use natriuretic peptides in combination with other markers of risk including biomarkers of necrosis and inflammation. This review will summarize the scientific rationale and clinical evidence supporting measurement of natriuretic peptides for risk stratification in acute coronary syndromes. Future research is needed to identify therapies of particular benefit for patients with ACS and natriuretic peptide elevation.

  14. Haemodynamic effects of vasoactive agents following chronic state of high cardiac output in anaesthetized rats.

    PubMed

    Guo, Liang; Tabrizchi, Reza

    2008-05-31

    The arteriovenous fistula model of circulation can produce a high output and low peripheral resistance situation. Here, we have examined the effects of noradrenaline, vasopressin and sodium nitroprusside on cardiac index, mean arterial blood pressure, venous tone, resistance to venous return, arterial resistance, and blood volume in chronically shunted anaesthetized rats. The cardiac index of rats with chronic arteriovenous fistula (AVF) was significantly higher (36.65+/-2.28 ml/min per 100 g; (mean+/-S.E.M.; n=24) in comparison to sham-operated rats (20.04+/-0.86 ml/min per 100 g; mean+/-S.E.M.; n=8). Cardiac index did not significantly change during the infusion of noradrenaline (1.0, 3.0 and 10 microg/kg per min), vasopressin (10, 30, 100 ng/kg per min) or sodium nitroprusside (0.1, 0.3 and 1.0 microg/kg per min) compared to saline infusion in AVF animals. Infusion of noradrenaline significantly increased heart rate, dP/dt, mean circulatory filling pressure (Pmcf) and resistance to venous return without affecting mean arterial blood pressure when compared to saline infusion. Administration of vasopressin significantly increased dP/dt, mean arterial blood pressure, and Pmcf without affecting heart rate, resistance to venous return or arterial resistance compared to saline infusion. Infusion of sodium nitroprusside did not significantly affect any haemodynamic parameter measured when compared to saline infusion. The results indicate that the presence of chronic AVF alters responsiveness of the various segments of the circulatory system to vasoactive agents. Moreover, it produces a major impediment to overall changes that can normally be induced following the infusion of such agents.

  15. HBOC Vasoactivity: Interplay Between Nitric Oxide Scavenging and Capacity to Generate Bioactive Nitric Oxide Species

    PubMed Central

    Friedman, Joel M.

    2013-01-01

    Abstract Significance: Despite many advances in blood substitute research, the development of materials that are effective in maintaining blood volume and oxygen delivery remains a priority for emergency care and trauma. Clinical trials on hemoglobin (Hb)-based oxygen carriers (HBOCs) have not provided information on the mechanism of toxicity, although all commercial formulations have safety concerns. Specifically, it is important to reconcile the different hypotheses of Hb toxicity, such as nitric oxide (NO) depletion and oxidative reactions, to provide a coherent molecular basis for designing a safe HBOC. Recent Advances: HBOCs with different sizes often exhibit differences in the degree of HBOC-induced vasoactivity. This has been attributed to differences in the degree of NO scavenging and in the extent of Hb extravasation. Additionally, it is appears that Hb can undergo reactions that compensate for NO scavenging by generating bioactive forms of NO. Critical Issues: Engineering modifications to enhance bioactive NO production can result in diminished oxygen delivery by virtue of increased oxygen affinity. This strategy can prevent the HBOC from fulfilling the intended goal on preserving oxygenation; however, the NO production effects will increase perfusion and oxygen transport. Future Directions: Hb modifications influence NO scavenging and the capacity of certain HBOCs to compensate for NO scavenging through nitrite-mediated reactions that generate bioactive NO. Based on the current understanding of these NO-related factors, possible synthetic strategies are presented that address how HBOC formulations can be prepared that: (i) effectively deliver oxygen, (ii) maintain tissue perfusion, and (iii) limit/reverse underlying inflammation within the vasculature. Antioxid. Redox Signal. 18, 2284–2297. PMID:23249305

  16. Tissue viability imaging: microvascular response to vasoactive drugs induced by iontophoresis.

    PubMed

    Henricson, Joakim; Nilsson, Anders; Tesselaar, Erik; Nilsson, Gert; Sjöberg, Folke

    2009-09-01

    When one is studying the physiology of the cutaneous microcirculation there is a need for relevant non-invasive and versatile techniques. In this study we used a new optical device, the tissue viability imager (TiVi), to map changes in cutaneous microvascular concentrations of red blood cells during iontophoresis of vasoactive substances (noradrenaline (NA) and phenylephrine (Phe) for vasoconstriction and acetylcholine (ACh) and sodium nitroprusside (SNP) for vasodilatation). We aimed to present data both individually and pooled, using a four-variable logistic dose response model that is commonly used in similar in vitro vascular studies. The accuracy of the TiVi was also investigated by calculating the coefficient of variation and comparing it with similar tests previously done using laser Doppler imaging. Tests were also performed using the TiVi and LDPI simultaneously to further compare the two methods. Results showed that the TiVi is capable of quantifying vascular responses to iontophorised noradrenaline and phenylephrine without the need to increase background flow first. Fitting the TiVi data to the dose response model resulted in ED(50)-values with narrow confidence intervals and acceptable r(2) values. Mean ED(50)-values for the TiVi did not differ significantly from similar values obtained using laser Doppler. Results further seem to suggest that when the blood perfusion increases during vasodilatation in skin the initial phase relies mainly on an increase in red blood cell concentration whereas the further perfusion increase is due to an increase in red blood cell velocity.

  17. Vasoactive neuroendocrine responses associated with tolerance to lower body negative pressure in humans

    NASA Technical Reports Server (NTRS)

    Convertino, V. A.; Sather, T. M.

    2000-01-01

    The purpose of this investigation was to test the hypothesis that peripheral vasoconstriction and orthostatic tolerance are associated with increased circulating plasma concentrations of noradrenaline, vasopressin and renin-angiotensin. Sixteen men were categorized as having high (HT, n=9) or low (LT, n=7) tolerance to lower body negative pressure (LBNP) based on whether the endpoint of their pre-syncopal-limited LBNP (peak LBNP) exposure exceeded -60 mmHg. The two groups were matched for age, height, weight, leg volume, blood volume and maximal oxygen uptake, as well as baseline blood volume and plasma concentrations of vasoactive hormones. Peak LBNP induced similar reductions in mean arterial pressure in both groups. The reduction in leg arterial pulse volume (measured by impedance rheography), an index of peripheral vascular constriction, from baseline to peak LBNP was greater (P<0.05) in the HT group (-0.041 +/- 0.005 ml 100 ml-1) compared to the reduction in the LT group (-0. 025 +/- 0.003 ml 100 ml-1). Greater peak LBNP in the HT group was associated with higher (P<0.05) average elevations in plasma concentrations of vasopressin (pVP, Delta=+7.2 +/- 2.0 pg ml-1) and plasma renin-angiotensin (PRA, Delta=+2.9 +/- 1.3 ng Ang II ml-1 h-1) compared to average elevations of pVP (+2.2 +/- 1.0 pg ml-1) and PRA (+0.1 +/- 0.1 ng Ang II ml-1 h-1) in the LT group. Plasma noradrenaline concentrations were increased (P<0.05) from baseline to peak LBNP in both HT and LT groups, with no statistically distinguishable difference between groups. These data suggest that the renin-angiotensin and vasopressin systems may contribute to sustaining arterial pressure and orthostatic tolerance by their vasoconstrictive actions.

  18. Changes of vasoactive polypeptides during postoperative hypertensive crisis in patients with hypertensive intracerebral hemorrhage.

    PubMed

    Wang, Zhi; Wang, Xue-feng; Wang, Chao; Luan, Wen-zhong

    2007-12-05

    Hypertensive crisis could be found after operation in patients with hypertensive intracerebral hemorrhage (HICH). The aim of this study was to explore the changes and the roles of some vasoactive polypeptides during postoperative hypertensive crisis in patients with HICH. A total of 31 patients, who were admitted for craniotomy, were enrolled into this study. After the operation, the patients were divided into three groups. Group I consisted of 9 patients with postoperative hypertensive crisis, and group II was composed of 13 patients without postoperative hypertensive crisis. Nine patients, who denied history of hypertension or HICH, were set as group III. The levels of some vasoactivators in the three groups were measured before and after the operation. The differences in the results among the groups were analyzed using the ANOVA. The data collected before and after the operation in the group I was compared by Wilcoxon test. The concentration of endothelin in group I was significantly higher than that in group III (P < 0.05). The level of thromboxane A2 and the ratio of thromboxane B2 to 6-keto-PGF1a in group I were significantly higher than those in the other two groups (P < 0.05). In group I, the levels of plasma renin activity, angiotensin II, aldosterone, catecholamine, and endothelin before the operation were significantly higher than those determined after the operation (P > 0.05). Postoperative hypertensive crisis may be due to the increased thromboxane A2 and relatively inadequate prostacyclin, especially 6-keto-PGF1a. The increased level of endothelin and intraoperative stimulation also play a certain role in the development of postoperative hypertensive crisis.

  19. Intramural distribution of immunoreactive vasoactive intestinal polypeptide (VIP), substance P, somatostatin and mammalian bombesin in the oesophago-gastro-pyloric region of the human gut.

    PubMed

    Ferri, G L; Adrian, T E; Soimero, L; Blank, M; Cavalli, D; Biliotti, G; Polak, J M; Bloom, S R

    1989-04-01

    The intramural distribution of vasoactive intestinal polypeptide (VIP), substance P, somatostatin and mammalian bombesin was studied in the oesophago-gastro-pyloric region of the human gut. At each of 21 sampling sites encompassing this entire area, the gut wall was separated into mucosa, submucosa and muscularis externa, and extracted for radioimmunoassay. VIP levels in the mucosa were very high in the proximal oesophagus (1231 +/- 174 pmol/g, mean +/- SEM) and showed varied, but generally decreasing concentrations towards the stomach, followed by a clear-cut increase across the pyloric canal (distal antrum: 73 +/- 16 pmol/g, proximal duodenum: 366 +/- 62 pmol/g); consistent levels were found in submucosa and muscle (200-400 pmol/g) at most sites, the stomach again showing lower concentrations. By contrast, substance P was present in small amounts as far as the proximal stomach, but sharply increased across the pyloric canal, especially in mucosa and submucosa (distal antrum: 20 +/- 6.5 and 5.5 +/- 1.3 pmol/g; proximal duodenum: 62 +/- 8.5 and 34 +/- 11 pmol/g, respectively). Somatostatin concentrations were very low in the mucosa of the oesophagus and stepwise increased in the cardiac, mid-gastric and pyloric mucosa (cardia: 224 +/- 72 pmol/g; distal antrum: 513 +/- 152 pmol/g; proximal duodenum: 1013 +/- 113 pmol/g); concentrations in the submucosa and muscularis were generally low, with the exception of antrum and duodenum. Mammalian bombesin was comparatively well represented throughout the oesophageal muscularis (5-8 pmol/g), but most abundant in the stomach in all layers (oxyntic mucosa: 24 +/- 2.7 pmol/g; submucosa: 20 +/- 5.7 pmol/g; muscle: 28 +/- 5.0 pmol/g).(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Glucagon-related peptides in the mouse retina and the effects of deprivation of form vision.

    PubMed

    Mathis, Ute; Schaeffel, Frank

    2007-02-01

    In chickens, retinal glucagon amacrine cells play an important role in emmetropization, since they express the transcription factor ZENK (also known as NGFI-A, zif268, tis8, cef5, Krox24) in correlation with the sign of imposed image defocus. Pharmacological studies have shown that glucagon can act as a stop signal for axial eye growth, making it a promising target for pharmacological intervention of myopia. Unfortunately, in mammalian retina, glucagon itself has not yet been detected by immunohistochemical staining. To learn more about its possible role in emmetropization in mammals, we studied the expression of different members of the glucagon hormone family in mouse retina, and whether their abundance is regulated by visual experience. Black wildtype C57BL/6 mice, raised under a 12/12 h light/dark cycle, were studied at postnatal ages between P29 and P40. Frosted hemispherical thin plastic shells (diffusers) were placed in front of the right eyes to impose visual conditions that are known to induce myopia. The left eyes remained uncovered and served as controls. Transversal retinal cryostat sections were single- or double-labeled by indirect immunofluorescence for early growth response protein 1 (Egr-1, the mammalian ortholog of ZENK), glucagon, glucagon-like peptide-2 (GLP-2), glucose-dependent insulinotropic polypeptide (GIP), peptide histidine isoleucine (PHI), growth hormone-releasing hormone (GHRH), pituitary adenylate cyclase-activating polypeptide (PACAP), secretin, and vasoactive intestinal polypeptide (VIP). In total, retinas of 45 mice were studied, 28 treated with diffusers, and 17 serving as controls. Glucagon itself was not detected in mouse retina. VIP, PHI, PACAP and GIP were localized. VIP was co-localized with PHI and Egr-1, which itself was strongly regulated by retinal illumination. Diffusers, applied for various durations (1, 2, 6, and 24 h) had no effect on the expression of VIP, PHI, PACAP, and GIP, at least at the protein level. Similarly

  1. Peptide chemistry toolbox - Transforming natural peptides into peptide therapeutics.

    PubMed

    Erak, Miloš; Bellmann-Sickert, Kathrin; Els-Heindl, Sylvia; Beck-Sickinger, Annette G

    2018-06-01

    The development of solid phase peptide synthesis has released tremendous opportunities for using synthetic peptides in medicinal applications. In the last decades, peptide therapeutics became an emerging market in pharmaceutical industry. The need for synthetic strategies in order to improve peptidic properties, such as longer half-life, higher bioavailability, increased potency and efficiency is accordingly rising. In this mini-review, we present a toolbox of modifications in peptide chemistry for overcoming the main drawbacks during the transition from natural peptides to peptide therapeutics. Modifications at the level of the peptide backbone, amino acid side chains and higher orders of structures are described. Furthermore, we are discussing the future of peptide therapeutics development and their impact on the pharmaceutical market. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. What peptides these deltorphins be.

    PubMed

    Lazarus, L H; Bryant, S D; Cooper, P S; Salvadori, S

    1999-02-01

    The deltorphins are a class of highly selective delta-opioid heptapeptides from the skin of the Amazonian frogs Phyllomedusa sauvagei and P. bicolor. The first of these fascinating peptides came to light in 1987 by cloning of the cDNA of from frog skins, while the other members of this family were identified either by cDNA or isolation of the peptides. The distinctive feature of deltorphins is the presence of a naturally occurring D-enantiomer at the second position in their common N-terminal sequence, Tyr-D-Xaa-Phe, comparable to dermorphin, which is the prototype of a group of mu-selective opioids from the same source. The D-amino acid and the anionic residues, either Glu or Asp, as well as their unique amino acid compositions are responsible for the remarkable biostability, high delta-receptor affinity, bioactivity and peptide conformation. This review summarizes a decade of research from many laboratories that defined which residues and substituents in the deltorphins interact with the delta-receptor and characterized pharmacological and physiological activities in vitro and in vivo. It begins with a historical description of the topic and presents general schema for the synthesis of peptide analogues of deltorphins A, B and C as a means to document the methods employed in producing a myriad of analogues. Structure activity studies of the peptides and their pharmacological activities in vitro are detailed in abundantly tabulated data. A brief compendium of the current level of knowledge of the delta-receptor assists the reader to appreciate the rationale for the design of these analogues. Discussion of the conformation of these peptides addresses how structure leads to further hypotheses regarding ligand receptor interaction. The review ends with a broad discussion of the potential applications of these peptides in clinical and therapeutic settings.

  3. Vasoactive intestinal polypeptide mediates cholecystokinin-induced relaxation of the sphincter of Oddi.

    PubMed Central

    Wiley, J W; O'Dorisio, T M; Owyang, C

    1988-01-01

    This study evaluates the hypothesis that cholecystokinin (CCK) relaxes the sphincter of Oddi via vasoactive intestinal polypeptide (VIP). Isolated canine sphincter of Oddi were suspended in organ baths under standard conditions. Responses to cholecystokinin octapeptide (CCK-8) and VIP were recorded on a pen recorder via an isometric transducer. 10(-11)-10(-7) M CCK-8 and 4 X 10(-11)-5 X 10(-7) M VIP generated dose-related sphincter of Oddi relaxation, which was unaffected by atropine, propranolol, and phentolamine. The effect of CCK-8 was antagonized by dibutyryl cGMP (Bt2 cGMP) (10(-3) M), the VIP-antagonist (N-Ac-Tyr1, D-Phe2)-growth hormone-releasing factor-(1-29)-NH2, and abolished by tetrodotoxin. In contrast, VIP's relaxing action was tetrodotoxin insensitive. 10(-11)-10(-7) M CCK-8 stimulated dose-dependent release of VIP (0.5-2.2 fm/ml.mg tissue), which was not inhibited by atropine, propranolol, and phentolamine, but was antagonized by 10(-3) M Bt2 cGMP and tetrodotoxin. In addition CCK-8 and VIP generated dose-related (10(-10)-10(-7) M) increases in sphincter of Oddi cAMP levels that were not affected by atropine, propranolol, and phentolamine. Furthermore, 10(-5)-10(-2) M 8-bromo-cAMP caused dose-dependent relaxation of the sphincter of Oddi. In separate studies, a 2-h incubation in physiological solution containing 12 parts/1,000 of rabbit VIP antiserum antagonized sphincter relaxation caused by 4 nM CCK-8 and 6 nM VIP. The antiserum also significantly decreased the sphincter of Oddi cAMP level stimulated by 4 nM CCK-8 by 48 +/- 15%. These studies demonstrate that CCK-8 relaxes the canine sphincter of Oddi via a noncholinergic, nonadrenergic neural pathway involving VIP. The intracellular mechanism mediating CCK/VIP relaxation involves generation of cAMP. Images PMID:3384954

  4. Timing of antibiotics, volume, and vasoactive infusions in children with sepsis admitted to intensive care.

    PubMed

    van Paridon, Bregje M; Sheppard, Cathy; G, Garcia Guerra; Joffe, Ari R

    2015-08-17

    Early administration of antibiotics for sepsis, and of fluid boluses and vasoactive agents for septic shock, is recommended. Evidence for this in children is limited. The Alberta Sepsis Network prospectively enrolled eligible children admitted to the Pediatric Intensive Care Unit (PICU) with sepsis from 04/2012-10/2014. Demographics, severity of illness, and outcomes variables were prospectively entered into the ASN database after deferred consent. Timing of interventions were determined by retrospective chart review using a study manual and case-report-form. We aimed to determine the association of intervention timing and outcome in children with sepsis. Univariate (t-test and Fisher's Exact) and multiple linear regression statistics evaluated predictors of outcomes of PICU length of stay (LOS) and ventilation days. Seventy-nine children, age median 60 (IQR 22-133) months, 40 (51%) female, 39 (49%) with severe underlying co-morbidity, 44 (56%) with septic shock, and median PRISM-III 10.5 [IQR 6.0-17.0] were enrolled. Most patients presented in an ED: 36 (46%) at an outlying hospital ED, and 21 (27%) at the Children's Hospital ED. Most infections were pneumonia with/without empyema (42, 53%), meningitis (11, 14%), or bacteremia (10, 13%). The time from presentation to acceptable antibiotic administration was a median of 115.0 [IQR 59.0-323.0] minutes; 20 (25%) of patients received their antibiotics in the first hour from presentation. Independent predictors of PICU LOS were PRISM-III, and severe underlying co-morbidity, but not time to antibiotics. In the septic shock subgroup, the volume of fluid boluses given in the first 2 hours was independently associated with longer PICU LOS (effect size 0.22 days; 95% CI 0.5, 0.38; per ml/kg). Independent predictors of ventilator days were PRISM-III score and severe underlying co-morbidity. In the septic shock subgroup, volume of fluid boluses in the first 2 hours was independently associated with more ventilator days

  5. Skin blood flow response in the rat model of wound healing: expression of vasoactive factors.

    PubMed

    Rendell, Marc S; Johnson, Mark L; Smith, Denae; Finney, David; Capp, Christopher; Lammers, Rebecca; Lancaster, Scott

    2002-09-01

    Although the microvascular blood flow response to wounding is predominantly vasodilation at skin sites with nutritive capillary perfusion (NUTR), there is a significant vasoconstrictive response at sites with high arteriovenous perfusion (AV). There may be a difference between NUTR and AV sites in the vasoactive factors which mediate the blood flow response to wounding. We measured the levels of mRNA expression of several potential mediators of the blood flow response to assess this possible difference. We measured skin blood flow at wounds placed at the back, a NUTR site, and at the paw, an AV site, in 12 Wistar Kyoto rats. Measurements were performed at baseline and then at 7 days post wounding. There was a significant increase in blood flow at back wound sites, with a rise from 4.1 +/- 0.3 ml/min/100 g to 9.8 +/- 1.9 ml/min/100 g. At the undisturbed wound perimeter, outside the zone of granulation tissue, flow rose to 7.3 +/- 1.1 ml/min/100 g. At the paw wound site, Day 0 flow was 8.8 +/- 0.8 ml/min/100 g. At 7 days, there was a significant decrease in flow at wound center to 5.5 +/- 0.5 ml/min/100 g. We measured the levels of inducible nitric oxide synthetase (iNOS), endothelin, endothelin receptor, vascular endothelial growth factor (VEGF), and keratinocyte growth factor (KGF) gene mRNAs using reverse transcriptase PCR. There was a 10-fold increase in NOS mRNA in granulation tissue of both wounds on Day 7. There was a lesser but still substantial increase in the wound perimeter tissue. Levels of endothelin mRNA in the wound and wound perimeter were significantly lower at the paw than at the back. At baseline, the level of endothelin receptor B (ETrB) mRNA was greater at the back than at the paw. Wounding resulted in a substantial increase in EtrB mRNA levels in granulation tissue, reaching the same level at the back and paw wounds. There was also a substantial rise in EtrB mRNA levels at the paw wound perimeter, so that there was a reversal of the baseline

  6. Sensitivity to food additives, vaso-active amines and salicylates: a review of the evidence.

    PubMed

    Skypala, Isabel J; Williams, M; Reeves, L; Meyer, R; Venter, C

    2015-01-01

    Although there is considerable literature pertaining to IgE and non IgE-mediated food allergy, there is a paucity of information on non-immune mediated reactions to foods, other than metabolic disorders such as lactose intolerance. Food additives and naturally occurring 'food chemicals' have long been reported as having the potential to provoke symptoms in those who are more sensitive to their effects. Diets low in 'food chemicals' gained prominence in the 1970s and 1980s, and their popularity remains, although the evidence of their efficacy is very limited. This review focuses on the available evidence for the role and likely adverse effects of both added and natural 'food chemicals' including benzoate, sulphite, monosodium glutamate, vaso-active or biogenic amines and salicylate. Studies assessing the efficacy of the restriction of these substances in the diet have mainly been undertaken in adults, but the paper will also touch on the use of such diets in children. The difficulty of reviewing the available evidence is that few of the studies have been controlled and, for many, considerable time has elapsed since their publication. Meanwhile dietary patterns and habits have changed hugely in the interim, so the conclusions may not be relevant for our current dietary norms. The conclusion of the review is that there may be some benefit in the removal of an additive or a group of foods high in natural food chemicals from the diet for a limited period for certain individuals, providing the diagnostic pathway is followed and the foods are reintroduced back into the diet to assess for the efficacy of removal. However diets involving the removal of multiple additives and food chemicals have the very great potential to lead to nutritional deficiency especially in the paediatric population. Any dietary intervention, whether for the purposes of diagnosis or management of food allergy or food intolerance, should be adapted to the individual's dietary habits and a suitably

  7. Solar abundance of silicon

    SciTech Connect

    Holweger, H.

    1973-07-01

    An analysis of 19 photospheric Si I lines whose oscillator strengths have recently been detertmined by Garz (1973) leads to a solar abundance of silicon, log epsilon /sub Si/ = 7.65 plus or minus 0.07, on the scale where log epsilon /sub H/ = 12. Together with the sodium abundance determained earlier by the same method, a solar abundance ratio /sup epsilon /Na//sup epsilon /Si = 0.045 ( plus or minus 10%) results. Within the error limits this a grees wtth the meteoritic ratio found in carbonaceous chondrites. Results concerning line-broadening by hydrogen are discussed. (auth)

  8. Estimating abundance: Chapter 27

    USGS Publications Warehouse

    Royle, J. Andrew

    2016-01-01

    This chapter provides a non-technical overview of ‘closed population capture–recapture’ models, a class of well-established models that are widely applied in ecology, such as removal sampling, covariate models, and distance sampling. These methods are regularly adopted for studies of reptiles, in order to estimate abundance from counts of marked individuals while accounting for imperfect detection. Thus, the chapter describes some classic closed population models for estimating abundance, with considerations for some recent extensions that provide a spatial context for the estimation of abundance, and therefore density. Finally, the chapter suggests some software for use in data analysis, such as the Windows-based program MARK, and provides an example of estimating abundance and density of reptiles using an artificial cover object survey of Slow Worms (Anguis fragilis).

  9. OXYGEN ABUNDANCES IN CEPHEIDS

    SciTech Connect

    Luck, R. E.; Andrievsky, S. M.; Korotin, S. N.

    2013-07-01

    Oxygen abundances in later-type stars, and intermediate-mass stars in particular, are usually determined from the [O I] line at 630.0 nm, and to a lesser extent, from the O I triplet at 615.7 nm. The near-IR triplets at 777.4 nm and 844.6 nm are strong in these stars and generally do not suffer from severe blending with other species. However, these latter two triplets suffer from strong non-local thermodynamic equilibrium (NLTE) effects and thus see limited use in abundance analyses. In this paper, we derive oxygen abundances in a large sample of Cepheids using the near-IR triplets from an NLTEmore » analysis, and compare those abundances to values derived from a local thermodynamic equilibrium (LTE) analysis of the [O I] 630.0 nm line and the O I 615.7 nm triplet as well as LTE abundances for the 777.4 nm triplet. All of these lines suffer from line strength problems making them sensitive to either measurement complications (weak lines) or to line saturation difficulties (strong lines). Upon this realization, the LTE results for the [O I] lines and the O I 615.7 nm triplet are in adequate agreement with the abundance from the NLTE analysis of the near-IR triplets.« less

  10. Immunogold staining procedure for the localisation of regulatory peptides.

    PubMed

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

    1982-01-01

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

  11. Lactoferricin B-derived peptides with inhibitory effects on ECE-dependent vasoconstriction.

    PubMed

    Fernández-Musoles, Ricardo; López-Díez, José Javier; Torregrosa, Germán; Vallés, Salvador; Alborch, Enrique; Manzanares, Paloma; Salom, Juan B

    2010-10-01

    Endothelin-converting enzyme (ECE), a key peptidase in the endothelin (ET) system, cleaves inactive big ET-1 to produce active ET-1, which binds to ET(A) receptors to exert its vasoconstrictor and pressor effects. ECE inhibition could be beneficial in the treatment of hypertension. In this study, a set of eight lactoferricin B (LfcinB)-derived peptides, previously characterized in our laboratory as angiotensin-converting enzyme (ACE) inhibitory peptides, was examined for their inhibitory effects on ECE. In vitro inhibitory effects on ECE activity were assessed using both the synthetic fluorogenic peptide substrate V (FPS V) and the natural substrate big ET-1. To study vasoactive effects, an ex vivo functional assay was developed using isolated rabbit carotid artery segments. With FPS V, only four LfcinB-derived peptides induced inhibition of ECE activity, whereas the eight peptides showed ECE inhibitory effects with big ET-1 as substrate. Regarding the ex vivo assays, six LfcinB-derived peptides showed inhibition of big ET-1-induced, ECE-dependent vasoconstriction. A positive correlation between the inhibitory effects of LfcinB-derived peptides on ECE activity when using big ET-1 and the inhibitory effects on ECE-dependent vasoconstriction was shown. ECE-independent vasoconstriction induced by ET-1 was not affected, thus discarding effects of LfcinB-derived peptides on ET(A) receptors or intracellular signal transduction mechanisms. In conclusion, a combined in vitro and ex vivo method to assess the effects of potentially antihypertensive peptides on the ET system has been developed and applied to show the inhibitory effects on ECE-dependent vasoconstriction of six LfcinB-derived peptides, five of which were dual vasopeptidase (ACE/ECE) inhibitors. Copyright © 2010 Elsevier Inc. All rights reserved.

  12. Nitroso-sulfide coupled signaling triggers specific vasoactive effects in the intrarenal arteries of patients with arterial hypertension.

    PubMed

    Cacanyiova, S; Berenyiova, A; Balis, P; Kristek, F; Grman, M; Ondrias, K; Breza, J; Breza, J

    2017-08-01

    In normotensive conditions, it has been confirmed that S-nitrosothiols (RSNO), can interact with hydrogen sulfide (H 2 S) and create new substances with specific vasoactive effects. This interaction could also represent a new regulator signaling pathway in conditions of hypertension. Until now, these effects were studied only in normotensive rats, and they have not been carried out in humans yet. We investigated the vasoactive effects of the products of the H 2 S/S-nitrosoglutathione (S/GSNO) interaction in lobar arteries (LA) isolated from the nephrectomized kidneys of patients suffering from arterial hypertension and in renal arteries (RA) of spontaneously hypertensive rats (SHR). The changes in the isometric tension of pre-contracted arteries were evaluated. Acetylcholine-induced vasorelaxation of LA was reduced compared to the effect induced by an NO donor, sodium nitroprusside suggesting an endothelium dysfunction. While 1 μmol/L Na2S had a minimal effect on the vascular tone, the concentration 20 μmol/L evoked a slight vasorelaxation. GSNO at 0.1 μmol/L induced vasorelaxation, which was less pronounced compared to the effect induced by 1 μmol/L. The S/GSNO products (final concentration 0.1 μmol/L) prepared as the mixture of GSNO (0.1 μmol/L) + Na2S (1 μmol/L) induced a higher vasorelaxation compared to GSNO (0.1 μmol/L) alone only in the 5 th minute and without the differences in the speed. On the other hand, the S/GSNO products (final concentration 1 μmol/L) prepared as the mixture of GSNO (1 μmol/L) + Na2S (10 μmol/L) induced a higher and faster vasorelaxation compared to the effect induced by GSNO (1 μmol/L) alone. In RA of SHR this S/GSNO products induced similar vasorelaxation (higher and faster than GSNO) with involvement of HNO (partially) and cGMP as mediators. However, the products of the H 2 S/NO donor (DEA NONOate) manifested differently than S/GSNO indicating the unique interaction between GSNO and H 2 S. In this study, we confirmed

  13. [Changes in prescription patterns for peripheral and cerebral vasoactive drugs before and after establishing prescription standards in France].

    PubMed

    Vuittenez, F; Guignard, E; Comte, S

    1999-01-23

    Assess changes in the number of prescriptions for peripheral and cerebral vasoactive drugs for the treatment of lower limb arteritis and cerebrovascular disease since the promulgation in 1995 of prescription standards for the treatment of lower limb arteritis. Assess compliance to prescription standards with a detailed analysis of patient features, prescriptions written for lower limb arteritis, cerebrovascular disease and concomitant diseases and evaluate changes in treatment costs for lower limb arteritis and cerebrovascular disease as well as cost of the full prescription, including treatments for associated diseases. This study was based on data recorded during the Permanent Study of Medical Prescriptions conducted from March 1994 to February 1995 and from March 1995 to February 1996 by the IMS. Prescription costs were established from the National Description Files of the IMS. Treatment costs were expressed as public price (FF) tax included. Prescriptions meeting the following criteria were selected for each period: prescriptions written by general practitioners for drugs with peripheral and cerebral vasoactivity (excepting calcium antagonists with a cerebral target) belonging to the Anatomic Therapeutic Classes C4A1 of the European Pharmaceutical Marketing Research Association, Bromly 1996; prescriptions for diagnoses 447.6 (arteritis) and 437.9 (cerebrovascular disease) according to the 9th WHO classification. A random sample of 500 prescriptions was selected to calculate costs. Since the advent of the prescription standards in 1995, prescriptions have dropped off by 6.3% for lower limb arteritis and by 14.8% for cerebrovascular disease. There was a 3.7 point decline in the percentage of multiple prescriptions of vasoactive drugs for lower limb arteritis (21.7% prior to March 1995 versus 18% after promulgation of the prescription standards, p > 0.1) and a 1.8 increase in the percentage of multiple prescriptions for cerebrovascular disease (14% prior to March

  14. Effects of protease activated receptor (PAR)2 blocking peptide on endothelin-1 levels in kidney tissues in endotoxemic rat mode.

    PubMed

    Jesmin, Subrina; Shimojo, Nobutake; Yamaguchi, Naoto; Mowa, Chishimba Nathan; Oki, Masami; Zaedi, Sohel; Sultana, Sayeeda Nusrat; Rahman, Arifur; Islam, Majedul; Sawamura, Atsushi; Gando, Satoshi; Kawano, Satoru; Miyauchi, Takashi; Mizutani, Taro

    2014-05-02

    Septic shock, the severe form of sepsis, is associated with development of progressive damage in multiple organs. Kidney can be injured and its functions altered by activation of coagulation, vasoactive-peptide and inflammatory processes in sepsis. Endothelin (ET)-1, a potent vasoconstrictor, is implicated in the pathogenesis of sepsis and its complications. Protease-activated receptors (PARs) are shown to play an important role in the interplay between inflammation and coagulation. We examined the time-dependent alterations of ET-1 and inflammatory cytokine, such as tumor necrosis factor (TNF)-α in kidney tissue in lipopolysaccharide (LPS)-induced septic rat model and the effects of PAR2 blocking peptide on the LPS-induced elevations of renal ET-1 and TNF-α levels. Male Wistar rats at 8 weeks of age were administered with either saline solution or LPS at different time points (1, 3, 6 and 10h). Additionally, we treated LPS-administered rats with PAR2 blocking peptide for 3h to assess whether blockade of PAR2 has a regulatory role on the ET-1 level in septic kidney. An increase in ET-1 peptide level was observed in kidney tissue after LPS administration time-dependently. Levels of renal TNF-α peaked (around 12-fold) at 1h of sepsis. Interestingly, PAR2 blocking peptide normalized the LPS-induced elevations of renal ET-1 and TNF-α levels. The present study reveals a distinct chronological expression of ET-1 and TNF-α in LPS-administered renal tissues and that blockade of PAR2 may play a crucial role in treating renal injury, via normalization of inflammation, coagulation and vaso-active peptide. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Stellar Oxygen Abundances

    NASA Astrophysics Data System (ADS)

    King, Jeremy

    1994-04-01

    This dissertation addresses several issues concerning stellar oxygen abundances. The 7774 {\\AA} O I triplet equivalent widths of Abia & Rebolo [1989, AJ, 347, 186] for metal-poor dwarfs are found to be systematically too high. I also argue that current effective temperatures used in halo star abundance studies may be ~150 K too low. New color-Teff relations are derived for metal-poor stars. Using the revised Teff values and improved equivalent widths for the 7774A O I triplet, the mean [O/Fe] ratio for a handful of halo stars is found to be +0.52 with no dependence on Teff or [Fe/H]. Possible cosmological implications of the hotter Teff scale are discussed along with additional evidence supporting the need for a higher temperature scale for metal-poor stars. Our Teff scale leads to a Spite Li plateau value of N(Li)=2.28 +/- 0.09. A conservative minimal primordial value of N(Li)=2.35 is inferred. If errors in the observations and models are considered, consistency with standard models of Big Bang nucleosynthesis is still achieved with this larger Li abundance. The revised Teff scale raises the observed B/Be ratio of HD 140283 from 10 to 12, making its value more comfortably consistent with the production of the observed B and Be by ordinary spallation. Our Teff values are found to be in good agreement with values predicted from both the Victoria and Yale isochrone color-Teff relations. Thus, it appears likely that no changes in globular cluster ages would result. Next, we examine the location of the break in the [O/Fe] versus [Fe/H] plane in a quantitative fashion. Analysis of a relatively homogeneous data set does not favor any unique break point in the range -1.7 /= -3), in agreement with the new results for halo dwarfs. We find that the gap in the observed [O/H] distribution, noted by Wheeler et al

  16. Multiplex De Novo Sequencing of Peptide Antibiotics

    NASA Astrophysics Data System (ADS)

    Mohimani, Hosein; Liu, Wei-Ting; Yang, Yu-Liang; Gaudêncio, Susana P.; Fenical, William; Dorrestein, Pieter C.; Pevzner, Pavel A.

    Proliferation of drug-resistant diseases raises the challenge of searching for new, more efficient antibiotics. Currently, some of the most effective antibiotics (i.e., Vancomycin and Daptomycin) are cyclic peptides produced by non-ribosomal biosynthetic pathways. The isolation and sequencing of cyclic peptide antibiotics, unlike the same activity with linear peptides, is time-consuming and error-prone. The dominant technique for sequencing cyclic peptides is NMR-based and requires large amounts (milligrams) of purified materials that, for most compounds, are not possible to obtain. Given these facts, there is a need for new tools to sequence cyclic NRPs using picograms of material. Since nearly all cyclic NRPs are produced along with related analogs, we develop a mass spectrometry approach for sequencing all related peptides at once (in contrast to the existing approach that analyzes individual peptides). Our results suggest that instead of attempting to isolate and NMR-sequence the most abundant compound, one should acquire spectra of many related compounds and sequence all of them simultaneously using tandem mass spectrometry. We illustrate applications of this approach by sequencing new variants of cyclic peptide antibiotics from Bacillus brevis, as well as sequencing a previously unknown familiy of cyclic NRPs produced by marine bacteria.

  17. Benefits of smart pumps for automated changeovers of vasoactive drug infusion pumps: a quasi-experimental study.

    PubMed

    Cour, M; Hernu, R; Bénet, T; Robert, J M; Regad, D; Chabert, B; Malatray, A; Conrozier, S; Serra, P; Lassaigne, M; Vanhems, P; Argaud, L

    2013-11-01

    Manual changeover of vasoactive drug infusion pumps (CVIP) frequently lead to haemodynamic instability. Some of the newest smart pumps allow automated CVIP. The aim of this study was to compare automated CVIP with manual 'Quick Change' relays. We performed a prospective, quasi-experimental study, in a university-affiliated intensive care unit (ICU). All adult patients receiving continuous i.v. infusion of vasoactive drugs were included. CVIP were successively performed manually (Phase 1) and automatically (Phase 2) during two 6-month periods. The primary endpoint was the frequency of haemodynamic incidents related to the relays, which were defined as variations of mean arterial pressure >15 mm Hg or heart rate >15 bpm. The secondary endpoints were the nursing time dedicated to relays and the number of interruptions in care because of CVIP. A multivariate mixed effects logistic regression was fitted for analytic analysis. We studied 1329 relays (Phase 1: 681, Phase 2: 648) from 133 patients (Phase 1: 63, Phase 2: 70). Incidents related to CVIP decreased from 137 (20%) in Phase 1 to 73 (11%) in Phase 2 (P<0.001). Automated relays were independently associated with a 49% risk reduction of CVIP-induced incidents (adjusted OR=0.51, 95% confidence interval 0.34-0.77, P=0.001). Time dedicated to the relays and the number of interruptions in care to manage CVIP were also significantly reduced with automated relays vs manual relays (P=0.001). These results demonstrate the benefits of automated CVIP using smart pumps in limiting the frequency of haemodynamic incidents related to relays and in reducing the nursing workload.

  18. Treatment with low-dose atorvastatin, losartan, and their combination increases expression of vasoactive-related genes in rat aortas.

    PubMed

    Lunder, Mojca; Drevenšek, Gorazd; Černe, Darko; Marc, Janja; Janić, Miodrag; Šabovič, Mišo

    2013-03-01

    Recently it has been shown that statins and angiotensin receptor blockers (ARBs) at low doses express beneficial pleiotropic vascular effects. We aimed to explore whether these drugs at low doses induce the expression of vasoactive-related genes. Sixty adult Wistar rats were treated with low-dose atorvastatin (2 mg/kg), low-dose losartan (5 mg/kg), their combination or saline daily for 4, 6, or 8 weeks. Expression of the vasoactive-related genes endothelin receptor type A (EDNRA), endothelial nitric oxide synthase 3 (NOS3), inducible nitric oxide synthase 2 (NOS2), and angiotensin II receptor type 1 (AGTRL1a) was measured in isolated thoracic aortas. Expression of EDNRA gradually decreased, the lowest values being obtained after 8 weeks (low-dose atorvastatin, losartan [1.6- and 1-7-fold vs controls, respectively; both P < .05], and the combination [2.3-fold vs control, P < .001]). The highest values of NOS3 were obtained after 6 weeks (low-dose atorvastatin, losartan, and their combination, 3.1-fold, P < .01; 3.4-fold, P < .001; and 3.6-fold, P < .001 vs controls, respectively) and then declined after 8 weeks. The combination was more effective in inducing total NOS3 expression when compared to the separate drugs (1.4-fold; P < .05). Importantly, expression of NOS3 was associated with increased plasma NO levels and positively correlated with thoracic aorta relaxation. No changes in expression of NOS2 and AGTRL1a were observed. We showed that low-dose atorvastatin or losartan and especially their combination increases the expression of NOS3 and decreases the expression of EDNRA. These findings are valuable in explaining the effectiveness of the "low-dose pharmacological approach" for improvement in arterial function.

  19. Delivery of platinum(IV) drug to subcutaneous tumor and lung metastasis using bradykinin-potentiating peptide-decorated chitosan nanoparticles.

    PubMed

    Wang, Xin; Yang, Chenchen; Zhang, Yajun; Zhen, Xu; Wu, Wei; Jiang, Xiqun

    2014-08-01

    Selectively activating tumor vessels to increase drug delivery and reduce interstitial fluid pressure of tumors is actively pursued. Here we developed a vasoactive peptide-decorated chitosan nanoparticles for enhancing drug accumulation and penetration in subcutaneous tumor and lung metastasis. The vasoactive peptide used here is bradykinin-potentiating peptide (BPP) containing 9 amino acid residues and the drug is bioreductively sensitive platinum(IV) compound which becomes cisplatin in intracellular reductive environments. Both peptide and drug are covalently linked with chitosan nanoparticles with a diameter of 120 nm. We demonstrate that BPP-decorated chitosan nanoparticles increase the tumorous vascular permeability and reduce the interstitial fluid pressure of tumor simultaneously, both of which improve the penetration of nanoparticles in tumor tissues. The in vivo biodistribution and tumor inhibition examinations demonstrate that the BPP-decorated nanoparticle formulation has more superior efficacy in enhancing drug accumulation in tumor, restraining tumor growth and prolonging the lifetime of tumor-bearing mice than free drug and non-decorated nanoparticle formulation. Meanwhile, the drug accumulation in the lung with metastasis reaches 17% and 20% injected dose per gram of lung for the chitosan nanoparticles without and with BPP decoration, respectively, which is 10-fold larger than that of free cisplatin. The examination of lung metastasis inhibition further indicates that BPP-decorated chitosan nanoparticle formulations can more effectively inhibit lung metastasis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Regulatory Peptides in Plants.

    PubMed

    Vanyushin, B F; Ashapkin, V V; Aleksandrushkina, N I

    2017-02-01

    Many different peptides regulating cell differentiation, growth, and development are found in plants. Peptides participate in regulation of plant ontogenesis starting from pollination, pollen tube growth, and the very early stages of embryogenesis, including formation of embryo and endosperm. They direct differentiation of meristematic stem cells, formation of tissues and individual organs, take part in regulation of aging, fruit maturation, and abscission of plant parts associated with apoptosis. Biological activity of peptides is observed at very low concentrations, and it has mainly signal nature and hormonal character. "Mature" peptides appear mainly due to processing of protein precursors with (or without) additional enzymatic modifications. Plant peptides differ in origin, structure, and functional properties. Their specific action is due to binding with respective receptors and interactions with various proteins and other factors. Peptides can also regulate physiological functions by direct peptide-protein interactions. Peptide action is coordinated with the action of known phytohormones (auxins, cytokinins, and others); thus, peptides control phytohormonal signal pathways.

  1. Functional significance of bioactive peptides derived from soybean.

    PubMed

    Singh, Brij Pal; Vij, Shilpa; Hati, Subrota

    2014-04-01

    Biologically active peptides play an important role in metabolic regulation and modulation. Several studies have shown that during gastrointestinal digestion, food processing and microbial proteolysis of various animals and plant proteins, small peptides can be released which possess biofunctional properties. These peptides are to prove potential health-enhancing nutraceutical for food and pharmaceutical applications. The beneficial health effects of bioactive peptides may be several like antihypertensive, antioxidative, antiobesity, immunomodulatory, antidiabetic, hypocholesterolemic and anticancer. Soybeans, one of the most abundant plant sources of dietary protein, contain 36-56% of protein. Recent studies showed that soy milk, an aqueous extract of soybean, and its fermented product have great biological properties and are a good source of bioactive peptides. This review focuses on bioactive peptides derived from soybean; we illustrate their production and biofunctional attributes. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Atrial natriuretic peptide stimulates salt secretion by shark rectal gland by releasing VIP

    SciTech Connect

    Silva, P.; Stoff, J.S.; Solomon, R.J.

    1987-01-01

    Salt secretion by the isolated perfused rectal gland of the spiny dogfish shark, Squalus acanthias, is stimulated by synthetic rat atrial natriuretic peptide (ANP II) as well as extracts of shark heart, but not by 8-bromo-cyclic guanosine 5'-monophosphate. Cardiac peptides have no effect on isolated rectal gland cells or perfused tubules, suggesting that stimulation requires an intact gland. The stimulation of secretion by ANP II is eliminated by maneuvers that block neurotransmitter release. Cardiac peptides stimulate the release of vasoactive intestinal peptide (VIP), known to be present in rectal glands nerves, into the venous effluent of perfused glands in parallelmore » with their stimulation of salt secretion, but the release of VIP induced by ANP II is prevented by perfusion with procaine. VIP was measured by radioimmunoassay. Cardiac peptides thus appear to regulate rectal gland secretion by releasing VIP from neural stores within the gland. It is possible that other physiological effects of these hormones might be explained by an action to enhanced local release of neurotransmitters.« less

  3. Pharmacologic Effects in vivo in Brain by Vector-Mediated Peptide Drug Delivery

    NASA Astrophysics Data System (ADS)

    Bickel, Ulrich; Yoshikawa, Takayoshi; Landaw, Elliot M.; Faull, Kym F.; Pardridge, William M.

    1993-04-01

    Pharmacologic effects in brain caused by systemic administration of neuropeptides are prevented by poor transport of the peptide through the brain vascular endothelium, which comprises the blood-brain barrier in vivo. In the present study, successful application of a chimeric peptide approach to enhance drug delivery through the blood-brain barrier for the purpose of achieving a central nervous system pharmacologic effect is described. The chimeric peptide was formed by linkage of a potent vasoactive intestinal peptide (VIP) analogue, which had been monobiotinylated, to a drug transport vector. The vector consisted of a covalent conjugate of avidin and the OX26 monoclonal antibody to the transferrin receptor. Owing to the high concentration of transferrin receptors on brain capillary endothelia, OX26 targets brain and undergoes receptor-mediated transcytosis through the blood-brain barrier. Systemic infusion of low doses (12 μg/kg) of the VIP chimeric peptide in rats resulted in an in vivo central nervous system pharmacologic effect: a 65% increase in cerebral blood flow. Biotinylated VIP analogue without the brain transport vector was ineffective.

  4. Peptides, Peptidomimetics, and Polypeptides from Marine Sources: A Wealth of Natural Sources for Pharmaceutical Applications

    PubMed Central

    Sable, Rushikesh; Parajuli, Pravin; Jois, Seetharama

    2017-01-01

    Nature provides a variety of peptides that are expressed in most living species. Evolutionary pressure and natural selection have created and optimized these peptides to bind to receptors with high affinity. Hence, natural resources provide an abundant chemical space to be explored in peptide-based drug discovery. Marine peptides can be extracted by simple solvent extraction techniques. The advancement of analytical techniques has made it possible to obtain pure peptides from natural resources. Extracted peptides have been evaluated as possible therapeutic agents for a wide range of diseases, including antibacterial, antifungal, antidiabetic and anticancer activity as well as cardiovascular and neurotoxin activity. Although marine resources provide thousands of possible peptides, only a few peptides derived from marine sources have reached the pharmaceutical market. This review focuses on some of the peptides derived from marine sources in the past ten years and gives a brief review of those that are currently in clinical trials or on the market. PMID:28441741

  5. Gastrointestinal neuroendocrine peptides/amines in inflammatory bowel disease

    PubMed Central

    El-Salhy, Magdy; Solomon, Tefera; Hausken, Trygve; Gilja, Odd Helge; Hatlebakk, Jan Gunnar

    2017-01-01

    Inflammatory bowel disease (IBD) is a chronic recurrent condition whose etiology is unknown, and it includes ulcerative colitis, Crohn’s disease, and microscopic colitis. These three diseases differ in clinical manifestations, courses, and prognoses. IBD reduces the patients’ quality of life and is an economic burden to both the patients and society. Interactions between the gastrointestinal (GI) neuroendocrine peptides/amines (NEPA) and the immune system are believed to play an important role in the pathophysiology of IBD. Moreover, the interaction between GI NEPA and intestinal microbiota appears to play also a pivotal role in the pathophysiology of IBD. This review summarizes the available data on GI NEPA in IBD, and speculates on their possible role in the pathophysiology and the potential use of this information when developing treatments. GI NEPA serotonin, the neuropeptide Y family, and substance P are proinflammatory, while the chromogranin/secretogranin family, vasoactive intestinal peptide, somatostatin, and ghrelin are anti-inflammatory. Several innate and adaptive immune cells express these NEPA and/or have receptors to them. The GI NEPA are affected in patients with IBD and in animal models of human IBD. The GI NEPA are potentially useful for the diagnosis and follow-up of the activity of IBD, and are candidate targets for treatments of this disease. PMID:28811704

  6. Adult cystic fibrosis: postprandial response of gut regulatory peptides.

    PubMed

    Allen, J M; Penketh, A R; Adrian, T E; Lee, Y C; Sarson, D L; Hodson, M E; Batten, J C; Bloom, S R

    1983-12-01

    Responses of 11 gastrointestinal regulatory peptides to a standard test meal were assessed in 10 adult patients with cystic fibrosis. The basal plasma neurotensin was significantly elevated in patients with cystic fibrosis, being 31.5 +/- 6.1 pmol/L compared with a control value of 10.3 +/- 1.5 pmol/L (p less than 0.005). Plasma neurotensin remained elevated throughout the test period. Basal plasma enteroglucagon was similarly elevated, the patients with fibrocystic disease having levels of 51.3 +/- 4.6 pmol/L compared to controls with levels of 33.2 +/- 6.7 pmol/L (p less than 0.02). There was, however, no significant difference in postprandial levels of plasma enteroglucagon. Postprandial motilin was significantly elevated in the patients with cystic fibrosis; this elevation is in contrast with previous findings in children. Release of gastric inhibitory polypeptide was impaired, while release of cholecystokinin showed no significant difference in control values, although there was a tendency for delay. There was no significant postprandial rise of pancreatic polypeptide in the patients, whose levels were grossly lower than controls. Insulin showed a delayed response. No significant differences were observed between patients and controls in levels of gastrin, pancreatic glucagon, somatostatin, or vasoactive intestinal peptide. The elevation of plasma neurotensin and enteroglucagon in the basal state may reflect an adaptive response and may be part of the improved digestive function in adults compared with children with fibrocystic disease.

  7. Antimicrobial Peptides in 2014

    PubMed Central

    Wang, Guangshun; Mishra, Biswajit; Lau, Kyle; Lushnikova, Tamara; Golla, Radha; Wang, Xiuqing

    2015-01-01

    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. PMID:25806720

  8. PH dependent adhesive peptides

    DOEpatents

    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.

  9. Multifactorial Understanding of Ion Abundance in Tandem Mass Spectrometry Experiments.

    PubMed

    Fazal, Zeeshan; Southey, Bruce R; Sweedler, Jonathan V; Rodriguez-Zas, Sandra L

    2013-01-29

    In a bottom-up shotgun approach, the proteins of a mixture are enzymatically digested, separated, and analyzed via tandem mass spectrometry. The mass spectra relating fragment ion intensities (abundance) to the mass-to-charge are used to deduce the amino acid sequence and identify the peptides and proteins. The variables that influence intensity were characterized using a multi-factorial mixed-effects model, a ten-fold cross-validation, and stepwise feature selection on 6,352,528 fragment ions from 61,543 peptide ions. Intensity was higher in fragment ions that did not have neutral mass loss relative to any mass loss or that had a +1 charge state. Peptide ions classified for proton mobility as non-mobile had lowest intensity of all mobility levels. Higher basic residue (arginine, lysine or histidine) counts in the peptide ion and low counts in the fragment ion were associated with lower fragment ion intensities. Higher counts of proline in peptide and fragment ions were associated with lower intensities. These results are consistent with the mobile proton theory. Opposite trends between peptide and fragment ion counts and intensity may be due to the different impact of factor under consideration at different stages of the MS/MS experiment or to the different distribution of observations across peptide and fragment ion levels. Presence of basic residues at all three positions next to the fragmentation site was associated with lower fragment ion intensity. The presence of proline proximal to the fragmentation site enhanced fragmentation and had the opposite trend when located distant from the site. A positive association between fragment ion intensity and presence of sulfur residues (cysteine and methionine) on the vicinity of the fragmentation site was identified. These results highlight the multi-factorial nature of fragment ion intensity and could improve the algorithms for peptide identification and the simulation in tandem mass spectrometry experiments.

  10. Multifactorial Understanding of Ion Abundance in Tandem Mass Spectrometry Experiments

    PubMed Central

    Fazal, Zeeshan; Southey, Bruce R; Sweedler, Jonathan V.; Rodriguez-Zas, Sandra L.

    2013-01-01

    In a bottom-up shotgun approach, the proteins of a mixture are enzymatically digested, separated, and analyzed via tandem mass spectrometry. The mass spectra relating fragment ion intensities (abundance) to the mass-to-charge are used to deduce the amino acid sequence and identify the peptides and proteins. The variables that influence intensity were characterized using a multi-factorial mixed-effects model, a ten-fold cross-validation, and stepwise feature selection on 6,352,528 fragment ions from 61,543 peptide ions. Intensity was higher in fragment ions that did not have neutral mass loss relative to any mass loss or that had a +1 charge state. Peptide ions classified for proton mobility as non-mobile had lowest intensity of all mobility levels. Higher basic residue (arginine, lysine or histidine) counts in the peptide ion and low counts in the fragment ion were associated with lower fragment ion intensities. Higher counts of proline in peptide and fragment ions were associated with lower intensities. These results are consistent with the mobile proton theory. Opposite trends between peptide and fragment ion counts and intensity may be due to the different impact of factor under consideration at different stages of the MS/MS experiment or to the different distribution of observations across peptide and fragment ion levels. Presence of basic residues at all three positions next to the fragmentation site was associated with lower fragment ion intensity. The presence of proline proximal to the fragmentation site enhanced fragmentation and had the opposite trend when located distant from the site. A positive association between fragment ion intensity and presence of sulfur residues (cysteine and methionine) on the vicinity of the fragmentation site was identified. These results highlight the multi-factorial nature of fragment ion intensity and could improve the algorithms for peptide identification and the simulation in tandem mass spectrometry experiments. PMID

  11. Voluntary scheduled exercise alters diurnal rhythms of behaviour, physiology and gene expression in wild-type and vasoactive intestinal peptide-deficient mice

    PubMed Central

    Schroeder, Analyne M; Truong, Danny; Loh, Dawn H; Jordan, Maria C; Roos, Kenneth P; Colwell, Christopher S

    2012-01-01

    The circadian system co-ordinates the temporal patterning of behaviour and many underlying biological processes. In some cases, the regulated outputs of the circadian system, such as activity, may be able to feed back to alter core clock processes. In our studies, we used four wheel-access conditions (no access; free access; early night; and late night) to manipulate the duration and timing of activity while under the influence of a light–dark cycle. In wild-type mice, scheduled wheel access was able to increase ambulatory activity, inducing a level of exercise driven at various phases of the light–dark cycle. Scheduled exercise also manipulated the magnitude and phasing of the circadian-regulated outputs of heart rate and body temperature. At a molecular level, the phasing and amplitude of PER2::LUCIFERASE (PER2::LUC) expression rhythms in the SCN and peripheral tissues of Per2::Luc knockin mice were altered by scheduled exercise. We then tested whether scheduled wheel access could improve deficits observed in vasointestinal polypeptide-deficient mice under the influence of a light–dark cycle. We found that scheduled wheel access during the late night improved many of the behavioural, physiological and molecular deficits previously described in vasointestinal polypeptide-deficient mice. Our results raise the possibility that scheduled exercise could be used as a tool to modulate daily rhythms and, when applied, may counteract some of the negative impacts of ageing and disease on the circadian system. PMID:22988135

  12. Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage

    PubMed Central

    St John, Ashley L; Rathore, Abhay PS; Raghavan, Bhuvanakantham; Ng, Mah-Lee; Abraham, Soman N

    2013-01-01

    Dengue Virus (DENV), a flavivirus spread by mosquito vectors, can cause vascular leakage and hemorrhaging. However, the processes that underlie increased vascular permeability and pathological plasma leakage during viral hemorrhagic fevers are largely unknown. Mast cells (MCs) are activated in vivo during DENV infection, and we show that this elevates systemic levels of their vasoactive products, including chymase, and promotes vascular leakage. Treatment of infected animals with MC-stabilizing drugs or a leukotriene receptor antagonist restores vascular integrity during experimental DENV infection. Validation of these findings using human clinical samples revealed a direct correlation between MC activation and DENV disease severity. In humans, the MC-specific product, chymase, is a predictive biomarker distinguishing dengue fever (DF) and dengue hemorrhagic fever (DHF). Additionally, our findings reveal MCs as potential therapeutic targets to prevent DENV-induced vasculopathy, suggesting MC-stabilizing drugs should be evaluated for their effectiveness in improving disease outcomes during viral hemorrhagic fevers. DOI: http://dx.doi.org/10.7554/eLife.00481.001 PMID:23638300

  13. Brain oxygenation with a non-vasoactive perfluorocarbon emulsion in a rat model of traumatic brain injury.

    PubMed

    Abutarboush, Rania; Mullah, Saad H; Saha, Biswajit K; Haque, Ashraful; Walker, Peter B; Aligbe, Chioma; Pappas, Georgina; Tran Ho, Lam Thuy Vi; Arnaud, Francoise G; Auker, Charles R; McCarron, Richard M; Scultetus, Anke H; Moon-Massat, Paula

    2018-04-01

    The aim of this study was to assess, in two experiments, the safety and efficacy of the PFC emulsion Oxycyte as an oxygen therapeutic for TBI to test the hypothesis that early administration of this oxygen-carrying fluid post-TBI would improve brain tissue oxygenation (P bt O 2 ). The first experiment assessed the effects of Oxycyte on cerebral vasoactivity in healthy, uninjured rats using intravital microscopy. The second experiment investigated the effect of Oxycyte on cerebral P bt O 2 using the PQM in TBI model. Animals in the Oxycyte group received a single injection of Oxycyte (6 mL/kg) shortly after TBI, while NON animals received no treatment. Oxycyte did not cause vasoconstriction in small- (<50 μm) or medium- (50-100 μm) sized pial arterioles nor did it cause a significant change in blood pressure. Treatment with Oxycyte while breathing 100% O 2 did not improve P bt O 2 . However, in rats ventilated with ~40% O 2 , P bt O 2 improved to near pre-TBI values within 105 minutes after Oxycyte injection. Although Oxycyte did not cause cerebral vasoconstriction, its use at the dose tested while breathing 100% O 2 did not improve P bt O 2 following TBI. However, Oxycyte treatment while breathing a lower enriched oxygen concentration may improve P bt O 2 after TBI. © 2018 John Wiley & Sons Ltd.

  14. Calcitonin gene-related peptide stimulates proliferation of human endothelial cells.

    PubMed Central

    Haegerstrand, A; Dalsgaard, C J; Jonzon, B; Larsson, O; Nilsson, J

    1990-01-01

    The effects of the vasoactive perivascular neuropeptides calcitonin gene-related peptide (CGRP), neurokinin A (NKA), neuropeptide Y (NPY), and vasoactive intestinal polypeptide (VIP) on proliferation of cultured human umbilical vein endothelial cells (HUVECs) were investigated. CGRP was shown to increase both cell number and DNA synthesis, whereas NKA, NPY, and VIP were ineffective. 125I-labeled CGRP was shown to bind to HUVECs and this binding was displaced by addition of unlabeled CGRP, suggesting the existence of specific CGRP receptors. The effect of CGRP on formation of adenosine 3',5'-cyclic monophosphate (cAMP) and inositol phosphates (InsP), two intracellular messengers known to be involved in regulation of cell proliferation, was investigated. CGRP stimulated cAMP formation but was without effect on the formation of InsP. Proliferation, as well as cAMP formation, was also stimulated by cholera toxin. Basic fibroblast growth factor stimulated growth without affecting cAMP or InsP formation, whereas thrombin, which increased InsP formation, did not stimulate proliferation. We thus suggest that CGRP may act as a local factor stimulating proliferation of endothelial cells; that the mechanism of action is associated with cAMP formation; and that this effect of CGRP may be important for formation of new vessels during physiological and pathophysiological events such as ischemia, inflammation, and wound healing. PMID:2159144

  15. Calcitonin gene-related peptide stimulates proliferation of human endothelial cells.

    PubMed

    Haegerstrand, A; Dalsgaard, C J; Jonzon, B; Larsson, O; Nilsson, J

    1990-05-01

    The effects of the vasoactive perivascular neuropeptides calcitonin gene-related peptide (CGRP), neurokinin A (NKA), neuropeptide Y (NPY), and vasoactive intestinal polypeptide (VIP) on proliferation of cultured human umbilical vein endothelial cells (HUVECs) were investigated. CGRP was shown to increase both cell number and DNA synthesis, whereas NKA, NPY, and VIP were ineffective. 125I-labeled CGRP was shown to bind to HUVECs and this binding was displaced by addition of unlabeled CGRP, suggesting the existence of specific CGRP receptors. The effect of CGRP on formation of adenosine 3',5'-cyclic monophosphate (cAMP) and inositol phosphates (InsP), two intracellular messengers known to be involved in regulation of cell proliferation, was investigated. CGRP stimulated cAMP formation but was without effect on the formation of InsP. Proliferation, as well as cAMP formation, was also stimulated by cholera toxin. Basic fibroblast growth factor stimulated growth without affecting cAMP or InsP formation, whereas thrombin, which increased InsP formation, did not stimulate proliferation. We thus suggest that CGRP may act as a local factor stimulating proliferation of endothelial cells; that the mechanism of action is associated with cAMP formation; and that this effect of CGRP may be important for formation of new vessels during physiological and pathophysiological events such as ischemia, inflammation, and wound healing.

  16. Cell Penetrating Peptides and Cationic Antibacterial Peptides

    PubMed Central

    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

  17. Actinide abundances in ordinary chondrites

    NASA Technical Reports Server (NTRS)

    Hagee, B.; Bernatowicz, T. J.; Podosek, F. A.; Johnson, M. L.; Burnett, D. S.

    1990-01-01

    Measurements of actinide and light REE (LREE) abundances and of phosphate abundances in equilibrated ordinary chondrites were obtained and were used to define the Pu abundance in the solar system and to determine the degree of variation of actinide and LREE abundances. The results were also used to compare directly the Pu/U ratio with the earlier obtained ratio determined indirectly, as (Pu/Nd)x(Nd/U), assuming that Pu behaves chemically as a LREE. The data, combined with high-accuracy isotope-dilution data from the literature, show that the degree of gram-scale variability of the Th, U, and LREE abundances for equilibrated ordinary chondrites is a factor of 2-3 for absolute abundances and up to 50 percent for relative abundances. The observed variations are interpreted as reflecting the differences in the compositions and/or proportions of solar nebula components accreted to ordinary chondrite parent bodies.

  18. Plant peptide hormone signalling.

    PubMed

    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.

  19. Twilight of Abundance

    NASA Astrophysics Data System (ADS)

    Archibald, David

    2014-03-01

    Baby boomers enjoyed the most benign period in human history: fifty years of relative peace, cheap energy, plentiful grain supply, and a warming climate due to the highest solar activity for 8,000 years. The party is over - prepare for the twilight of abundance. David Archibald reveals the grim future the world faces on its current trajectory: massive fuel shortages, the bloodiest warfare in human history, a global starvation crisis, and a rapidly cooling planet. Archibald combines pioneering science with keen economic knowledge to predict the global disasters that could destroy civilization as we know it - disasters that are waiting just around the corner. But there's good news, too: We can have a good future if we prepare for it. Advanced, civilized countries can have a permanently high standard of living if they choose to invest in the technologies that will get them there. Archibald, a climate scientist as well as an inventor and a financial specialist, explains which scientific breakthroughs can save civilization in the coming crisis - if we can cut through the special interest opposition to these innovations and allow free markets to flourish.

  20. Peptide synthesis in early earth hydrothermal systems

    USGS Publications Warehouse

    Lemke, K.H.; Rosenbauer, R.J.; Bird, D.K.

    2009-01-01

    We report here results from experiments and thermodynamic calculations that demonstrate a rapid, temperature-enhanced synthesis of oligopeptides from the condensation of aqueous glycine. Experiments were conducted in custom-made hydrothermal reactors, and organic compounds were characterized with ultraviolet-visible procedures. A comparison of peptide yields at 260??C with those obtained at more moderate temperatures (160??C) gives evidence of a significant (13 kJ ?? mol-1) exergonic shift. In contrast to previous hydrothermal studies, we demonstrate that peptide synthesis is favored in hydrothermal fluids and that rates of peptide hydrolysis are controlled by the stability of the parent amino acid, with a critical dependence on reactor surface composition. From our study, we predict that rapid recycling of product peptides from cool into near-supercritical fluids in mid-ocean ridge hydrothermal systems will enhance peptide chain elongation. It is anticipated that the abundant hydrothermal systems on early Earth could have provided a substantial source of biomolecules required for the origin of life. Astrobiology 9, 141-146. ?? 2009 Mary Ann Liebert, Inc. 2009.

  1. Gastrin-Releasing Peptide and Glucose Metabolism Following Pancreatitis.

    PubMed

    Pendharkar, Sayali A; Drury, Marie; Walia, Monika; Korc, Murray; Petrov, Maxim S

    2017-08-01

    Gastrin-releasing peptide (GRP) is a pluripotent peptide that has been implicated in both gastrointestinal inflammatory states and classical chronic metabolic diseases such as diabetes. Abnormal glucose metabolism (AGM) after pancreatitis, an exemplar inflammatory disease involving the gastrointestinal tract, is associated with persistent low-grade inflammation and altered secretion of pancreatic and gut hormones as well as cytokines. While GRP is involved in secretion of many of them, it is not known whether GRP has a role in AGM. Therefore, we aimed to investigate the association between GRP and AGM following pancreatitis. Fasting blood samples were collected to measure GRP, blood glucose, insulin, amylin, glucagon, pancreatic polypeptide (PP), somatostatin, cholecystokinin, gastric-inhibitory peptide (GIP), gastrin, ghrelin, glicentin, glucagon-like peptide-1 and 2, oxyntomodulin, peptide YY (PYY), secretin, vasoactive intestinal peptide, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP)-1, and interleukin-6. Modified Poisson regression analysis and linear regression analyses were conducted. Four statistical models were used to adjust for demographic, metabolic, and pancreatitis-related risk factors. A total of 83 individuals after an episode of pancreatitis were recruited. GRP was significantly associated with AGM, consistently in all four models (P -trend < 0.05), and fasting blood glucose contributed 17% to the variance of GRP. Further, GRP was significantly associated with glucagon (P < 0.003), MCP-1 (P < 0.025), and TNF-α (P < 0.025) - consistently in all four models. GRP was also significantly associated with PP and PYY in three models (P < 0.030 for both), and with GIP and glicentin in one model (P = 0.001 and 0.024, respectively). Associations between GRP and other pancreatic and gut hormones were not significant. GRP is significantly increased in patients with AGM after pancreatitis and is associated with increased levels of pro

  2. Gastrin-Releasing Peptide and Glucose Metabolism Following Pancreatitis

    PubMed Central

    Pendharkar, Sayali A.; Drury, Marie; Walia, Monika; Korc, Murray; Petrov, Maxim S.

    2017-01-01

    Background Gastrin-releasing peptide (GRP) is a pluripotent peptide that has been implicated in both gastrointestinal inflammatory states and classical chronic metabolic diseases such as diabetes. Abnormal glucose metabolism (AGM) after pancreatitis, an exemplar inflammatory disease involving the gastrointestinal tract, is associated with persistent low-grade inflammation and altered secretion of pancreatic and gut hormones as well as cytokines. While GRP is involved in secretion of many of them, it is not known whether GRP has a role in AGM. Therefore, we aimed to investigate the association between GRP and AGM following pancreatitis. Methods Fasting blood samples were collected to measure GRP, blood glucose, insulin, amylin, glucagon, pancreatic polypeptide (PP), somatostatin, cholecystokinin, gastric-inhibitory peptide (GIP), gastrin, ghrelin, glicentin, glucagon-like peptide-1 and 2, oxyntomodulin, peptide YY (PYY), secretin, vasoactive intestinal peptide, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP)-1, and interleukin-6. Modified Poisson regression analysis and linear regression analyses were conducted. Four statistical models were used to adjust for demographic, metabolic, and pancreatitis-related risk factors. Results A total of 83 individuals after an episode of pancreatitis were recruited. GRP was significantly associated with AGM, consistently in all four models (P -trend < 0.05), and fasting blood glucose contributed 17% to the variance of GRP. Further, GRP was significantly associated with glucagon (P < 0.003), MCP-1 (P < 0.025), and TNF-α (P < 0.025) - consistently in all four models. GRP was also significantly associated with PP and PYY in three models (P < 0.030 for both), and with GIP and glicentin in one model (P = 0.001 and 0.024, respectively). Associations between GRP and other pancreatic and gut hormones were not significant. Conclusion GRP is significantly increased in patients with AGM after pancreatitis and is

  3. Physiological effects of major up-regulated Alnus glutinosa peptides on Frankia sp. ACN14a.

    PubMed

    Carro, Lorena; Pujic, Petar; Alloisio, Nicole; Fournier, Pascale; Boubakri, Hasna; Poly, Franck; Rey, Marjolaine; Heddi, Abdelaziz; Normand, Philippe

    2016-07-01

    Alnus glutinosa has been shown previously to synthesize, in response to nodulation by Frankia sp. ACN14a, an array of peptides called Alnus symbiotic up-regulated peptides (ASUPs). In a previous study one peptide (Ag5) was shown to bind to Frankia nitrogen-fixing vesicles and to modify their porosity. Here we analyse four other ASUPs, alongside Ag5, to determine whether they have different physiological effects on in vitro grown Frankia sp. ACN14a. The five studied peptides were shown to have different effects on nitrogen fixation, respiration, growth, the release of ions and amino acids, as well as on cell clumping and cell lysis. The mRNA abundance for all five peptides was quantified in symbiotic nodules and one (Ag11) was found to be more abundant in the meristem part of the nodule. These findings point to some peptides having complementary effects on Frankia cells.

  4. Molecular Cloning and Characterization of Two Pig Vasoactive Intestinal Polypeptide Receptors (VPAC1-R and VPAC2-R)

    PubMed Central

    He, Xiaping; Meng, Fengyan; Wang, Yajun

    2014-01-01

    We here report the cloning, tissue expression, and functional analyses of the two pig vasoactive intestinal polypeptide (VIP) receptors (pVPAC1-R and pVPAC2-R). The cloned full-length pVPAC1-R and pVPAC2-R share high structural similarity with their mammalian counterparts. Functional assay revealed that the full-length pVPAC1-R and pVPAC2-R-expressed Chinese hamster ovary (CHO) cells could be activated by pVIP and pPACAP38 potently, indicating that pVPAC1-R and pVPAC2-R are capable of binding VIP and pituitary adenylate cyclase-activating polypeptide (PACAP). In addition to the identification of the transcripts encoding the two full-length receptors, multiple splice transcript variants were isolated. Comparison with the pig genome database revealed that pVPAC1-R and pVPAC2-R share a unique gene structure with 14 exons different from other vertebrates. Reverse transcription and polymerase chain reaction (RT-PCR) assays further showed that the transcript encoding the full-length pVPAC2-R is widely expressed in all adult tissues whereas the splice variants of pVPAC1-R are predominantly expressed in all tissues instead of the transcript encoding the full-length receptor, hinting that pVPAC2-R may play more important roles than pVPAC1-R in mediating VIP and PACAP actions. Our present findings help to elucidate the important role of VIP and PACAP and promote to rethink of their species-specific physiological roles including their actions in regulation of phenotypic traits in pigs. PMID:24520933

  5. Framework of collagen type I - vasoactive vessels structuring invariant geometric attractor in cancer tissues: insight into biological magnetic field.

    PubMed

    Díaz, Jairo A; Murillo, Mauricio F; Jaramillo, Natalia A

    2009-01-01

    In a previous research, we have described and documented self-assembly of geometric triangular chiral hexagon crystal-like complex organizations (GTCHC) in human pathological tissues. This article documents and gathers insights into the magnetic field in cancer tissues and also how it generates an invariant functional geometric attractor constituted for collider partners in their entangled environment. The need to identify this hierarquic attractor was born out of the concern to understand how the vascular net of these complexes are organized, and to determine if the spiral vascular subpatterns observed adjacent to GTCHC complexes and their assembly are interrelational. The study focuses on cancer tissues and all the macroscopic and microscopic material in which GTCHC complexes are identified, which have been overlooked so far, and are rigorously revised. This revision follows the same parameters that were established in the initial phase of the investigation, but with a new item: the visualization and documentation of external dorsal serous vascular bed areas in spatial correlation with the localization of GTCHC complexes inside the tumors. Following the standard of the electro-optical collision model, we were able to reproduce and replicate collider patterns, that is, pairs of left and right hand spin-spiraled subpatterns, associated with the orientation of the spinning process that can be an expansion or contraction disposition of light particles. Agreement between this model and tumor data is surprisingly close; electromagnetic spiral patterns generated were identical at the spiral vascular arrangement in connection with GTCHC complexes in malignant tumors. These findings suggest that the framework of collagen type 1 - vasoactive vessels that structure geometric attractors in cancer tissues with invariant morphology sets generate collider partners in their magnetic domain with opposite biological behavior. If these principles are incorporated into nanomaterial

  6. Vascular responses of the extremities to transdermal application of vasoactive agents in Caucasian and African descent individuals.

    PubMed

    Maley, Matthew J; House, James R; Tipton, Michael J; Eglin, Clare M

    2015-08-01

    Individuals of African descent (AFD) are more susceptible to non-freezing cold injury than Caucasians (CAU) which may be due, in part, to differences in the control of skin blood flow. We investigated the skin blood flow responses to transdermal application of vasoactive agents. Twenty-four young males (12 CAU and 12 AFD) undertook three tests in which iontophoresis was used to apply acetylcholine (ACh 1 w/v %), sodium nitroprusside (SNP 0.01 w/v %) and noradrenaline (NA 0.5 mM) to the skin. The skin sites tested were: volar forearm, non-glabrous finger and toe, and glabrous finger (pad) and toe (pad). In response to SNP on the forearm, AFD had less vasodilatation for a given current application than CAU (P = 0.027-0.004). ACh evoked less vasodilatation in AFD for a given application current in the non-glabrous finger and toe compared with CAU (P = 0.043-0.014) with a lower maximum vasodilatation in the non-glabrous finger (median [interquartile], AFD n = 11, 41[234] %, CAU n = 12, 351[451] %, P = 0.011) and non-glabrous toe (median [interquartile], AFD n = 9, 116[318] %, CAU n = 12, 484[720] %, P = 0.018). ACh and SNP did not elicit vasodilatation in the glabrous skin sites of either group. There were no ethnic differences in response to NA. AFD have an attenuated endothelium-dependent vasodilatation in non-glabrous sites of the fingers and toes compared with CAU. This may contribute to lower skin temperature following cold exposure and the increased risk of cold injuries experienced by AFD.

  7. Effects of vasoactive intestinal polypeptide on antigen-induced bronchoconstriction and thromboxane release in guinea-pig lung.

    PubMed Central

    Ciabattoni, G.; Montuschi, P.; Currò, D.; Togna, G.; Preziosi, P.

    1993-01-01

    1. Exogenous vasoactive intestinal polypeptide (VIP) infused into the pulmonary artery of isolated and ventilated lungs of guinea-pigs decreased, in a dose-dependent fashion (1.0-10.0 nmol), airway resistance and thromboxane B2 (TXB2, the stable hydrolysis product of TXA2) release in the perfusion medium. Prostacyclin (PGI2) synthesis, as reflected by the release of its stable hydrolysis product 6-oxo-PGF1 alpha, was unaffected. Pretreatment with the 5-lipoxygenase inhibitor BWA4c (3.5 x 10(-5) M) did not modify the bronchodilatory effect of VIP or its inhibitory action on TXB2 release. 2. Basal release of immunoreactive VIP from perfused lungs decreased from an initial value of 0.96 +/- 0.10 ng min-1 (mean +/- s.e.mean) in the first 2 min to an average of 0.58 +/- 0.10 ng min-1 in the following 15-20 min. 3. Antigen challenge with ovalbumin (0.1%) in sensitized lungs caused an anaphylactic reaction in 45% of tested lungs, concomitant with a 5 fold increase in both VIP and TXB2 release. Tetrodotoxin pretreatment (10(-6) M) reduced basal VIP release by > 80% and abolished the VIP increase observed during anaphylaxis, without modifying TXB2 release or the bronchoconstrictor response. 4. Indomethacin (10(-6) M) inhibited TXB2 synthesis and release by > 90%, delayed the bronchoconstrictor response and blunted the increased VIP release during lung anaphylaxis, without influencing basal VIP release. 5. The 5-lipoxygenase inhibitor BWA4c (3.5 x 10(-5) M) blunted the increase of TXB2 and VIP release from guinea-pig lung and attenuated the bronchoconstrictor response following ovalbumin challenge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8495242

  8. Antimicrobial Peptides in Reptiles

    PubMed Central

    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

  9. Peptides in melanoma therapy.

    PubMed

    Mocellin, Simone

    2012-01-01

    Peptides derived from tumor associated antigens can be utilized to elicit a therapeutically effective immune response against melanoma in experimental models. However, patient vaccination with peptides - although it is often followed by the induction of melanoma- specific T lymphocytes - is rarely associated with tumor response of clinical relevance. In this review I summarize the principles of peptide design as well as the results so far obtained in the clinical setting while treating cutaneous melanoma by means of this active immunotherapy strategy. I also discuss some immunological and methodological issues that might be helpful for the successful development of peptide-based vaccines.

  10. Insulin C-peptide test

    MedlinePlus

    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 ...

  11. Regulatory peptides in the plasma of patients with chronic cardiac failure at rest and during exercise.

    PubMed

    Nicholls, D P; Riley, M; Elborn, J S; Stanford, C F; Shaw, C; McKillop, J M; Buchanan, K D

    1992-10-01

    The levels of several regulatory peptides were measured in peripheral plasma samples from individuals with chronic cardiac failure (CCF) and matched controls in both the resting state and during a short period of maximal exercise. Basal levels of noradrenaline (NA; 705 +/- 114 vs 195 +/- 54 ng.l-1; mean +/- SEM; P < 0.05), plasma renin activity (PRA; 12.9 +/- 2.9 vs 2.1 +/- 0.3 ng AI ml-1.h-1; P < 0.05) and aldosterone (ALDO; 325 +/- 49 vs 87 +/- 8 ng.l-1; P < 0.05) were all raised in the patients with CCF, and increased further with exercise. Basal circulating levels of atrial natriuretic peptide (ANP) were also significantly higher in the CCF group compared to controls (136 +/- 35 vs 27 +/- 5 ng.l-1; P < 0.01), but the response to exercise was attenuated, so that at peak exercise, no significant difference was observed. Basal circulating levels of gastrin-releasing peptide (GRP) (29 +/- 4 vs 40 +/- 4 ng.l-1; P < 0.05) and secretin (13 +/- 1 vs 32 +/- 4 ng.l-1; P < 0.05) were significantly lower in the CCF group when compared to controls and there was no significant change in the levels of either peptide with exercise. Levels of neurokinin A (NKA), neuropeptide Y (NPY) and neurotensin (NT) were somewhat higher in patients, but the differences were not significant, and there were no changes during exercise. There were also no significant differences in the levels of vasoactive intestinal peptide (VIP), glucose-dependent insulinotropic polypeptide (GIP), insulin or glucagon in either experimental group both before and during exercise. We have therefore identified different circulating levels of certain regulatory peptides in patients with CCF, but the significance of these remains unclear.

  12. Peptide bioregulators inhibit apoptosis.

    PubMed

    Khavinson, V K; Kvetnoii, I M

    2000-12-01

    The effects of peptide bioregulators epithalon and vilon on the dynamics of irradiation-induced apoptotic death of spleen lymphocytes in rats indicate that these agents inhibit physiologically programmed cell death. The antiapoptotic effect of vilon was more pronounced, which corroborates the concept on tissue-specific effect of peptide bioregulators.

  13. Peptide Vaccines for Leishmaniasis.

    PubMed

    De Brito, Rory C F; Cardoso, Jamille M De O; Reis, Levi E S; Vieira, Joao F; Mathias, Fernando A S; Roatt, Bruno M; Aguiar-Soares, Rodrigo Dian D O; Ruiz, Jeronimo C; Resende, Daniela de M; Reis, Alexandre B

    2018-01-01

    Due to an increase in the incidence of leishmaniases worldwide, the development of new strategies such as prophylactic vaccines to prevent infection and decrease the disease have become a high priority. Classic vaccines against leishmaniases were based on live or attenuated parasites or their subunits. Nevertheless, the use of whole parasite or their subunits for vaccine production has numerous disadvantages. Therefore, the use of Leishmania peptides to design more specific vaccines against leishmaniases seems promising. Moreover, peptides have several benefits in comparison with other kinds of antigens, for instance, good stability, absence of potentially damaging materials, antigen low complexity, and low-cost to scale up. By contrast, peptides are poor immunogenic alone, and they need to be delivered correctly. In this context, several approaches described in this review are useful to solve these drawbacks. Approaches, such as, peptides in combination with potent adjuvants, cellular vaccinations, adenovirus, polyepitopes, or DNA vaccines have been used to develop peptide-based vaccines. Recent advancements in peptide vaccine design, chimeric, or polypeptide vaccines and nanovaccines based on particles attached or formulated with antigenic components or peptides have been increasingly employed to drive a specific immune response. In this review, we briefly summarize the old, current, and future stands on peptide-based vaccines, describing the disadvantages and benefits associated with them. We also propose possible approaches to overcome the related weaknesses of synthetic vaccines and suggest future guidelines for their development.

  14. Evidence against vasoactive intestinal polypeptide (VIP) as a dilator and in favour of substance P as a constrictor in airway neurogenic responses.

    PubMed Central

    Karlsson, J. A.; Persson, C. G.

    1983-01-01

    Propranolol-resistant neurogenic relaxation persisted in (carbachol-contracted) guinea-pig tracheae already relaxed by supramaximal concentrations of vasoactive intestinal polypeptide (VIP). Also, VIP relaxed preparations that were under neurogenic inhibition. In hilus bronchi, about 60% of a neurogenic contraction was atropine-resistant. (Arg5, D-Trp7.9) SP 5-11 specifically antagonized this contraction and those produced by exogenous substance P. Substance P, but not VIP, seems to be involved in nerve-mediated effects on guinea-pig airway tone. PMID:6197124

  15. Evidence against vasoactive intestinal polypeptide (VIP) as a dilator and in favour of substance P as a constrictor in airway neurogenic responses.

    PubMed

    Karlsson, J A; Persson, C G

    1983-07-01

    Propranolol-resistant neurogenic relaxation persisted in (carbachol-contracted) guinea-pig tracheae already relaxed by supramaximal concentrations of vasoactive intestinal polypeptide (VIP). Also, VIP relaxed preparations that were under neurogenic inhibition. In hilus bronchi, about 60% of a neurogenic contraction was atropine-resistant. (Arg5, D-Trp7.9) SP 5-11 specifically antagonized this contraction and those produced by exogenous substance P. Substance P, but not VIP, seems to be involved in nerve-mediated effects on guinea-pig airway tone.

  16. Antimicrobial Peptides from Fish

    PubMed Central

    Masso-Silva, Jorge A.; Diamond, Gill

    2014-01-01

    Antimicrobial peptides (AMPs) are found widely distributed through Nature, and participate in the innate host defense of each species. Fish are a great source of these peptides, as they express all of the major classes of AMPs, including defensins, cathelicidins, hepcidins, histone-derived peptides, and a fish-specific class of the cecropin family, called piscidins. As with other species, the fish peptides exhibit broad-spectrum antimicrobial activity, killing both fish and human pathogens. They are also immunomodulatory, and their genes are highly responsive to microbes and innate immuno-stimulatory molecules. Recent research has demonstrated that some of the unique properties of fish peptides, including their ability to act even in very high salt concentrations, make them good potential targets for development as therapeutic antimicrobials. Further, the stimulation of their gene expression by exogenous factors could be useful in preventing pathogenic microbes in aquaculture. PMID:24594555

  17. The cuticular localization of integument peptides from particular routing categories.

    PubMed

    Locke, M; Kiss, A; Sass, M

    1994-10-01

    The distribution of integument peptides in relation to chitin and structural features has been studied in the surface epidermis of the caterpillar of Calpodes ethlius by immunoblotting and immunogold labelling using antibodies prepared to peptides isolated from lamellate endocuticle or from hemolymph. The intermoult cuticle consists of an epicuticle, an endocuticle of many chitin containing lamellae, and a chitin containing assembly zone directly above the apical epidermal microvilli and the perimicrovillar space. During the intermoult, the epidermis secretes peptides constitutively, that is, secretory vesicles containing peptides exocytose without accumulating, traverse the perimicrovillar space and form lamellae in the assembly zone. At moulting, the epidermis deposits ecdysial droplets in addition. These interrupt the last few lamellae which later go on to become the perforated ecdysial membrane. The integument is involved with four routing classes of peptide. Secretion is apical into the cuticle (C), basal into the hemolymph (H), bidirectional (BD), or transported to the cuticle across the epidermis from the hemolymph (T). Some peptides change their routing at moulting. There are several patterns of localization. (1) C and BD cuticular peptides occur mainly in chitin containing lamellate cuticle. (2) Some are also present in epicuticle, and are therefore not obligatorily linked to chitin or matrix between chitin fibers. Cuticular peptides that also occur in the hemolymph are glycosylated, whereas most that are only secreted apically into the cuticle are not. All BD but few C peptides carry alpha-D-glucose/alpha-D-mannose. Some C and BD peptides carry N-acetyl glucosamine. (3) C36 extracted from cuticle has most N-acetyl glucosamine and colocalizes with chitin rather than the protein matrix. It is therefore probably the main link between chitin fibers and the matrix. (4) H235 is barely detectable at the apical cell surface during the intermoult but is abundant

  18. Uncovering the design rules for peptide synthesis of metal nanoparticles.

    PubMed

    Tan, Yen Nee; Lee, Jim Yang; Wang, Daniel I C

    2010-04-28

    Peptides are multifunctional reagents (reducing and capping agents) that can be used for the synthesis of biocompatible metal nanoparticles under relatively mild conditions. However, the progress in peptide synthesis of metal nanoparticles has been slow due to the lack of peptide design rules. It is difficult to establish sequence-reactivity relationships from peptides isolated from biological sources (e.g., biomineralizing organisms) or selected by combinatorial display libraries because of their widely varying compositions and structures. The abundance of random and inactive amino acid sequences in the peptides also increases the difficulty in knowledge extraction. In this study, a "bottom-up" approach was used to formulate a set of rudimentary rules for the size- and shape-controlled peptide synthesis of gold nanoparticles from the properties of the 20 natural alpha-amino acids for AuCl(4)(-) reduction and binding to Au(0). It was discovered that the reduction capability of a peptide depends on the presence of certain reducing amino acid residues, whose activity may be regulated by neighboring residues with different Au(0) binding strengths. Another finding is the effect of peptide net charge on the nucleation and growth of the Au nanoparticles. On the basis of these understandings, several multifunctional peptides were designed to synthesize gold nanoparticles in different morphologies (nanospheres and nanoplates) and with sizes tunable by the strategic placement of selected amino acid residues in the peptide sequence. The methodology presented here and the findings are useful for establishing the scientific basis for the rational design of peptides for the synthesis of metal nanostructures.

  19. Relative and accurate measurement of protein abundance using 15N stable isotope labeling in Arabidopsis (SILIA).

    PubMed

    Guo, Guangyu; Li, Ning

    2011-07-01

    In the quantitative proteomic studies, numerous in vitro and in vivo peptide labeling strategies have been successfully applied to measure differentially regulated protein and peptide abundance. These approaches have been proven to be versatile and repeatable in biological discoveries. (15)N metabolic labeling is one of these widely adopted and economical methods. However, due to the differential incorporation rates of (15)N or (14)N, the labeling results produce imperfectly matched isotopic envelopes between the heavy and light nitrogen-labeled peptides. In the present study, we have modified the solid Arabidopsis growth medium to standardize the (15)N supply, which led to a uniform incorporation of (15)N into the whole plant protein complement. The incorporation rate (97.43±0.11%) of (15)N into (15)N-coded peptides was determined by correlating the intensities of peptide ions with the labeling efficiencies according to Gaussian distribution. The resulting actual incorporation rate (97.44%) and natural abundance of (15)N/(14)N-coded peptides are used to re-calculate the intensities of isotopic envelopes of differentially labeled peptides, respectively. A modified (15)N/(14)N stable isotope labeling strategy, SILIA, is assessed and the results demonstrate that this approach is able to differentiate the fold change in protein abundance down to 10%. The machine dynamic range limitation and purification step will make the precursor ion ratio deriving from the actual ratio fold change. It is suggested that the differentially mixed (15)N-coded and (14)N-coded plant protein samples that are used to establish the protein abundance standard curve should be prepared following a similar protein isolation protocol used to isolate the proteins to be quantitated. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  20. Comparison of Urine and Plasma Peptidome Indicates Selectivity in Renal Peptide Handling.

    PubMed

    Magalhães, Pedro; Pontillo, Claudia; Pejchinovski, Martin; Siwy, Justyna; Krochmal, Magdalena; Makridakis, Manousos; Carrick, Emma; Klein, Julie; Mullen, William; Jankowski, Joachim; Vlahou, Antonia; Mischak, Harald; Schanstra, Joost P; Zürbig, Petra; Pape, Lars

    2018-04-03

    Urine is considered to be produced predominantly as a result of plasma filtration in the kidney. However, the origin of the native peptides present in urine has never been investigated in detail. Therefore, the authors aimed to obtain a first insight into the origin of urinary peptides based on a side-by-side comprehensive analysis of the plasma and urine peptidome. Twenty-two matched urine and plasma samples are analyzed for their peptidome using capillary electrophoresis coupled to mass spectrometry (CE-MS; for relative quantification) and CE or LC coupled to tandem mass spectrometry (CE- or LC-MS/MS; for peptide identification). The overlap and association of abundance of the different peptides present in these two body fluids are evaluated. The authors are able to identify 561 plasma and 1461 urinary endogenous peptides. Only 90 peptides are detectable in both urine and plasma. No significant correlation is found when comparing the abundance of these common peptides, with the exception of collagen fragments. This observation is also supported when comparing published peptidome data from both plasma and urine. Most of the plasma peptides are not detectable in urine, possibly due to tubular reabsorption. The majority of urinary peptides may in fact originate in the kidney. The notable exception is collagen fragments, which indicates potential selective exclusion of these peptides from tubular reabsorption. Experimental verification of this hypothesis is warranted. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Using Data Independent Acquisition (DIA) to Model High-responding Peptides for Targeted Proteomics Experiments*

    PubMed Central

    Searle, Brian C.; Egertson, Jarrett D.; Bollinger, James G.; Stergachis, Andrew B.; MacCoss, Michael J.

    2015-01-01

    Targeted mass spectrometry is an essential tool for detecting quantitative changes in low abundant proteins throughout the proteome. Although selected reaction monitoring (SRM) is the preferred method for quantifying peptides in complex samples, the process of designing SRM assays is laborious. Peptides have widely varying signal responses dictated by sequence-specific physiochemical properties; one major challenge is in selecting representative peptides to target as a proxy for protein abundance. Here we present PREGO, a software tool that predicts high-responding peptides for SRM experiments. PREGO predicts peptide responses with an artificial neural network trained using 11 minimally redundant, maximally relevant properties. Crucial to its success, PREGO is trained using fragment ion intensities of equimolar synthetic peptides extracted from data independent acquisition experiments. Because of similarities in instrumentation and the nature of data collection, relative peptide responses from data independent acquisition experiments are a suitable substitute for SRM experiments because they both make quantitative measurements from integrated fragment ion chromatograms. Using an SRM experiment containing 12,973 peptides from 724 synthetic proteins, PREGO exhibits a 40–85% improvement over previously published approaches at selecting high-responding peptides. These results also represent a dramatic improvement over the rules-based peptide selection approaches commonly used in the literature. PMID:26100116

  2. Oxygen abundances in halo stars

    NASA Astrophysics Data System (ADS)

    Bessell, Michael S.; Sutherland, Ralph S.; Ruan, Kui

    1991-12-01

    The present study determines the oxygen abundance for a sample of metal-poor G dwarfs by analysis of OH lines between 3080 and 3200 A and the permitted high-excitation far-red O I triple. The oxygen abundances determined from the low-excitation OH lines are up to 0.55 dex lower than those measured from the high-excitation O I lines. The abundances for the far-red O I triplet lines agree with those rederived from Abia and Rebolo (1989), and the abundances from the OH lines in dwarfs and giants are in agreement with the rederived O abundances of Barbuy (1988) and others from the forbidden resonance O I line. Because the chi = 0.1.7 eV OH lines are formed in the same layers as the majority of Fe, Ti, and other neutral metal lines used for abundance analyses, it is argued that the OH lines and the forbidden O I line yield the true oxygen abundances relative to the metals.

  3. Effect of calcitonin on gastrointestinal regulatory peptides in man.

    PubMed

    Stevenson, J C; Adrian, T E; Christofides, N D; Bloom, S R

    1985-05-01

    A major physiological role of calcitonin in humans appears to be regulation of skeletal turnover. It has been suggested that another function of calcitonin is to prevent post-prandial rises in calcium, particularly in animals, but the importance of such a function in man remains to be determined. Although it is known that calcitonin has an inhibitory effect on the secretion of gastrin and insulin, its actions on other gut and pancreatic hormones have not previously been studied. To investigate interrelations between calcitonin and gastrointestinal regulatory peptides, 0.5 mg synthetic human calcitonin was administered to 10 fasting patients. No changes in the plasma concentrations of glucose, somatostatin, neurotensin, enteroglucagon, vasoactive intestinal polypeptide or bombesin were observed. In contrast, profound falls in the circulating levels of gastrin, insulin and pancreatic glucagon were seen, reaching a maximum shortly after the peak of plasma calcitonin concentration. Marked changes were also observed in the levels of motilin, pancreatic polypeptide and, to a lesser extent, gastric inhibitory polypeptide, but the maximal falls occurred about 40 min later, coinciding with a significant fall in serum calcium. It is possible that the effect of calcitonin on these hormones was direct, perhaps receptor-mediated. The falls in levels of motilin and pancreatic polypeptide could have been further enhanced by changes in extracellular calcium ion concentrations. Whether any of these effects of calcitonin occur physiologically remains to be determined. However, these findings suggest new therapeutic possibilities for calcitonin.

  4. Abnormalities of peptide metabolism in Alzheimer disease.

    PubMed

    Panchal, Maï; Rholam, Mohamed; Brakch, Noureddine

    2004-10-01

    The steady-state level of peptide hormones represents a balance between their biosynthesis and proteolytic processing by convertases and their catabolism by proteolytic enzymes. Low levels of neuropeptide Y, somatostatin and corticotropin-releasing factor, described in Alzheimer disease (AD), were related to a defect in proteolytic processing of their protein precursors. In contrast the abundance of beta-amyloid peptides, the major protein constituents of senile plaques is likely related to inefficient catabolism. Therefore, attention is mainly focused on convertases that generate active peptides and counter-regulatory proteases that are involved in their catabolism. Some well-described proteases such as NEP are thought to be involved in beta-amyloid catabolism. The search of other possible candidates represents a primary effort in the field. A variety of vascular risk factors such as diabetes, hypertension and arteriosclerosis suggest that the functional vascular defect contributes to AD pathology. It has also been described that beta-amyloid peptides potentiate endothelin-1 induced vasoconstriction. In this review, we will critically evaluate evidence relating proteases implicated in amyloid protein precursor proteolytic processing and beta-amyloid catabolism.

  5. Evaluating Ga-68 Peptide Conjugates for Targeting VPAC Receptors: Stability and Pharmacokinetics.

    PubMed

    Kumar, Pardeep; Tripathi, Sushil K; Chen, C P; Wickstrom, Eric; Thakur, Mathew L

    2018-05-25

    In recent years, considerable progress has been made in the use of gallium-68 labeled receptor-specific peptides for imaging oncologic diseases. The objective was to examine the stability and pharmacokinetics of [ 68 Ga]NODAGA and DOTA-peptide conjugate targeting VPAC [combined for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP)] receptors on tumor cells. A VPAC receptor-specific peptide was chosen as a model peptide and conjugated to NODAGA and DOTA via solid-phase synthesis. The conjugates were characterized by HPLC and MALDI-TOF. Following Ga-68 chelation, the radiochemical purity of Ga-68 labeled peptide conjugate was determined by radio-HPLC. The stability was tested against transmetallation using 100 nM Fe 3+ /Zn 2+ /Ca 2+ ionic solution and against transchelation using 200 μM DTPA solution. The ex vivo and in vivo stability of the Ga-68 labeled peptide conjugate was tested in mouse plasma and urine. Receptor specificity was determined ex vivo by cell binding assays using human breast cancer BT474 cells. Positron emission tomography (PET)/X-ray computed tomography (CT) imaging, tissue distribution, and blocking studies were performed in mice bearing BT474 xenografts. The chemical and radiochemical purity was greater than 95 % and both conjugates were stable against transchelation and transmetallation. Ex vivo stability at 60 min showed that the NODAGA-peptide-bound Ga-68 reduced to 42.1 ± 3.7 % (in plasma) and 37.4 ± 2.9 % (in urine), whereas the DOTA-peptide-bound Ga-68 was reduced to 1.2 ± 0.3 % (in plasma) and 4.2 ± 0.4 % (in urine) at 60 min. Similarly, the in vivo stability for [ 68 Ga]NODAGA-peptide was decreased to 2.1 ± 0.2 % (in plasma) and 2.2 ± 0.4 % (in urine). For [ 68 Ga]DOTA-peptide, it was decreased to 1.4 ± 0.3 % (in plasma) and 1.2 ± 0.4 % (in urine) at 60 min. The specific BT474 cell binding was 53.9 ± 0.8 % for [ 68 Ga]NODAGA-peptide

  6. Characterization of Residual Medium Peptides from Yersinia pestis Cultures

    SciTech Connect

    Clowers, Brian H.; Wunschel, David S.; Kreuzer, Helen W.

    2013-04-03

    Using a range of common microbial medium formulations (TSB, BHI, LB, and G-media), two attenuated strains of Y. pestis (KIM D27 (pgm-) and KIMD1 lcr-) were cultivated in triplicate. These cellular suspensions were used to develop a method of extracting residual medium peptides from the final microbial preparation to assess their relative abundance and identity. Across the conditions examined, which included additional cellular washing and different forms of microbial inactivation, residual medium peptides were detected. Despite the range of growth medium sources used and the associated manufacturing processes used in their production, a high degree of peptide similarity was observedmore » for a given medium recipe. These results demonstrate that residual medium peptides are retained using traditional microbial cultivation techniques and may be used to inform forensic investigations with respect to production deduction.« less

  7. The boron abundance of Procyon

    NASA Technical Reports Server (NTRS)

    Lemke, Michael; Lambert, David L.; Edvardsson, Bengt

    1993-01-01

    The B I 2496.8 A resonance line and HST/GHRS echelle spectra are used with model atmospheres and synthetic spectra to derive the B abundance of the F dwarfs Procyon (Alpha Canis Minoris), Theta Ursae Majoris, and Iota Pegasi. The B abundance of Theta UMa and Iota Peg is similar to that derived by Boesgaard and Heacox (1978) from the B II resonance line in spectra of A- and B-type stars. These two dwarfs show normal abundances of Li, Be, and B. Procyon, which is highly depleted in Li and Be, is depleted in B by a factor of at least 3. Comparison of the spectra of Procyon and the halo dwarf HD 140283 shows that the B abundance assigned by Duncan et al. (1992) to three halo dwarfs is not greatly overestimated as a result of contamination of the B I line by an unidentified line.

  8. Therapeutic peptides: new arsenal against drug resistant pathogens.

    PubMed

    Mok, Wendy W K; Li, Yingfu

    2014-01-01

    Our incessant tug-of-war with multidrug resistant pathogenic bacteria has prompted researchers to explore novel methods of designing therapeutics in order to defend ourselves against infectious diseases. Combined advances in whole genome analysis, bioinformatics algorithms, and biochemical techniques have led to the discovery and subsequent characterization of an abundant array of functional small peptides in microorganisms and multicellular organisms. Typically classified as having 10 to 100 amino acids, many of these peptides have been found to have dual activities, executing important defensive and regulatory functions in their hosts. In higher organisms, such as mammals, plants, and fungi, host defense peptides have been shown to have immunomodulatory and antimicrobial properties. In microbes, certain growth-inhibiting peptides have been linked to the regulation of diverse cellular processes. Examples of these processes include quorum sensing, stress response, cell differentiation, biofilm formation, pathogenesis, and multidrug tolerance. In this review, we will present a comprehensive overview of the discovery, characteristics, and functions of host- and bacteria-derived peptides with antimicrobial activities. The advantages and possible shortcomings of using these peptides as antimicrobial agents and targets will also be discussed. We will further examine current efforts in engineering synthetic peptides to be used as therapeutics and/or drug delivery vehicles.

  9. Pituitary adenylate cyclase-activating polypeptide is a potent broad-spectrum antimicrobial peptide: Structure-activity relationships.

    PubMed

    Starr, Charles G; Maderdrut, Jerome L; He, Jing; Coy, David H; Wimley, William C

    2018-06-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP) is a naturally occurring cationic peptide with potent immunosuppressant and cytoprotective activities. We now show that full length PACAP38 and to a lesser extent, the truncated form PACAP27, and the closely related vasoactive intestinal peptide (VIP) and secretin had antimicrobial activity against the Gram-negative bacteria Escherichia coli in the radial diffusion assay. PACAP38 was more potent than either the bovine neutrophil antimicrobial peptide indolicidin or the synthetic antimicrobial peptide ARVA against E. coli. PACAP38 also had activity against the Gram-positive bacteria Staphylococcus aureus in the same assay with comparable potency to indolicidin and ARVA. In the more stringent broth dilution assay, PACAP38 had moderate sterilizing activity against E. coli, and potent sterilizing activity against the Gram-negative bacteria Pseudomonas aeruginosa. PACAP27, VIP and secretin were much less active than PACAP38 in this assay. PACAP38 also had some activity against the Gram-positive bacteria Bacillus cereus in the broth dilution assay. Many exopeptidase-resistant analogs of PACAP38, including both receptor agonists and antagonists, had antimicrobial activities equal to, or better than PACAP38, in both assays. PACAP38 made the membranes of E. coli permeable to SYTOX Green, suggesting a classical membrane lytic mechanism. These data suggest that analogs of PACPAP38 with a wide range of useful biological activities can be made by judicious substitutions in the sequence. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Optimization for Peptide Sample Preparation for Urine Peptidomics

    SciTech Connect

    Sigdel, Tara K.; Nicora, Carrie D.; Hsieh, Szu-Chuan

    2014-02-25

    Analysis of native or endogenous peptides in biofluids can provide valuable insights into disease mechanisms. Furthermore, the detected peptides may also have utility as potential biomarkers for non-invasive monitoring of human diseases. The non-invasive nature of urine collection and the abundance of peptides in the urine makes analysis by high-throughput ‘peptidomics’ methods , an attractive approach for investigating the pathogenesis of renal disease. However, urine peptidomics methodologies can be problematic with regards to difficulties associated with sample preparation. The urine matrix can provide significant background interference in making the analytical measurements that it hampers both the identification of peptides andmore » the depth of the peptidomics read when utilizing LC-MS based peptidome analysis. We report on a novel adaptation of the standard solid phase extraction (SPE) method to a modified SPE (mSPE) approach for improved peptide yield and analysis sensitivity with LC-MS based peptidomics in terms of time, cost, clogging of the LC-MS column, peptide yield, peptide quality, and number of peptides identified by each method. Expense and time requirements were comparable for both SPE and mSPE, but more interfering contaminants from the urine matrix were evident in the SPE preparations (e.g., clogging of the LC-MS columns, yellowish background coloration of prepared samples due to retained urobilin, lower peptide yields) when compared to the mSPE method. When we compared data from technical replicates of 4 runs, the mSPE method provided significantly improved efficiencies for the preparation of samples from urine (e.g., mSPE peptide identification 82% versus 18% with SPE; p = 8.92E-05). Additionally, peptide identifications, when applying the mSPE method, highlighted the biology of differential activation of urine peptidases during acute renal transplant rejection with distinct laddering of specific peptides, which was obscured for most

  11. Combining Ultracentrifugation and Peptide Termini Group-specific Immunoprecipitation for Multiplex Plasma Protein Analysis

    PubMed Central

    Volk, Sonja; Schreiber, Thomas D.; Eisen, David; Wiese, Calvin; Planatscher, Hannes; Pynn, Christopher J.; Stoll, Dieter; Templin, Markus F.; Joos, Thomas O.; Pötz, Oliver

    2012-01-01

    Blood plasma is a valuable source of potential biomarkers. However, its complexity and the huge dynamic concentration range of its constituents complicate its analysis. To tackle this problem, an immunoprecipitation strategy was employed using antibodies directed against short terminal epitope tags (triple X proteomics antibodies), which allow the enrichment of groups of signature peptides derived from trypsin-digested plasma. Isolated signature peptides are subsequently detected using MALDI-TOF/TOF mass spectrometry. Sensitivity of the immunoaffinity approach was, however, compromised by the presence of contaminant peaks derived from the peptides of nontargeted high abundant proteins. A closer analysis of the enrichment strategy revealed nonspecific peptide binding to the solid phase affinity matrix as the major source of the contaminating peptides. We therefore implemented a sucrose density gradient ultracentrifugation separation step into the procedure. This yielded a 99% depletion of contaminating peptides from a sucrose fraction containing 70% of the peptide-antibody complexes and enabled the detection of the previously undetected low abundance protein filamin-A. Assessment of this novel approach using 15 different triple X proteomics antibodies demonstrated a more consistent detection of a greater number of targeted peptides and a significant reduction in the intensity of nonspecific peptides. Ultracentrifugation coupled with immunoaffinity MS approaches presents a powerful tool for multiplexed plasma protein analysis without the requirement for demanding liquid chromatography separation techniques. PMID:22527512

  12. Interstellar abundances - Gas and dust

    NASA Technical Reports Server (NTRS)

    Field, G. B.

    1974-01-01

    Data on abundances of interstellar atoms, ions and molecules in front of zeta Oph are assembled and analyzed. The gas-phase abundances of at least 11 heavy elements are significantly lower, relative to hydrogen, than in the solar system. The abundance deficiencies of certain elements correlate with the temperatures derived theoretically for particle condensation in stellar atmospheres or nebulae, suggesting that these elements have condensed into dust grains near stars. There is evidence that other elements have accreted onto such grains after their arrival in interstellar space. The extinction spectrum of zeta Oph can be explained qualitatively and, to a degree, quantitatively by dust grains composed of silicates, graphite, silicon carbide, and iron, with mantles composed of complex molecules of H, C, N, and O. This composition is consistent with the observed gas-phase deficiencies.

  13. Robust Abundance Estimation in Animal Abundance Surveys with Imperfect Detection

    EPA Science Inventory

    Surveys of animal abundance are central to the conservation and management of living natural resources. However, detection uncertainty complicates the sampling process of many species. One sampling method employed to deal with this problem is depletion (or removal) surveys in whi...

  14. Absolute Quantification of Middle- to High-Abundant Plasma Proteins via Targeted Proteomics.

    PubMed

    Dittrich, Julia; Ceglarek, Uta

    2017-01-01

    The increasing number of peptide and protein biomarker candidates requires expeditious and reliable quantification strategies. The utilization of liquid chromatography coupled to quadrupole tandem mass spectrometry (LC-MS/MS) for the absolute quantitation of plasma proteins and peptides facilitates the multiplexed verification of tens to hundreds of biomarkers from smallest sample quantities. Targeted proteomics assays derived from bottom-up proteomics principles rely on the identification and analysis of proteotypic peptides formed in an enzymatic digestion of the target protein. This protocol proposes a procedure for the establishment of a targeted absolute quantitation method for middle- to high-abundant plasma proteins waiving depletion or enrichment steps. Essential topics as proteotypic peptide identification and LC-MS/MS method development as well as sample preparation and calibration strategies are described in detail.

  15. Visualization and dissemination of multidimensional proteomics data comparing protein abundance during Caenorhabditis elegans development.

    PubMed

    Riffle, Michael; Merrihew, Gennifer E; Jaschob, Daniel; Sharma, Vagisha; Davis, Trisha N; Noble, William S; MacCoss, Michael J

    2015-11-01

    Regulation of protein abundance is a critical aspect of cellular function, organism development, and aging. Alternative splicing may give rise to multiple possible proteoforms of gene products where the abundance of each proteoform is independently regulated. Understanding how the abundances of these distinct gene products change is essential to understanding the underlying mechanisms of many biological processes. Bottom-up proteomics mass spectrometry techniques may be used to estimate protein abundance indirectly by sequencing and quantifying peptides that are later mapped to proteins based on sequence. However, quantifying the abundance of distinct gene products is routinely confounded by peptides that map to multiple possible proteoforms. In this work, we describe a technique that may be used to help mitigate the effects of confounding ambiguous peptides and multiple proteoforms when quantifying proteins. We have applied this technique to visualize the distribution of distinct gene products for the whole proteome across 11 developmental stages of the model organism Caenorhabditis elegans. The result is a large multidimensional dataset for which web-based tools were developed for visualizing how translated gene products change during development and identifying possible proteoforms. The underlying instrument raw files and tandem mass spectra may also be downloaded. The data resource is freely available on the web at http://www.yeastrc.org/wormpes/ . Graphical Abstract ᅟ.

  16. Visualization and Dissemination of Multidimensional Proteomics Data Comparing Protein Abundance During Caenorhabditis elegans Development

    NASA Astrophysics Data System (ADS)

    Riffle, Michael; Merrihew, Gennifer E.; Jaschob, Daniel; Sharma, Vagisha; Davis, Trisha N.; Noble, William S.; MacCoss, Michael J.

    2015-11-01

    Regulation of protein abundance is a critical aspect of cellular function, organism development, and aging. Alternative splicing may give rise to multiple possible proteoforms of gene products where the abundance of each proteoform is independently regulated. Understanding how the abundances of these distinct gene products change is essential to understanding the underlying mechanisms of many biological processes. Bottom-up proteomics mass spectrometry techniques may be used to estimate protein abundance indirectly by sequencing and quantifying peptides that are later mapped to proteins based on sequence. However, quantifying the abundance of distinct gene products is routinely confounded by peptides that map to multiple possible proteoforms. In this work, we describe a technique that may be used to help mitigate the effects of confounding ambiguous peptides and multiple proteoforms when quantifying proteins. We have applied this technique to visualize the distribution of distinct gene products for the whole proteome across 11 developmental stages of the model organism Caenorhabditis elegans. The result is a large multidimensional dataset for which web-based tools were developed for visualizing how translated gene products change during development and identifying possible proteoforms. The underlying instrument raw files and tandem mass spectra may also be downloaded. The data resource is freely available on the web at http://www.yeastrc.org/wormpes/.

  17. Sunspots, Starspots, and Elemental Abundances

    NASA Astrophysics Data System (ADS)

    Doschek, George A.; Warren, Harry P.

    2017-08-01

    The composition of plasma in solar and stellar atmospheres is not fixed, but varies from feature to feature. These variations are organized by the First Ionization Potential (FIP) of the element. Solar measurements often indicate that low FIP elements (< 10eV, such as Fe, Si, Mg) are enriched by factors of 3-4 in the corona relative to high FIP elements (>10 eV, such as C, N, O, Ar, He) compared to abundances in the photosphere. Stellar observations have also shown similar enrichments. An inverse FIP effect, where the low FIP elements are depleted, has been observed in stellar coronae of stars believed to have large starspots in their photospheres. The abundances are important for determining radiative loss rates in models, tracing the origin of the slow solar wind, and for understanding wave propagation in the chromosphere and corona. Recently, inverse FIP effects have been discovered in the Sun (Doschek, Warren, & Feldman 2015, ApJ, 808, L7) from spectra obtained by the Extreme-ultraviolet Imaging Spectrometer (EIS) on the Hinode spacecraft. The inverse FIP regions seem always to be near sunspots and cover only a very small area (characteristic length = a few arcseconds). However, in pursuing the search for inverse FIP regions, we have found that in some sunspot groups the coronal abundance at a temperature of 3-4 MK can be near photospheric over much larger areas of the sun near the sunspots (e.g., 6,000 arcsec2). Also, sometimes the abundances at 3-4 MK are in between coronal and photospheric values. This can occur in small areas of an active region. It is predicted (Laming 2015, Sol. Phys., 12, 2) that the FIP effect should be highly variable in the corona. Several examples of coronal abundance variations are presented. Our work indicates that a comprehensive re-investigation of solar abundances is highly desirable. This work is supported by a NASA Hinode grant.

  18. Coronal Abundances and Their Variation

    NASA Technical Reports Server (NTRS)

    Saba, Julia L. R.

    1996-01-01

    This contract supported the investigation of elemental abundances in the solar corona, principally through analysis of high-resolution soft X-ray spectra from the Flat Crystal Spectrometer on NASA's Solar Maximum Mission. The goals of the study were a characterization of the mean values of relative abundances of elements accessible in the FCS data, and information on the extent and circumstances of their variability. This is the Final Report, summarizing the data analysis and reporting activities which occurred during the period of performance, June 1993 - December 1996.

  19. Peptide Integrated Optics.

    PubMed

    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.

  20. Antimicrobial Peptides from Plants

    PubMed Central

    Tam, James P.; Wang, Shujing; Wong, Ka H.; Tan, Wei Liang

    2015-01-01

    Plant antimicrobial peptides (AMPs) have evolved differently from AMPs from other life forms. They are generally rich in cysteine residues which form multiple disulfides. In turn, the disulfides cross-braced plant AMPs as cystine-rich peptides to confer them with extraordinary high chemical, thermal and proteolytic stability. The cystine-rich or commonly known as cysteine-rich peptides (CRPs) of plant AMPs are classified into families based on their sequence similarity, cysteine motifs that determine their distinctive disulfide bond patterns and tertiary structure fold. Cystine-rich plant AMP families include thionins, defensins, hevein-like peptides, knottin-type peptides (linear and cyclic), lipid transfer proteins, α-hairpinin and snakins family. In addition, there are AMPs which are rich in other amino acids. The ability of plant AMPs to organize into specific families with conserved structural folds that enable sequence variation of non-Cys residues encased in the same scaffold within a particular family to play multiple functions. Furthermore, the ability of plant AMPs to tolerate hypervariable sequences using a conserved scaffold provides diversity to recognize different targets by varying the sequence of the non-cysteine residues. These properties bode well for developing plant AMPs as potential therapeutics and for protection of crops through transgenic methods. This review provides an overview of the major families of plant AMPs, including their structures, functions, and putative mechanisms. PMID:26580629

  1. Selective enrichment and desalting of hydrophilic peptides using graphene oxide.

    PubMed

    Jiang, Miao; Qi, Linyu; Liu, Peiru; Wang, Zijun; Duan, Zhigui; Wang, Ying; Liu, Zhonghua; Chen, Ping

    2016-08-01

    The wide variety and low abundance of peptides in tissue brought great difficulties to the separation and identification of peptides, which is not in favor of the development of peptidomics. RP-HPLC, which could purify small molecules based on their hydrophobicity, has been widely used in the separation and enrichment of peptide due to its fast, good reproducibility and high resolution. However, RP-HPLC requires the instrument and expensive C18 column and its sample capacity is also limited. Recently, graphene oxide has been applied to the adsorption of amino acids. However, the enrichment efficiency and selectivity of graphene oxide for peptides remain unclear. In this study, the adsorption efficiency and selectivity of graphene oxide and RP-C18 matrix were compared on trypsinized α-actin and also on tissue extracts from pituitary gland and hippocampus. For α-actin, there exhibit similar elution peaks for total trypsinized products and those adsorpted by GO and C18 matrix. But peptides adsorbed by GO showed the higher hydrophilic peaks than which adsorbed by C18 matrix. The resulted RP-HPLC profile showed that most of peptides enriched by graphene oxide were eluted at low concentration of organic solvent, while peptides adsorbed by RP-C18 matrix were mostly eluted at relatively high concentration. Moreover, mass spectrometry analysis suggested that, in pituitary sample, there were 495 peptides enriched by graphene oxide, 447 peptides enriched by RP-C18 matrix while in hippocampus sample 333 and 243 peptides respectively. The GRAVY value analysis suggested that the graphene oxide has a stronger adsorption for highly hydrophilic peptides compared to the RP-C18 matrix. Furthermore, the combination of these two methods could notably increase the number of identification peptides but also the number of predicted protein precursors. Our study provided a new thought to the role of graphene oxide during the enrichment of peptides from tissue which should be useful for

  2. Actinide abundances in ordinary chondrites

    USGS Publications Warehouse

    Hagee, B.; Bernatowicz, T.J.; Podosek, F.A.; Johnson, M.L.; Burnett, D.S.; Tatsumoto, M.

    1990-01-01

    Measurements of 244Pu fission Xe, U, Th, and light REE (LREE) abundances, along with modal petrographic determinations of phosphate abundances, were carried out on equilibrated ordinary chondrites in order to define better the solar system Pu abundance and to determine the degree of variation of actinide and LREE abundances. Our data permit comparison of the directly measured Pu/ U ratio with that determined indirectly as (Pu/Nd) ?? (Nd/U) assuming that Pu behaves chemically as a LREE. Except for Guaren??a, and perhaps H chondrites in general, Pu concentrations are similar to that determined previously for St. Se??verin, although less precise because of higher trapped Xe contents. Trapped 130Xe 136Xe ratios appear to vary from meteorite to meteorite, but, relative to AVCC, all are similar in the sense of having less of the interstellar heavy Xe found in carbonaceous chondrite acid residues. The Pu/U and Pu/Nd ratios are consistent with previous data for St. Se??verin, but both tend to be slightly higher than those inferred from previous data on Angra dos Reis. Although significant variations exist, the distribution of our Th/U ratios, along with other precise isotope dilution data for ordinary chondrites, is rather symmetric about the CI chondrite value; however, actinide/(LREE) ratios are systematically lower than the CI value. Variations in actinide or LREE absolute and relative abundances are interpreted as reflecting differences in the proportions and/or compositions of more primitive components (chondrules and CAI materials?) incorporated into different regions of the ordinary chondrite parent bodies. The observed variations of Th/U, Nd/U, or Ce/U suggest that measurements of Pu/U on any single equilibrated ordinary chondrite specimen, such as St. Se??verin, should statistically be within ??20-30% of the average solar system value, although it is also clear that anomalous samples exist. ?? 1990.

  3. Abundance estimation and conservation biology

    USGS Publications Warehouse

    Nichols, J.D.; MacKenzie, D.I.

    2004-01-01

    Abundance is the state variable of interest in most population–level ecological research and in most programs involving management and conservation of animal populations. Abundance is the single parameter of interest in capture–recapture models for closed populations (e.g., Darroch, 1958; Otis et al., 1978; Chao, 2001). The initial capture–recapture models developed for partially (Darroch, 1959) and completely (Jolly, 1965; Seber, 1965) open populations represented efforts to relax the restrictive assumption of population closure for the purpose of estimating abundance. Subsequent emphases in capture–recapture work were on survival rate estimation in the 1970’s and 1980’s (e.g., Burnham et al., 1987; Lebreton et al.,1992), and on movement estimation in the 1990’s (Brownie et al., 1993; Schwarz et al., 1993). However, from the mid–1990’s until the present time, capture–recapture investigators have expressed a renewed interest in abundance and related parameters (Pradel, 1996; Schwarz & Arnason, 1996; Schwarz, 2001). The focus of this session was abundance, and presentations covered topics ranging from estimation of abundance and rate of change in abundance, to inferences about the demographic processes underlying changes in abundance, to occupancy as a surrogate of abundance. The plenary paper by Link & Barker (2004) is provocative and very interesting, and it contains a number of important messages and suggestions. Link & Barker (2004) emphasize that the increasing complexity of capture–recapture models has resulted in large numbers of parameters and that a challenge to ecologists is to extract ecological signals from this complexity. They offer hierarchical models as a natural approach to inference in which traditional parameters are viewed as realizations of stochastic processes. These processes are governed by hyperparameters, and the inferential approach focuses on these hyperparameters. Link & Barker (2004) also suggest that our attention

  4. Immunotherapy with Allergen Peptides

    PubMed Central

    2007-01-01

    Specific allergen immunotherapy (SIT) is disease-modifying and efficacious. However, the use of whole allergen preparations is associated with frequent allergic adverse events during treatment. Many novel approaches are being designed to reduce the allergenicity of immunotherapy preparations whilst maintaining immunogenicity. One approach is the use of short synthetic peptides which representing dominant T cell epitopes of the allergen. Short peptides exhibit markedly reduced capacity to cross link IgE and activate mast cells and basophils, due to lack of tertiary structure. Murine pre-clinical studies have established the feasibility of this approach and clinical studies are currently in progress in both allergic and autoimmune diseases. PMID:20525144

  5. Antimicrobial Peptides and Nanotechnology, Recent Advances and Challenges.

    PubMed

    Biswaro, Lubhandwa S; da Costa Sousa, Mauricio G; Rezende, Taia M B; Dias, Simoni C; Franco, Octavio L

    2018-01-01

    Antimicrobial peptides are sequences of amino acids, which present activity against microorganisms. These peptides were discovered over 70 years ago, and are abundant in nature from soil bacteria, insects, amphibians to mammals and plants. They vary in amino acids number, the distance between amino acids within individual peptide structure, net charge, solubility and other physical chemical properties as well as differ in mechanism of action. These peptides may provide an alternative treatment to conventional antibiotics, which encounter resistance such as the peptide nisin applied in treating methicillin resistant Staphylococcus aureus (MRSA) or may behave synergistically with known antibiotics against parasites for instance, nisin Z when used in synergy with ampicillin reported better activity against Pseudomonas fluorescens than when the antibiotic was alone. AMPs are known to be active against viruses, bacteria, fungi and protozoans. Nanotechnology is an arena which explores the synthesis, characterization and application of an array of delivery systems at a one billionth of meter scale. Such systems are implemented to deliver drugs, proteins, vaccines, and peptides. The role of nanotechnology in delivering AMPs is still at its early development stage. There are challenges of incorporating AMPs into drug delivery system. This review intends to explore in depth, the role of nanotechnology in delivering AMPs as well as presenting the current advances and accompanying challenges of the technology.

  6. Discovery of 12-mer peptides that bind to wood lignin

    PubMed Central

    Yamaguchi, Asako; Isozaki, Katsuhiro; Nakamura, Masaharu; Takaya, Hikaru; Watanabe, Takashi

    2016-01-01

    Lignin, an abundant terrestrial polymer, is the only large-volume renewable feedstock composed of an aromatic skeleton. Lignin has been used mostly as an energy source during paper production; however, recent interest in replacing fossil fuels with renewable resources has highlighted its potential value in providing aromatic chemicals. Highly selective degradation of lignin is pivotal for industrial production of paper, biofuels, chemicals, and materials. However, few studies have examined natural and synthetic molecular components recognizing the heterogeneous aromatic polymer. Here, we report the first identification of lignin-binding peptides possessing characteristic sequences using a phage display technique. The consensus sequence HFPSP was found in several lignin-binding peptides, and the outer amino acid sequence affected the binding affinity of the peptides. Substitution of phenylalanine7 with Ile in the lignin-binding peptide C416 (HFPSPIFQRHSH) decreased the affinity of the peptide for softwood lignin without changing its affinity for hardwood lignin, indicating that C416 recognised structural differences between the lignins. Circular dichroism spectroscopy demonstrated that this peptide adopted a highly flexible random coil structure, allowing key residues to be appropriately arranged in relation to the binding site in lignin. These results provide a useful platform for designing synthetic and biological catalysts selectively bind to lignin. PMID:26903196

  7. Characterization of atrial natriuretic peptide degradation by cell-surface peptidase activity on endothelial cells

    NASA Technical Reports Server (NTRS)

    Frost, S. J.; Whitson, P. A.

    1993-01-01

    Atrial natriuretic peptide (ANP) is a fluid-regulating peptide hormone that promotes vasorelaxation, natriuresis, and diuresis. The mechanisms for the release of ANP and for its clearance from the circulation play important roles in modulating its biological effects. Recently, we have reported that the cell surface of an endothelial cell line, CPA47, could degrade 125I-ANP in the presence of EDTA. In this study, we have characterized this degradation of 125I-ANP. The kinetics of ANP degradation by the surface of CPA47 cells were first order, with a Km of 320 +/- 60 nM and Vmax of 35 +/- 14 pmol of ANP degraded/10 min/10(5) cells at pH 7.4. ANP is degraded by the surface of CPA47 cells over a broad pH range from 7.0-8.5. Potato carboxypeptidase inhibitor and bestatin inhibited 125I-ANP degradation, suggesting that this degradative activity on the surface of CPA47 cells has exopeptidase characteristics. The selectivity of CPA47 cell-surface degradation of ANP was demonstrated when 125I-ANP degradation was inhibited in the presence of neuropeptide Y and angiotensin I and II but not bradykinin, bombesin, endothelin-1, or substance P. The C-terminal amino acids phe26 and tyr28 were deduced to be important for ANP interaction with the cell-surface peptidase(s) based on comparison of the IC50 of various ANP analogues and other natriuretic peptides for the inhibition of ANP degradation. These data suggest that a newly characterized divalent cation-independent exopeptidase(s) that selectively recognizes ANP and some other vasoactive peptides exists on the surface of endothelial cells.

  8. Accumulation of deaminated peptides in anoxic sediments of Santa Barbara Basin

    NASA Astrophysics Data System (ADS)

    Abdulla, Hussain A.; Burdige, David J.; Komada, Tomoko

    2018-02-01

    Proteins represent the most abundant class of biomolecules in marine sinking particles and microbial biomass, yet their cycling in marine sediments is not fully understood. To investigate whether some portion of hydrolyzed proteins escapes complete remineralization and accumulate in the pore waters, we analyzed dissolved organic matter from the anoxic sediments of Santa Barbara Basin, California, by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FTICR-MS). The results showed an increase in the molecular diversity and abundance of dissolved organic nitrogen (DON) formulas with depth. A comparison of the detected DON formulas to a database of small peptides (2-4 amino acid sequences) returned 119 matches, and these formulas were most abundant near the sediment surface. When we compared our detected formulas to all possible structures that would result from deamination of peptides in the database, we found 680 formula matches. However, these molecular formulas can represent hundreds of different structural isomers (in the present case as many as 3257 different deaminated peptide structures), which cannot be distinguished by the FTICR-MS settings that were used. Analysis of amino acid sequences suggests that these deaminated peptides may be the products of selective degradation of source proteins in marine sediments. We hypothesize that these deaminated peptides accumulate in the pore waters due to extracellular proteinases being inhibited from completely hydrolyzing specific peptides to free amino acids. We suggest that anaerobic microbes deaminate peptides largely to produce H2, which is ultimately used as a reducing agent by other sediment microbes (e.g. CO2 reduction by methanogens). Simple calculations suggest that deaminated peptides may represent ∼25-45% of DOC accumulating in these sediment pore waters. Unlike rapid remineralization of free amino acids, peptide deamination leaves behind the peptide carbon skeleton. Molecular structures of these

  9. Superior Cervical Ganglia Neurons Induce Foxp3+ Regulatory T Cells via Calcitonin Gene-Related Peptide.

    PubMed

    Szklany, Kirsten; Ruiter, Evelyn; Mian, Firoz; Kunze, Wolfgang; Bienenstock, John; Forsythe, Paul; Karimi, Khalil

    2016-01-01

    The nervous and immune systems communicate bidirectionally, utilizing diverse molecular signals including cytokines and neurotransmitters to provide an integrated response to changes in the body's internal and external environment. Although, neuro-immune interactions are becoming better understood under inflammatory circumstances and it has been evidenced that interaction between neurons and T cells results in the conversion of encephalitogenic T cells to T regulatory cells, relatively little is known about the communication between neurons and naïve T cells. Here, we demonstrate that following co-culture of naïve CD4+ T cells with superior cervical ganglion neurons, the percentage of Foxp3 expressing CD4+CD25+ cells significantly increased. This was mediated in part by immune-regulatory cytokines TGF-β and IL-10, as well as the neuropeptide calcitonin gene-related peptide while vasoactive intestinal peptide was shown to play no role in generation of T regulatory cells. Additionally, T cells co-cultured with neurons showed a decrease in the levels of pro-inflammatory cytokine IFN-γ released upon in vitro stimulation. These findings suggest that the generation of Tregs may be promoted by naïve CD4+ T cell: neuron interaction through the release of neuropeptide CGRP.

  10. Halobacterium salinarum NRC-1 PeptideAtlas: strategies for targeted proteomics

    PubMed Central

    Van, Phu T.; Schmid, Amy K.; King, Nichole L.; Kaur, Amardeep; Pan, Min; Whitehead, Kenia; Koide, Tie; Facciotti, Marc T.; Goo, Young-Ah; Deutsch, Eric W.; Reiss, David J.; Mallick, Parag; Baliga, Nitin S.

    2009-01-01

    The relatively small numbers of proteins and fewer possible posttranslational modifications in microbes provides a unique opportunity to comprehensively characterize their dynamic proteomes. We have constructed a Peptide Atlas (PA) for 62.7% of the predicted proteome of the extremely halophilic archaeon Halobacterium salinarum NRC-1 by compiling approximately 636,000 tandem mass spectra from 497 mass spectrometry runs in 88 experiments. Analysis of the PA with respect to biophysical properties of constituent peptides, functional properties of parent proteins of detected peptides, and performance of different mass spectrometry approaches has helped highlight plausible strategies for improving proteome coverage and selecting signature peptides for targeted proteomics. Notably, discovery of a significant correlation between absolute abundances of mRNAs and proteins has helped identify low abundance of proteins as the major limitation in peptide detection. Furthermore we have discovered that iTRAQ labeling for quantitative proteomic analysis introduces a significant bias in peptide detection by mass spectrometry. Therefore, despite identifying at least one proteotypic peptide for almost all proteins in the PA, a context-dependent selection of proteotypic peptides appears to be the most effective approach for targeted proteomics. PMID:18652504

  11. Halobacterium salinarum NRC-1 PeptideAtlas: toward strategies for targeted proteomics and improved proteome coverage.

    PubMed

    Van, Phu T; Schmid, Amy K; King, Nichole L; Kaur, Amardeep; Pan, Min; Whitehead, Kenia; Koide, Tie; Facciotti, Marc T; Goo, Young Ah; Deutsch, Eric W; Reiss, David J; Mallick, Parag; Baliga, Nitin S

    2008-09-01

    The relatively small numbers of proteins and fewer possible post-translational modifications in microbes provide a unique opportunity to comprehensively characterize their dynamic proteomes. We have constructed a PeptideAtlas (PA) covering 62.7% of the predicted proteome of the extremely halophilic archaeon Halobacterium salinarum NRC-1 by compiling approximately 636 000 tandem mass spectra from 497 mass spectrometry runs in 88 experiments. Analysis of the PA with respect to biophysical properties of constituent peptides, functional properties of parent proteins of detected peptides, and performance of different mass spectrometry approaches has highlighted plausible strategies for improving proteome coverage and selecting signature peptides for targeted proteomics. Notably, discovery of a significant correlation between absolute abundances of mRNAs and proteins has helped identify low abundance of proteins as the major limitation in peptide detection. Furthermore, we have discovered that iTRAQ labeling for quantitative proteomic analysis introduces a significant bias in peptide detection by mass spectrometry. Therefore, despite identifying at least one proteotypic peptide for almost all proteins in the PA, a context-dependent selection of proteotypic peptides appears to be the most effective approach for targeted proteomics.

  12. C-Peptide Test

    MedlinePlus

    ... Cancer Therapy Glucose Tests Gonorrhea Testing Gram Stain Growth Hormone Haptoglobin hCG Pregnancy hCG Tumor Marker HDL Cholesterol ... splits apart and forms one molecule of C-peptide and one molecule of insulin . Insulin is the hormone that is vital for the body to use ...

  13. Antimicrobial Peptides: An Introduction.

    PubMed

    Haney, Evan F; Mansour, Sarah C; Hancock, Robert E W

    2017-01-01

    The "golden era" of antibiotic discovery has long passed, but the need for new antibiotics has never been greater due to the emerging threat of antibiotic resistance. This urgency to develop new antibiotics has motivated researchers to find new methods to combat pathogenic microorganisms resulting in a surge of research focused around antimicrobial peptides (AMPs; also termed host defense peptides) and their potential as therapeutics. During the past few decades, more than 2000 AMPs have been identified from a diverse range of organisms (animals, fungi, plants, and bacteria). While these AMPs share a number of common features and a limited number of structural motifs; their sequences, activities, and targets differ considerably. In addition to their antimicrobial effects, AMPs can also exhibit immunomodulatory, anti-biofilm, and anticancer activities. These diverse functions have spurred tremendous interest in research aimed at understanding the activity of AMPs, and various protocols have been described to assess different aspects of AMP function including screening and evaluating the activities of natural and synthetic AMPs, measuring interactions with membranes, optimizing peptide function, and scaling up peptide production. Here, we provide a general overview of AMPs and introduce some of the methodologies that have been used to advance AMP research.

  14. Brain Peptides and Psychopharmacology

    ERIC Educational Resources Information Center

    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)

  15. Element abundances at high redshift

    NASA Technical Reports Server (NTRS)

    Meyer, David M.; Welty, D. E.; York, D. G.

    1989-01-01

    Abundances of Si(+), S(+), Cr(+), Mn(+), Fe(_), and Zn(+) are considered for two absorption-line systems in the spectrum of the QSO PKS 0528 - 250. Zinc and sulfur are underabundant, relative to H, by a factor of 10 compared to their solar and Galactic interstellar abundances. The silicon-, chromium-, iron-, and nickel-to-hydrogen ratios are less than the solar values and comparable to the local interstellar ratios. A straightforward interpretation is that nucleosynthesis in these high-redshift systems has led to only about one-tenth as much heavy production as in the gas clouds around the sun, and that the amount of the observed underabundances attributable to grain depletion is small. The dust-to-gas ratio in these clouds is less than 8 percent of the Galactic value.

  16. Abundance of nitrogen in QSOs

    SciTech Connect

    Shields, G.A.

    1976-03-01

    Models of photoionized QSO emission-line regions show that measurements of O iii/N iv/C iv or N iii/C iii can yield the C/N/O ratios to an accuracy of a factor 2 or better. The N iii/C iii intensity ratios observed for the QSO PKS 1756+237 (z=1.72) implies a N/C abundance ratio 5 times larger than the solar value. This is comparable with the nitrogen overabundance in the nuclei of nearby galaxies, and it points to advanced chemical evolution in this QSO, with Zapproximately-greater-thanZ/sub sun/. Such a large abundance of nitrogen appears to be exceptional; composite spectra indicate that most QSOs havemore » (N/O) approximately one-fourth to one-half the solar value. (AIP)« less

  17. Coronal abundances and their variation

    NASA Technical Reports Server (NTRS)

    Saba, Julia L. R.

    1994-01-01

    This contract supports the investigation of elemental abundances in the solar corona, principally through analysis of high-resolution software X-ray spectra from the Flat Crystal Spectrometer on NASA's Solar Maximum Mission. The goals of the study are a characterization of the mean values of relative abundances of elements accessible in the FCS data, and information on the extent and circumstances of their variability. This report is a summation of the data analysis and reporting activities which occurred since the last report, submitted two months early, in April 1994, to facilitate evaluation of the first year's progress for contract renewal. Hence this report covers the period 15 April 1994 - 15 December 1994. A list of publications resulting from this research is included.

  18. Use of a porous silicon-gold plasmonic nanostructure to enhance serum peptide signals in MALDI-TOF analysis.

    PubMed

    Li, Xiao; Tan, Jie; Yu, Jiekai; Feng, Jiandong; Pan, Aiwu; Zheng, Shu; Wu, Jianmin

    2014-11-07

    Small peptides in serum are potential biomarkers for the diagnosis of cancer and other diseases. The identification of peptide biomarkers in human plasma/serum has become an area of high interest in medical research. However, the direct analysis of peptides in serum samples using mass spectrometry is challenging due to the low concentration of peptides and the high abundance of high-molecular-weight proteins in serum, the latter of which causes severe signal suppression. Herein, we reported that porous semiconductor-noble metal hybrid nanostructures can both eliminate the interference from large proteins in serum samples and significantly enhance the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) yields of peptides captured on the nanostructure. Serum peptide fingerprints with high fidelity can be acquired rapidly, and successful discrimination of colorectal cancer patients based on peptide fingerprints is demonstrated. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Peptides and Ageing.

    PubMed

    Khavinson, Vladimir Kh

    2002-01-01

    A technology has been developed for manufacturing of biologically active complex peptide preparations from extracts of different tissues. In particular, the pineal preparation (Epithalamin) augments the in vitro outgrowth of explants from the pineal gland but not from other tissues, the latter being stimulated by peptide preparations from respective tissues. Epithalamin increases melatonin production by the pineal gland of rats, improves immunological parameters in rats and mice, produces anticarcinogenic effects in different experimental models, stimulates antioxidant defenses, and restores the reproductive function in old rats. These effects are combined in the ability of Epithalamin to increase the lifespan in rats, mice, and fruit flies. Many of these effects are reproduced in clinical trials, which have demonstrated the geroprotector activity of Epithalamin in humans. Among the effects of the thymic preparation Thymalin, those related to its ability to stimulate immunity are the most prominent. This ability is associated with anticarcinogenic and geroprotector activities. Clinical trials of the peptide preparations obtained from other organs including the prostate, the cerebral cortex, and the eye retina, have demonstrated beneficial effects reflected by the improvement of the conditions of respective organs. Based on the data about the amino acid compositions of the peptide preparations, novel principles of the design of biologically active short peptides possessing tissue-specific activities has been developed. Dipeptides specific for the thymus and tetrapeptides specific for the heart, liver, brain cortex, and pineal glands stimulate the in vitro outgrowth of explants of respective organs. Interestingly, for eye retina and the pineal gland, a common tetrapeptide Ala-Glu-Asp-Gly (Epitalon) has been designed, probably reflecting the common embryonal origin of these two organs. Epitalon reproduces the effects of Epithalamin including those related to its

  20. Chlorine Abundances in Martian Meteorites

    NASA Technical Reports Server (NTRS)

    Bogard, D.D.; Garrison, D.H.; Park, J.

    2009-01-01

    Chlorine measurements made in martian surface rocks by robotic spacecraft typically give Chlorine (Cl) abundances of approximately 0.1-0.8%. In contrast, Cl abundances in martian meteorites appear lower, although data is limited, and martian nakhlites were also subjected to Cl contamination by Mars surface brines. Chlorine abundances reported by one lab for whole rock (WR) samples of Shergotty, ALH77005, and EET79001 range 108-14 ppm, whereas Cl in nakhlites range 73-1900 ppm. Measurements of Cl in various martian weathering phases of nakhlites varied 0.04-4.7% and reveal significant concentration of Cl by martian brines Martian meteorites contain much lower Chlorine than those measured in martian surface rocks and give further confirmation that Cl in these surface rocks was introduced by brines and weathering. It has been argued that Cl is twice as effective as water in lowering the melting point and promoting melting at shallower martian depths, and that significant Cl in the shergottite source region would negate any need for significant water. However, this conclusion was based on experiments that utilized Cl concentrations more analogous to martian surface rocks than to shergottite meteorites, and may not be applicable to shergottites.

  1. Possible role of bioactive peptides in the regulation of human detrusor smooth muscle - functional effects in vitro and immunohistochemical presence.

    PubMed

    Uckert, Stefan; Stief, Christian G; Lietz, Burckhard; Burmester, Martin; Jonas, Udo; Machtens, Stefan A

    2002-09-01

    Results from basic research implicate a role for bioactive peptides in controlling the mammalian lower urinary tract. Although various peptides are assumed to be involved in the potentiaton or inhibition of cholinergic or purinergic activity in the urinary bladder, there is still much controversy regarding the mode of action and functional significance of such peptides in detrusor smooth muscle. Thus, we evaluated the functional effects of atrial natriuretic peptide (ANP), calcitonin gene related peptide (CGRP), endothelin 1 (ET-1), substance P (SP) and vasoactive intestinal polypeptide (VIP) on isolated strip preparations of human detrusor smooth muscle and determined the presence of those peptides in the human detrusor by means of immunohistochemistry. The effects of peptides on isometric tension of isolated detrusor strip preparations and on tissue levels of cyclic nucleotides cAMP and cGMP were compared to those of adenylyl cyclase activator forskolin (F), nitric oxide donor Na(+)-nitroprusside (SNP) and non-specific phosphodiesterase (PDE) inhibitor papaverine (P). The effects of the compounds on isometric tension of isolated human detrusor smooth muscle were examined using the organ bath technique. To determine time- and dose-dependent effects on cyclic nucleotide levels, bladder strips were exposed to increasing doses of F, SNP, P, ANP, CGRP and VIP, then rapidly frozen in liquid nitrogen and homogenised in the frozen state. cAMP and cGMP were extracted and assayed using specific radioimmunoassays. The presence of peptides was investigated by light microscopy using the Avidin-Biotin-Complex (ABC) method. F, P and VIP most effectively reversed the carbachol-induced tension of isolated human detrusor strips. Relaxing effects of ANP, CGRP and SNP were negligible. In contrast, ET-1 and SP elicited dose-dependent contractions of the tissue. The relaxing effects of F, P and VIP were accompanied by an increase in cAMP and cGMP levels, respectively. Light microscopy

  2. Biochemical functionalization of peptide nanotubes with phage displayed peptides

    NASA Astrophysics Data System (ADS)

    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.

  3. Analysis of Intrinsic Peptide Detectability via Integrated Label-Free and SRM-Based Absolute Quantitative Proteomics.

    PubMed

    Jarnuczak, Andrew F; Lee, Dave C H; Lawless, Craig; Holman, Stephen W; Eyers, Claire E; Hubbard, Simon J

    2016-09-02

    Quantitative mass spectrometry-based proteomics of complex biological samples remains challenging in part due to the variability and charge competition arising during electrospray ionization (ESI) of peptides and the subsequent transfer and detection of ions. These issues preclude direct quantification from signal intensity alone in the absence of a standard. A deeper understanding of the governing principles of peptide ionization and exploitation of the inherent ionization and detection parameters of individual peptides is thus of great value. Here, using the yeast proteome as a model system, we establish the concept of peptide F-factor as a measure of detectability, closely related to ionization efficiency. F-factor is calculated by normalizing peptide precursor ion intensity by absolute abundance of the parent protein. We investigated F-factor characteristics in different shotgun proteomics experiments, including across multiple ESI-based LC-MS platforms. We show that F-factors mirror previously observed physicochemical predictors as peptide detectability but demonstrate a nonlinear relationship between hydrophobicity and peptide detectability. Similarly, we use F-factors to show how peptide ion coelution adversely affects detectability and ionization. We suggest that F-factors have great utility for understanding peptide detectability and gas-phase ion chemistry in complex peptide mixtures, selection of surrogate peptides in targeted MS studies, and for calibration of peptide ion signal in label-free workflows. Data are available via ProteomeXchange with identifier PXD003472.

  4. [Distiller Yeasts Producing Antibacterial Peptides].

    PubMed

    Klyachko, E V; Morozkina, E V; Zaitchik, B Ts; Benevolensky, S V

    2015-01-01

    A new method of controlling lactic acid bacteria contamination was developed with the use of recombinant Saccharomyces cerevisiae strains producing antibacterial peptides. Genes encoding the antibacterial peptides pediocin and plantaricin with codons preferable for S. cerevisiae were synthesized, and a system was constructed for their secretory expression. Recombinant S. cerevisiae strains producing antibacterial peptides effectively inhibit the growth of Lactobacillus sakei, Pediacoccus pentasaceus, Pediacoccus acidilactici, etc. The application of distiller yeasts producing antibacterial peptides enhances the ethanol yield in cases of bacterial contamination. Recombinant yeasts producing the antibacterial peptides pediocin and plantaricin can successfully substitute the available industrial yeast strains upon ethanol production.

  5. Peptide Signaling in Plant Development

    PubMed Central

    Katsir, Leron; Davies, Kelli A.; Bergmann, Dominique C.; Laux, Thomas

    2011-01-01

    Cell-to-cell communication is integral to the evolution of multicellularity. In plant development, peptide signals relay information coordinating cell proliferation and differentiation. These peptides are often encoded by gene families and bind to corresponding families of receptors. The precise spatiotemporal expression of signals and their cognate receptors underlies developmental patterning, and expressional and biochemical changes over evolutionary time have likely contributed to the refinement and complexity of developmental programs. Here, we discuss two major plant peptide families which have central roles in plant development: the CLAVATA3/ENDOSPERM SURROUNDING REGION (CLE) peptide family and the EPIDERMAL PATTERNING FACTOR (EPF) family. We discuss how specialization has enabled the CLE peptides to modulate stem cell differentiation in various tissue types, and how differing activities of EPF peptides precisely regulate the stomatal developmental program, and we examine the contributions of these peptide families to plant development from an evolutionary perspective. PMID:21549958

  6. Ligand-regulated peptide aptamers.

    PubMed

    Miller, Russell A

    2009-01-01

    The peptide aptamer approach employs high-throughput selection to identify members of a randomized peptide library displayed from a scaffold protein by virtue of their interaction with a target molecule. Extending this approach, we have developed a peptide aptamer scaffold protein that can impart small-molecule control over the aptamer-target interaction. This ligand-regulated peptide (LiRP) scaffold, consisting of the protein domains FKBP12, FRB, and GST, binds to the cell-permeable small-molecule rapamycin and the binding of this molecule can prevent the interaction of the randomizable linker region connecting FKBP12 with FRB. Here we present a detailed protocol for the creation of a peptide aptamer plasmid library, selection of peptide aptamers using the LiRP scaffold in a yeast two-hybrid system, and the screening of those peptide aptamers for a ligand-regulated interaction.

  7. Peptide profiling and the bioactivity character of yogurt in the simulated gastrointestinal digestion.

    PubMed

    Jin, Yan; Yu, Yang; Qi, Yanxia; Wang, Fangjun; Yan, Jiaze; Zou, Hanfa

    2016-06-01

    This study investigated the relationship between peptide profiles and the bioactivity character of yogurt in simulated gastrointestinal trials. A total of 250, 434 and 466 peptides were identified by LC-MS/MS analyses of yogurt, gastric digest and pancreatic digest. Forty peptides of yogurt survived in gastrointestinal digestion. κ-CN and β-CN contributed the diversity of peptides during the fermentation process and gastrointestinal digestion, respectively. The favorite of κ-CN by lactic acid bacteria complemented gut digestion by hydrolyzing κ-CN, the low abundance milk proteins. The potential bioactivities were evaluated by in vitro ACE and DPP-IV inhibition assays. The ACE inhibition rate of the pancreatic digests was ~4 - and ~2 - fold greater than that of yogurt and the gastric digests. The ACE inhibitory peptides generated during gastrointestinal digestion improved the ACE inhibitory activity of the gastric and pancreatic digests. The DPP-IV inhibition rate of the pancreatic digest was ~6 - and ~3 - fold greater than that of yogurt and the gastric digest. The numbers of potential DPP-IV inhibitory peptides were positively correlated to the DPP-IV inhibitory activity of the gastric and pancreatic digests. The present study describes the characters and bioactivities of peptides from yogurt in a simulated gastrointestinal digestion. The number of peptides identified from yogurt and gastrointestinal digests by LC-MS/MS increased in the simulated gastrointestinal trials. The in vitro ACE and DPP-IV inhibition bioactivities revealed that the bioactivity of yogurt was enhanced during gastrointestinal digestion. The correlation between peptides and bioactivity in vitro indicated that not only the peptides amount but also the proportion of peptides with high bioactivities contributed to increased bioactivity during gastrointestinal digestion. The study of peptides identified from yogurt and digests revealed that the number of released peptides was not determined

  8. Stable-isotope-labeled Histone Peptide Library for Histone Post-translational Modification and Variant Quantification by Mass Spectrometry *

    PubMed Central

    Lin, Shu; Wein, Samuel; Gonzales-Cope, Michelle; Otte, Gabriel L.; Yuan, Zuo-Fei; Afjehi-Sadat, Leila; Maile, Tobias; Berger, Shelley L.; Rush, John; Lill, Jennie R.; Arnott, David; Garcia, Benjamin A.

    2014-01-01

    To facilitate accurate histone variant and post-translational modification (PTM) quantification via mass spectrometry, we present a library of 93 synthetic peptides using Protein-Aqua™ technology. The library contains 55 peptides representing different modified forms from histone H3 peptides, 23 peptides representing H4 peptides, 5 peptides representing canonical H2A peptides, 8 peptides representing H2A.Z peptides, and peptides for both macroH2A and H2A.X. The PTMs on these peptides include lysine mono- (me1), di- (me2), and tri-methylation (me3); lysine acetylation; arginine me1; serine/threonine phosphorylation; and N-terminal acetylation. The library was subjected to chemical derivatization with propionic anhydride, a widely employed protocol for histone peptide quantification. Subsequently, the detection efficiencies were quantified using mass spectrometry extracted ion chromatograms. The library yields a wide spectrum of detection efficiencies, with more than 1700-fold difference between the peptides with the lowest and highest efficiencies. In this paper, we describe the impact of different modifications on peptide detection efficiencies and provide a resource to correct for detection biases among the 93 histone peptides. In brief, there is no correlation between detection efficiency and molecular weight, hydrophobicity, basicity, or modification type. The same types of modifications may have very different effects on detection efficiencies depending on their positions within a peptide. We also observed antagonistic effects between modifications. In a study of mouse trophoblast stem cells, we utilized the detection efficiencies of the peptide library to correct for histone PTM/variant quantification. For most histone peptides examined, the corrected data did not change the biological conclusions but did alter the relative abundance of these peptides. For a low-abundant histone H2A variant, macroH2A, the corrected data led to a different conclusion than the

  9. Abundance measurements in stellar environments

    SciTech Connect

    Leone, F.

    Most of what we know about stars, and systems of stars, is derived from the analysis of their electromagnetic radiation. This lesson is an attempt to describe to Physicists, without any Astrophysical background, the framework to understand the present status of abundance determination in stellar environments and its limit. These notes are dedicated to the recently passed, November 21, 2013, Prof. Dimitri Mihalas who spent his life confuting the 19th century positivist philosopher Auguste Comte who stated that we shall not at all be able to determine the chemical composition of stars.

  10. The solar abundance of Oxygen

    NASA Astrophysics Data System (ADS)

    Grevesse, N.

    2009-07-01

    With Martin Asplund (Max Planck Institute of Astrophysics, Garching) and Jacques Sauval (Observatoire Royal de Belgique, Brussels) I recently published detailed reviews on the solar chemical composition ({Asplund et al. 2005}, {Grevesse et al. 2007}). A new one, with Pat Scott (Stockholm University) as additional co-author, will appear in Annual Review of Astronomy and Astrophysics ({Asplund et al. 2009}). Here we briefly analyze recent works on the solar abundance of Oxygen and recommend a value of 8.70 in the usual astronomical scale.

  11. Avian host defense peptides.

    PubMed

    Cuperus, Tryntsje; Coorens, Maarten; van Dijk, Albert; Haagsman, Henk P

    2013-11-01

    Host defense peptides (HDPs) are important effector molecules of the innate immune system of vertebrates. These antimicrobial peptides are also present in invertebrates, plants and fungi. HDPs display broad-spectrum antimicrobial activities and fulfill an important role in the first line of defense of many organisms. It is becoming increasingly clear that in the animal kingdom the functions of HDPs are not confined to direct antimicrobial actions. Research in mammals has indicated that HDPs have many immunomodulatory functions and are also involved in other physiological processes ranging from development to wound healing. During the past five years our knowledge about avian HDPs has increased considerably. This review addresses our current knowledge on the evolution, regulation and biological functions of HDPs of birds. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Peptide YY kinetics and effects on blood pressure and circulating pancreatic and gastrointestinal hormones and metabolites in man.

    PubMed

    Adrian, T E; Sagor, G R; Savage, A P; Bacarese-Hamilton, A J; Hall, G M; Bloom, S R

    1986-10-01

    Peptide YY (PYY) is a 36 amino acid peptide produced by mucosal endocrine cells of the ileum and colon which inhibits acid secretion and intestinal transit in man. To assess its effects on metabolites and digestive hormones PYY was infused into 18 fasting normal subjects at three dose levels (0.06, 0.19, and 0.57 pmol kg-1 min-1), each for a period of 1 h. During the infusions mean plasma PYY levels increased by 8, 25, and 73 pmol/liter, respectively. The mean disappearance half-time on stopping the infusions was 9.2 +/- 0.4 (SEM) min. The mean MCR was 7.3 +/- 0.7 ml kg-1 min-1 and the apparent volume of distribution was calculated to be 94 +/- 9 ml kg-1. During the highest dose infusion there was a significant increase in both systolic and diastolic blood pressure, of 8.6 +/- 3.7 mmHg (P less than 0.05) and 10.9 +/- 3.0 mmHg (P less than 0.01), respectively. PYY caused a significant 50% reduction in plasma pancreatic polypeptide concentrations (P less than 0.05) and a 55% reduction in circulating motilin levels (P less than 0.05). PYY had no significant effect on circulating concentrations of insulin, glucagon, gastrin, gastric inhibitory peptide, neurotensin, enteroglucagon, or vasoactive intestinal peptide. PYY also had no significant effect on circulating concentrations of glucose, lactate, glycerol, or nonesterified fatty acids. This recently discovered human intestinal hormonal peptide thus has significant effects both on gastrointestinal hormones (motilin and pancreatic polypeptide) and blood pressure in man, but appears not to influence glucose or lipid metabolism.

  13. Isolation and quantitation of a minor determinant of hen egg white lysozyme bound to I-Ak by using peptide-specific immunoaffinity.

    PubMed

    Gugasyan, R; Vidavsky, I; Nelson, C A; Gross, M L; Unanue, E R

    1998-12-01

    We report here the identification and quantitation of a minor epitope from hen egg white lysozyme (HEL) isolated from the class II MHC molecule I-Ak of APCs. We isolated and concentrated the peptides from the I-Ak extracts by a peptide-specific mAba, followed by their examination by electrospray mass spectrometry. This initial step improved the isolation, recovery, and quantitation and allowed us to identify 13 different minor peptides using the Ab specific for the HEL tryptic fragment 34-45. The HEL peptides varied on both the amino and carboxy termini. The shortest peptide was a 13-mer (residues 33-45), and the longest peptide was a 19-mer (residues 31-49). The two most abundant were 31-47 (1.3 pmol) and 31-46 (1 pmol), while the least abundant were 31-45 (40 fmol) and 32-45 (4 fmol). Only 0.3% of the total class II molecules were occupied by this family of HEL peptides. The amount of the 31-47 peptide, the predominant member of this series, was 22 times lower than that of 48-62, the major epitope of HEL. The 31-47 peptide bound about 20-fold weaker to I-Ak compared with the dominant 48-62 peptide. Thus, the lower abundance of the minor epitope correlated with its weaker binding strength.

  14. New Potent Membrane-Targeting Antibacterial Peptides from Viral Capsid Proteins

    PubMed Central

    Dias, Susana A.; Freire, João M.; Pérez-Peinado, Clara; Domingues, Marco M.; Gaspar, Diana; Vale, Nuno; Gomes, Paula; Andreu, David; Henriques, Sónia T.; Castanho, Miguel A. R. B.; Veiga, Ana S.

    2017-01-01

    The increasing prevalence of multidrug-resistant bacteria urges the development of new antibacterial agents. With a broad spectrum activity, antimicrobial peptides have been considered potential antibacterial drug leads. Using bioinformatic tools we have previously shown that viral structural proteins are a rich source for new bioactive peptide sequences, namely antimicrobial and cell-penetrating peptides. Here, we test the efficacy and mechanism of action of the most promising peptides among those previously identified against both Gram-positive and Gram-negative bacteria. Two cell-penetrating peptides, vCPP 0769 and vCPP 2319, have high antibacterial activity against Staphylococcus aureus, MRSA, Escherichia coli, and Pseudomonas aeruginosa, being thus multifunctional. The antibacterial mechanism of action of the two most active viral protein-derived peptides, vAMP 059 and vCPP 2319, was studied in detail. Both peptides act on both Gram-positive S. aureus and Gram-negative P. aeruginosa, with bacterial cell death occurring within minutes. Also, these peptides cause bacterial membrane permeabilization and damage of the bacterial envelope of P. aeruginosa cells. Overall, the results show that structural viral proteins are an abundant source for membrane-active peptides sequences with strong antibacterial properties. PMID:28522994

  15. A Web Server and Mobile App for Computing Hemolytic Potency of Peptides

    NASA Astrophysics Data System (ADS)

    Chaudhary, Kumardeep; Kumar, Ritesh; Singh, Sandeep; Tuknait, Abhishek; Gautam, Ankur; Mathur, Deepika; Anand, Priya; Varshney, Grish C.; Raghava, Gajendra P. S.

    2016-03-01

    Numerous therapeutic peptides do not enter the clinical trials just because of their high hemolytic activity. Recently, we developed a database, Hemolytik, for maintaining experimentally validated hemolytic and non-hemolytic peptides. The present study describes a web server and mobile app developed for predicting, and screening of peptides having hemolytic potency. Firstly, we generated a dataset HemoPI-1 that contains 552 hemolytic peptides extracted from Hemolytik database and 552 random non-hemolytic peptides (from Swiss-Prot). The sequence analysis of these peptides revealed that certain residues (e.g., L, K, F, W) and motifs (e.g., “FKK”, “LKL”, “KKLL”, “KWK”, “VLK”, “CYCR”, “CRR”, “RFC”, “RRR”, “LKKL”) are more abundant in hemolytic peptides. Therefore, we developed models for discriminating hemolytic and non-hemolytic peptides using various machine learning techniques and achieved more than 95% accuracy. We also developed models for discriminating peptides having high and low hemolytic potential on different datasets called HemoPI-2 and HemoPI-3. In order to serve the scientific community, we developed a web server, mobile app and JAVA-based standalone software (http://crdd.osdd.net/raghava/hemopi/).

  16. A Web Server and Mobile App for Computing Hemolytic Potency of Peptides.

    PubMed

    Chaudhary, Kumardeep; Kumar, Ritesh; Singh, Sandeep; Tuknait, Abhishek; Gautam, Ankur; Mathur, Deepika; Anand, Priya; Varshney, Grish C; Raghava, Gajendra P S

    2016-03-08

    Numerous therapeutic peptides do not enter the clinical trials just because of their high hemolytic activity. Recently, we developed a database, Hemolytik, for maintaining experimentally validated hemolytic and non-hemolytic peptides. The present study describes a web server and mobile app developed for predicting, and screening of peptides having hemolytic potency. Firstly, we generated a dataset HemoPI-1 that contains 552 hemolytic peptides extracted from Hemolytik database and 552 random non-hemolytic peptides (from Swiss-Prot). The sequence analysis of these peptides revealed that certain residues (e.g., L, K, F, W) and motifs (e.g., "FKK", "LKL", "KKLL", "KWK", "VLK", "CYCR", "CRR", "RFC", "RRR", "LKKL") are more abundant in hemolytic peptides. Therefore, we developed models for discriminating hemolytic and non-hemolytic peptides using various machine learning techniques and achieved more than 95% accuracy. We also developed models for discriminating peptides having high and low hemolytic potential on different datasets called HemoPI-2 and HemoPI-3. In order to serve the scientific community, we developed a web server, mobile app and JAVA-based standalone software (http://crdd.osdd.net/raghava/hemopi/).

  17. Elemental Abundances in NGC 3516

    NASA Technical Reports Server (NTRS)

    Turner, T. J.; Kraemer, S. B.; Mushotzky, R. F.; George, I. M.; Gabel, J. R.

    2003-01-01

    We present Reflection Grating Spectrometer data from an XMM-Newton observation of the Seyfert 1 galaxy NGC 3516, taken while the continuum source was in an extremely low flux state. This observation offers a rare opportunity for a detailed study of emission from a Seyfert 1 galaxy as these are usually dominated by high nuclear continuum levels and heavy absorption. The spectrum shows numerous narrow emission lines (FWHM approximately less than 1300 kilometers per second) in the 0.3 - 2 keV range, including the H-like lines of C, N, and O and the He-like lines of N, O and Ne. The emission-line ratios and the narrow width of the radiative recombination continuum of CVI indicate that the gas is photoionized and of fairly low temperature (kT approximately less than 0.01 keV). The availability of emission lines from different elements for two iso-electronic sequences allows us to constrain the element abundances. These data show that the N lines are far stronger than would be expected from gas of solar abundances. Based on our photoionization models we find that nitrogen is overabundant in the central regions of the galaxy, compared to carbon, oxygen and neon by at least a factor of 2.5. We suggest that this is the result of secondary production of nitrogen in intermediate mass stars, and indicative of the history of star formation in NGC 3516.

  18. Vasonatrin peptide: a unique synthetic natriuretic and vasorelaxing peptide.

    PubMed Central

    Wei, C M; Kim, C H; Miller, V M; Burnett, J C

    1993-01-01

    This study reports the cardiovascular and renal actions of a novel and newly synthesized 27-amino acid peptide termed vasonatrin peptide (VNP). VNP is a chimera of atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP). This synthetic peptide possesses the 22-amino acid structure of CNP, which is a cardiovascular selective peptide of endothelial origin and is structurally related to ANP. VNP also possesses the five-amino acid COOH terminus of ANP. The current study demonstrates both in vitro and in vivo that VNP possesses the venodilating actions of CNP, the natriuretic actions of ANP, and unique arterial vasodilating actions not associated with either ANP or CNP. Images PMID:8408658

  19. Double-Blind Prospective Randomized Controlled Trial of Dopamine Versus Epinephrine as First-Line Vasoactive Drugs in Pediatric Septic Shock.

    PubMed

    Ventura, Andréa M C; Shieh, Huei Hsin; Bousso, Albert; Góes, Patrícia F; de Cássia F O Fernandes, Iracema; de Souza, Daniela C; Paulo, Rodrigo Locatelli Pedro; Chagas, Fabiana; Gilio, Alfredo E

    2015-11-01

    The primary outcome was to compare the effects of dopamine or epinephrine in severe sepsis on 28-day mortality; secondary outcomes were the rate of healthcare-associated infection, the need for other vasoactive drugs, and the multiple organ dysfunction score. Double-blind, prospective, randomized controlled trial from February 1, 2009, to July 31, 2013. PICU, Hospital Universitário da Universidade de São Paulo, Brazil. Consecutive children who are 1 month to 15 years old and met the clinical criteria for fluid-refractory septic shock. Exclusions were receiving vasoactive drug(s) prior to hospital admission, having known cardiac disease, having already participated in the trial during the same hospital stay, refusing to participate, or having do-not-resuscitate orders. Patients were randomly assigned to receive either dopamine (5-10 μg/kg/min) or epinephrine (0.1-0.3 μg/kg/min) through a peripheral or intraosseous line. Patients not reaching predefined stabilization criteria after the maximum dose were classified as treatment failure, at which point the attending physician gradually stopped the study drug and started another catecholamine. Physiologic and laboratory data were recorded. Baseline characteristics were described as proportions and mean (± SD) and compared using appropriate statistical tests. Multiple regression analysis was performed, and statistical significance was defined as a p value of less than 0.05. Baseline characteristics and therapeutic interventions for the 120 children enrolled (63, dopamine; 57, epinephrine) were similar. There were 17 deaths (14.2%): 13 (20.6%) in the dopamine group and four (7%) in the epinephrine group (p=0.033). Dopamine was associated with death (odds ratio, 6.5; 95% CI, 1.1-37.8; p=0.037) and healthcare-associated infection (odds ratio, 67.7; 95% CI, 5.0-910.8; p=0.001). The use of epinephrine was associated with a survival odds ratio of 6.49. Dopamine was associated with an increased risk of death and healthcare

  20. Correlation of Noninvasive Blood Pressure and Invasive Intra-arterial Blood Pressure in Patients Treated with Vasoactive Medications in a Neurocritical Care Unit.

    PubMed

    Saherwala, Ali A; Stutzman, Sonja E; Osman, Mohamed; Kalia, Junaid; Figueroa, Stephen A; Olson, DaiWai M; Aiyagari, Venkatesh

    2018-03-22

    The correlation between noninvasive (oscillometric) blood pressure (NBP) and intra-arterial blood pressure (IAP) in critically ill patients receiving vasoactive medications in a Neurocritical Care Unit has not been systematically studied. The purpose of this study is to examine the relationship between simultaneously measured NBP and IAP recordings in these patients. Prospective observational study of patients (N = 70) admitted to a neurocritical care unit receiving continuous vasopressor or antihypertensive infusions. Paired NBP/IAP observations along with covariate and demographic data were abstracted via chart audit. Analysis was performed using SAS v9.4. A total of 2177 paired NBP/IAP observations from 70 subjects (49% male, 63% white, mean age 59 years) receiving vasopressors (n = 21) or antihypertensive agents (n = 49) were collected. Paired t test analysis showed significant differences between NBP versus IAP readings: ([systolic blood pressure (SBP): mean = 136 vs. 140 mmHg; p < 0.0001], [diastolic blood pressure (DBP): mean = 70 vs. 68 mmHg, p < 0.0001], [mean arterial blood pressure (MAP): mean = 86 vs. 90 mmHg, p < 0.0001]). Bland-Altman plots for MAP, SBP, and DBP demonstrate good inter-method agreement between paired measures (excluding outliers) and demonstrate NBP-IAP SBP differences at extremes of blood pressures. Pearson correlation coefficients show strong positive correlations for paired MAP (r = 0.82), SBP (r = 0.84), and DBP (r = 0.73) recordings. An absolute NBP-IAP SBP difference of > 20 mmHg was seen in ~ 20% of observations of nicardipine, ~ 25% of observations of norepinephrine, and ~ 35% of observations of phenylephrine. For MAP, the corresponding numbers were ~ 10, 15, and 25% for nicardipine, norepinephrine, and phenylephrine, respectively. Despite overall strong positive correlations between paired NBP and IAP readings of MAP and SBP, clinically relevant differences in blood pressure are frequent. When

  1. Collagen peptide-based biomaterials for protein delivery and peptide-promoted self-assembly of gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Ernenwein, Dawn M.

    2011-12-01

    Bottom-up self-assembly of peptides has driven the research progress for the following two projects: protein delivery vehicles of collagen microflorettes and the assembly of gold nanoparticles with coiled-coil peptides. Collagen is the most abundant protein in the mammals yet due to immunogenic responses, batch-to-batch variability and lack of sequence modifications, synthetic collagen has been designed to self-assemble into native collagen-like structures. In particular with this research, metal binding ligands were incorporated on the termini of collagen-like peptides to generate micron-sized particles, microflorettes. The over-arching goal of the first research project is to engineer MRI-active microflorettes, loaded with His-tagged growth factors with differential release rates while bound to stem cells that can be implemented toward regenerative cell-based therapies. His-tagged proteins, such as green fluorescent protein, have successfully been incorporated on the surface and throughout the microflorettes. Protein release was monitored under physiological conditions and was related to particle degradation. In human plasma full release was obtained within six days. Stability of the microflorettes under physiological conditions was also examined for the development of a therapeutically relevant delivery agent. Additionally, MRI active microflorettes have been generated through the incorporation of a gadolinium binding ligand, DOTA within the collagen-based peptide sequence. To probe peptide-promoted self-assemblies of gold nanoparticles (GNPs) by non-covalent, charge complementary interactions, a highly anionic coiled-coil peptide was designed and synthesized. Upon formation of peptide-GNP interactions, the hydrophobic domain of the coiled-coil were shown to promote the self-assembly of peptide-GNPs clustering. Hydrophobic forces were found to play an important role in the assembly process, as a peptide with an equally overall negative charge, but lacking an

  2. Design, synthesis and in vitro evaluation of heterobivalent peptidic radioligands targeting both GRP- and VPAC1-Receptors concomitantly overexpressed on various malignancies - Is the concept feasible?

    PubMed

    Lindner, Simon; Fiedler, Luise; Wängler, Björn; Bartenstein, Peter; Schirrmacher, Ralf; Wängler, Carmen

    2018-05-29

    Radiolabeled heterobivalent peptidic ligands (HBPLs), being able to address different receptors, are highly interesting tumor imaging agents as they can offer multiple advantages over monovalent peptide receptor ligands. However, few examples of radiolabeled HBPLs have been described so far. One promising approach is the combination of gastrin-releasing peptide receptor (GRPR)- and vasoactive intestinal peptide receptor subtype 1 (VPAC 1 R)-targeting peptides into one single radioligand since gastrinomas, prostate and breast cancer have been shown to concomitantly or complementarily overexpress both receptors. Here we report the design and synthesis of different HBPLs, comprising a GRPR-binding (BBN 7-14 ) and a VPAC 1 R-targeting (PACAP-27) peptide. The heterodimers were varied with regard to the distance between the peptide binders and the steric rigidity of the systems. We radiolabeled the HBPLs 19-23 as well as their monomeric reference standards 26 and 27 with 68 Ga, achieving radiochemical yields and purities of 95-99% and non-optimized molar activities of 25-61 GBq/μmol. We tested the stability of the radioligands and further evaluated them in vitro regarding their uptake in different prostate carcinoma cell lines (PC-3, DU-145 and VCaP cells). We found that the heterobivalent substances [ 68 Ga]19 - [ 68 Ga]23 showed comparable uptakes into the tumor cells to those of the respective monomers [ 68 Ga]26 and [ 68 Ga]27, indicating that both peptides are still able to address their target receptors. Furthermore, the obtained results indicate that in case of overall low receptor densities, heterobivalent peptides surpass peptide monomers in tumor cell uptake. Most importantly, it could be shown by blocking studies that both peptide parts of the HBPL [ 68 Ga]19 contributed to tumor cell uptake in VCaP cells, expressing both receptor types. Thus, we describe here the first examples of HBPLs being able to address the GRPR as well as the VPAC 1 R and have the

  3. Antimicrobial Peptides: A Promising Therapeutic Strategy in Tackling Antimicrobial Resistance.

    PubMed

    Nuti, Ramya; Goud, Nerella S; Saraswati, A Prasanth; Alvala, Ravi; Alvala, Mallika

    2017-01-01

    Antimicrobial resistance (AMR) has posed a serious threat to global public health and it requires immediate action, preferably long term. Current drug therapies have failed to curb this menace due to the ability of microbes to circumvent the mechanisms through which the drugs act. From the drug discovery point of view, the majority of drugs currently employed for antimicrobial therapy are small molecules. Recent trends reveal a surge in the use of peptides as drug candidates as they offer remarkable advantages over small molecules. Newer synthetic strategies like organometalic complexes, Peptide-polymer conjugates, solid phase, liquid phase and recombinant DNA technology encouraging the use of peptides as therapeutic agents with a host of chemical functions, and tailored for specific applications. In the last decade, many peptide based drugs have been successfully approved by the Food and Drug Administration (FDA). This success can be attributed to their high specificity, selectivity and efficacy, high penetrability into the tissues, less immunogenicity and less tissue accumulation. Considering the enormity of AMR, the use of Antimicrobial Peptides (AMPs) can be a viable alternative to current therapeutics strategies. AMPs are naturally abundant allowing synthetic chemists to develop semi-synthetics peptide molecules. AMPs have a broad spectrum of activity towards microbes and they possess the ability to bypass the resistance induction mechanisms of microbes. The present review focuses on the potential applications of AMPs against various microbial disorders and their future prospects. Several resistance mechanisms and their strategies have also been discussed to highlight the importance in the current scenario. Breakthroughs in AMP designing, peptide synthesis and biotechnology have shown promise in tackling this challenge and has revived the interest of using AMPs as an important weapon in fighting AMR. Copyright© Bentham Science Publishers; For any queries

  4. Absolute quantification of microbial taxon abundances.

    PubMed

    Props, Ruben; Kerckhof, Frederiek-Maarten; Rubbens, Peter; De Vrieze, Jo; Hernandez Sanabria, Emma; Waegeman, Willem; Monsieurs, Pieter; Hammes, Frederik; Boon, Nico

    2017-02-01

    High-throughput amplicon sequencing has become a well-established approach for microbial community profiling. Correlating shifts in the relative abundances of bacterial taxa with environmental gradients is the goal of many microbiome surveys. As the abundances generated by this technology are semi-quantitative by definition, the observed dynamics may not accurately reflect those of the actual taxon densities. We combined the sequencing approach (16S rRNA gene) with robust single-cell enumeration technologies (flow cytometry) to quantify the absolute taxon abundances. A detailed longitudinal analysis of the absolute abundances resulted in distinct abundance profiles that were less ambiguous and expressed in units that can be directly compared across studies. We further provide evidence that the enrichment of taxa (increase in relative abundance) does not necessarily relate to the outgrowth of taxa (increase in absolute abundance). Our results highlight that both relative and absolute abundances should be considered for a comprehensive biological interpretation of microbiome surveys.

  5. Therapeutic peptides for cancer therapy. Part II - cell cycle inhibitory peptides and apoptosis-inducing peptides.

    PubMed

    Raucher, Drazen; Moktan, Shama; Massodi, Iqbal; Bidwell, Gene L

    2009-10-01

    Therapeutic peptides have great potential as anticancer agents owing to their ease of rational design and target specificity. However, their utility in vivo is limited by low stability and poor tumor penetration. The authors review the development of peptide inhibitors with potential for cancer therapy. Peptides that arrest the cell cycle by mimicking CDK inhibitors or induce apoptosis directly are discussed. The authors searched Medline for articles concerning the development of therapeutic peptides and their delivery. Inhibition of cancer cell proliferation directly using peptides that arrest the cell cycle or induce apoptosis is a promising strategy. Peptides can be designed that interact very specifically with cyclins and/or cyclin-dependent kinases and with members of apoptotic cascades. Use of these peptides is not limited by their design, as a rational approach to peptide design is much less challenging than the design of small molecule inhibitors of specific protein-protein interactions. However, the limitations of peptide therapy lie in the poor pharmacokinetic properties of these large, often charged molecules. Therefore, overcoming the drug delivery hurdles could open the door for effective peptide therapy, thus making an entirely new class of molecules useful as anticancer drugs.

  6. A peptide-retrieval strategy enables significant improvement of quantitative performance without compromising confidence of identification.

    PubMed

    Tu, Chengjian; Shen, Shichen; Sheng, Quanhu; Shyr, Yu; Qu, Jun

    2017-01-30

    Reliable quantification of low-abundance proteins in complex proteomes is challenging largely owing to the limited number of spectra/peptides identified. In this study we developed a straightforward method to improve the quantitative accuracy and precision of proteins by strategically retrieving the less confident peptides that were previously filtered out using the standard target-decoy search strategy. The filtered-out MS/MS spectra matched to confidently-identified proteins were recovered, and the peptide-spectrum-match FDR were re-calculated and controlled at a confident level of FDR≤1%, while protein FDR maintained at ~1%. We evaluated the performance of this strategy in both spectral count- and ion current-based methods. >60% increase of total quantified spectra/peptides was respectively achieved for analyzing a spike-in sample set and a public dataset from CPTAC. Incorporating the peptide retrieval strategy significantly improved the quantitative accuracy and precision, especially for low-abundance proteins (e.g. one-hit proteins). Moreover, the capacity of confidently discovering significantly-altered proteins was also enhanced substantially, as demonstrated with two spike-in datasets. In summary, improved quantitative performance was achieved by this peptide recovery strategy without compromising confidence of protein identification, which can be readily implemented in a broad range of quantitative proteomics techniques including label-free or labeling approaches. We hypothesize that more quantifiable spectra and peptides in a protein, even including less confident peptides, could help reduce variations and improve protein quantification. Hence the peptide retrieval strategy was developed and evaluated in two spike-in sample sets with different LC-MS/MS variations using both MS1- and MS2-based quantitative approach. The list of confidently identified proteins using the standard target-decoy search strategy was fixed and more spectra/peptides with less

  7. Metal abundance of Tal 13

    SciTech Connect

    Zinn, R.; Diaz, A.I.

    1982-08-01

    Low-resolution spectrograms have been obtained of the three RR Lyrae variables in the distant and very sparse globular cluster Pal 13. A comparison of these spectrograms with similar ones of several RR Lyrae variables in the globular clusters M4, M5, and M22 reveals that Pal 13 is intermediate to M5 and M22 in metal abundance. A value of (Fe/H) = -1.67 +- 0.15 is obtained for Pal 13 by adopting Zinn's (1980a (Astrophys. J. Suppl. 42,19)) values of (Fe/H) for these other clusters. Pal 13 is another example of a distant halo object that is not extremely metal poor.

  8. Hematite Abundance Map at Echo

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This image shows the hematite abundance map for a portion of the Meridiani Planum rock outcrop near where the Mars Exploration Rover Opportunity landed. It was acquired by the rover's miniature thermal emission spectrometer instrument from a spot called 'Echo.' Portions of the inner crater wall in this region appear rich in hematite (red). The sharp boundary from hematite-rich to hematite-poor (yellow and green) surfaces corresponds to a change in the surface texture and color. The hematite-rich surfaces have ripple-like forms suggesting wind transported hematite to these surfaces. The bounce marks produced during landing at the base of the slope on the left are low in hematite (blue). The hematite grains that originally covered the surface were pushed below the surface by the lander, exposing a soil that has less hematite.

  9. Serum Stabilities of Short Tryptophan- and Arginine-Rich Antimicrobial Peptide Analogs

    PubMed Central

    Nguyen, Leonard T.; Chau, Johnny K.; Perry, Nicole A.; de Boer, Leonie; Zaat, Sebastian A. J.; Vogel, Hans J.

    2010-01-01

    Background Several short antimicrobial peptides that are rich in tryptophan and arginine residues were designed with a series of simple modifications such as end capping and cyclization. The two sets of hexapeptides are based on the Trp- and Arg-rich primary sequences from the “antimicrobial centre” of bovine lactoferricin as well as an antimicrobial sequence obtained through the screening of a hexapeptide combinatorial library. Methodology/Principal Findings HPLC, mass spectrometry and antimicrobial assays were carried out to explore the consequences of the modifications on the serum stability and microbicidal activity of the peptides. The results show that C-terminal amidation increases the antimicrobial activity but that it makes little difference to its proteolytic degradation in human serum. On the other hand, N-terminal acetylation decreases the peptide activities but significantly increases their protease resistance. Peptide cyclization of the hexameric peptides was found to be highly effective for both serum stability and antimicrobial activity. However the two cyclization strategies employed have different effects, with disulfide cyclization resulting in more active peptides while backbone cyclization results in more proteolytically stable peptides. However, the benefit of backbone cyclization did not extend to longer 11-mer peptides derived from the same region of lactoferricin. Mass spectrometry data support the serum stability assay results and allowed us to determine preferred proteolysis sites in the peptides. Furthermore, isothermal titration calorimetry experiments showed that the peptides all had weak interactions with albumin, the most abundant protein in human serum. Conclusions/Significance Taken together, the results provide insight into the behavior of the peptides in human serum and will therefore aid in advancing antimicrobial peptide design towards systemic applications. PMID:20844765

  10. Palila abundance estimates and trends

    USGS Publications Warehouse

    Banko, Paul C.; Brink, Kevin W.; Camp, Richard

    2014-01-01

    The palila (Loxioides bailleui) population was surveyed annually during 1998−2014 on Mauna Kea Volcano to determine abundance, population trend, and spatial distribution. In the latest surveys, the 2013 population was estimated at 1,492−2,132 birds (point estimate: 1,799) and the 2014 population was estimated at 1,697−2,508 (point estimate: 2,070). Similar numbers of palila were detected during the first and subsequent counts within each year during 2012−2014, and there was no difference in their detection probability due to count sequence. This suggests that greater precision in population estimates can be achieved if future surveys include repeat visits. No palila were detected outside the core survey area in 2013 or 2014, suggesting that most if not all palila inhabit the western slope during the survey period. Since 2003, the size of the area containing all annual palila detections do not indicate a significant change among years, suggesting that the range of the species has remained stable; although this area represents only about 5% of its historical extent. During 1998−2003, palila numbers fluctuated moderately (coefficient of variation [CV] = 0.21). After peaking in 2003, population estimates declined steadily through 2011; since 2010, estimates have fluctuated moderately above the 2011 minimum (CV = 0.18). The average rate of decline during 1998−2014 was 167 birds per year with very strong statistical support for an overall declining trend in abundance. Over the 16-year monitoring period, the estimated rate of change equated to a 68% decline in the population.

  11. Improving Peptide Applications Using Nanotechnology.

    PubMed

    Narayanaswamy, Radhika; Wang, Tao; Torchilin, Vladimir P

    2016-01-01

    Peptides are being successfully used in various fields including therapy and drug delivery. With advancement in nanotechnology and targeted delivery carrier systems, suitable modification of peptides has enabled achievement of many desirable goals over-riding some of the major disadvantages associated with the delivery of peptides in vivo. Conjugation or physical encapsulation of peptides to various nanocarriers, such as liposomes, micelles and solid-lipid nanoparticles, has improved their in vivo performance multi-fold. The amenability of peptides to modification in chemistry and functionalization with suitable nanocarriers are very relevant aspects in their use and have led to the use of 'smart' nanoparticles with suitable linker chemistries that favor peptide targeting or release at the desired sites, minimizing off-target effects. This review focuses on how nanotechnology has been used to improve the number of peptide applications. The paper also focuses on the chemistry behind peptide conjugation to nanocarriers, the commonly employed linker chemistries and the several improvements that have already been achieved in the areas of peptide use with the help of nanotechnology.

  12. Peptides that influence membrane topology

    NASA Astrophysics Data System (ADS)

    Wong, Gerard C. L.

    2014-03-01

    We examine the mechanism of a range of polypeptides that influence membrane topology, including antimicrobial peptides, cell penetrating peptides, viral fusion peptides, and apoptosis proteins, and show how a combination of geometry, coordination chemistry, and soft matter physics can be used to approach a unified understanding. We will also show how such peptides can impact biomedical problems such as auto-immune diseases (psoriasis, lupus), infectious diseases (viral and bacterial infections), and mitochondrial pathologies (under-regulated apoptosis leads to neurodegenerative diseases whereas over-regulated apoptosis leads to cancer.)

  13. Biodiscovery of aluminum binding peptides

    NASA Astrophysics Data System (ADS)

    Adams, Bryn L.; Sarkes, Deborah A.; Finch, Amethist S.; Hurley, Margaret M.; Stratis-Cullum, Dimitra

    2013-05-01

    Cell surface peptide display systems are large and diverse libraries of peptides (7-15 amino acids) which are presented by a display scaffold hosted by a phage (virus), bacteria, or yeast cell. This allows the selfsustaining peptide libraries to be rapidly screened for high affinity binders to a given target of interest, and those binders quickly identified. Peptide display systems have traditionally been utilized in conjunction with organic-based targets, such as protein toxins or carbon nanotubes. However, this technology has been expanded for use with inorganic targets, such as metals, for biofabrication, hybrid material assembly and corrosion prevention. While most current peptide display systems employ viruses to host the display scaffold, we have recently shown that a bacterial host, Escherichia coli, displaying peptides in the ubiquitous, membrane protein scaffold eCPX can also provide specific peptide binders to an organic target. We have, for the first time, extended the use of this bacterial peptide display system for the biodiscovery of aluminum binding 15mer peptides. We will present the process of biopanning with macroscopic inorganic targets, binder enrichment, and binder isolation and discovery.

  14. The PeptideAtlas Project.

    PubMed

    Deutsch, Eric W

    2010-01-01

    PeptideAtlas is a multi-species compendium of peptides observed with tandem mass spectrometry methods. Raw mass spectrometer output files are collected from the community and reprocessed through a uniform analysis and validation pipeline that continues to advance. The results are loaded into a database and the information derived from the raw data is returned to the community via several web-based data exploration tools. The PeptideAtlas resource is useful for experiment planning, improving genome annotation, and other data mining projects. PeptideAtlas has become especially useful for planning targeted proteomics experiments.

  15. Effect of chronic, extrinsic denervation on functional NANC innervation with vasoactive intestinal polypeptide and substance P in longitudinal muscle of rat jejunum.

    PubMed

    Kasparek, M S; Fatima, J; Iqbal, C W; Duenes, J A; Sarr, M G

    2008-03-01

    Intestinal denervation contributes to enteric motor dysfunction after intestinal transplantation [small bowel transplantation (SBT)]. Our aim was to determine long-term effects of extrinsic denervation on functional non-adrenergic, non-cholinergic innervation with vasoactive intestinal polypeptide (VIP) and substance P. Contractile activity of jejunal longitudinal muscle from six age-matched, naïve control rats (NC) and eight rats 1 year after syngeneic SBT were studied in tissue chambers. Spontaneous contractile activity did not differ between groups. Exogenous VIP inhibited contractile activity dose-dependently in both groups, greater in NC than in SBT. The VIP antagonist ([D-p-Cl-Phe(6),Leu(17)]-VIP) and the nitric oxide synthase inhibitor l-N(G)-nitro arginine prevented inhibition by exogenous VIP and electrical field stimulation (EFS) in both groups. Exogenous substance P increased contractile activity dose-dependently, greater in NC than in SBT. The substance P antagonist ([D-Pro(2),D-Trp(7,9)]-substance P) inhibited effects of exogenous substance P and increased the EFS-induced inhibitory response. Immunohistofluorescence showed staining for tyrosine hydroxylase in the jejunoileum 1 year after SBT suggesting sympathetic reinnervation. In rat jejunal longitudinal muscle after chronic denervation, response to exogenous VIP and substance P is decreased, while endogenous release of both neurotransmitters is preserved. These alterations in excitatory and inhibitory pathways occur despite extrinsic reinnervation and might contribute to enteric motor dysfunction after SBT.

  16. Effect of chronic, extrinsic denervation on functional NANC innervation with vasoactive intestinal polypeptide and substance P in longitudinal muscle of rat jejunum1

    PubMed Central

    KASPAREK, M. S.; FATIMA, J.; IQBAL, C. W.; DUENES, J. A.; SARR, M. G.

    2008-01-01

    Intestinal denervation contributes to enteric motor dysfunction after intestinal transplantation [small bowel transplantation (SBT)]. Our aim was to determine long-term effects of extrinsic denervation on functional non-adrenergic, non-cholinergic innervation with vasoactive intestinal polypeptide (VIP) and substance P. Contractile activity of jejunal longitudinal muscle from six age-matched, naïve control rats (NC) and eight rats 1 year after syngeneic SBT were studied in tissue chambers. Spontaneous contractile activity did not differ between groups. Exogenous VIP inhibited contractile activity dose-dependently in both groups, greater in NC than in SBT. The VIP antagonist ([D-p-Cl-Phe6,Leu17]-VIP) and the nitric oxide synthase inhibitor L-NG-nitro arginine prevented inhibition by exogenous VIP and electrical field stimulation (EFS) in both groups. Exogenous substance P increased contractile activity dose-dependently, greater in NC than in SBT. The substance P antagonist ([D-Pro2,D-Trp7,9]-substance P) inhibited effects of exogenous substance P and increased the EFS-induced inhibitory response. Immunohistofluorescence showed staining for tyrosine hydroxylase in the jejunoileum 1 year after SBT suggesting sympathetic reinnervation. In rat jejunal longitudinal muscle after chronic denervation, response to exogenous VIP and substance P is decreased, while endogenous release of both neurotransmitters is preserved. These alterations in excitatory and inhibitory pathways occur despite extrinsic reinnervation and might contribute to enteric motor dysfunction after SBT. PMID:17971029

  17. Peptides and Food Intake

    PubMed Central

    Sobrino Crespo, Carmen; Perianes Cachero, Aránzazu; Puebla Jiménez, Lilian; Barrios, Vicente; Arilla Ferreiro, Eduardo

    2014-01-01

    The mechanisms for controlling food intake involve mainly an interplay between gut, brain, and adipose tissue (AT), among the major organs. Parasympathetic, sympathetic, and other systems are required for communication between the brain satiety center, gut, and AT. These neuronal circuits include a variety of peptides and hormones, being ghrelin the only orexigenic molecule known, whereas the plethora of other factors are inhibitors of appetite, suggesting its physiological relevance in the regulation of food intake and energy homeostasis. Nutrients generated by food digestion have been proposed to activate G-protein-coupled receptors on the luminal side of enteroendocrine cells, e.g., the L-cells. This stimulates the release of gut hormones into the circulation such as glucagon-like peptide-1 (GLP-1), oxyntomodulin, pancreatic polypeptides, peptide tyrosine tyrosine, and cholecystokinin, which inhibit appetite. Ghrelin is a peptide secreted from the stomach and, in contrast to other gut hormones, plasma levels decrease after a meal and potently stimulate food intake. Other circulating factors such as insulin and leptin relay information regarding long-term energy stores. Both hormones circulate at proportional levels to body fat content, enter the CNS proportionally to their plasma levels, and reduce food intake. Circulating hormones can influence the activity of the arcuate nucleus (ARC) neurons of the hypothalamus, after passing across the median eminence. Circulating factors such as gut hormones may also influence the nucleus of the tractus solitarius (NTS) through the adjacent circumventricular organ. On the other hand, gastrointestinal vagal afferents converge in the NTS of the brainstem. Neural projections from the NTS, in turn, carry signals to the hypothalamus. The ARC acts as an integrative center, with two major subpopulations of neurons influencing appetite, one of them coexpressing neuropeptide Y and agouti-related protein (AgRP) that increases food

  18. Amyloid-β peptide structure in aqueous solution varies with fragment size

    NASA Astrophysics Data System (ADS)

    Wise-Scira, Olivia; Xu, Liang; Kitahara, Taizo; Perry, George; Coskuner, Orkid

    2011-11-01

    Various fragment sizes of the amyloid-β (Aβ) peptide have been utilized to mimic the properties of the full-length Aβ peptide in solution. Among these smaller fragments, Aβ16 and Aβ28 have been investigated extensively. In this work, we report the structural and thermodynamic properties of the Aβ16, Aβ28, and Aβ42 peptides in an aqueous solution environment. We performed replica exchange molecular dynamics simulations along with thermodynamic calculations for investigating the conformational free energies, secondary and tertiary structures of the Aβ16, Aβ28, and Aβ42 peptides. The results show that the thermodynamic properties vary from each other for these peptides. Furthermore, the secondary structures in the Asp1-Lys16 and Asp1-Lys28 regions of Aβ42 cannot be completely captured by the Aβ16 and Aβ28 fragments. For example, the β-sheet structures in the N-terminal region of Aβ16 and Aβ28 are either not present or the abundance is significantly decreased in Aβ42. The α-helix and β-sheet abundances in Aβ28 and Aβ42 show trends - to some extent - with the potential of mean forces but no such trend could be obtained for Aβ16. Interestingly, Arg5 forms salt bridges with large abundances in all three peptides. The formation of a salt bridge between Asp23-Lys28 is more preferred over the Glu22-Lys28 salt bridge in Aβ28 but this trend is vice versa for Aβ42. This study shows that the Asp1-Lys16 and Asp1-Lys28 regions of the full length Aβ42 peptide cannot be completely mimicked by studying the Aβ16 and Aβ28 peptides.

  19. Mass Spectrometry of Human Leukocyte Antigen Class I Peptidomes Reveals Strong Effects of Protein Abundance and Turnover on Antigen Presentation*

    PubMed Central

    Bassani-Sternberg, Michal; Pletscher-Frankild, Sune; Jensen, Lars Juhl; Mann, Matthias

    2015-01-01

    HLA class I molecules reflect the health state of cells to cytotoxic T cells by presenting a repertoire of endogenously derived peptides. However, the extent to which the proteome shapes the peptidome is still largely unknown. Here we present a high-throughput mass-spectrometry-based workflow that allows stringent and accurate identification of thousands of such peptides and direct determination of binding motifs. Applying the workflow to seven cancer cell lines and primary cells, yielded more than 22,000 unique HLA peptides across different allelic binding specificities. By computing a score representing the HLA-I sampling density, we show a strong link between protein abundance and HLA-presentation (p < 0.0001). When analyzing overpresented proteins – those with at least fivefold higher density score than expected for their abundance – we noticed that they are degraded almost 3 h faster than similar but nonpresented proteins (top 20% abundance class; median half-life 20.8h versus 23.6h, p < 0.0001). This validates protein degradation as an important factor for HLA presentation. Ribosomal, mitochondrial respiratory chain, and nucleosomal proteins are particularly well presented. Taking a set of proteins associated with cancer, we compared the predicted immunogenicity of previously validated T-cell epitopes with other peptides from these proteins in our data set. The validated epitopes indeed tend to have higher immunogenic scores than the other detected HLA peptides. Remarkably, we identified five mutated peptides from a human colon cancer cell line, which have very recently been predicted to be HLA-I binders. Altogether, we demonstrate the usefulness of combining MS-analysis with immunogenesis prediction for identifying, ranking, and selecting peptides for therapeutic use. PMID:25576301

  20. Surface abundances of ON stars

    NASA Astrophysics Data System (ADS)

    Martins, F.; Simón-Díaz, S.; Palacios, A.; Howarth, I.; Georgy, C.; Walborn, N. R.; Bouret, J.-C.; Barbá, R.

    2015-06-01

    Context. Massive stars burn hydrogen through the CNO cycle during most of their evolution. When mixing is efficient or when mass transfer in binary systems occurs, chemically processed material is observed at the surface of O and B stars. Aims: ON stars show stronger lines of nitrogen than morphologically normal counterparts. Whether this corresponds to the presence of material processed through the CNO cycle is not known. Our goal is to answer this question. Methods: We performed a spectroscopic analysis of a sample of ON stars with atmosphere models. We determined the fundamental parameters as well as the He, C, N, and O surface abundances. We also measured the projected rotational velocities. We compared the properties of the ON stars to those of normal O stars. Results: We show that ON stars are usually rich in helium. Their CNO surface abundances are fully consistent with predictions of nucleosynthesis. ON stars are more chemically evolved and rotate - on average - faster than normal O stars. Evolutionary models including rotation cannot account for the extreme enrichment observed among ON main sequence stars. Some ON stars are members of binary systems, but others are single stars as indicated by stable radial velocities. Mass transfer is therefore not a simple explanation for the observed chemical properties. Conclusions: We conclude that ON stars show extreme chemical enrichment at their surface, consistent with nucleosynthesis through the CNO cycle. Its origin is not clear at present. Based on observations obtained 1) at the Anglo-Australian Telescope; 2) at the Canada-France-Hawaii Telescope (CFHT), which is operated by the National Research Council (NRC) of Canada, the Institut National des Science de l'Univers of the Centre National de la Recherche Scientifique (CNRS) of France, and the University of Hawaii; 3) at the ESO/La Silla Observatory under programs 081.D-2008, 083.D-0589, 086.D-0997; 4) the Nordic Optical Telescope, operated on the island of La

  1. Mineral Abundances in Martian Soils

    NASA Astrophysics Data System (ADS)

    Martel, L. M. V.

    2011-01-01

    Using traditional geochemical calculations with in situ Martian cosmochemical data researchers Harry (Hap) McSween Jr. and Ian McGlynn (University of Tennessee) and Deanne Rogers (SUNY at Stony Brook) have developed a method for identifying the major and minor minerals in soils at the Mars Exploration Rovers (MER) landing sites. The team used information from the MER Athena instrument package operating on Mars since January, 2004. They created two models using MiniTES spectra, Alpha Particle X-ray Spectrometer (APXS) data, and Mossbauer spectrometer data to calculate the mineralogy of average dark soils on the Gusev crater plains and on Meridiani Planum, located on opposite sides of Mars. Soils at both locations are similarly composed of minerals derived from the comminution of basalts (about three quarters by weight) and other minerals derived from rocks altered by chemical weathering (about one quarter by weight). This mixture of possibly unrelated materials (primary and altered) might mean that the alteration of soil did not occur in place and that the basaltic and alteration suites of minerals came from different sources. The nearly identical modal mineralogy at two widely-separated locations on the planet supports a previous hypothesis based on comparable chemical compositions that soils have been homogenized, if not globally then at least over large areas of the Martian surface. Yet, global maps of orbital remote sensing data have not shown surface abundances of alteration minerals as high as those in the Martian soils.

  2. Palila abundance estimates and trend

    USGS Publications Warehouse

    Camp, Richad; Banko, Paul C.

    2012-01-01

    The Palila (Loxioides bailleui) is an endangered, seed-eating, finch-billed honeycreeper found only on Hawai`i Island. Once occurring on the islands of Kaua`i and O`ahu and Mauna Loa and Hualālai volcanoes of Hawai`i, Palila are now found only in subalpine, dry-forest habitats on Mauna Kea (Banko et al. 2002). Previous analyses showed that Palila numbers fluctuated throughout the 1980s and 1990s but declined rapidly and steadily since 2003 (Jacobi et al. 1996, Leonard et al. 2008, Banko et al. 2009, Gorresen et al. 2009, Banko et al. in press). The aim of this report is to update abundance estimates for the Palila based on the 2012 surveys. We assess Palila trends over two periods: 1) the long-term trend during 1998–2012 and 2) the short-term trajectory between 2003 and 2012. The first period evaluates the population trend for the entire time series since additional transects were established (Johnson et al. 2006). These additional transects were established to produce a more precise population estimate and provide more complete coverage of the Palila range. The initial year for short-term trajectory was chosen subjectively to coincide with the recent decline in the Palila population. Additionally, stations in the core Palila habitat were surveyed on two occasions in 2012, thus allowing us to address the question of how repeat samples improve estimate precision.

  3. Identification of snake bradykinin-potentiating peptides (BPPs)-simile sequences in rat brain--Potential BPP-like precursor protein?

    PubMed

    Campeiro, Joana D'Arc; Neshich, Izabella P; Sant'Anna, Osvaldo A; Lopes, Robson; Ianzer, Danielle; Assakura, Marina T; Neshich, Goran; Hayashi, Mirian A F

    2015-08-01

    Bradykinin-potentiating peptides (BPPs) from the South American pit viper snake venom were the first natural inhibitors of the human angiotensin I-converting enzyme (ACE) described. The pioneer characterization of the BPPs precursor from the snake venom glands by our group showed for the first time the presence of the C-type natriuretic peptide (CNP) in this same viper precursor protein. The confirmation of the BPP/CNP expression in snake brain regions correlated with neuroendocrine functions stimulated us to pursue the physiological correlates of these vasoactive peptides in mammals. Notably, several snake toxins were shown to have endogenous physiological correlates in mammals. In the present work, we expressed in bacteria the BPPs domain of the snake venom gland precursor protein, and this purified recombinant protein was used to raise specific polyclonal anti-BPPs antibodies. The correspondent single protein band immune-recognized in adult rat brain cytosol was isolated by 2D-SDS/PAGE and/or HPLC, before characterization by MS fingerprint analysis, which identified this protein as superoxide dismutase (SOD, EC 1.15.1.1), a classically known enzyme with antioxidant activity and important roles in the blood pressure modulation. In silico analysis showed the exposition of the BPP-like peptide sequences on the surface of the 3D structure of rat SOD. These peptides were chemically synthesized to show the BPP-like biological activities in ex vivo and in vivo pharmacological bioassays. Taken together, our data suggest that SOD protein have the potential to be a source for putative BPP-like bioactive peptides, which once released may contribute to the blood pressure control in mammals. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Separomics applied to the proteomics and peptidomics of low-abundance proteins: Choice of methods and challenges - A review.

    PubMed

    Baracat-Pereira, Maria Cristina; de Oliveira Barbosa, Meire; Magalhães, Marcos Jorge; Carrijo, Lanna Clicia; Games, Patrícia Dias; Almeida, Hebréia Oliveira; Sena Netto, José Fabiano; Pereira, Matheus Rodrigues; de Barros, Everaldo Gonçalves

    2012-06-01

    The enrichment and isolation of proteins are considered limiting steps in proteomic studies. Identification of proteins whose expression is transient, those that are of low-abundance, and of natural peptides not described in databases, is still a great challenge. Plant extracts are in general complex, and contaminants interfere with the identification of proteins involved in important physiological processes, such as plant defense against pathogens. This review discusses the challenges and strategies of separomics applied to the identification of low-abundance proteins and peptides in plants, especially in plants challenged by pathogens. Separomics is described as a group of methodological strategies for the separation of protein molecules for proteomics. Several tools have been used to remove highly abundant proteins from samples and also non-protein contaminants. The use of chromatographic techniques, the partition of the proteome into subproteomes, and an effort to isolate proteins in their native form have allowed the isolation and identification of rare proteins involved in different processes.

  5. Urinary Peptides in Rett Syndrome.

    ERIC Educational Resources Information Center

    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)

  6. The good taste of peptides.

    PubMed

    Temussi, Piero A

    2012-02-01

    The taste of peptides is seldom one of the most relevant issues when one considers the many important biological functions of this class of molecules. However, peptides generally do have a taste, covering essentially the entire range of established taste modalities: sweet, bitter, umami, sour and salty. The last two modalities cannot be attributed to peptides as such because they are due to the presence of charged terminals and/or charged side chains, thus reflecting only the zwitterionic nature of these compounds and/or the nature of some side chains but not the electronic and/or conformational features of a specific peptide. The other three tastes, that is, sweet, umami and bitter, are represented by different families of peptides. This review describes the main peptides with a sweet, umami or bitter taste and their relationship with food acceptance or rejection. Particular emphasis will be given to the sweet taste modality, owing to the practical and scientific relevance of aspartame, the well-known sweetener, and to the theoretical importance of sweet proteins, the most potent peptide sweet molecules. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.

  7. Hypothalamic Agouti-Related Peptide mRNA is Elevated During Natural and Stress-Induced Anorexia.

    PubMed

    Dunn, I C; Wilson, P W; D'Eath, R B; Boswell, T

    2015-09-01

    As part of their natural lives, animals can undergo periods of voluntarily reduced food intake and body weight (i.e. animal anorexias) that are beneficial for survival or breeding, such as during territorial behaviour, hibernation, migration and incubation of eggs. For incubation, a change in the defended level of body weight or 'sliding set point' appears to be involved, although the neural mechanisms reponsible for this are unknown. We investigated how neuropeptide gene expression in the arcuate nucleus of the domestic chicken responded to a 60-70% voluntary reduction in food intake measured both after incubation and after an environmental stressor involving transfer to unfamiliar housing. We hypothesised that gene expression would not change in these circumstances because the reduced food intake and body weight represented a defended level in birds with free access to food. Unexpectedly, we observed increased gene expression of the orexigenic peptide agouti-related peptide (AgRP) in both incubating and transferred animals compared to controls. Also pro-opiomelanocortin (POMC) mRNA was higher in incubating hens and significantly increased 6 days after exposure to the stressor. Conversely expression of neuropeptide Y and cocaine- and amphetamine-regulated transcript gene was unchanged in both experimental situations. We conclude that AgRP expression remains sensitive to the level of energy stores during natural anorexias, which is of adaptive advantage, although its normal orexigenic effects are over-ridden by inhibitory signals. In the case of stress-induced anorexia, increased POMC may contribute to this inhibitory role, whereas, for incubation, reduced feeding may also be associated with increased expression in the hypothalamus of the anorexigenic peptide vasoactive intestinal peptide. © 2015 British Society for Neuroendocrinology.

  8. Endogenous Human Milk Peptide Release Is Greater after Preterm Birth than Term Birth123

    PubMed Central

    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

    2015-01-01

    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 enzymatic activity, thereby resulting in an altered peptide profile. Objective: This study examined differences in peptides present between milk from women delivering at term and women delivering prematurely. Methods: 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 (<14, 14–28, 29–41, and 42–58 d). Results: Preterm milk peptide counts, ion abundance, and concentration were significantly higher in preterm milk than 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. Conclusion: 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. PMID:25540406

  9. Fe(+) chemical ionization of peptides.

    PubMed

    Speir, J P; Gorman, G S; Amster, I J

    1993-02-01

    Laser-desorbed peptide neutral molecules were allowed to react with Fe(+) in a Fourier transform mass spectrometer, using the technique of laser desorption/chemical ionization. The Fe(+) ions are formed by laser ablation of a steel target, as well as by dissociative charge-exchange ionization of ferrocene with Ne(+). Prior to reaction with laser-desorbed peptide molecules, Fe(+) ions undergo 20-100 thermalizin collisions with xenon to reduce the population of excited-state metal ion species. The Fe(+) ions that have not experienced thermalizing collisions undergo charge exchange with peptide molecules. Iron ions that undergo thermalizing collisions before they are allowed to react with peptides are found to undergo charge exchange and to form adduct species [M + Fe(+)] and fragment ions that result from the loss of small, stable molecules, such as H2O, CO, and CO2, from the metal ion-peptide complex.

  10. Phage selection of peptide "microantibodies".

    PubMed

    Fujiwara, Daisuke; Fujii, Ikuo

    2013-01-01

    A bioactive peptide capable of inhibiting protein-protein interactions has the potential to be a molecular tool for biological studies and a therapeutic by disrupting aberrant interactions involved in diseases. We have developed combinatorial libraries of peptides with helix-loop-helix structure, from which the isolated peptides have the constrained structure to reduce entropy costs in binding, resulting in high binding affinities for target molecules. Previously, we designed a de novo peptide of helix-loop-helix structure that we termed a "microantibody." Using the microantibody as a library scaffold, we have constructed a phage-display library to successfully isolate molecular-targeting peptides against a cytokine receptor (granulocyte colony-stimulating factor receptor), a protein kinase (Aurora-A), and a ganglioside (GM1). Protocols in this article describe a general procedure for the library construction and the library screening.

  11. Peptides and peptidomimetics as immunomodulators

    PubMed Central

    Gokhale, Ameya S; Satyanarayanajois, Seetharama

    2014-01-01

    Peptides and peptidomimetics can function as immunomodulating agents by either blocking the immune response or stimulating the immune response to generate tolerance. Knowledge of B- or T-cell epitopes along with conformational constraints is important in the design of peptide-based immunomodulating agents. Work on the conformational aspects of peptides, synthesis and modified amino acid side chains have contributed to the development of a new generation of therapeutic agents for autoimmune diseases and cancer. The design of peptides/peptidomimetics for immunomodulation in autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, systemic lupus and HIV infection is reviewed. In cancer therapy, peptide epitopes are used in such a way that the body is trained to recognize and fight the cancer cells locally as well as systemically. PMID:25186605

  12. Maize Bioactive Peptides against Cancer

    NASA Astrophysics Data System (ADS)

    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.

  13. Mass spectrometry analysis and in silico prediction of allergenicity of peptides in tryptic hydrolysates of the proteins from Ruditapes philippinarum.

    PubMed

    Yu, Yue; Liu, Hongwei; Tu, Maolin; Qiao, Meiling; Wang, Zhenyu; Du, Ming

    2017-12-01

    Ruditapes philippinarum is nutrient-rich and widely-distributed, but little attention has been paid to the identification and characterization of the bioactive peptides in the bivalve. In the present study, we evaluated the peptides of the R. philippinarum that were enzymolysised by trypsin using a combination of ultra-performance liquid chromatography separation and electrospray ionization quadrupole time-of-flight tandem mass spectrometry, followed by data processing and sequence-similarity database searching. The potential allergenicity of the peptides was assessed in silico. The enzymolysis was performed under the conditions: E:S 3:100 (w/w), pH 9.0, 45 °C for 4 h. After separation and detection, the Swiss-Prot database and a Ruditapes philippinarum sequence database were used: 966 unique peptides were identified by non-error tolerant database searching; 173 peptides matching 55 precursor proteins comprised highly conserved cytoskeleton proteins. The remaining 793 peptides were identified from the R. philippinarum sequence database. The results showed that 510 peptides were labeled as allergens and 31 peptides were potential allergens; 425 peptides were predicted to be nonallergenic. The abundant peptide information contributes to further investigations of the structure and potential function of R. philippinarum. Additional in vitro studies are required to demonstrate and ensure the correct production of the hydrolysates for use in the food industry with respect to R. philippinarum. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  14. Molecular recognition and regulation of human angiotensin-I converting enzyme (ACE) activity by natural inhibitory peptides

    PubMed Central

    Masuyer, Geoffrey; Schwager, Sylva L. U.; Sturrock, Edward D.; Isaac, R. Elwyn; Acharya, K. Ravi

    2012-01-01

    Angiotensin-I converting enzyme (ACE), a two-domain dipeptidylcarboxypeptidase, is a key regulator of blood pressure as a result of its critical role in the renin-angiotensin-aldosterone and kallikrein-kinin systems. Hence it is an important drug target in the treatment of cardiovascular diseases. ACE is primarily known for its ability to cleave angiotensin I (Ang I) to the vasoactive octapeptide angiotensin II (Ang II), but is also able to cleave a number of other substrates including the vasodilator bradykinin and N-acetyl-Ser-Asp-Lys-Pro (Ac-SDKP), a physiological modulator of hematopoiesis. For the first time we provide a detailed biochemical and structural basis for the domain selectivity of the natural peptide inhibitors of ACE, bradykinin potentiating peptide b and Ang II. Moreover, Ang II showed selective competitive inhibition of the carboxy-terminal domain of human somatic ACE providing evidence for a regulatory role in the human renin-angiotensin system (RAS). PMID:23056909

  15. Cyclic peptides and their interaction with peptide coated surfaces

    NASA Astrophysics Data System (ADS)

    Palmer, F.; Tünnemann, R.; Leipert, D.; Stingel, C.; Jung, G.; Hoffmann, V.

    2001-05-01

    Focusing on biochemical and pharmaceutical inhibitor systems the interaction of cyclic peptides with model peptides have been investigated by ATR-FTIR-spectroscopy. Information about the participation of special functional groups e.g. COOH, COO -, NH 3+ or peptide backbone was gathered by observing cyclohexapeptides (c(X 1LX 2LX 3)) which are interacting with covalently coated Si-ATR-crystals ( L-arginine, tripeptide I (aNS), tripeptide II (SNa)). To determine the interaction, further studies about the band sequence (1800-1500 cm -1) for non-adsorbed cyclohexapeptides and for the interaction with the silicon surface (SiOH) were necessary. The spectra of the interacting cyclohexapeptides with the SiOH-groups were treated like reference spectra for the evaluation of the peptide-peptide interaction. Based on these spectra, we can conclude that there is peptide-peptide interaction with the coating and not with the residual OH-groups. Determination of interaction mechanisms was done by spectra which represent adsorbed molecules only. The amount of adsorbed molecules was considerably less than a monolayer. Therefore the intensities of the spectra are about 10 -4 absorbance units. The spectra contain information about both changes of the coating and of the cyclohexapeptide.

  16. Cathepsin-Mediated Cleavage of Peptides from Peptide Amphiphiles Leads to Enhanced Intracellular Peptide Accumulation

    SciTech Connect

    Acar, Handan; Samaeekia, Ravand; Schnorenberg, Mathew R.

    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 twomore » 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.« less

  17. SWATH Mass Spectrometry Performance Using Extended Peptide MS/MS Assay Libraries*

    PubMed Central

    Wu, Jemma X.; Song, Xiaomin; Pascovici, Dana; Zaw, Thiri; Care, Natasha; Krisp, Christoph; Molloy, Mark P.

    2016-01-01

    The use of data-independent acquisition methods such as SWATH for mass spectrometry based proteomics is usually performed with peptide MS/MS assay libraries which enable identification and quantitation of peptide peak areas. Reference assay libraries can be generated locally through information dependent acquisition, or obtained from community data repositories for commonly studied organisms. However, there have been no studies performed to systematically evaluate how locally generated or repository-based assay libraries affect SWATH performance for proteomic studies. To undertake this analysis, we developed a software workflow, SwathXtend, which generates extended peptide assay libraries by integration with a local seed library and delivers statistical analysis of SWATH-quantitative comparisons. We designed test samples using peptides from a yeast extract spiked into peptides from human K562 cell lysates at three different ratios to simulate protein abundance change comparisons. SWATH-MS performance was assessed using local and external assay libraries of varying complexities and proteome compositions. These experiments demonstrated that local seed libraries integrated with external assay libraries achieve better performance than local assay libraries alone, in terms of the number of identified peptides and proteins and the specificity to detect differentially abundant proteins. Our findings show that the performance of extended assay libraries is influenced by the MS/MS feature similarity of the seed and external libraries, while statistical analysis using multiple testing corrections increases the statistical rigor needed when searching against large extended assay libraries. PMID:27161445

  18. SWATH Mass Spectrometry Performance Using Extended Peptide MS/MS Assay Libraries.

    PubMed

    Wu, Jemma X; Song, Xiaomin; Pascovici, Dana; Zaw, Thiri; Care, Natasha; Krisp, Christoph; Molloy, Mark P

    2016-07-01

    The use of data-independent acquisition methods such as SWATH for mass spectrometry based proteomics is usually performed with peptide MS/MS assay libraries which enable identification and quantitation of peptide peak areas. Reference assay libraries can be generated locally through information dependent acquisition, or obtained from community data repositories for commonly studied organisms. However, there have been no studies performed to systematically evaluate how locally generated or repository-based assay libraries affect SWATH performance for proteomic studies. To undertake this analysis, we developed a software workflow, SwathXtend, which generates extended peptide assay libraries by integration with a local seed library and delivers statistical analysis of SWATH-quantitative comparisons. We designed test samples using peptides from a yeast extract spiked into peptides from human K562 cell lysates at three different ratios to simulate protein abundance change comparisons. SWATH-MS performance was assessed using local and external assay libraries of varying complexities and proteome compositions. These experiments demonstrated that local seed libraries integrated with external assay libraries achieve better performance than local assay libraries alone, in terms of the number of identified peptides and proteins and the specificity to detect differentially abundant proteins. Our findings show that the performance of extended assay libraries is influenced by the MS/MS feature similarity of the seed and external libraries, while statistical analysis using multiple testing corrections increases the statistical rigor needed when searching against large extended assay libraries. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Expression analysis and identification of antimicrobial peptide transcripts from six North American frog species

    USGS Publications Warehouse

    Robertson, Laura S.; Fellers, Gary M.; Marranca, Jamie Marie; Kleeman, Patrick M.

    2013-01-01

    Frogs secrete antimicrobial peptides onto their skin. We describe an assay to preserve and analyze antimicrobial peptide transcripts from field-collected skin secretions that will complement existing methods for peptide analysis. We collected skin secretions from 4 North American species in the field in California and 2 species in the laboratory. Most frogs appeared healthy after release; however, Rana boylii in the Sierra Nevada foothills, but not the Coast Range, showed signs of morbidity and 2 died after handling. The amount of total RNA extracted from skin secretions was higher in R. boylii and R. sierrae compared to R. draytonii, and much higher compared to Pseudacris regilla. Interspecies variation in amount of RNA extracted was not explained by size, but for P. regilla it depended upon collection site and date. RNA extracted from skin secretions from frogs handled with bare hands had poor quality compared to frogs handled with gloves or plastic bags. Thirty-four putative antimicrobial peptide precursor transcripts were identified. This study demonstrates that RNA extracted from skin secretions collected in the field is of high quality suitable for use in sequencing or quantitative PCR (qPCR). However, some species do not secrete profusely, resulting in very little extracted RNA. The ability to measure transcript abundance of antimicrobial peptides in field-collected skin secretions complements proteomic analyses and may provide insight into transcriptional mechanisms that could affect peptide abundance.

  20. Peptide-formation on cysteine-containing peptide scaffolds

    NASA Technical Reports Server (NTRS)

    Chu, B. C.; Orgel, L. E.

    1999-01-01

    Monomeric cysteine residues attached to cysteine-containing peptides by disulfide bonds can be activated by carbonyldiimidazole. If two monomeric cysteine residues, attached to a 'scaffold' peptide Gly-Cys-Glyn-Cys-Glu10, (n = 0, 1, 2, 3) are activated, they react to form the dipeptide Cys-Cys. in 25-65% yield. Similarly, the activation of a cysteine residue attached to the 'scaffold' peptide Gly-Cys-Gly-Glu10 in the presence of Arg5 leads to the formation of Cys-Arg5 in 50% yield. The significance of these results for prebiotic chemistry is discussed.

  1. Suppression of vasoactive intestinal polypeptide in the suprachiasmatic nucleus leads to aging-like alterations in cAMP rhythms and activation of gonadotropin-releasing hormone neurons.

    PubMed

    Gerhold, Lynnette M; Rosewell, Katherine L; Wise, Phyllis M

    2005-01-05

    Input from the suprachiasmatic nucleus (SCN) to gonadotropin-releasing hormone (GnRH) neurons is critical to the occurrence of regular cyclic GnRH secretion. It is thought that an essential neuropeptide in the SCN that communicates this cyclic information to GnRH neurons is vasoactive intestinal polypeptide (VIP) and that it may act through cAMP. We tested the hypothesis that (1) aging involves a blunting of cAMP diurnal rhythmicity in the SCN; (2) administration of antisense oligonucleotides (anti-oligos) against VIP, which produces an aging-like pattern in VIP, would lead to an aging-like suppression of cAMP; and (3) this in turn would lead to inhibition of the steroid-induced activation of GnRH neurons. We measured cAMP concentrations in the SCN and rostral preoptic nucleus throughout the day in young and middle-aged rats that were ovariectomized (OVX) or OVX and treated with estradiol. Our results show that cAMP concentrations exhibit a diurnal rhythm in young rats, and that this rhythm is totally abolished by the time rats are middle age. Administration of antisense oligonucleotides against VIP or random oligos suppresses VIP concentrations and abolishes the cAMP rhythm, leading to significantly reduced activation of GnRH neurons. Together, these findings strongly suggest that the SCN conveys diurnal information to GnRH neurons by driving VIP-dependent cAMP rhythms. In addition, aging involves deterioration in this VIP-driven rhythmicity, which impacts the ability of steroids to induce GnRH neuronal activation.

  2. Differential roles of endothelin-1 ETA and ETB receptors and vasoactive intestinal polypeptide in regulation of the airways and the pulmonary vasculature in isolated rat lung.

    PubMed

    Janosi, Tibor; Peták, Ferenc; Fontao, Fabienne; Morel, Denis R; Beghetti, Maurice; Habre, Walid

    2008-11-01

    The available treatment strategies against pulmonary hypertension include the administration of endothelin-1 (ET-1) receptor subtype blockers (ET(A) and ET(B) antagonists); vasoactive intestinal polypeptide (VIP) has recently been suggested as a potential new therapeutic agent. We set out to investigate the ability of these agents to protect against the vasoconstriction and impairment of lung function commonly observed in patients with pulmonary hypertension. An ET(A) blocker (BQ123), ET(B) blocker (BQ788), a combination of these selective blockers (ET(A) + ET(B) blockers) or VIP (V6130) was administered into the pulmonary circulation in four groups of perfused normal rat lungs. Pulmonary vascular resistance (PVR) and forced oscillatory lung input impedance (Z(L)) were measured in all groups under baseline conditions and at 1 min intervals following ET-1 administrations. The airway resistance, inertance, tissue damping and elastance were extracted from the Z(L) spectra. While VIP, ET(A) blocker and combined ET(A) and ET(B) blockers significantly prevented the pulmonary vasoconstriction induced by ET-1, ET(B) blockade enhanced the ET-1-induced increases in PVR. In contrast, the ET(A) and ET(B) blockers markedly elevated the ET-1-induced increases in airway resistance, while VIP blunted this constrictor response. Our results suggest that VIP potently acts against the airway and pulmonary vascular constriction mediated by endothelin-1, while the ET(A) and ET(B) blockers exert a differential effect between airway resistance and PVR.

  3. Peptide-containing nerve fibres in the gut wall in Crohn's disease.

    PubMed Central

    Sjölund, K; Schaffalitzky, O B; Muckadell, D E; Fahrenkrug, J; Håkanson, R; Peterson, B G; Sundler, F

    1983-01-01

    Neurones containing VIP, substance P, or enkephalin were studied by immunocytochemistry in intestinal specimens from 27 patients with Crohn's disease. Also several endocrine cell systems in the gut were examined. The results were compared with those from a control group of 26 patients. The relative frequency of various endocrine cells did not differ overtly from that in controls. Vasoactive intestinal polypeptide and substance P nerve fibres were distributed in all layers of the gut wall, including the submucosal and myenteric plexuses, whereas enkephalin fibres were restricted to the smooth muscle layer and the myenteric plexus. The distribution and frequency of the peptide-containing nerve fibres were the same in Crohn's disease patients as in control patients. A proportion of these nerve fibres, however, were notably coarse in the Crohn's disease patients. This was particularly apparent in the afflicted parts of the intestine although it was noted also in non-afflicted parts. The concentration of VIP and substance P (expressed as pmol/g wet weight) did not, however, exceed that of the control group. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:6192043

  4. Extracting Both Peptide Sequence and Glycan Structural Information by 157 nm Photodissociation of N-Linked Glycopeptides

    PubMed Central

    Zhang, Liangyi; Reilly, James P.

    2009-01-01

    157 nm photodissociation of N-linked glycopeptides was investigated in MALDI tandem time-of-flight (TOF) and linear ion trap mass spectrometers. Singly-charged glycopeptides yielded abundant peptide and glycan fragments. The peptide fragments included a series of x-, y-, v- and w- ions with the glycan remaining intact. These provide information about the peptide sequence and the glycosylation site. In addition to glycosidic fragments, abundant cross-ring glycan fragments that are not observed in low-energy CID were detected. These fragments provide insight into the glycan sequence and linkages. Doubly-charged glycopeptides generated by nanospray in the linear ion trap mass spectrometer also yielded peptide and glycan fragments. However, the former were dominated by low-energy fragments such as b- and y- type ions while glycan was primarily cleaved at glycosidic bonds. PMID:19113943

  5. Selection of peptides interfering with protein-protein interaction.

    PubMed

    Gaida, Annette; Hagemann, Urs B; Mattay, Dinah; Räuber, Christina; Müller, Kristian M; Arndt, Katja M

    2009-01-01

    Cell physiology depends on a fine-tuned network of protein-protein interactions, and misguided interactions are often associated with various diseases. Consequently, peptides, which are able to specifically interfere with such adventitious interactions, are of high interest for analytical as well as medical purposes. One of the most abundant protein interaction domains is the coiled-coil motif, and thus provides a premier target. Coiled coils, which consist of two or more alpha-helices wrapped around each other, have one of the simplest interaction interfaces, yet they are able to confer highly specific homo- and heterotypic interactions involved in virtually any cellular process. While there are several ways to generate interfering peptides, the combination of library design with a powerful selection system seems to be one of the most effective and promising approaches. This chapter guides through all steps of such a process, starting with library options and cloning, detailing suitable selection techniques and ending with purification for further down-stream characterization. Such generated peptides will function as versatile tools to interfere with the natural function of their targets thereby illuminating their down-stream signaling and, in general, promoting understanding of factors leading to specificity and stability in protein-protein interactions. Furthermore, peptides interfering with medically relevant proteins might become important diagnostics and therapeutics.

  6. Phage display peptide libraries: deviations from randomness and correctives

    PubMed Central

    Ryvkin, Arie; Ashkenazy, Haim; Weiss-Ottolenghi, Yael; Piller, Chen; Pupko, Tal; Gershoni, Jonathan M

    2018-01-01

    Abstract Peptide-expressing phage display libraries are widely used for the interrogation of antibodies. Affinity selected peptides are then analyzed to discover epitope mimetics, or are subjected to computational algorithms for epitope prediction. A critical assumption for these applications is the random representation of amino acids in the initial naïve peptide library. In a previous study, we implemented next generation sequencing to evaluate a naïve library and discovered severe deviations from randomness in UAG codon over-representation as well as in high G phosphoramidite abundance causing amino acid distribution biases. In this study, we demonstrate that the UAG over-representation can be attributed to the burden imposed on the phage upon the assembly of the recombinant Protein 8 subunits. This was corrected by constructing the libraries using supE44-containing bacteria which suppress the UAG driven abortive termination. We also demonstrate that the overabundance of G stems from variant synthesis-efficiency and can be corrected using compensating oligonucleotide-mixtures calibrated by mass spectroscopy. Construction of libraries implementing these correctives results in markedly improved libraries that display random distribution of amino acids, thus ensuring that enriched peptides obtained in biopanning represent a genuine selection event, a fundamental assumption for phage display applications. PMID:29420788

  7. Abundance of introduced species at home predicts abundance away in herbaceous communities

    USGS Publications Warehouse

    Firn, Jennifer; Moore, Joslin L.; MacDougall, Andrew S.; Borer, Elizabeth T.; Seabloom, Eric W.; HilleRisLambers, Janneke; Harpole, W. Stanley; Cleland, Elsa E.; Brown, Cynthia S.; Knops, Johannes M.H.; Prober, Suzanne M.; Pyke, David A.; Farrell, Kelly A.; Bakker, John D.; O'Halloran, Lydia R.; Adler, Peter B.; Collins, Scott L.; D'Antonio, Carla M.; Crawley, Michael J.; Wolkovich, Elizabeth M.; La Pierre, Kimberly J.; Melbourne, Brett A.; Hautier, Yann; Morgan, John W.; Leakey, Andrew D.B.; Kay, Adam; McCulley, Rebecca; Davies, Kendi F.; Stevens, Carly J.; Chu, Cheng-Jin; Holl, Karen D.; Klein, Julia A.; Fay, Phillip A.; Hagenah, Nicole; Kirkman, Kevin P.; Buckley, Yvonne M.

    2011-01-01

    Many ecosystems worldwide are dominated by introduced plant species, leading to loss of biodiversity and ecosystem function. A common but rarely tested assumption is that these plants are more abundant in introduced vs. native communities, because ecological or evolutionary-based shifts in populations underlie invasion success. Here, data for 26 herbaceous species at 39 sites, within eight countries, revealed that species abundances were similar at native (home) and introduced (away) sites - grass species were generally abundant home and away, while forbs were low in abundance, but more abundant at home. Sites with six or more of these species had similar community abundance hierarchies, suggesting that suites of introduced species are assembling similarly on different continents. Overall, we found that substantial changes to populations are not necessarily a pre-condition for invasion success and that increases in species abundance are unusual. Instead, abundance at home predicts abundance away, a potentially useful additional criterion for biosecurity programmes.

  8. MS/MS library facilitated MRM quantification of native peptides prepared by denaturing ultrafiltration

    PubMed Central

    2012-01-01

    Naturally occurring native peptides provide important information about physiological states of an organism and its changes in disease conditions but protocols and methods for assessing their abundance are not well-developed. In this paper, we describe a simple procedure for the quantification of non-tryptic peptides in body fluids. The workflow includes an enrichment step followed by two-dimensional fractionation of native peptides and MS/MS data management facilitating the design and validation of LC- MRM MS assays. The added value of the workflow is demonstrated in the development of a triplex LC-MRM MS assay used for quantification of peptides potentially associated with the progression of liver disease to hepatocellular carcinoma. PMID:22304756

  9. Peptides Labeled with Pyridinium Salts for Sensitive Detection and Sequencing by Electrospray Tandem Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Waliczek, Mateusz; Kijewska, Monika; Rudowska, Magdalena; Setner, Bartosz; Stefanowicz, Piotr; Szewczuk, Zbigniew

    2016-11-01

    Mass spectrometric analysis of trace amounts of peptides may be problematic due to the insufficient ionization efficiency resulting in limited sensitivity. One of the possible ways to overcome this problem is the application of ionization enhancers. Herein we developed new ionization markers based on 2,4,6-triphenylpyridinium and 2,4,6-trimethylpyridinium salts. Using of inexpensive and commercially available pyrylium salt allows selective derivatization of primary amino groups, especially those sterically unhindered, such as ɛ-amino group of lysine. The 2,4,6-triphenylpyridinium modified peptides generate in MS/MS experiments an abundant protonated 2,4,6-triphenylpyridinium ion. This fragment is a promising reporter ion for the multiple reactions monitoring (MRM) analysis. In addition, the fixed positive charge of the pyridinium group enhances the ionization efficiency. Other advantages of the proposed ionization enhancers are the simplicity of derivatization of peptides and the possibility of convenient incorporation of isotopic labels into derivatized peptides.

  10. PECAN: library-free peptide detection for data-independent acquisition tandem mass spectrometry data

    SciTech Connect

    Ting, Ying S.; Egertson, Jarrett D.; Bollinger, James G.

    Data-independent acquisition (DIA) is an emerging mass spectrometry (MS)-based technique for unbiased and reproducible measurement of protein mixtures. DIA tandem mass spectrometry spectra are often highly multiplexed, containing product ions from multiple cofragmenting precursors. Detecting peptides directly from DIA data is therefore challenging; most DIA data analyses require spectral libraries. Here we present PECECAN (http://pecan.maccosslab.org), a library-free, peptide-centric tool that robustly and accurately detects peptides directly from DIA data. PECECAN reports evidence of detection based on product ion scoring, which enables detection of low-abundance analytes with poor precursor ion signal. We demonstrate the chromatographic peak picking accuracy and peptide detectionmore » capability of PECECAN, and we further validate its detection with data-dependent acquisition and targeted analyses. Lastly, we used PECECAN to build a plasma proteome library from DIA data and to query known sequence variants.« less

  11. LC-MS/MS Identification of Species-Specific Muscle Peptides in Processed Animal Proteins.

    PubMed

    Marchis, Daniela; Altomare, Alessandra; Gili, Marilena; Ostorero, Federica; Khadjavi, Amina; Corona, Cristiano; Ru, Giuseppe; Cappelletti, Benedetta; Gianelli, Silvia; Amadeo, Francesca; Rumio, Cristiano; Carini, Marina; Aldini, Giancarlo; Casalone, Cristina

    2017-12-06

    An innovative analytical strategy has been applied to identify signature peptides able to distinguish among processed animal proteins (PAPs) derived from bovine, pig, fish, and milk products. Proteomics was first used to elucidate the proteome of each source. Starting from the identified proteins and using a funnel based approach, a set of abundant and well characterized peptides with suitable physical-chemical properties (signature peptides) and specific for each source was selected. An on-target LC-ESI-MS/MS method (MRM mode) was set up using standard peptides and was then applied to selectively identify the PAP source and also to distinguish proteins from bovine carcass and milk proteins. We believe that the method described meets the request of the European Commission which has developed a strategy for gradually lifting the "total ban" toward "species to species ban", therefore requiring official methods for species-specific discrimination in feed.

  12. Development and Testing of a 212Pb/212Bi Peptide for Targeting Metastatic Melanoma

    SciTech Connect

    Fisher, Darrell R.

    2012-10-25

    The purpose of this project is to develop a new radiolabeled peptide for imaging and treating metastatic melanoma. The immunoconjugate consists of a receptor-specific peptide that targets melanoma cells. The beta-emitter lead-212 (half-life = 10.4 hours) is linked by coordination chemistry to the peptide. After injection, the peptide targets melanoma receptors on the surfaces of melanoma cells. Lead-212 decays to the alpha-emitter bismuth-212 (half-life = 60 minutes). Alpha-particles that hit melanoma cell nuclei are likely to kill the melanoma cell. For cancer cell imaging, the lead-212 is replaced by lead-203 (half-life = 52 hours). Lead-203 emits 279 keV photons (80.1%more » abundance) that can be imaged and measured for biodistribution analysis, cancer imaging, and quantitative dosimetry.« less

  13. Therapeutic Properties and Biological Benefits of Marine-Derived Anticancer Peptides

    PubMed Central

    Kang, Hee Kyoung; Choi, Moon-Chang; Seo, Chang Ho; Park, Yoonkyung

    2018-01-01

    Various organisms exist in the oceanic environment. These marine organisms provide an abundant source of potential medicines. Many marine peptides possess anticancer properties, some of which have been evaluated for treatment of human cancer in clinical trials. Marine anticancer peptides kill cancer cells through different mechanisms, such as apoptosis, disruption of the tubulin-microtubule balance, and inhibition of angiogenesis. Traditional chemotherapeutic agents have side effects and depress immune responses. Thus, the research and development of novel anticancer peptides with low toxicity to normal human cells and mechanisms of action capable of avoiding multi-drug resistance may provide a new method for anticancer treatment. This review provides useful information on the potential of marine anticancer peptides for human therapy. PMID:29558431

  14. Climate and local abundance in freshwater fishes

    PubMed Central

    Knouft, Jason H.; Anthony, Melissa M.

    2016-01-01

    Identifying factors regulating variation in numbers of individuals among populations across a species' distribution is a fundamental goal in ecology. A common prediction, often referred to as the abundant-centre hypothesis, suggests that abundance is highest near the centre of a species' range. However, because of the primary focus on the geographical position of a population, this framework provides little insight into the environmental factors regulating local abundance. While range-wide variation in population abundance associated with environmental conditions has been investigated in terrestrial species, the relationship between climate and local abundance in freshwater taxa across species' distributions is not well understood. We used GIS-based temperature and precipitation data to determine the relationships between climatic conditions and range-wide variation in local abundance for 19 species of North American freshwater fishes. Climate predicted a portion of the variation in local abundance among populations for 18 species. In addition, the relationship between climatic conditions and local abundance varied among species, which is expected as lineages partition the environment across geographical space. The influence of local habitat quality on species persistence is well documented; however, our results also indicate the importance of climate in regulating population sizes across a species geographical range, even in aquatic taxa. PMID:27429769

  15. Effects of Chemical Structure on Hydrolysis Pathways of Small Peptides in Coastal Seawater

    NASA Astrophysics Data System (ADS)

    Liu, S.; Reyna, N. E.; Hamdan, L. J.; Liu, Z.

    2016-02-01

    Deciphering peptide hydrolysis pathways is key to understanding the mechanism of peptide hydrolysis, in particular the types of extracellular enzymes that are active in seawater. From the hydrolyzed fragments of small peptides, one can estimate the role of amino-, carboxy-, and endopeptidases in a quantitative way. In this study, we incubated several small peptides with different amino acid compositions, alanine-valine-phenylalanine-alanine (AVFA), phenylalanine-alanine-serine-tryptophan-glycine-alanine (FASWGA), VFA, SWGA, VVFA, arginine-valine-phenylalanine-alanine (RVFA), SVFA, aspartic acid-valine-phenylalanine-alanine (DVFA), trialanine (AAA), and AVF in two coastal seawaters (ship channel seawater in the western Gulf of Mexico and Sta. C6 seawater in the northern Gulf of Mexico). In both seawaters, aminopeptidases played a more dominant role (22-67%) in hydrolyzing peptides with hydrophobic amino acid at the N-terminus, such as AVFA, VVFA, VFA, and AAA, or with basic amino acid at the N-terminus (RVFA), as compared to those with N-terminal polar amino acid (SVFA, SWGA) or acidic amino acid (DVFA) (0-24%). This result indicates that amino acid composition in a peptide structure affects how the peptide is hydrolyzed. We also found that peptides in the C6 seawater were hydrolyzed dominantly by aminopeptidases (10-59%), while those in the ship channel seawater also by endo- or carboxypeptidases (9-69%). This pattern suggests that peptide hydrolysis pathways depend on specific environment conditions, such as bacterial community structure, that can lead to variations in abundances or activities among amino-, carboxy- and endopeptidases. Overall, the results provide insights into the effects of chemical structure and seawater environment on peptide hydrolysis pathways.

  16. Food-derived immunomodulatory peptides.

    PubMed

    Santiago-López, Lourdes; Hernández-Mendoza, Adrián; Vallejo-Cordoba, Belinda; Mata-Haro, Verónica; González-Córdova, Aarón F

    2016-08-01

    Food proteins contain specific amino acid sequences within their structures that may positively impact bodily functions and have multiple immunomodulatory effects. The functional properties of these specific sequences, also referred to as bioactive peptides, are revealed only after the degradation of native proteins during digestion processes. Currently, milk proteins have been the most explored source of bioactive peptides, which presents an interesting opportunity for the dairy industry. However, plant- and animal-derived proteins have also been shown to be important sources of bioactive peptides. This review summarizes the in vitro and in vivo evidence of the role of various food proteins as sources of immunomodulatory peptides and discusses the possible pathways involving these properties. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  17. Modification Site Localization in Peptides.

    PubMed

    Chalkley, Robert J

    2016-01-01

    There are a large number of search engines designed to take mass spectrometry fragmentation spectra and match them to peptides from proteins in a database. These peptides could be unmodified, but they could also bear modifications that were added biologically or during sample preparation. As a measure of reliability for the peptide identification, software normally calculates how likely a given quality of match could have been achieved at random, most commonly through the use of target-decoy database searching (Elias and Gygi, Nat Methods 4(3): 207-214, 2007). Matching the correct peptide but with the wrong modification localization is not a random match, so results with this error will normally still be assessed as reliable identifications by the search engine. Hence, an extra step is required to determine site localization reliability, and the software approaches to measure this are the subject of this part of the chapter.

  18. Peptide nanostructures in biomedical technology.

    PubMed

    Feyzizarnagh, Hamid; Yoon, Do-Young; Goltz, Mark; Kim, Dong-Shik

    2016-09-01

    Nanostructures of peptides have been investigated for biomedical applications due to their unique mechanical and electrical properties in addition to their excellent biocompatibility. Peptides may form fibrils, spheres and tubes in nanoscale depending on the formation conditions. These peptide nanostructures can be used in electrical, medical, dental, and environmental applications. Applications of these nanostructures include, but are not limited to, electronic devices, biosensing, medical imaging and diagnosis, drug delivery, tissue engineering and stem cell research. This review offers a discussion of basic synthesis methods, properties and application of these nanomaterials. The review concludes with recommendations and future directions for peptide nanostructures. WIREs Nanomed Nanobiotechnol 2016, 8:730-743. doi: 10.1002/wnan.1393 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

  19. Cardioprotective peptides from marine sources.

    PubMed

    Harnedy, Padraigín A; FitzGerald, Richard J

    2013-05-01

    Elevated blood pressure or hypertension is one of the fastest growing health problems worldwide. Although the etiology of essential hypertension has a genetic component, dietary factors play an important role. With the high costs and adverse side-effects associated with synthetic antihypertensive drugs and the awareness of the link between diet and health there has been increased focus on identification of food components that may contribute to cardiovascular health. In recent years special interest has been paid to the cardioprotective activity of peptides derived from food proteins including marine proteins. These peptides are latent within the sequence of the parent protein and only become active when released by proteolytic digestion during gastrointestinal digestion or through food processing. Current data on antihypertensive activity of marine-derived protein hydrolysates/peptides in animal and human studies is reviewed herein. Furthermore, products containing protein hydrolysates/peptides from marine origin with antihypertensive effects are discussed.

  20. Marine Peptides: Bioactivities and Applications

    PubMed Central

    Cheung, Randy Chi Fai; Ng, Tzi Bun; Wong, Jack Ho

    2015-01-01

    Peptides are important bioactive natural products which are present in many marine species. These marine peptides have high potential nutraceutical and medicinal values because of their broad spectra of bioactivities. Their antimicrobial, antiviral, antitumor, antioxidative, cardioprotective (antihypertensive, antiatherosclerotic and anticoagulant), immunomodulatory, analgesic, anxiolytic anti-diabetic, appetite suppressing and neuroprotective activities have attracted the attention of the pharmaceutical industry, which attempts to design them for use in the treatment or prevention of various diseases. Some marine peptides or their derivatives have high commercial values and had reached the pharmaceutical and nutraceutical markets. A large number of them are already in different phases of the clinical and preclinical pipeline. This review highlights the recent research in marine peptides and the trends and prospects for the future, with special emphasis on nutraceutical and pharmaceutical development into marketed products. PMID:26132844

  1. Biomedical Applications of Organometal-Peptide Conjugates

    NASA Astrophysics Data System (ADS)

    Metzler-Nolte, Nils

    Peptides are well suited as targeting vectors for the directed delivery of metal-based drugs or probes for biomedical investigations. This chapter describes synthetic strategies for the preparation of conjugates of medically interesting peptides with covalently bound metal complexes. Peptides that were used include neuropeptides (enkephalin, neuropeptide Y, neurotensin), uptake peptides (TAT and poly-Arg), and intracellular localization sequences. To these peptides, a whole variety of transition metal complexes has been attached in recent years by solid-phase peptide synthesis (SPPS) techniques. The metal complex can be attached to the peptide on the resin as part of the SPPS scheme. Alternatively, the metal complex may be attached to the peptide as a postsynthetic modification. Advantages as well as disadvantages for either strategy are discussed. Biomedical applications include radiopharmaceutical applications, anticancer and antibacterial activity, metal-peptide conjugates as targeted CO-releasing molecules, and metal-peptide conjugates in biosensor applications.

  2. The anti-inflammatory peptide stearyl-norleucine-VIP delays disease onset and extends survival in a rat model of inherited amyotrophic lateral sclerosis.

    PubMed

    Goursaud, Stéphanie; Schäfer, Sabrina; Dumont, Amélie O; Vergouts, Maxime; Gallo, Alessandro; Desmet, Nathalie; Deumens, Ronald; Hermans, Emmanuel

    2015-01-01

    Vasoactive intestinal peptide (VIP) has potent immune modulatory actions that may influence the course of neurodegenerative disorders associated with chronic inflammation. Here, we show the therapeutic benefits of a modified peptide agonist stearyl-norleucine-VIP (SNV) in a transgenic rat model of amyotrophic lateral sclerosis (mutated superoxide dismutase 1, hSOD1(G93A)). When administered by systemic every-other-day intraperitoneal injections during a period of 80 days before disease, SNV delayed the onset of motor dysfunction by no less than three weeks, while survival was extended by nearly two months. SNV-treated rats showed reduced astro- and microgliosis in the lumbar ventral spinal cord and a significant degree of motor neuron preservation. Throughout the treatment, SNV promoted the expression of the anti-inflammatory cytokine interleukin-10 as well as neurotrophic factors commonly considered as beneficial in amyotrophic lateral sclerosis management (glial derived neuroptrophic factor, insulin like growth factor, brain derived neurotrophic factor). The peptide nearly totally suppressed the expression of tumor necrosis factor-α and repressed the production of the pro-inflammatory mediators interleukin-1β, nitric oxide and of the transcription factor nuclear factor kappa B. Inhibition of tumor necrosis factor-α likely accounted for the observed down-regulation of nuclear factor kappa B that modulates the transcription of genes specifically involved in amyotrophic lateral sclerosis (sod1 and the glutamate transporter slc1a2). In line with this, levels of human superoxide dismutase 1 mRNA and protein were decreased by SNV treatment, while the expression and activity of the glutamate transporter-1 was promoted. Considering the large diversity of influences of this peptide on both clinical features of the disease and associated biochemical markers, we propose that SNV or related peptides may constitute promising candidates for amyotrophic lateral sclerosis

  3. Immunomagnetic separation of human myeloperoxidase using an antibody-mimicking peptide identified by phage display.

    PubMed

    Yun, Soi; Ryu, Hyunmin; Lee, E K

    2017-09-10

    Phage display biopanning is a powerful in vitro selection process for screening and identifying peptides that bind to a target protein of interest. With the aim of replacing antibodies in immuno-diagnostic applications, we identified peptides whose binding characteristics mimicked those of anti-human myeloperoxidase (hMPO), a biomarker for acute cardiac diseases. Based on ELISA results from four phage clones, we selected and chemically synthesized a 12-mer peptide (SYIEPPERHRHR). Quartz crystal microbalance and surface plasmon resonance analyses revealed that the molar binding equilibrium ratio of the synthesized peptide was 0.023, approximately 43-fold lower than that of the anti-hMPO antibody. The dissociation constant (K d ) was 57nM, which was comparable to that of the native antibody (83nM). Next, we biotinylated the peptide at its N-terminus and attached the biotinylated peptide to the surface of streptavidin-coated magnetic particles to assess its ability to selectively capture hMPO. The binding equilibrium data were similar to the previous analyses; specifically, around 0.021mol peptide bound to 1mol of hMPO. Antigen capture was found to be selective and to be relatively little influenced by the presence of human serum albumin (HSA), an abundant constituent of serum. Our work demonstrates the potential of immunomagnetic isolation to achieve selective capture of a low-concentration antigen from complex solutions such as serum. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Influence of Coronal Abundance Variations

    NASA Technical Reports Server (NTRS)

    Scargle, Jeffrey D. (Technical Monitor); Kashyap, Vinay

    2005-01-01

    The PI of this project was Jeff Scargle of NASA/Ames. Co-I's were Alma Connors of Eureka Scientific/Wellesley, and myself. Part of the work was subcontracted to Eureka Scientific via SAO, with Vinay Kashyap as PI. This project was originally assigned grant number NCC2-1206, and was later changed to NCC2-1350 for administrative reasons. The goal of the project was to obtain, derive, and develop statistical and data analysis tools that would be of use in the analyses of high-resolution, high-sensitivity data that are becoming available with new instruments. This is envisioned as a cross-disciplinary effort with a number of "collaborators" including some at SA0 (Aneta Siemiginowska, Peter Freeman) and at the Harvard Statistics department (David van Dyk, Rostislav Protassov, Xiao-li Meng, Epaminondas Sourlas, et al). We have developed a new tool to reliably measure the metallicities of thermal plasma. It is unfeasible to obtain high-resolution grating spectra for most stars, and one must make the best possible determination based on lower-resolution, CCD-type spectra. It has been noticed that most analyses of such spectra have resulted in measured metallicities that were significantly lower than when compared with analyses of high- resolution grating data where available (see, e.g., Brickhouse et al., 2000, ApJ 530,387). Such results have led to the proposal of the existence of so-called Metal Abundance Deficient, or "MAD" stars (e.g., Drake, J.J., 1996, Cool Stars 9, ASP Conf.Ser. 109, 203). We however find that much of these analyses may be systematically underestimating the metallicities, and using a newly developed method to correctly treat the low-counts regime at the high-energy tail of the stellar spectra (van Dyk et al. 2001, ApJ 548,224), have found that the metallicities of these stars are generally comparable to their photospheric values. The results were reported at the AAS (Sourlas, Yu, van Dyk, Kashyap, and Drake, 2000, BAAS 196, v32, #54.02), and at the

  5. Plant peptides in defense and signaling.

    PubMed

    Marmiroli, Nelson; Maestri, Elena

    2014-06-01

    This review focuses on plant peptides involved in defense against pathogen infection and those involved in the regulation of growth and development. Defense peptides, defensins, cyclotides and anti-microbial peptides are compared and contrasted. Signaling peptides are classified according to their major sites of activity. Finally, a network approach to creating an interactomic peptide map is described. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Flanking signal and mature peptide residues influence signal peptide cleavage

    PubMed Central

    Choo, Khar Heng; Ranganathan, Shoba

    2008-01-01

    Background Signal peptides (SPs) mediate the targeting of secretory precursor proteins to the correct subcellular compartments in prokaryotes and eukaryotes. Identifying these transient peptides is crucial to the medical, food and beverage and biotechnology industries yet our understanding of these peptides remains limited. This paper examines the most common type of signal peptides cleavable by the endoprotease signal peptidase I (SPase I), and the residues flanking the cleavage sites of three groups of signal peptide sequences, namely (i) eukaryotes (Euk) (ii) Gram-positive (Gram+) bacteria, and (iii) Gram-negative (Gram-) bacteria. Results In this study, 2352 secretory peptide sequences from a variety of organisms with amino-terminal SPs are extracted from the manually curated SPdb database for analysis based on physicochemical properties such as pI, aliphatic index, GRAVY score, hydrophobicity, net charge and position-specific residue preferences. Our findings show that the three groups share several similarities in general, but they display distinctive features upon examination in terms of their amino acid compositions and frequencies, and various physico-chemical properties. Thus, analysis or prediction of their sequences should be separated and treated as distinct groups. Conclusion We conclude that the peptide segment recognized by SPase I extends to the start of the mature protein to a limited extent, upon our survey of the amino acid residues surrounding the cleavage processing site. These flanking residues possibly influence the cleavage processing and contribute to non-canonical cleavage sites. Our findings are applicable in defining more accurate prediction tools for recognition and identification of cleavage site of SPs. PMID:19091014

  7. Monitoring Butterfly Abundance: Beyond Pollard Walks

    PubMed Central

    Pellet, Jérôme; Bried, Jason T.; Parietti, David; Gander, Antoine; Heer, Patrick O.; Cherix, Daniel; Arlettaz, Raphaël

    2012-01-01

    Most butterfly monitoring protocols rely on counts along transects (Pollard walks) to generate species abundance indices and track population trends. It is still too often ignored that a population count results from two processes: the biological process (true abundance) and the statistical process (our ability to properly quantify abundance). Because individual detectability tends to vary in space (e.g., among sites) and time (e.g., among years), it remains unclear whether index counts truly reflect population sizes and trends. This study compares capture-mark-recapture (absolute abundance) and count-index (relative abundance) monitoring methods in three species (Maculinea nausithous and Iolana iolas: Lycaenidae; Minois dryas: Satyridae) in contrasted habitat types. We demonstrate that intraspecific variability in individual detectability under standard monitoring conditions is probably the rule rather than the exception, which questions the reliability of count-based indices to estimate and compare specific population abundance. Our results suggest that the accuracy of count-based methods depends heavily on the ecology and behavior of the target species, as well as on the type of habitat in which surveys take place. Monitoring programs designed to assess the abundance and trends in butterfly populations should incorporate a measure of detectability. We discuss the relative advantages and inconveniences of current monitoring methods and analytical approaches with respect to the characteristics of the species under scrutiny and resources availability. PMID:22859980

  8. Neurons immunoreactive for vasoactive intestinal polypeptide in the rat primary somatosensory cortex: morphology and spatial relationship to barrel-related columns.

    PubMed

    Bayraktar, T; Welker, E; Freund, T F; Zilles, K; Staiger, J F

    2000-05-08

    Vasoactive intestinal polypeptide (VIP) in neocortex affects neuronal excitability as well as cortical blood flow and metabolism. Interneurons immunoreactive for VIP (VIP-IR neurons) are characterized by their predominantly bipolar appearance and the radial orientation of their main dendrites. In order to determine whether the morphology of VIP-IR neurons is related to the functional organization of the cortex into vertical columns, we combined both immunostaining of neurons containing VIP and cytochrome oxidase histochemistry for visualizing barrels, morphological layer IV correlates of functional columns, in the primary somatosensory (barrel) cortex of rats. VIP-IR neurons were localized in supragranular (48%), granular (16%), and infragranular layers (36%) as well as in the white matter. In the granular layer, a clear trend that more neurons were located in interbarrel septa rather than in barrels could be observed, resulting in a neuronal density which was about one-third higher in the septal area. VIP-IR neurons from the different cortical layers were three-dimensionally reconstructed from serial sections by using a computer microscope system. The neurons were mostly bipolar. Striking morphological differences in both axonal and dendritic trees were found between neurons whose cell bodies were located in supragranular, granular, and the upper part of infragranular layers, and those whose cell bodies were located in the area below. The former had dendrites which often reached layer I, where they bifurcated several times, and axonal trees which were particularly oriented vertically, with a tangential extent smaller than the width of barrels. Therefore, these neurons were mostly confined to either a barrel- or septum-related column. By contrast, the dendrites of neurons of the latter group did not reach the granular layer. Furthermore, these neurons had axons with sometimes very long horizontal collaterals, which often spanned two, in one case three, barrel

  9. Peptides and Anti-peptide Antibodies for Small and Medium Scale Peptide and Anti-peptide Affinity Microarrays: Antigenic Peptide Selection, Immobilization, and Processing.

    PubMed

    Zhang, Fan; Briones, Andrea; Soloviev, Mikhail

    2016-01-01

    This chapter describes the principles of selection of antigenic peptides for the development of anti-peptide antibodies for use in microarray-based multiplex affinity assays and also with mass-spectrometry detection. The methods described here are mostly applicable to small to medium scale arrays. Although the same principles of peptide selection would be suitable for larger scale arrays (with 100+ features) the actual informatics software and printing methods may well be different. Because of the sheer number of proteins/peptides to be processed and analyzed dedicated software capable of processing all the proteins and an enterprise level array robotics may be necessary for larger scale efforts. This report aims to provide practical advice to those who develop or use arrays with up to ~100 different peptide or protein features.

  10. Predicting the Dynamics of Protein Abundance

    PubMed Central

    Mehdi, Ahmed M.; Patrick, Ralph; Bailey, Timothy L.; Bodén, Mikael

    2014-01-01

    Protein synthesis is finely regulated across all organisms, from bacteria to humans, and its integrity underpins many important processes. Emerging evidence suggests that the dynamic range of protein abundance is greater than that observed at the transcript level. Technological breakthroughs now mean that sequencing-based measurement of mRNA levels is routine, but protocols for measuring protein abundance remain both complex and expensive. This paper introduces a Bayesian network that integrates transcriptomic and proteomic data to predict protein abundance and to model the effects of its determinants. We aim to use this model to follow a molecular response over time, from condition-specific data, in order to understand adaptation during processes such as the cell cycle. With microarray data now available for many conditions, the general utility of a protein abundance predictor is broad. Whereas most quantitative proteomics studies have focused on higher organisms, we developed a predictive model of protein abundance for both Saccharomyces cerevisiae and Schizosaccharomyces pombe to explore the latitude at the protein level. Our predictor primarily relies on mRNA level, mRNA–protein interaction, mRNA folding energy and half-life, and tRNA adaptation. The combination of key features, allowing for the low certainty and uneven coverage of experimental observations, gives comparatively minor but robust prediction accuracy. The model substantially improved the analysis of protein regulation during the cell cycle: predicted protein abundance identified twice as many cell-cycle-associated proteins as experimental mRNA levels. Predicted protein abundance was more dynamic than observed mRNA expression, agreeing with experimental protein abundance from a human cell line. We illustrate how the same model can be used to predict the folding energy of mRNA when protein abundance is available, lending credence to the emerging view that mRNA folding affects translation

  11. Predicting the dynamics of protein abundance.

    PubMed

    Mehdi, Ahmed M; Patrick, Ralph; Bailey, Timothy L; Bodén, Mikael

    2014-05-01

    Protein synthesis is finely regulated across all organisms, from bacteria to humans, and its integrity underpins many important processes. Emerging evidence suggests that the dynamic range of protein abundance is greater than that observed at the transcript level. Technological breakthroughs now mean that sequencing-based measurement of mRNA levels is routine, but protocols for measuring protein abundance remain both complex and expensive. This paper introduces a Bayesian network that integrates transcriptomic and proteomic data to predict protein abundance and to model the effects of its determinants. We aim to use this model to follow a molecular response over time, from condition-specific data, in order to understand adaptation during processes such as the cell cycle. With microarray data now available for many conditions, the general utility of a protein abundance predictor is broad. Whereas most quantitative proteomics studies have focused on higher organisms, we developed a predictive model of protein abundance for both Saccharomyces cerevisiae and Schizosaccharomyces pombe to explore the latitude at the protein level. Our predictor primarily relies on mRNA level, mRNA-protein interaction, mRNA folding energy and half-life, and tRNA adaptation. The combination of key features, allowing for the low certainty and uneven coverage of experimental observations, gives comparatively minor but robust prediction accuracy. The model substantially improved the analysis of protein regulation during the cell cycle: predicted protein abundance identified twice as many cell-cycle-associated proteins as experimental mRNA levels. Predicted protein abundance was more dynamic than observed mRNA expression, agreeing with experimental protein abundance from a human cell line. We illustrate how the same model can be used to predict the folding energy of mRNA when protein abundance is available, lending credence to the emerging view that mRNA folding affects translation efficiency

  12. Prolonged treatment with transcutaneous electrical nerve stimulation (TENS) modulates neuro-gastric motility and plasma levels of vasoactive intestinal peptide (VIP), motilin and interleukin-6 (IL-6) in systemic sclerosis.

    PubMed

    McNearney, Terry A; Sallam, Hanaa S; Hunnicutt, Sonya E; Doshi, Dipti; Chen, Jiande D Z

    2013-01-01

    We assessed the effects of transcutaneous electrical nerve stimulation (TENS) on neurogastric functioning in scleroderma patients. Seventeen SSc patients underwent 30 min TENS treatment >10Hz at GI acupuncture points PC6 and ST36, once (acute TENS) and then after two weeks of TENS sessions for 30 min twice daily (prolonged TENS). Data collected at Visits 1 and 2 included gastric myoelectrical activity (GMA) by surface electrogastrography (EGG), heart rate variability (HRV) by surface electrocardiography (EKG), GI specific symptoms and health related SF-36 questionnaires. Plasma VIP, motilin and IL-6 levels were determined. Statistical analyses were performed by Student's t-test, Spearman Rank and p-values <0.05 were considered significant. 1. Only after prolonged TENS, the percentages of normal slow waves and average slow wave coupling (especially channels 1, 2 reflecting gastric pacemaker and corpus regions) were significantly increased; 2. the percentage of normal slow waves was significantly correlated to sympathovagal balance; 3. Mean plasma VIP and motilin levels were significantly decreased after acute TENS, (vs. baseline), generally maintained in the prolonged TENS intervals. Compared to baseline, mean plasma IL-6 levels were significantly increased after acute TENS, but significantly decreased after prolonged TENS. 4. After prolonged TENS, the frequency of awakening due to abdominal pain and abdominal bloating were significantly and modestly decreased, respectively. In SSc patients, two weeks of daily TENS improved patient GMA scores, lowered plasma VIP, motilin and IL-6 levels and improved association between GMA and sympathovagal balance. This supports the therapeutic potential of prolonged TENS to enhance gastric myoelectrical functioning in SSc.

  13. Interstellar Abundances Toward X Per, Revisited

    NASA Technical Reports Server (NTRS)

    Valencic, Lynne A.; Smith, Randall K.

    2014-01-01

    The nearby X-ray binary X Per (HD 24534) provides a useful beacon with which to measure elemental abundances in the local ISM. We examine absorption features of 0, Mg, and Si along this line of sight using spectra from the Chandra Observatory's LETG/ ACIS-S and XMM-Newton's RGS instruments. In general, we find that the abundances and their ratios are similar to those of young F and G stars and the most recent solar values. We compare our results with abundances required by dust grain models.

  14. Interstellar Abundances Toward X Per, Revisited

    NASA Technical Reports Server (NTRS)

    Valencic, Lynne A.; Smith, Randall K.

    2012-01-01

    The nearby X-ray binary X Per (HD 24534) provides a useful beacon with which to measure elemental abundances in the local ISM. We examine absorption features of O, Mg, and Si along this line of sight using spectra from the Chandra Observatory's LETG/ACIS-S and XMM-Newton's RGS instruments. In general, we find that the abundances and their ratios are similar to those of young F and G stars and the most recent solar values. We compare our results with abundances required by dust grain models.

  15. Plasma proteomic analysis reveals altered protein abundances in cardiovascular disease.

    PubMed

    Lygirou, Vasiliki; Latosinska, Agnieszka; Makridakis, Manousos; Mullen, William; Delles, Christian; Schanstra, Joost P; Zoidakis, Jerome; Pieske, Burkert; Mischak, Harald; Vlahou, Antonia

    2018-04-17

    Cardiovascular disease (CVD) describes the pathological conditions of the heart and blood vessels. Despite the large number of studies on CVD and its etiology, its key modulators remain largely unknown. To this end, we performed a comprehensive proteomic analysis of blood plasma, with the scope to identify disease-associated changes after placing them in the context of existing knowledge, and generate a well characterized dataset for further use in CVD multi-omics integrative analysis. LC-MS/MS was employed to analyze plasma from 32 subjects (19 cases of various CVD phenotypes and 13 controls) in two steps: discovery (13 cases and 8 controls) and test (6 cases and 5 controls) set analysis. Following label-free quantification, the detected proteins were correlated to existing plasma proteomics datasets (plasma proteome database; PPD) and functionally annotated (Cytoscape, Ingenuity Pathway Analysis). Differential expression was defined based on identification confidence (≥ 2 peptides per protein), statistical significance (Mann-Whitney p value ≤ 0.05) and a minimum of twofold change. Peptides detected in at least 50% of samples per group were considered, resulting in a total of 3796 identified proteins (838 proteins based on ≥ 2 peptides). Pathway annotation confirmed the functional relevance of the findings (representation of complement cascade, fibrin clot formation, platelet degranulation, etc.). Correlation of the relative abundance of the proteins identified in the discovery set with their reported concentrations in the PPD was significant, confirming the validity of the quantification method. The discovery set analysis revealed 100 differentially expressed proteins between cases and controls, 39 of which were verified (≥ twofold change) in the test set. These included proteins already studied in the context of CVD (such as apolipoprotein B, alpha-2-macroglobulin), as well as novel findings (such as low density lipoprotein receptor related

  16. PEPA test: fast and powerful differential analysis from relative quantitative proteomics data using shared peptides.

    PubMed

    Jacob, Laurent; Combes, Florence; Burger, Thomas

    2018-06-18

    We propose a new hypothesis test for the differential abundance of proteins in mass-spectrometry based relative quantification. An important feature of this type of high-throughput analyses is that it involves an enzymatic digestion of the sample proteins into peptides prior to identification and quantification. Due to numerous homology sequences, different proteins can lead to peptides with identical amino acid chains, so that their parent protein is ambiguous. These so-called shared peptides make the protein-level statistical analysis a challenge and are often not accounted for. In this article, we use a linear model describing peptide-protein relationships to build a likelihood ratio test of differential abundance for proteins. We show that the likelihood ratio statistic can be computed in linear time with the number of peptides. We also provide the asymptotic null distribution of a regularized version of our statistic. Experiments on both real and simulated datasets show that our procedures outperforms state-of-the-art methods. The procedures are available via the pepa.test function of the DAPAR Bioconductor R package.

  17. Perspectives and Peptides of the Next Generation

    NASA Astrophysics Data System (ADS)

    Brogden, Kim A.

    Shortly after their discovery, antimicrobial peptides from prokaryotes and eukaryotes were recognized as the next potential generation of pharmaceuticals to treat antibiotic-resistant bacterial infections and septic shock, to preserve food, or to sanitize surfaces. Initial research focused on identifying the spectrum of antimicrobial agents, determining the range of antimicrobial activities against bacterial, fungal, and viral pathogens, and assessing the antimicrobial activity of synthetic peptides versus their natural counterparts. Subsequent research then focused on the mechanisms of antimicrobial peptide activity in model membrane systems not only to identify the mechanisms of antimicrobial peptide activity in microorganisms but also to discern differences in cytotoxicity for prokaryotic and eukaryotic cells. Recent, contemporary work now focuses on current and future efforts to construct hybrid peptides, peptide congeners, stabilized peptides, peptide conjugates, and immobilized peptides for unique and specific applications to control the growth of microorganisms in vitro and in vivo.

  18. Sequencing Cyclic Peptides by Multistage Mass Spectrometry

    PubMed Central

    Mohimani, Hosein; Yang, Yu-Liang; Liu, Wei-Ting; Hsieh, Pei-Wen; Dorrestein, Pieter C.; Pevzner, Pavel A.

    2012-01-01

    Some of the most effective antibiotics (e.g., Vancomycin and Daptomycin) are cyclic peptides produced by non-ribosomal biosynthetic pathways. While hundreds of biomedically important cyclic peptides have been sequenced, the computational techniques for sequencing cyclic peptides are still in their infancy. Previous methods for sequencing peptide antibiotics and other cyclic peptides are based on Nuclear Magnetic Resonance spectroscopy, and require large amount (miligrams) of purified materials that, for most compounds, are not possible to obtain. Recently, development of mass spectrometry based methods has provided some hope for accurate sequencing of cyclic peptides using picograms of materials. In this paper we develop a method for sequencing of cyclic peptides by multistage mass spectrometry, and show its advantages over single stage mass spectrometry. The method is tested on known and new cyclic peptides from Bacillus brevis, Dianthus superbus and Streptomyces griseus, as well as a new family of cyclic peptides produced by marine bacteria. PMID:21751357

  19. Exploration of the Medicinal Peptide Space.

    PubMed

    Gevaert, Bert; Stalmans, Sofie; Wynendaele, Evelien; Taevernier, Lien; Bracke, Nathalie; D'Hondt, Matthias; De Spiegeleer, Bart

    2016-01-01

    The chemical properties of peptide medicines, known as the 'medicinal peptide space' is considered a multi-dimensional subset of the global peptide space, where each dimension represents a chemical descriptor. These descriptors can be linked to biofunctional, medicinal properties to varying degrees. Knowledge of this space can increase the efficiency of the peptide-drug discovery and development process, as well as advance our understanding and classification of peptide medicines. For 245 peptide drugs, already available on the market or in clinical development, multivariate dataexploration was performed using peptide relevant physicochemical descriptors, their specific peptidedrug target and their clinical use. Our retrospective analysis indicates that clusters in the medicinal peptide space are located in a relatively narrow range of the physicochemical space: dense and empty regions were found, which can be explored for the discovery of novel peptide drugs.

  20. Stochastic species abundance models involving special copulas

    NASA Astrophysics Data System (ADS)

    Huillet, Thierry E.

    2018-01-01

    Copulas offer a very general tool to describe the dependence structure of random variables supported by the hypercube. Inspired by problems of species abundances in Biology, we study three distinct toy models where copulas play a key role. In a first one, a Marshall-Olkin copula arises in a species extinction model with catastrophe. In a second one, a quasi-copula problem arises in a flagged species abundance model. In a third model, we study completely random species abundance models in the hypercube as those, not of product type, with uniform margins and singular. These can be understood from a singular copula supported by an inflated simplex. An exchangeable singular Dirichlet copula is also introduced, together with its induced completely random species abundance vector.

  1. Vasoactive mediators and splanchnic perfusion.

    PubMed

    Reilly, P M; Bulkley, G B

    1993-02-01

    To provide an overview of the splanchnic hemodynamic response to circulatory shock. Previous studies performed in our own laboratory, as well as a computer-assisted search of the English language literature (MEDLINE, 1966 to 1991), followed by a selective review of pertinent articles. Studies were selected that demonstrated relevance to the splanchnic hemodynamic response to circulatory shock, either by investigating the pathophysiology or documenting the sequelae. Article selection included clinical studies as well as studies in appropriate animal models. Pertinent data were abstracted from the cited articles. The splanchnic hemodynamic response to circulatory shock is characterized by a selective vasoconstriction of the mesenteric vasculature mediated largely by the renin-angiotensin axis. This vasospasm, while providing a natural selective advantage to the organism in mild-to-moderate shock (preserving relative perfusion of the heart, kidneys, and brain), may, in more severe shock, cause consequent loss of the gut epithelial barrier, or even hemorrhagic gastritis, ischemic colitis, or ischemic hepatitis. From a physiologic standpoint, nonpulsatile cardiopulmonary bypass, a controlled form of circulatory shock, has been found experimentally to significantly increase circulating levels of angiotensin II, the hormone responsible for this selective splanchnic vasoconstriction. While angiotensin II has been viewed primarily as the mediator responsible for the increased total vascular resistance seen during (and after) cardiopulmonary bypass, it may also cause the disproportionate decrease in mesenteric perfusion, as measured in human subjects by intraluminal gastric tonometry and galactose clearance by the liver, as well as the consequent development of the multiple organ failure syndrome seen in 1% to 5% of patients after cardiac surgery.

  2. Coronae of Stars with Supersolar Elemental Abundances

    NASA Technical Reports Server (NTRS)

    Peretz, Uria; Behar, Ehud; Drake, Stephen A.

    2015-01-01

    Coronal elemental abundances are known to deviate from the photospheric values of their parent star, with the degree of deviation depending on the first ionization potential (FIP). This study focuses on the coronal composition of stars with supersolar photospheric abundances. We present the coronal abundances of six such stars: 11 LMi, iota Hor, HR 7291, tau Boo, and alpha Cen A and B. These stars all have high-statistics X-ray spectra, three of which are presented for the first time. The abundances we measured were obtained using the line-resolved spectra of the Reflection Grating Spectrometer (RGS) in conjunction with the higher throughput EPIC-pn camera spectra onboard the XMM-Newton observatory. A collisionally ionized plasma model with two or three temperature components is found to represent the spectra well. All elements are found to be consistently depleted in the coronae compared to their respective photospheres. For 11 LMi and tau Boo no FIP effect is present, while iota Hor, HR 7291, and alpha Cen A and B show a clear FIP trend. These conclusions hold whether the comparison is made with solar abundances or the individual stellar abundances. Unlike the solar corona, where low-FIP elements are enriched, in these stars the FIP effect is consistently due to a depletion of high-FIP elements with respect to actual photospheric abundances. A comparison with solar (instead of stellar) abundances yields the same fractionation trend as on the Sun. In both cases, a similar FIP bias is inferred, but different fractionation mechanisms need to be invoked.

  3. Composition and abundance of tree regeneration

    Treesearch

    Todd F. Hutchinson; Elaine Kennedy Sutherland; Charles T. Scott

    2003-01-01

    The composition and abundance of tree seedlings and saplings in the four study areas in southern Ohio were related to soil moisture via a GIS-derived integrated moisture index and to soil texture and fertility. For seedlings, the total abundance of small stems (less than 30 cm tall) was significantly greater on xeric plots (81,987/ha) than on intermediate (54,531/ha)...

  4. Twilight reloaded: the peptide experience

    PubMed Central

    Weichenberger, Christian X.; Pozharski, Edwin; Rupp, Bernhard

    2017-01-01

    The de facto commoditization of biomolecular crystallography as a result of almost disruptive instrumentation automation and continuing improvement of software allows any sensibly trained structural biologist to conduct crystallo­graphic studies of biomolecules with reasonably valid outcomes: that is, models based on properly interpreted electron density. Robust validation has led to major mistakes in the protein part of structure models becoming rare, but some depositions of protein–peptide complex structure models, which generally carry significant interest to the scientific community, still contain erroneous models of the bound peptide ligand. Here, the protein small-molecule ligand validation tool Twilight is updated to include peptide ligands. (i) The primary technical reasons and potential human factors leading to problems in ligand structure models are presented; (ii) a new method used to score peptide-ligand models is presented; (iii) a few instructive and specific examples, including an electron-density-based analysis of peptide-ligand structures that do not contain any ligands, are discussed in detail; (iv) means to avoid such mistakes and the implications for database integrity are discussed and (v) some suggestions as to how journal editors could help to expunge errors from the Protein Data Bank are provided. PMID:28291756

  5. Twilight reloaded: the peptide experience.

    PubMed

    Weichenberger, Christian X; Pozharski, Edwin; Rupp, Bernhard

    2017-03-01

    The de facto commoditization of biomolecular crystallography as a result of almost disruptive instrumentation automation and continuing improvement of software allows any sensibly trained structural biologist to conduct crystallographic studies of biomolecules with reasonably valid outcomes: that is, models based on properly interpreted electron density. Robust validation has led to major mistakes in the protein part of structure models becoming rare, but some depositions of protein-peptide complex structure models, which generally carry significant interest to the scientific community, still contain erroneous models of the bound peptide ligand. Here, the protein small-molecule ligand validation tool Twilight is updated to include peptide ligands. (i) The primary technical reasons and potential human factors leading to problems in ligand structure models are presented; (ii) a new method used to score peptide-ligand models is presented; (iii) a few instructive and specific examples, including an electron-density-based analysis of peptide-ligand structures that do not contain any ligands, are discussed in detail; (iv) means to avoid such mistakes and the implications for database integrity are discussed and (v) some suggestions as to how journal editors could help to expunge errors from the Protein Data Bank are provided.

  6. TEA: A Code Calculating Thermochemical Equilibrium Abundances

    NASA Astrophysics Data System (ADS)

    Blecic, Jasmina; Harrington, Joseph; Bowman, M. Oliver

    2016-07-01

    We present an open-source Thermochemical Equilibrium Abundances (TEA) code that calculates the abundances of gaseous molecular species. The code is based on the methodology of White et al. and Eriksson. It applies Gibbs free-energy minimization using an iterative, Lagrangian optimization scheme. Given elemental abundances, TEA calculates molecular abundances for a particular temperature and pressure or a list of temperature-pressure pairs. We tested the code against the method of Burrows & Sharp, the free thermochemical equilibrium code Chemical Equilibrium with Applications (CEA), and the example given by Burrows & Sharp. Using their thermodynamic data, TEA reproduces their final abundances, but with higher precision. We also applied the TEA abundance calculations to models of several hot-Jupiter exoplanets, producing expected results. TEA is written in Python in a modular format. There is a start guide, a user manual, and a code document in addition to this theory paper. TEA is available under a reproducible-research, open-source license via https://github.com/dzesmin/TEA.

  7. Report on carbon and nitrogen abundance studies

    NASA Technical Reports Server (NTRS)

    Boehm-Vitense, Erika

    1991-01-01

    The aim of the proposal was to determine the nitrogen to carbon abundance ratios from transition layer lines in stars with different T(sub eff) and luminosities. The equations which give the surface emission line fluxes and the measured ratio of the NV to CIV emission line fluxes are presented and explained. The abundance results are compared with those of photospheric abundance studies for stars in common with the photospheric investigations. The results show that the analyses are at least as accurate as the photospheric determinations. These studies can be extended to F and early G stars for which photospheric abundance determinations for giants are hard to do because molecular bands become too weak. The abundance determination in the context of stellar evolution is addressed. The N/C abundance ratio increases steeply at the point of evolution for which the convection zone reaches deepest. Looking at the evolution of the rotation velocities v sin i, a steep decrease in v sin i is related to the increasing depth of the convection zone. It is concluded that the decrease in v sin i for T(sub eff) less than or approximately = 5800 K is most probably due to the rearrangement of the angular momentum in the stars due to deep convective mixing. It appears that the convection zone is rotating with nearly depth independent angular momentum. Other research results and ongoing projects are discussed.

  8. TEA: A CODE CALCULATING THERMOCHEMICAL EQUILIBRIUM ABUNDANCES

    SciTech Connect

    Blecic, Jasmina; Harrington, Joseph; Bowman, M. Oliver, E-mail: jasmina@physics.ucf.edu

    2016-07-01

    We present an open-source Thermochemical Equilibrium Abundances (TEA) code that calculates the abundances of gaseous molecular species. The code is based on the methodology of White et al. and Eriksson. It applies Gibbs free-energy minimization using an iterative, Lagrangian optimization scheme. Given elemental abundances, TEA calculates molecular abundances for a particular temperature and pressure or a list of temperature–pressure pairs. We tested the code against the method of Burrows and Sharp, the free thermochemical equilibrium code Chemical Equilibrium with Applications (CEA), and the example given by Burrows and Sharp. Using their thermodynamic data, TEA reproduces their final abundances, but withmore » higher precision. We also applied the TEA abundance calculations to models of several hot-Jupiter exoplanets, producing expected results. TEA is written in Python in a modular format. There is a start guide, a user manual, and a code document in addition to this theory paper. TEA is available under a reproducible-research, open-source license via https://github.com/dzesmin/TEA.« less

  9. Modeling abundance effects in distance sampling

    USGS Publications Warehouse

    Royle, J. Andrew; Dawson, D.K.; Bates, S.

    2004-01-01

    Distance-sampling methods are commonly used in studies of animal populations to estimate population density. A common objective of such studies is to evaluate the relationship between abundance or density and covariates that describe animal habitat or other environmental influences. However, little attention has been focused on methods of modeling abundance covariate effects in conventional distance-sampling models. In this paper we propose a distance-sampling model that accommodates covariate effects on abundance. The model is based on specification of the distance-sampling likelihood at the level of the sample unit in terms of local abundance (for each sampling unit). This model is augmented with a Poisson regression model for local abundance that is parameterized in terms of available covariates. Maximum-likelihood estimation of detection and density parameters is based on the integrated likelihood, wherein local abundance is removed from the likelihood by integration. We provide an example using avian point-transect data of Ovenbirds (Seiurus aurocapillus) collected using a distance-sampling protocol and two measures of habitat structure (understory cover and basal area of overstory trees). The model yields a sensible description (positive effect of understory cover, negative effect on basal area) of the relationship between habitat and Ovenbird density that can be used to evaluate the effects of habitat management on Ovenbird populations.

  10. Antimicrobial Peptides from Marine Proteobacteria

    PubMed Central

    Desriac, Florie; Jégou, Camille; Balnois, Eric; Brillet, Benjamin; Le Chevalier, Patrick; Fleury, Yannick

    2013-01-01

    After years of inadequate use and the emergence of multidrug resistant (MDR) strains, the efficiency of “classical” antibiotics has decreased significantly. New drugs to fight MDR strains are urgently needed. Bacteria hold much promise as a source of unusual bioactive metabolites. However, the potential of marine bacteria, except for Actinomycetes and Cyanobacteria, has been largely underexplored. In the past two decades, the structures of several antimicrobial compounds have been elucidated in marine Proteobacteria. Of these compounds, polyketides (PKs), synthesised by condensation of malonyl-coenzyme A and/or acetyl-coenzyme A, and non-ribosomal peptides (NRPs), obtained through the linkage of (unusual) amino acids, have recently generated particular interest. NRPs are good examples of naturally modified peptides. Here, we review and compile the data on the antimicrobial peptides isolated from marine Proteobacteria, especially NRPs. PMID:24084784

  11. Antiviral active peptide from oyster

    NASA Astrophysics Data System (ADS)

    Zeng, Mingyong; Cui, Wenxuan; Zhao, Yuanhui; Liu, Zunying; Dong, Shiyuan; Guo, Yao

    2008-08-01

    An active peptide against herpes virus was isolated from the enzymic hydrolysate of oyster ( Crassostrea gigas) and purified with the definite direction hydrolysis technique in the order of alcalase and bromelin. The hydrolysate was fractioned into four ranges of molecular weight (>10 kDa, 10 5 kDa, 5 1 kDa and <1 kDa) using ultrafiltration membranes and dialysis. The fraction of 10 5 kDa was purified using consecutive chromatographic methods including DEAE Sephadex A-25 column, Sephadex G-25 column, and high performance liquid chromatogram (HPLC) by activity-guided isolation. The antiviral effect of the obtained peptide on herpetic virus was investigated in Vero cells by observing cytopathic effect (CPE). The result shows that the peptide has high inhibitory activity on herpetic virus.

  12. Antimicrobial Peptide Production and Purification.

    PubMed

    Suda, Srinivas; Field, Des; Barron, Niall

    2017-01-01

    Antimicrobial peptides (AMPs) are natural defense compounds which are synthesized as ribosomal gene-encoded pre-peptides and produced by all living organisms. AMPs are small peptides, usually cationic and typically have hydrophobic residues which interact with cell membranes and have either a narrow or broad spectrum of biological activity. AMPs are isolated from the natural host or heterologously expressed in other hosts such as Escherichia coli. The proto-typical lantibiotic Nisin is a widely used AMP that is produced by the food-grade organism Lactococcus lactis. Although AMP production and purification procedures require optimization for individual AMPs, the Nisin production and purification protocol outlined in this chapter can be easily applied with minor modifications for the production and purification of other lantibiotics or AMPs. While Nisin is produced and secreted into the supernatant, steps to recover Nisin from both cell-free supernatant and cell pellet are outlined in detail.

  13. Membrane Perturbation Induced by Interfacially Adsorbed Peptides

    PubMed Central

    Zemel, Assaf; Ben-Shaul, Avinoam; May, Sylvio

    2004-01-01

    The structural and energetic characteristics of the interaction between interfacially adsorbed (partially inserted) α-helical, amphipathic peptides and the lipid bilayer substrate are studied using a molecular level theory of lipid chain packing in membranes. The peptides are modeled as “amphipathic cylinders” characterized by a well-defined polar angle. Assuming two-dimensional nematic order of the adsorbed peptides, the membrane perturbation free energy is evaluated using a cell-like model; the peptide axes are parallel to the membrane plane. The elastic and interfacial contributions to the perturbation free energy of the “peptide-dressed” membrane are evaluated as a function of: the peptide penetration depth into the bilayer's hydrophobic core, the membrane thickness, the polar angle, and the lipid/peptide ratio. The structural properties calculated include the shape and extent of the distorted (stretched and bent) lipid chains surrounding the adsorbed peptide, and their orientational (C-H) bond order parameter profiles. The changes in bond order parameters attendant upon peptide adsorption are in good agreement with magnetic resonance measurements. Also consistent with experiment, our model predicts that peptide adsorption results in membrane thinning. Our calculations reveal pronounced, membrane-mediated, attractive interactions between the adsorbed peptides, suggesting a possible mechanism for lateral aggregation of membrane-bound peptides. As a special case of interest, we have also investigated completely hydrophobic peptides, for which we find a strong energetic preference for the transmembrane (inserted) orientation over the horizontal (adsorbed) orientation. PMID:15189858

  14. Clustering in the stellar abundance space

    NASA Astrophysics Data System (ADS)

    Boesso, R.; Rocha-Pinto, H. J.

    2018-03-01

    We have studied the chemical enrichment history of the interstellar medium through an analysis of the n-dimensional stellar abundance space. This work is a non-parametric analysis of the stellar chemical abundance space. The main goal is to study the stars from their organization within this abundance space. Within this space, we seek to find clusters (in a statistical sense), that is, stars likely to share similar chemo-evolutionary history, using two methods: the hierarchical clustering and the principal component analysis. We analysed some selected abundance surveys available in the literature. For each sample, we labelled the group of stars according to its average abundance curve. In all samples, we identify the existence of a main enrichment pattern of the stars, which we call chemical enrichment flow. This flow is set by the structured and well-defined mean rate at which the abundances of the interstellar medium increase, resulting from the mixture of the material ejected from the stars and stellar mass-loss and interstellar medium gas. One of the main results of our analysis is the identification of subgroups of stars with peculiar chemistry. These stars are situated in regions outside of the enrichment flow in the abundance space. These peculiar stars show a mismatch in the enrichment rate of a few elements, such as Mg, Si, Sc and V, when compared to the mean enrichment rate of the other elements of the same stars. We believe that the existence of these groups of stars with peculiar chemistry may be related to the accretion of planetary material on to stellar surfaces or may be due to production of the same chemical element by different nucleosynthetic sites.

  15. Clonal growth and plant species abundance

    PubMed Central

    Herben, Tomáš; Nováková, Zuzana; Klimešová, Jitka

    2014-01-01

    Background and Aims Both regional and local plant abundances are driven by species' dispersal capacities and their abilities to exploit new habitats and persist there. These processes are affected by clonal growth, which is difficult to evaluate and compare across large numbers of species. This study assessed the influence of clonal reproduction on local and regional abundances of a large set of species and compared the predictive power of morphologically defined traits of clonal growth with data on actual clonal growth from a botanical garden. The role of clonal growth was compared with the effects of seed reproduction, habitat requirements and growth, proxied both by LHS (leaf–height–seed) traits and by actual performance in the botanical garden. Methods Morphological parameters of clonal growth, actual clonal reproduction in the garden and LHS traits (leaf-specific area – height – seed mass) were used as predictors of species abundance, both regional (number of species records in the Czech Republic) and local (mean species cover in vegetation records) for 836 perennial herbaceous species. Species differences in habitat requirements were accounted for by classifying the dataset by habitat type and also by using Ellenberg indicator values as covariates. Key Results After habitat differences were accounted for, clonal growth parameters explained an important part of variation in species abundance, both at regional and at local levels. At both levels, both greater vegetative growth in cultivation and greater lateral expansion trait values were correlated with higher abundance. Seed reproduction had weaker effects, being positive at the regional level and negative at the local level. Conclusions Morphologically defined traits are predictive of species abundance, and it is concluded that simultaneous investigation of several such traits can help develop hypotheses on specific processes (e.g. avoidance of self-competition, support of offspring) potentially

  16. Novel formulations for antimicrobial peptides.

    PubMed

    Carmona-Ribeiro, Ana Maria; de Melo Carrasco, Letícia Dias

    2014-10-09

    Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy.

  17. Novel Formulations for Antimicrobial Peptides

    PubMed Central

    Carmona-Ribeiro, Ana Maria; Carrasco, Letícia Dias de Melo

    2014-01-01

    Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy. PMID:25302615

  18. Peptides and the new endocrinology

    NASA Astrophysics Data System (ADS)

    Schwyzer, Robert

    1982-01-01

    The discovery of regulatory peptides common to the nervous and the endocrine systems (brain, gut, and skin) has brought about a revolution in our concepts of endocrinology and neurology. We are beginning to understand some of the complex interrelationships between soma and psyche that might, someday, be important for an integrated treatment of diseases. Examples of the actions of certain peptides in the periphery and in the central nervous system are given, and their biosynthesis and molecular anatomy as carriers for information are discussed.

  19. Biodiscovery of Aluminum Binding Peptides

    DTIC Science & Technology

    2013-08-01

    et al., "Biomimetic synthesis and patterning of silver nanoparticles ," Nat. Mater. 1(3), 169-172 (2002). [5] Van Dorst, B., et al., "Phage display...34Sequestration of zinc oxide by fimbrial designer chelators," Appl. Environ. Microbiol. 66(1), 10-14 (2000). [26] Hnilova, M., et al., "Peptide-directed co...biomaterial synthesis . Peptides have been developed that bind to a variety of inorganic materials, including metals1-6, oxides7, 8, alloys9, metal salts10

  20. An enhancer peptide for membrane-disrupting antimicrobial peptides

    PubMed Central

    2010-01-01

    Background NP4P is a synthetic peptide derived from a natural, non-antimicrobial peptide fragment (pro-region of nematode cecropin P4) by substitution of all acidic amino acid residues with amides (i.e., Glu → Gln, and Asp → Asn). Results In the presence of NP4P, some membrane-disrupting antimicrobial peptides (ASABF-α, polymyxin B, and nisin) killed microbes at lower concentration (e.g., 10 times lower minimum bactericidal concentration for ASABF-α against Staphylococcus aureus), whereas NP4P itself was not bactericidal and did not interfere with bacterial growth at ≤ 300 μg/mL. In contrast, the activities of antimicrobial agents with a distinct mode of action (indolicidin, ampicillin, kanamycin, and enrofloxacin) were unaffected. Although the membrane-disrupting activity of NP4P was slight or undetectable, ASABF-α permeabilized S. aureus membranes with enhanced efficacy in the presence of NP4P. Conclusions NP4P selectively enhanced the bactericidal activities of membrane-disrupting antimicrobial peptides by increasing the efficacy of membrane disruption against the cytoplasmic membrane. PMID:20152058

  1. Diversity of peptidic and proteinaceous toxins from social Hymenoptera venoms.

    PubMed

    Dos Santos-Pinto, José Roberto Aparecido; Perez-Riverol, Amilcar; Lasa, Alexis Musacchio; Palma, Mario Sergio

    2018-06-15

    Among venomous animals, Hymenoptera have been suggested as a rich source of natural toxins. Due to their broad ecological diversity, venom from Hymenoptera insects (bees, wasps and ants) have evolved differentially thus widening the types and biological functions of their components. To date, insect toxinology analysis have scarcely uncovered the complex composition of bee, wasp and ant venoms which include low molecular weight compounds, highly abundant peptides and proteins, including several allergens. In Hymenoptera, these complex mixtures of toxins represent a potent arsenal of biological weapons that are used for self-defense, to repel intruders and to capture prey. Consequently, Hymenoptera venom components have a broad range of pharmacological targets and have been extensively studied, as promising sources of new drugs and biopesticides. In addition, the identification and molecular characterization of Hymenoptera venom allergens have allowed for the rational design of component-resolved diagnosis of allergy, finally improving the outcome of venom immunotherapy (VIT). Until recently, a limited number of Hymenoptera venoms had been unveiled due to the technical limitations of the approaches used to date. Nevertheless, the application of novel techniques with high dynamic range has significantly increased the number of identified peptidic and proteinaceous toxins. Considering this, the present review summarizes the current knowledge about the most representative Hymenoptera venom peptides and proteins which are under study for a better understanding of the insect-caused envenoming process and the development of new drugs and biopesticides. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Current biochemistry, molecular biology, and clinical relevance of natriuretic peptides.

    PubMed

    Nishikimi, Toshio; Kuwahara, Koichiro; Nakao, Kazuwa

    2011-03-01

    The mammalian natriuretic peptide family consists of atrial (ANP), brain [B-type; BNP] and C-type natriuretic peptide (CNP) and three receptors, natriuretic receptors-A (NPR-A), -B (NPR-B) and -C (NPR-C). Both ANP and BNP are abundantly expressed in the heart and are secreted mainly from the atria and ventricles, respectively. By contrast, CNP is mainly expressed in the central nervous system, bone and vasculature. Plasma concentrations of both ANP and BNP are elevated in patients with cardiovascular disease, though the magnitude of the increase in BNP is usually greater than the increase in ANP. This makes BNP is a clinically useful diagnostic marker for several pathophysiological conditions, including heart failure, ventricular remodeling and pulmonary hypertension, among others. Recent studies have shown that in addition to BNP-32, proBNP-108 also circulates in human plasma and that levels of both forms are increased in heart failure. Furthermore, proBNP-108 is O-glycosylated and circulates at higher levels in patients with severe heart failure. In this review we discuss recent progress in our understanding of the biochemistry, molecular biology and clinical relevance of the natriuretic peptide system. Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  3. Antimicrobial peptides: Possible anti-infective agents.

    PubMed

    Lakshmaiah Narayana, Jayaram; Chen, Jyh-Yih

    2015-10-01

    Multidrug-resistant bacterial, fungal, viral, and parasitic infections are major health threats. The Infectious Diseases Society of America has expressed concern on the decrease of pharmaceutical companies working on antibiotic research and development. However, small companies, along with academic research institutes, are stepping forward to develop novel therapeutic methods to overcome the present healthcare situation. Among the leading alternatives to current drugs are antimicrobial peptides (AMPs), which are abundantly distributed in nature. AMPs exhibit broad-spectrum activity against a wide variety of bacteria, fungi, viruses, and parasites, and even cancerous cells. They also show potential immunomodulatory properties, and are highly responsive to infectious agents and innate immuno-stimulatory molecules. In recent years, many AMPs have undergone or are undergoing clinical development, and a few are commercially available for topical and other applications. In this review, we outline selected anion and cationic AMPs which are at various stages of development, from preliminary analysis to clinical drug development. Moreover, we also consider current production methods and delivery tools for AMPs, which must be improved for the effective use of these agents. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Infrared Multiphoton Dissociation of Peptide Cations in a Dual Pressure Linear Ion Trap Mass Spectrometer

    PubMed Central

    Gardner, Myles W.; Smith, Suncerae I.; Ledvina, Aaron R.; Madsen, James A.; Coon, Joshua J.; Schwartz, Jae C.; Stafford, George C.; Brodbelt, Jennifer S.

    2009-01-01

    A dual pressure linear ion trap mass spectrometer was modified to permit infrared multiphoton dissociation (IRMPD) in each of the two cells - the first a high pressure cell operated at nominally 5 × 10-3 Torr and the second a low pressure cell operated at nominally 3 × 10-4 Torr. When IRMPD was performed in the high pressure cell, most peptide ions did not undergo significant photodissociation; however, in the low pressure cell peptide cations were efficiently dissociated with less than 25 ms of IR irradiation regardless of charge state. IRMPD of peptide cations allowed the detection of low m/z product ions including the y1 fragments and immonium ions which are not typically observed by ion trap collision induced dissociation (CID). Photodissociation efficiencies of ~100% and MS/MS (tandem mass spectrometry) efficiencies of greater than 60% were observed for both multiply and singly protonated peptides. In general, higher sequence coverage of peptides was obtained using IRMPD over CID. Further, greater than 90% of the product ion current in the IRMPD mass spectra of doubly charged peptide ions was composed of singly charged product ions compared to the CID mass spectra in which the abundances of the multiply and singly charged product ions were equally divided. Highly charged primary product ions also underwent efficient photodissociation to yield singly charged secondary product ions, thus simplifying the IRMPD product ion mass spectra. PMID:19739654

  5. Marked differences between metalloproteases meprin A and B in substrate and peptide bond specificity.

    PubMed

    Bertenshaw, G P; Turk, B E; Hubbard, S J; Matters, G L; Bylander, J E; Crisman, J M; Cantley, L C; Bond, J S

    2001-04-20

    Meprin A and B are highly regulated, secreted, and cell-surface metalloendopeptidases that are abundantly expressed in the kidney and intestine. Meprin oligomers consist of evolutionarily related alpha and/or beta subunits. The work herein was carried out to identify bioactive peptides and proteins that are susceptible to hydrolysis by mouse meprins and kinetically characterize the hydrolysis. Gastrin-releasing peptide fragment 14-27 and gastrin 17, regulatory molecules of the gastrointestinal tract, were found to be the best peptide substrates for meprin A and B, respectively. Peptide libraries and a variety of naturally occurring peptides revealed that the meprin beta subunit has a clear preference for acidic amino acids in the P1 and P1' sites of substrates. The meprin alpha subunit selected for small (e.g. serine, alanine) or hydrophobic (e.g. phenylalanine) residues in the P1 and P1' sites, and proline was the most preferred amino acid at the P2' position. Thus, although the meprin alpha and beta subunits share 55% amino acid identity within the protease domain and are normally localized at the same tissue cell surfaces, they have very different substrate and peptide bond specificities indicating different functions. Homology models of the mouse meprin alpha and beta protease domains, based on the astacin crystal structure, revealed active site differences that can account for the marked differences in substrate specificity of the two subunits.

  6. Comprehensive Peptide Analysis of Mouse Brain Striatum Identifies Novel sORF-Encoded Polypeptides.

    PubMed

    Budamgunta, Harshavardhan; Olexiouk, Volodimir; Luyten, Walter; Schildermans, Karin; Maes, Evelyne; Boonen, Kurt; Menschaert, Gerben; Baggerman, Geert

    2018-04-30

    Bio-active peptides are involved in the regulation of most physiological processes in the body. Classical bio-active peptides (CBAPs) are cleaved from a larger precursor protein and stored in secretion vesicles from which they are released in the extracellular space. Recently, another non-classical type of bio-active peptides (NCBAPs) have gained interest. These typically are not secreted but instead appear to be translated from short open reading frames (sORF) and released directly into the cytoplasm. In contrast to CBAPs, these peptides are involved in the regulation of intra-cellular processes such as transcriptional control, calcium handling and DNA repair. However, bio-chemical evidence for the translation of sORFs remains elusive. Comprehensive analysis of sORF-encoded polypeptides (SEPs) is hampered by a number of methodological and biological challenges: the low molecular mass (many 4-10 kDa), the low abundance, transient expression and complications in data analysis. We developed a strategy to address a number of these issues. Our strategy is to exclude false positive identifications. in total sample, we identified 926 peptides originated from 37 known (neuro)peptide precursors in mouse striatum,. In addition, four SEPs were identified including NoBody, a SEP that was previously discovered in humans and three novel SEPS from 5' untranslated transcript regions (UTRs). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Streptavidin-binding peptides and uses thereof

    NASA Technical Reports Server (NTRS)

    Wilson, David S. (Inventor); Szostak, Jack W. (Inventor); Keefe, Anthony D. (Inventor)

    2005-01-01

    The invention provides peptides with high affinity for streptavidin. These peptides may be expressed as part of fusion proteins to facilitate the detection, quantitation, and purification of proteins of interest.

  8. Streptavidin-binding peptides and uses thereof

    NASA Technical Reports Server (NTRS)

    Szostak, Jack W. (Inventor); Keefe, Anthony D. (Inventor); Wilson, David S. (Inventor)

    2006-01-01

    The invention provides peptides with high affinity for streptavidin. These peptides may be expressed as part of fusion proteins to facilitate the detection, quantitation, and purification of proteins of interest.

  9. Boosting production yield of biomedical peptides

    NASA Technical Reports Server (NTRS)

    Manatt, S. L.

    1978-01-01

    Nuclear magnetic resonance (NMR) technique is employed to monitor synthesis of biomedical peptides. Application of NMR technique may improve production yields of insulin, ACTH, and growth hormones, as well as other synthesized biomedical peptides.

  10. Identification of tissue-specific targeting peptide

    NASA Astrophysics Data System (ADS)

    Jung, Eunkyoung; Lee, Nam Kyung; Kang, Sang-Kee; Choi, Seung-Hoon; Kim, Daejin; Park, Kisoo; Choi, Kihang; Choi, Yun-Jaie; Jung, Dong Hyun

    2012-11-01

    Using phage display technique, we identified tissue-targeting peptide sets that recognize specific tissues (bone-marrow dendritic cell, kidney, liver, lung, spleen and visceral adipose tissue). In order to rapidly evaluate tissue-specific targeting peptides, we performed machine learning studies for predicting the tissue-specific targeting activity of peptides on the basis of peptide sequence information using four machine learning models and isolated the groups of peptides capable of mediating selective targeting to specific tissues. As a representative liver-specific targeting sequence, the peptide "DKNLQLH" was selected by the sequence similarity analysis. This peptide has a high degree of homology with protein ligands which can interact with corresponding membrane counterparts. We anticipate that our models will be applicable to the prediction of tissue-specific targeting peptides which can recognize the endothelial markers of target tissues.

  11. Investigating Endogenous Peptides and Peptidases using Peptidomics

    PubMed Central

    Tinoco, Arthur D.; Saghatelian, Alan

    2012-01-01

    Rather than simply being protein degradation products, peptides have proven to be important bioactive molecules. Bioactive peptides act as hormones, neurotransmitters and antimicrobial agents in vivo. The dysregulation of bioactive peptide signaling is also known to be involved in disease, and targeting peptide hormone pathways has been successful strategy in the development of novel therapeutics. The importance of bioactive peptides in biology has spurred research to elucidate the function and regulation of these molecules. Classical methods for peptide analysis have relied on targeted immunoassays, but certain scientific questions necessitated a broader and more detailed view of the peptidome–all the peptides in a cell, tissue or organism. In this review we discuss how peptidomics has emerged to fill this need through the application of advanced liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods that provide unique insights into peptide activity and regulation. PMID:21786763

  12. Accurate abundance determinations in S stars

    NASA Astrophysics Data System (ADS)

    Neyskens, P.; Van Eck, S.; Plez, B.; Goriely, S.; Siess, L.; Jorissen, A.

    2011-12-01

    S-type stars are thought to be the first objects, during their evolution on the asymptotic giant branch (AGB), to experience s-process nucleosynthesis and third dredge-ups, and therefore to exhibit s-process signatures in their atmospheres. Until present, the modeling of these processes is subject to large uncertainties. Precise abundance determinations in S stars are of extreme importance for constraining e.g., the depth and the formation of the 13C pocket. In this paper a large grid of MARCS model atmospheres for S stars is used to derive precise abundances of key s-process elements and iron. A first estimation of the atmospheric parameters is obtained using a set of well-chosen photometric and spectroscopic indices for selecting the best model atmosphere of each S star. Abundances are derived from spectral line synthesis, using the selected model atmosphere. Special interest is paid to technetium, an element without stable isotopes. Its detection in stars is considered as the best possible signature that the star effectively populates the thermally-pulsing AGB (TP-AGB) phase of evolution. The derived Tc/Zr abundances are compared, as a function of the derived [Zr/Fe] overabundances, with AGB stellar model predictions. The computed [Zr/Fe] overabundances are in good agreement with the AGB stellar evolution model predictions, while the Tc/Zr abundances are slightly over-predicted. This discrepancy can help to set stronger constraints on nucleosynthesis and mixing mechanisms in AGB stars.

  13. Abundances in Eight M31 Planetary Nebulae

    NASA Astrophysics Data System (ADS)

    Hensley, Kerry G.; Kwitter, Karen B.; Corradi, Romano; Galera-Rosillo, R.; Balick, Bruce; Henry, Richard B. C.

    2014-06-01

    As part of a continuing project using planetary nebulae (PNe) to study the chemical evolution and formation history of M31 (see accompanying poster by Balick et al.), we obtained spectra of eight PNe in the fall of 2013 with the OSIRIS spectrograph on the GTC. All of these PNe are located outside M31’s inner disk and bulge. Spectral coverage extended from 3700-7800Å with a resolution of ~6 Å. Especially important in abundance determinations is the detection of the weak, temperature-sensitive auroral line of [O III], at 4363Å, which is often contaminated by Hg I 4358Å from streetlights; the remoteness of the GTC eliminated this difficulty. We reduced and measured the spectra using IRAF, and derived nebular diagnostics and abundances with ELSA, our in-house five-level-atom program. Here we report the chemical abundances determined from these spectra. The bottom line is that the oxygen abundances in these PNe are all within a factor of 2-3 of the solar value, (as are all the other M31 PNe our team has previously measured) despite the significant range of galactocentric distance. Future work will use these abundances to constrain models of the central star to estimate progenitor masses and ages. In particular we will use the results to investigate the hypothesis that these PNe might represent a population related to the encounter between M31 and M33 ~3 Gy ago. We gratefully acknowledge support from Williams College.

  14. RELATIVE ABUNDANCE MEASUREMENTS IN PLUMES AND INTERPLUMES

    SciTech Connect

    Guennou, C.; Hahn, M.; Savin, D. W., E-mail: cguennou@iac.es

    2015-07-10

    We present measurements of relative elemental abundances in plumes and interplumes. Plumes are bright, narrow structures in coronal holes that extend along open magnetic field lines far out into the corona. Previous work has found that in some coronal structures the abundances of elements with a low first ionization potential (FIP) <10 eV are enhanced relative to their photospheric abundances. This coronal-to-photospheric abundance ratio, commonly called the FIP bias, is typically 1 for elements with a high-FIP (>10 eV). We have used Extreme Ultraviolet Imaging Spectrometer observations made on 2007 March 13 and 14 over a ≈24 hr period tomore » characterize abundance variations in plumes and interplumes. To assess their elemental composition, we used a differential emission measure analysis, which accounts for the thermal structure of the observed plasma. We used lines from ions of iron, silicon, and sulfur. From these we estimated the ratio of the iron and silicon FIP bias relative to that for sulfur. From the results, we have created FIP-bias-ratio maps. We find that the FIP-bias ratio is sometimes higher in plumes than in interplumes and that this enhancement can be time dependent. These results may help to identify whether plumes or interplumes contribute to the fast solar wind observed in situ and may also provide constraints on the formation and heating mechanisms of plumes.« less

  15. Hierarchical models of animal abundance and occurrence

    USGS Publications Warehouse

    Royle, J. Andrew; Dorazio, R.M.

    2006-01-01

    Much of animal ecology is devoted to studies of abundance and occurrence of species, based on surveys of spatially referenced sample units. These surveys frequently yield sparse counts that are contaminated by imperfect detection, making direct inference about abundance or occurrence based on observational data infeasible. This article describes a flexible hierarchical modeling framework for estimation and inference about animal abundance and occurrence from survey data that are subject to imperfect detection. Within this framework, we specify models of abundance and detectability of animals at the level of the local populations defined by the sample units. Information at the level of the local population is aggregated by specifying models that describe variation in abundance and detection among sites. We describe likelihood-based and Bayesian methods for estimation and inference under the resulting hierarchical model. We provide two examples of the application of hierarchical models to animal survey data, the first based on removal counts of stream fish and the second based on avian quadrat counts. For both examples, we provide a Bayesian analysis of the models using the software WinBUGS.

  16. Peptides, polypeptides and peptide-polymer hybrids as nucleic acid carriers.

    PubMed

    Ahmed, Marya

    2017-10-24

    Cell penetrating peptides (CPPs), and protein transduction domains (PTDs) of viruses and other natural proteins serve as a template for the development of efficient peptide based gene delivery vectors. PTDs are sequences of acidic or basic amphipathic amino acids, with superior membrane trespassing efficacies. Gene delivery vectors derived from these natural, cationic and cationic amphipathic peptides, however, offer little flexibility in tailoring the physicochemical properties of single chain peptide based systems. Owing to significant advances in the field of peptide chemistry, synthetic mimics of natural peptides are often prepared and have been evaluated for their gene expression, as a function of amino acid functionalities, architecture and net cationic content of peptide chains. Moreover, chimeric single polypeptide chains are prepared by a combination of multiple small natural or synthetic peptides, which imparts distinct physiological properties to peptide based gene delivery therapeutics. In order to obtain multivalency and improve the gene delivery efficacies of low molecular weight cationic peptides, bioactive peptides are often incorporated into a polymeric architecture to obtain novel 'polymer-peptide hybrids' with improved gene delivery efficacies. Peptide modified polymers prepared by physical or chemical modifications exhibit enhanced endosomal escape, stimuli responsive degradation and targeting efficacies, as a function of physicochemical and biological activities of peptides attached onto a polymeric scaffold. The focus of this review is to provide comprehensive and step-wise progress in major natural and synthetic peptides, chimeric polypeptides, and peptide-polymer hybrids for nucleic acid delivery applications.

  17. Experimental Cancer Cachexia Changes Neuron Numbers and Peptide Levels in the Intestine: Partial Protective Effects after Dietary Supplementation with L-Glutamine

    PubMed Central

    Vicentini, Geraldo E.; Fracaro, Luciane; de Souza, Sara R. G.; Martins, Heber A.; Guarnier, Flávia A.; Zanoni, Jacqueline N.

    2016-01-01

    Gastrointestinal dysmotility frequently occurs in cancer cachexia and may result from damage to enteric innervation caused by oxidative stress, especially due to glutathione depletion. We assessed the effect of dietary supplementation with 20 g/kg l-glutamine (a glutathione precursor) on the intrinsic innervation of the enteric nervous system in healthy and Walker 256 tumor-bearing Wistar rats during the development of experimental cachexia (14 days), in comparison with non-supplemented rats, by using immunohistochemical methods and Western blotting. The total neural population and cholinergic subpopulation densities in the myenteric plexus, as well as the total population and VIPergic subpopulation in the submucosal plexus of the jejunum and ileum, were reduced in cachectic rats, resulting in adaptive morphometric alterations and an increase in vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) expression, suggesting a neuroplastic response. l-glutamine supplementation prevented decrease in myenteric neuronal density in the ileum, morphometric alterations in the neurons and nerve fibers (in both the plexuses of the jejunum and ileum), and the overexpression of VIP and CGRP. Cancer cachexia severely affected the intrinsic innervation of the jejunum and ileum to various degrees and this injury seems to be associated with adaptive neural plasticity. l-glutamine supplementation presented partial protective effects on the enteric innervation against cancer cachexia, possibly by attenuating oxidative stress. PMID:27635657

  18. Experimental Cancer Cachexia Changes Neuron Numbers and Peptide Levels in the Intestine: Partial Protective Effects after Dietary Supplementation with L-Glutamine.

    PubMed

    Vicentini, Geraldo E; Fracaro, Luciane; de Souza, Sara R G; Martins, Heber A; Guarnier, Flávia A; Zanoni, Jacqueline N

    2016-01-01

    Gastrointestinal dysmotility frequently occurs in cancer cachexia and may result from damage to enteric innervation caused by oxidative stress, especially due to glutathione depletion. We assessed the effect of dietary supplementation with 20 g/kg l-glutamine (a glutathione precursor) on the intrinsic innervation of the enteric nervous system in healthy and Walker 256 tumor-bearing Wistar rats during the development of experimental cachexia (14 days), in comparison with non-supplemented rats, by using immunohistochemical methods and Western blotting. The total neural population and cholinergic subpopulation densities in the myenteric plexus, as well as the total population and VIPergic subpopulation in the submucosal plexus of the jejunum and ileum, were reduced in cachectic rats, resulting in adaptive morphometric alterations and an increase in vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) expression, suggesting a neuroplastic response. l-glutamine supplementation prevented decrease in myenteric neuronal density in the ileum, morphometric alterations in the neurons and nerve fibers (in both the plexuses of the jejunum and ileum), and the overexpression of VIP and CGRP. Cancer cachexia severely affected the intrinsic innervation of the jejunum and ileum to various degrees and this injury seems to be associated with adaptive neural plasticity. l-glutamine supplementation presented partial protective effects on the enteric innervation against cancer cachexia, possibly by attenuating oxidative stress.

  19. Rare-earth abundances in chondritic meteorites

    NASA Technical Reports Server (NTRS)

    Evensen, N. M.; Hamilton, P. J.; Onions, R. K.

    1978-01-01

    Fifteen chondrites, including eight carbonaceous chondrites, were analyzed for rare earth element abundances by isotope dilution. Examination of REE for a large number of individual chondrites shows that only a small proportion of the analyses have flat unfractionated REE patterns within experimental error. While some of the remaining analyses are consistent with magmatic fractionation, many patterns, in particular those with positive Ce anomalies, can not be explained by known magmatic processes. Elemental abundance anomalies are found in all major chondrite classes. The persistence of anomalies in chondritic materials relatively removed from direct condensational processes implies that anomalous components are resistant to equilibrium or were introduced at a late stage of chondrite formation. Large-scale segregation of gas and condensate is implied, and bulk variations in REE abundances between planetary bodies is possible.

  20. Diverse CLE peptides from cyst nematode species

    USDA-ARS?s Scientific Manuscript database

    Plant CLAVATA3/ESR (CLE)-like peptides play diverse roles in plant growth and development including maintenance of the stem cell population in the root meristem. Small secreted peptides sharing similarity to plant CLE signaling peptides have been isolated from several cyst nematode species including...

  1. Tissue-specific effects of peptides.

    PubMed

    Khavinson, V K

    2001-08-01

    Synthetic peptides (cytogens) Cortagen, Epithalon, Livagen, and Vilon stimulated the growth of explants from rat brain cortex, subcortical structures, liver, and thymus, respectively, in organotypic cultures. These peptides produced tissue-specific effects: they stimulated the growth of explants from tissues, whose cytomedins (peptide complexes) were used for chemical synthesis.

  2. Toxins and antimicrobial peptides: interactions with membranes

    NASA Astrophysics Data System (ADS)

    Schlamadinger, Diana E.; Gable, Jonathan E.; Kim, Judy E.

    2009-08-01

    The innate immunity to pathogenic invasion of organisms in the plant and animal kingdoms relies upon cationic antimicrobial peptides (AMPs) as the first line of defense. In addition to these natural peptide antibiotics, similar cationic peptides, such as the bee venom toxin melittin, act as nonspecific toxins. Molecular details of AMP and peptide toxin action are not known, but the universal function of these peptides to disrupt cell membranes of pathogenic bacteria (AMPs) or a diverse set of eukaryotes and prokaryotes (melittin) is widely accepted. Here, we have utilized spectroscopic techniques to elucidate peptide-membrane interactions of alpha-helical human and mouse AMPs of the cathelicidin family as well as the peptide toxin melittin. The activity of these natural peptides and their engineered analogs was studied on eukaryotic and prokaryotic membrane mimics consisting of <200-nm bilayer vesicles composed of anionic and neutral lipids as well as cholesterol. Vesicle disruption, or peptide potency, was monitored with a sensitive fluorescence leakage assay. Detailed molecular information on peptidemembrane interactions and peptide structure was further gained through vibrational spectroscopy combined with circular dichroism. Finally, steady-state fluorescence experiments yielded insight into the local environment of native or engineered tryptophan residues in melittin and human cathelicidin embedded in bilayer vesicles. Collectively, our results provide clues to the functional structures of the engineered and toxic peptides and may impact the design of synthetic antibiotic peptides that can be used against the growing number of antibiotic-resistant pathogens.

  3. Identification of multifunctional peptides from human milk.

    PubMed

    Mandal, Santi M; Bharti, Rashmi; Porto, William F; Gauri, Samiran S; Mandal, Mahitosh; Franco, Octavio L; Ghosh, Ananta K

    2014-06-01

    Pharmaceutical industries have renewed interest in screening multifunctional bioactive peptides as a marketable product in health care applications. In this context, several animal and plant peptides with potential bioactivity have been reported. Milk proteins and peptides have received much attention as a source of health-enhancing components to be incorporated into nutraceuticals and functional foods. By using this source, 24 peptides have been fractionated and purified from human milk using RP-HPLC. Multifunctional roles including antimicrobial, antioxidant and growth stimulating activity have been evaluated in all 24 fractions. Nevertheless, only four fractions show multiple combined activities among them. Using a proteomic approach, two of these four peptides have been identified as lactoferrin derived peptide and kappa casein short chain peptide. Lactoferrin derived peptide (f8) is arginine-rich and kappa casein derived (f12) peptide is proline-rich. Both peptides (f8 and f12) showed antimicrobial activities against both Gram-positive and Gram-negative bacteria. Fraction 8 (f8) exhibits growth stimulating activity in 3T3 cell line and f12 shows higher free radical scavenging activity in comparison to other fractions. Finally, both peptides were in silico evaluated and some insights into their mechanism of action were provided. Thus, results indicate that these identified peptides have multiple biological activities which are valuable for the quick development of the neonate and may be considered as potential biotechnological products for nutraceutical industry. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Distinguishing d - and l -aspartic and isoaspartic acids in amyloid β peptides with ultrahigh resolution ion mobility spectrometry

    SciTech Connect

    Zheng, Xueyun; Deng, Liulin; Baker, Erin S.

    2017-01-01

    Ion mobility spectrometry (IMS) was utilized to separate Aβ peptide variants containing isomeric asparic and isoaspartic acid residues with either al- ord-form. The abundance of each variant is of great interest in Alzheimer's disease studies and also to evaluate how often these modifications are occurring in other environmental and biological samples.

  5. A strategy for absolute proteome quantification with mass spectrometry by hierarchical use of peptide-concatenated standards.

    PubMed

    Kito, Keiji; Okada, Mitsuhiro; Ishibashi, Yuko; Okada, Satoshi; Ito, Takashi

    2016-05-01

    The accurate and precise absolute abundance of proteins can be determined using mass spectrometry by spiking the sample with stable isotope-labeled standards. In this study, we developed a strategy of hierarchical use of peptide-concatenated standards (PCSs) to quantify more proteins over a wider dynamic range. Multiple primary PCSs were used for quantification of many target proteins. Unique "ID-tag peptides" were introduced into individual primary PCSs, allowing us to monitor the exact amounts of individual PCSs using a "secondary PCS" in which all "ID-tag peptides" were concatenated. Furthermore, we varied the copy number of the "ID-tag peptide" in each PCS according to a range of expression levels of target proteins. This strategy accomplished absolute quantification over a wider range than that of the measured ratios. The quantified abundance of budding yeast proteins showed a high reproducibility for replicate analyses and similar copy numbers per cell for ribosomal proteins, demonstrating the accuracy and precision of this strategy. A comparison with the absolute abundance of transcripts clearly indicated different post-transcriptional regulation of expression for specific functional groups. Thus, the approach presented here is a faithful method for the absolute quantification of proteomes and provides insights into biological mechanisms, including the regulation of expressed protein abundance. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Structure and further fragmentation of significant [a3 + Na - H]+ ions from sodium-cationized peptides.

    PubMed

    Wang, Huixin; Wang, Bing; Wei, Zhonglin; Zhang, Hao; Guo, Xinhua

    2015-01-01

    A good understanding of gas-phase fragmentation chemistry of peptides is important for accurate protein identification. Additional product ions obtained by sodiated peptides can provide useful sequence information supplementary to protonated peptides and improve protein identification. In this work, we first demonstrate that the sodiated a3 ions are abundant in the tandem mass spectra of sodium-cationized peptides although observations of a3 ions have rarely been reported in protonated peptides. Quantum chemical calculations combined with tandem mass spectrometry are used to investigate this phenomenon by using a model tetrapeptide GGAG. Our results reveal that the most stable [a3 + Na - H](+) ion is present as a bidentate linear structure in which the sodium cation coordinates to the two backbone carbonyl oxygen atoms. Due to structural inflexibility, further fragmentation of the [a3 + Na - H](+) ion needs to overcome several relatively high energetic barriers to form [b2 + Na - H](+) ion with a diketopiperazine structure. As a result, low abundance of [b2 + Na - H](+) ion is detected at relatively high collision energy. In addition, our computational data also indicate that the common oxazolone pathway to generate [b2 + Na - H](+) from the [a3 + Na - H](+) ion is unlikely. The present work provides a mechanistic insight into how a sodium ion affects the fragmentation behaviors of peptides. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Beryllium Abundances of Six Halo Stars

    NASA Astrophysics Data System (ADS)

    Thorburn, J. A.; Hobbs, L. M.

    1996-05-01

    High signal-to-noise (S/N≍80), high-resolution (R≍25 000) spectra of six warm halo stars have been obtained in the Be II λ3130 region. Beryllium abundances derived through spectrum synthesis are generally consistent with [Be/Fe]≍0 and probably do not support the simplest models of cosmic-ray nucleosynthesis. Alternative scenarios whereby energetic C, N, and O nuclei collide with ambient He nuclei-rather than the converse-are more compatible with the data. However, these observations constrain net Be production only. If Galactic astration of Be is important, then Be production mechanisms must be proportionally more efficient. In the case of the near twin stars HD 94028 and HD 194598, log(Be/H) differs by 0.3 dex despite effectively identical Li abundances. A difference in initial Be abundance rather than stellar depletion is proposed to account for the discrepancy. Our Be abundances are typically ˜0.3 dex lower than those reported by Boesgaard & King [Al, 106, 2309 (1993)] for five stars in common. The disparity in Be abundance scales is due to the combined influences of differences in assigned stellar parameters and overestimated Be ii λ3131.066 line strengths in the Boesgaard & King study. Systematic errors in published Be abundances may be greater than has previously been suggested. A consistency check of the line list used for the synthesis reveals an unidentified blending feature of moderate strength slightly blueward of λ3131.066 in the Sun. Results of the present investigation are not significantly influenced by the ambiguous identity of the contaminating feature. However, studies which include cooler, more metal-rich stars may, as a consequence of neglecting or improperly identifying this line, report incorrect slopes of log(Be/H) vs [Fe/H] or erroneously large scatter in log(Be/H).

  8. Large-scale mass spectrometric detection of variant peptides resulting from non-synonymous nucleotide differences

    PubMed Central

    Sheynkman, Gloria M.; Shortreed, Michael R.; Frey, Brian L.; Scalf, Mark; Smith, Lloyd M.

    2013-01-01

    Each individual carries thousands of non-synonymous single nucleotide variants (nsSNVs) in their genome, each corresponding to a single amino acid polymorphism (SAP) in the encoded proteins. It is important to be able to directly detect and quantify these variations at the protein level in order to study post-transcriptional regulation, differential allelic expression, and other important biological processes. However, such variant peptides are not generally detected in standard proteomic analyses, due to their absence from the generic databases that are employed for mass spectrometry searching. Here, we extend previous work that demonstrated the use of customized SAP databases constructed from sample-matched RNA-Seq data. We collected deep coverage RNA-Seq data from the Jurkat cell line, compiled the set of nsSNVs that are expressed, used this information to construct a customized SAP database, and searched it against deep coverage shotgun MS data obtained from the same sample. This approach enabled detection of 421 SAP peptides mapping to 395 nsSNVs. We compared these peptides to peptides identified from a large generic search database containing all known nsSNVs (dbSNP) and found that more than 70% of the SAP peptides from this dbSNP-derived search were not supported by the RNA-Seq data, and thus are likely false positives. Next, we increased the SAP coverage from the RNA-Seq derived database by utilizing multiple protease digestions, thereby increasing variant detection to 695 SAP peptides mapping to 504 nsSNV sites. These detected SAP peptides corresponded to moderate to high abundance transcripts (30+ transcripts per million, TPM). The SAP peptides included 192 allelic pairs; the relative expression levels of the two alleles were evaluated for 51 of those pairs, and found to be comparable in all cases. PMID:24175627

  9. Improving cardiac gap junction communication as a new antiarrhythmic mechanism: the action of antiarrhythmic peptides.

    PubMed

    Dhein, Stefan; Hagen, Anja; Jozwiak, Joanna; Dietze, Anna; Garbade, Jens; Barten, Markus; Kostelka, Martin; Mohr, Friedrich-Wilhelm

    2010-03-01

    Co-ordinated electrical activation of the heart is maintained by intercellular coupling of cardiomyocytes via gap junctional channels located in the intercalated disks. These channels consist of two hexameric hemichannels, docked to each other, provided by either of the adjacent cells. Thus, a complete gap junction channel is made from 12 protein subunits, the connexins. While 21 isoforms of connexins are presently known, cardiomyocytes typically are coupled by Cx43 (most abundant), Cx40 or Cx45. Some years ago, antiarrhythmic peptides were discovered and synthesised, which were shown to increase macroscopic gap junction conductance (electrical coupling) and enhance dye transfer (metabolic coupling). The lead substance of these peptides is AAP10 (H-Gly-Ala-Gly-Hyp-Pro-Tyr-CONH(2)), a peptide with a horseshoe-like spatial structure as became evident from two-dimensional nuclear magnetic resonance studies. A stable D: -amino-acid derivative of AAP10, rotigaptide, as well as a non-peptide analogue, gap-134, has been developed in recent years. Antiarrhythmic peptides act on Cx43 and Cx45 gap junctions but not on Cx40 channels. AAP10 has been shown to enhance intercellular communication in rat, rabbit and human cardiomyocytes. Antiarrhythmic peptides are effective against ventricular tachyarrhythmias, such as late ischaemic (type IB) ventricular fibrillation, CaCl(2) or aconitine-induced arrhythmia. Interestingly, the effect of antiarrhythmic peptides is higher in partially uncoupled cells and was shown to be related to maintained Cx43 phosphorylation, while arrhythmogenic conditions like ischaemia result in Cx43 dephosphorylation and intercellular decoupling. It is still a matter of debate whether these drugs also act against atrial fibrillation. The present review outlines the development of this group of peptides and derivatives, their mode of action and molecular mechanisms, and discusses their possible therapeutic potential.

  10. The Use of Chromium(III) to Supercharge Peptides by Protonation at Low Basicity Sites

    NASA Astrophysics Data System (ADS)

    Feng, Changgeng; Commodore, Juliette J.; Cassady, Carolyn J.

    2015-02-01

    The addition of chromium(III) nitrate to solutions of peptides with seven or more residues greatly increases the formation of doubly protonated peptides, [M + 2H]2+, by electrospray ionization. The test compound heptaalanine has only one highly basic site (the N-terminal amino group) and undergoes almost exclusive single protonation using standard solvents. When Cr(III) is added to the solution, abundant [M + 2H]2+ forms, which involves protonation of the peptide backbone or the C-terminus. Salts of Al(III), Mn(II), Fe(III), Fe(II), Cu(II), Zn (II), Rh(III), La(III), Ce(IV), and Eu(III) were also studied. Although several metal ions slightly enhance protonation, Cr(III) has by far the greatest ability to generate [M + 2H]2+. Cr(III) does not supercharge peptide methyl esters, which suggests that the mechanism involves interaction of Cr(III) with a carboxylic acid group. Other factors may include the high acidity of hexa-aquochromium(III) and the resistance of Cr(III) to reduction. Nitrate salts enhance protonation more than chloride salts and a molar ratio of 10:1 Cr(III):peptide produces the most intense [M + 2H]2+. Cr(III) also supercharges numerous other small peptides, including highly acidic species. For basic peptides, Cr(III) increases the charge state (2+ versus 1+) and causes the number of peptide molecules being protonated to double or triple. Chromium(III) does not supercharge the proteins cytochrome c and myoglobin. The ability of Cr(III) to enhance [M + 2H]2+ intensity may prove useful in tandem mass spectrometry because of the resulting overall increase in signal-to-noise ratio, the fact that [M + 2H]2+ generally dissociate more readily than [M + H]+, and the ability to produce [M + 2H]2+ precursors for electron-based dissociation techniques.

  11. Insect Peptides - Perspectives in Human Diseases Treatment.

    PubMed

    Chowanski, Szymon; Adamski, Zbigniew; Lubawy, Jan; Marciniak, Pawel; Pacholska-Bogalska, Joanna; Slocinska, Malgorzata; Spochacz, Marta; Szymczak, Monika; Urbanski, Arkadiusz; Walkowiak-Nowicka, Karolina; Rosinski, Grzegorz

    2017-01-01

    Insects are the largest and the most widely distributed group of animals in the world. Their diversity is a source of incredible variety of different mechanisms of life processes regulation. There are many agents that regulate immunology, reproduction, growth and development or metabolism. Hence, it seems that insects may be a source of numerous substances useful in human diseases treatment. Especially important in the regulation of insect physiology are peptides, like neuropeptides, peptide hormones or antimicrobial peptides. There are two main aspects where they can be helpful, 1) Peptides isolated from insects may become potential drugs in therapy of different diseases, 2) A lot of insect peptide hormones show structural or functional homology to mammalian peptide hormones and the comparative studies may give a new look on human disorders. In our review we focused on three group of insect derived peptides: 1) immune-active peptides, 2) peptide hormones and 3) peptides present in venoms. In our review we try to show the considerable potential of insect peptides in searching for new solutions for mammalian diseases treatment. We summarise the knowledge about properties of insect peptides against different virulent agents, anti-inflammatory or anti-nociceptive properties as well as compare insect and mammalian/vertebrate peptide endocrine system to indicate usefulness of knowledge about insect peptide hormones in drug design. The field of possible using of insect delivered peptide to therapy of various human diseases is still not sufficiently explored. Undoubtedly, more attention should be paid to insects due to searching new drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. ABUNDANT OR RARE? A HYBRID APPROACH FOR DETERMINING SPECIES RELATIVE ABUNDANCE AT AN ECOREGOIONAL SCALE

    EPA Science Inventory

    Everyone knows what abundant and rare species are, but quantifying the concept proves elusive. As part of an EPA/USGS project to assess near-coastal species vulnerability to climate change affects, we designed a hybrid approach to determine species relative abundance at an ecoreg...

  13. ABUNDANT OR RARE? A HYBRID APPROACH FOR DETERMINING SPECIES RELATIVE ABUNDANCE AT AN ECOREGOIONAL SCALE - 2014

    EPA Science Inventory

    Everyone knows what abundant and rare species are, but quantifying the concept proves elusive. As part of an EPA/USGS project to assess near-coastal species vulnerability to climate change affects, we designed a hybrid approach to determine species relative abundance at an ecoreg...

  14. Peptide secretion in the cutaneous glands of South American tree frog Phyllomedusa bicolor: an ultrastructural study.

    PubMed

    Lacombe, C; Cifuentes-Diaz, C; Dunia, I; Auber-Thomay, M; Nicolas, P; Amiche, M

    2000-09-01

    The development of the dermal glands of the arboreal frog Phyllomedusa bicolor was investigated by immunocytochemistry and electron microscopy. The 3 types of glands (mucous, lipid and serous) differed in size and secretory activity. The mucous and serous glands were apparent in the tadpole skin, whereas the lipid glands developed later in ontogenesis. The peptide antibiotics dermaseptins and the D-amino acid-containing peptide opioids dermorphins and deltorphins are abundant in the skin secretions of P. bicolor. Although these peptides differ in their structure and activity they are derived from precursors that have very similar preproregions. We used an antibody to the common preproregion of preprodermaseptins and preprodeltorphins and immunofluorescence analysis to show that only the serous glands are specifically involved in the biosynthesis and secretion of dermaseptins and deltorphins. Scanning and transmission electron microscopy revealed that the serous glands of P bicolor have morphological features, especially the secretory granules, which differ from those of the glands in Xenopus laevis skin.

  15. Physiological role of short peptides in nutrition.

    PubMed

    Tutel'yan, V A; Khavinson, V Kh; Malinin, V V

    2003-01-01

    Here we review new data about the physiological role of short peptides and their use as biologically active food additives (parapharmaceutics). Some approaches to the development of peptide preparations for peroral administration are considered and the mechanisms of nonspecific and tissue-specific effects produced by peroral peptide parapharmaceutics are discussed. Particular attention is given to biological properties of short peptides synthesized at the St. Petersburg Institute of Bioregulation and Gerontology. These peptides hold much promise for the synthesis of parapharmaceutics increasing organism's resistance to extreme factors and preventing accelerated aging and age-related diseases.

  16. Biomimetic graphene sensors: functionalizing graphene with peptides

    NASA Astrophysics Data System (ADS)

    Ishigami, Masa; Nyon Kim, Sang; Naik, Rajesh; Tatulian, Suren A.; Katoch, Jyoti

    2012-02-01

    Non-covalent biomimetic functionalization of graphene using peptides is one of more promising methods for producing novel sensors with high sensitivity and selectivity. Here we combine atomic force microscopy, Raman spectroscopy, and attenuated total reflection Fourier transform infrared spectroscopy to investigate peptide binding to graphene and graphite. We choose to study a dodecamer peptide identified with phage display to possess affinities for graphite and we find that the peptide forms a complex mesh-like structure upon adsorption on graphene. Moreover, optical spectroscopy reveals that the peptide binds non-covalently to graphene and possesses an optical signature of an ?-helical conformation on graphene.

  17. In Abundance: Networked Participatory Practices as Scholarship

    ERIC Educational Resources Information Center

    Stewart, Bonnie E.

    2015-01-01

    In an era of knowledge abundance, scholars have the capacity to distribute and share ideas and artifacts via digital networks, yet networked scholarship often remains unrecognized within institutional spheres of influence. Using ethnographic methods including participant observation, interviews, and document analysis, this study investigates…

  18. Photoelectric absorption cross sections with variable abundances

    NASA Technical Reports Server (NTRS)

    Balucinska-Church, Monika; Mccammon, Dan

    1992-01-01

    Polynomial fit coefficients have been obtained for the energy dependences of the photoelectric absorption cross sections of 17 astrophysically important elements. These results allow the calculation of X-ray absorption in the energy range 0.03-10 keV in material with noncosmic abundances.

  19. Cosmological evolution of the nitrogen abundance

    NASA Astrophysics Data System (ADS)

    Vangioni, Elisabeth; Dvorkin, Irina; Olive, Keith A.; Dubois, Yohan; Molaro, Paolo; Petitjean, Patrick; Silk, Joe; Kimm, Taysun

    2018-06-01

    The abundance of nitrogen in the interstellar medium is a powerful probe of star formation processes over cosmological time-scales. Since nitrogen can be produced both in massive and intermediate-mass stars with metallicity-dependent yields, its evolution is challenging to model, as evidenced by the differences between theoretical predictions and observations. In this work, we attempt to identify the sources of these discrepancies using a cosmic evolution model. To further complicate matters, there is considerable dispersion in the abundances from observations of damped Lyα absorbers (DLAs) at z ˜ 2-3. We study the evolution of nitrogen with a detailed cosmic chemical evolution model and find good agreement with these observations, including the relative abundances of (N/O) and (N/Si). We find that the principal contribution of nitrogen comes from intermediate-mass stars, with the exception of systems with the lowest N/H, where nitrogen production might possibly be dominated by massive stars. This last result could be strengthened if stellar rotation which is important at low metallicity can produce significant amounts of nitrogen. Moreover, these systems likely reside in host galaxies with stellar masses below 108.5 M⊙. We also study the origin of the observed dispersion in nitrogen abundances using the cosmological hydrodynamical simulations Horizon-AGN. We conclude that this dispersion can originate from two effects: difference in the masses of the DLA host galaxies, and difference in their position inside the galaxy.

  20. The Abundance of Large Arcs From CLASH

    NASA Astrophysics Data System (ADS)

    Xu, Bingxiao; Postman, Marc; Meneghetti, Massimo; Coe, Dan A.; Clash Team

    2015-01-01

    We have developed an automated arc-finding algorithm to perform a rigorous comparison of the observed and simulated abundance of large lensed background galaxies (a.k.a arcs). We use images from the CLASH program to derive our observed arc abundance. Simulated CLASH images are created by performing ray tracing through mock clusters generated by the N-body simulation calibrated tool -- MOKA, and N-body/hydrodynamic simulations -- MUSIC, over the same mass and redshift range as the CLASH X-ray selected sample. We derive a lensing efficiency of 15 ± 3 arcs per cluster for the X-ray selected CLASH sample and 4 ± 2 arcs per cluster for the simulated sample. The marginally significant difference (3.0 σ) between the results for the observations and the simulations can be explained by the systematically smaller area with magnification larger than 3 (by a factor of ˜4) in both MOKA and MUSIC mass models relative to those derived from the CLASH data. Accounting for this difference brings the observed and simulated arc statistics into full agreement. We find that the source redshift distribution does not have big impact on the arc abundance but the arc abundance is very sensitive to the concentration of the dark matter halos. Our results suggest that the solution to the "arc statistics problem" lies primarily in matching the cluster dark matter distribution.

  1. Abundances in very metal-poor stars

    NASA Astrophysics Data System (ADS)

    Johnson, Jennifer Anne

    We measured the abundances of 35 elements in 22 field red giants and a red giant in the globular cluster M92. We found the [Zn/Fe] ratio increases with decreasing [Fe/H], reaching ~0.3 at [Fe/H] = -3.0. While this is a larger [Zn/Fe] than found by previous investigators, it is not sufficient to account for the [Zn/Fe] observed in the damped Lyα systems. We test different models for the production of the s-process elements by comparing our [Y/Zr] values, which have been produced by the r- process, to predictions of what the s-process does not produce. We find that the models of Arlandini et al. (1999), which calculate s-process production in a model AGB star, agree the best. We then look at the r-process abundances across a wide range in mass. The [Y/Ba] values for most of our stars cluster around -0.30, but there are three outliers with [Y/Ba] values up to 1 dex higher. Thus the heavy element abundances do not show the same pattern from Z = 39 to Z = 56. However, our abundances ratios from Pd (Z = 46) to Yb (Z = 70) are consistent with a scaled solar system r- process pattern, arguing that at least the heavy r- process elements are made in a universal pattern. If we assume that this same pattern hold through thorium, we can determine the ages of our stars from the present abundance of radioactive thorium and an initial thorium abundance based on the abundance of stable heavy elements. Our results for five stars are consistent with those stars being the same age. Our mean age is 10.8 +/- 2 Gyr. However that result depends critically on the assumed Th/stable ratio, which we adopt from models of the r-process. For an average age of 15 Gyrs, the initial Th/Eu ratio we would need is 0.590. Finally, the [element/Fe] ratios for elements in the iron group and lower do not show any dispersion, unlike for the r- process elements such as Y and Ba. Therefore the individual contributions of supernovae have been erased for the lighter elements.

  2. Clonal growth and plant species abundance.

    PubMed

    Herben, Tomáš; Nováková, Zuzana; Klimešová, Jitka

    2014-08-01

    Both regional and local plant abundances are driven by species' dispersal capacities and their abilities to exploit new habitats and persist there. These processes are affected by clonal growth, which is difficult to evaluate and compare across large numbers of species. This study assessed the influence of clonal reproduction on local and regional abundances of a large set of species and compared the predictive power of morphologically defined traits of clonal growth with data on actual clonal growth from a botanical garden. The role of clonal growth was compared with the effects of seed reproduction, habitat requirements and growth, proxied both by LHS (leaf-height-seed) traits and by actual performance in the botanical garden. Morphological parameters of clonal growth, actual clonal reproduction in the garden and LHS traits (leaf-specific area - height - seed mass) were used as predictors of species abundance, both regional (number of species records in the Czech Republic) and local (mean species cover in vegetation records) for 836 perennial herbaceous species. Species differences in habitat requirements were accounted for by classifying the dataset by habitat type and also by using Ellenberg indicator values as covariates. After habitat differences were accounted for, clonal growth parameters explained an important part of variation in species abundance, both at regional and at local levels. At both levels, both greater vegetative growth in cultivation and greater lateral expansion trait values were correlated with higher abundance. Seed reproduction had weaker effects, being positive at the regional level and negative at the local level. Morphologically defined traits are predictive of species abundance, and it is concluded that simultaneous investigation of several such traits can help develop hypotheses on specific processes (e.g. avoidance of self-competition, support of offspring) potentially underlying clonal growth effects on abundance. Garden

  3. Detoxification depot for beta-amyloid peptides.

    PubMed

    Sundaram, Ranjini K; Kasinathan, Chinnaswamy; Stein, Stanley; Sundaram, Pazhani

    2008-02-01

    Alzheimer's Disease (AD) is caused by the deposition of insoluble and toxic amyloid peptides (Abeta) in the brain leading to memory loss and other associated neurodegenerative symptoms. To date there is limited treatment options and strategies for treating AD. Studies have shown that clearance of the amyloid plaques from the brain and thus from the blood could be effective in stopping and or delaying the progression of the disease. Small peptides derived from the Abeta-42 sequence, in particular KLVFF, have shown to be effective binders of Abeta peptides and thus could be useful in delaying progression of the disease. We have taken advantage of this property by generating the retro-inverso (RI) version of this peptide, ffvlk, in different formats. We are presenting a new detox gel system using poly ethylene glycol (PEG), polymerized and cross linked with the RI peptides. We hypothesize that detox gel incorporating RI peptides will act like a 'sink' to capture the Abeta peptides from the surrounding environment. We tested these detox gels for their ability to capture biotinylated Abeta-42 peptides in vitro. The results showed that the detox gels bound Abeta-42 peptides effectively and irreversibly. Gels incorporating the tetramer RI peptide exhibited maximum binding capacity. The detox gel could be a potential candidate for treatment strategies to deplete the brain of toxic amyloid peptides.

  4. Thermal relics: Do we know their abundances

    NASA Technical Reports Server (NTRS)

    Kamionkowski, Marc; Turner, Michael S.

    1990-01-01

    The relic abundance of a particle species that was once in thermal equilibrium in the expanding Universe depends upon a competition between the annihilation rate of the species and the expansion rate of the Universe. Assuming that the Universe is radiation dominated at early times the relic abundance is easy to compute and well known. At times earlier than about 1 sec after the bang there is little or no evidence that the Universe had to be radiation dominated, although that is the simplest and standard assumption. Because early-Universe relics are of such importance both to particle physics and to cosmology, three nonstandard possibilities are considered in detail for the Universe at the time a species' abundance froze in: energy density dominated by shear (i.e., anisotropic expansion), energy density dominated by some other nonrelativistic species, and energy density dominated by the kinetic energy of the scalar field that sets the gravitational constant in a Brans-Dicke-Jordan cosmological mode. In the second case the relic abundance is less than the standard value, while in the other two cases it can be enhanced by a significant factor. Two other more exotic possibilities for enhancing the relic abundance of a species are also mentioned--a larger value of Newton's constant at early times (e.g., as might occur in superstring or Kaluza-Klein theories) or a component of the energy density at early times with a very stiff equation of state (p greater than rho/3), e.g., a scalar field phi with potential V(phi) = Beta /phi/ (exp n) with n greater than 4. Results have implications for dark matter searches and searches for particle relics in general.

  5. Stellar Abundance Observations and Heavy Element Formation

    NASA Astrophysics Data System (ADS)

    Cowan, J. J.

    2005-05-01

    Abundance observations indicate the presence of rapid-neutron capture (i.e., r-process) elements in old Galactic halo and globular cluster stars. These observations provide insight into the nature of the earliest generations of stars in the Galaxy -- the progenitors of the halo stars -- responsible for neutron-capture synthesis of the heavy elements. Abundance comparisons among the r-process-rich halo stars show that the heaviest neutron-capture elements (i.e., Ba and above) are consistent with a scaled solar system r-process abundance distribution, while the lighter neutron-capture elements do not conform to the solar pattern. These comparisons suggest the possibility of two r-process sites in stars. The large star-to-star scatter observed in the abundances of neutron-capture element/iron ratios at low metallicities -- which disappears with increasing metallicity or [Fe/H] -- suggests the formation of these heavy elements (presumably from certain types of supernovae) was rare in the early Galaxy. The stellar abundances also indicate a change from the r-process to the slow neutron capture (i.e., s-) process at higher metallicities in the Galaxy and provide insight into Galactic chemical evolution. Finally, the detection of thorium and uranium in halo and globular cluster stars offers an independent age-dating technique that can put lower limits on the age of the Galaxy, and hence the Universe. This work has been supported in part by NSF grant AST 03-07279 (J.J.C.) and by STScI grants GO-8111, GO-8342 and GO-9359.

  6. Matrix suppression as a guideline for reliable quantification of peptides by matrix-assisted laser desorption ionization.

    PubMed

    Ahn, Sung Hee; Bae, Yong Jin; Moon, Jeong Hee; Kim, Myung Soo

    2013-09-17

    We propose to divide matrix suppression in matrix-assisted laser desorption ionization into two parts, normal and anomalous. In quantification of peptides, the normal effect can be accounted for by constructing the calibration curve in the form of peptide-to-matrix ion abundance ratio versus concentration. The anomalous effect forbids reliable quantification and is noticeable when matrix suppression is larger than 70%. With this 70% rule, matrix suppression becomes a guideline for reliable quantification, rather than a nuisance. A peptide in a complex mixture can be quantified even in the presence of large amounts of contaminants, as long as matrix suppression is below 70%. The theoretical basis for the quantification method using a peptide as an internal standard is presented together with its weaknesses. A systematic method to improve quantification of high concentration analytes has also been developed.

  7. Primary structure of the abundant seed albumin of Theobroma cacao by mass spectrometry.

    PubMed

    Kochhar, S; Gartenmann, K; Juillerat, M A

    2000-11-01

    The most abundant albumin present in seeds of Theobroma cacao was purified to apparent homogeneity as judged by high-performance liquid chromatography/electrospray ionization mass spectrometry (HPLC/ESI-MS), sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and NH(2)-terminal sequence analysis. Tryptic peptide mass fingerprinting of the purified protein by HPLC/ESI-MS showed the presence of 16 masses that matched the expected tryptic peptides corresponding to 95% of the translated amino acid sequence from the cDNA of the 21 kDa cocoa albumin. Collision-induced dissociation MS/MS analysis of the C-terminal peptide isolated from the CNBr cleavage products provided unequivocal evidence that the mature cocoa albumin protein is nine amino acid residues shorter than expected from the reported cDNA of its corresponding gene. The experimentally determined M(r) value of 20234 was in excellent agreement with the truncated version of the amino acid sequence. The purified cocoa albumin inhibited the catalytic activities of bovine trypsin and chymotrypsin. The inhibition was stoichiometric with 1 mol of trypsin or chymotrypsin being inhibited by 1 mol of inhibitor with apparent dissociation constants (K(i)) of 9.5 x 10(-8) and 2. 3 x 10(-6) M, respectively, for inhibitor binding at pH 8.5 and 37 degrees C. No inhibition of the catalytic activities of subtilisin, papain, pepsin, and cocoa endoproteases was detected under their optimal reaction conditions.

  8. Digestion proteomics: tracking lactoferrin truncation and peptide release during simulated gastric digestion.

    PubMed

    Grosvenor, Anita J; Haigh, Brendan J; Dyer, Jolon M

    2014-11-01

    The extent to which nutritional and functional benefit is derived from proteins in food is related to its breakdown and digestion in the body after consumption. Further, detailed information about food protein truncation during digestion is critical to understanding and optimising the availability of bioactives, in controlling and limiting allergen release, and in minimising or monitoring the effects of processing and food preparation. However, tracking the complex array of products formed during the digestion of proteins is not easily accomplished using classical proteomics. We here present and develop a novel proteomic approach using isobaric labelling to mapping and tracking protein truncation and peptide release during simulated gastric digestion, using bovine lactoferrin as a model food protein. The relative abundance of related peptides was tracked throughout a digestion time course, and the effect of pasteurisation on peptide release assessed. The new approach to food digestion proteomics developed here therefore appears to be highly suitable not only for tracking the truncation and relative abundance of released peptides during gastric digestion, but also for determining the effects of protein modification on digestibility and potential bioavailability.

  9. Ga2O3 photocatalyzed on-line tagging of cysteine to facilitate peptide mass fingerprinting.

    PubMed

    Qiao, Liang; Su, Fangzheng; Bi, Hongyan; Girault, Hubert H; Liu, Baohong

    2011-09-01

    β-Ga(2)O(3) is a wide-band-gap semiconductor having strong oxidation ability under light irradiation. Herein, the steel target plates modified with β-Ga(2)O(3) nanoparticles have been developed to carry out in-source photo-catalytic oxidative reactions for online peptide tagging during laser desorption/ionization mass spectrometry (LDI-MS) analysis. Under UV laser irradiation, β-Ga(2)O(3) can catalyze the photo-oxidation of 2-methoxyhydroquinone added to a sample mixture to 2-methoxy benzoquinone that can further react with the thiol groups of cysteine residues by Michael addition reaction. The tagging process leads to appearance of pairs of peaks with an m/z shift of 138.1Th. This online labelling strategy is demonstrated to be sensitive and efficient with a detection-limit at femtomole level. Using the strategy, the information on cysteine content in peptides can be obtained together with peptide mass, therefore constraining the database searching for an advanced identification of cysteine-containing proteins from protein mixtures. The current peptide online tagging method can be important for specific analysis of cysteine-containing proteins especially the low-abundant ones that cannot be completely isolated from other high-abundant non-cysteine-proteins. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. A synthetic peptide shows retro- and anterograde neuronal transport before disrupting the chemosensation of plant-pathogenic nematodes.

    PubMed

    Wang, Dong; Jones, Laura M; Urwin, Peter E; Atkinson, Howard J

    2011-03-07

    Cyst nematodes are a group of plant pathogens each with a defined host range that cause major losses to crops including potato, soybean and sugar beet. The infective mobile stage hatches from dormant eggs and moves a short distance through the soil to plant roots, which it then invades. A novel strategy for control has recently been proposed in which the plant is able to secrete a peptide which disorientates the infective stage and prevents invasion of the pathogen. This study provides indirect evidence to support the mechanism by which one such peptide disrupts chemosensory function in nematodes. The peptide is a disulphide-constrained 7-mer with the amino acid sequence CTTMHPRLC that binds to nicotinic acetylcholine receptors. A fluorescently tagged version of this peptide with both epifluorescent and confocal microscopy was used to demonstrate that retrograde transport occurs from an aqueous environment along bare-ending primary cilia of chemoreceptive sensilla. The peptide is transported to the cell bodies of these neurons and on to a limited number of other neurons to which they connect. It appears to be localised in both neuronal processes and organelles adjacent to nuclei of some neurons suggesting it could be transported through the Golgi apparatus. The peptide takes 2.5 h to reach the neuronal cell bodies. Comparative studies established that similar but less abundant uptake occurs for Caenorhabditis elegans along its well studied dye-filling chemoreceptive neurons. Incubation in peptide solution or root-exudate from transgenic plants that secrete the peptide disrupted normal orientation of infective cyst nematodes to host root diffusate. The peptide probably undergoes transport along the dye-filling non-cholinergic chemoreceptive neurons to their synapses where it is taken up by the interneurons to which they connect. Coordinated responses to chemoreception are disrupted when the sub-set of cholinergic interneurons secrete the peptide at synapses that

  11. EpiProfile Quantifies Histone Peptides With Modifications by Extracting Retention Time and Intensity in High-resolution Mass Spectra*

    PubMed Central

    Yuan, Zuo-Fei; Lin, Shu; Molden, Rosalynn C.; Cao, Xing-Jun; Bhanu, Natarajan V.; Wang, Xiaoshi; Sidoli, Simone; Liu, Shichong; Garcia, Benjamin A.

    2015-01-01

    Histone post-translational modifications contribute to chromatin function through their chemical properties which influence chromatin structure and their ability to recruit chromatin interacting proteins. Nanoflow liquid chromatography coupled with high resolution tandem mass spectrometry (nanoLC-MS/MS) has emerged as the most suitable technology for global histone modification analysis because of the high sensitivity and the high mass accuracy of this approach that provides confident identification. However, analysis of histones with this method is even more challenging because of the large number and variety of isobaric histone peptides and the high dynamic range of histone peptide abundances. Here, we introduce EpiProfile, a software tool that discriminates isobaric histone peptides using the distinguishing fragment ions in their tandem mass spectra and extracts the chromatographic area under the curve using previous knowledge about peptide retention time. The accuracy of EpiProfile was evaluated by analysis of mixtures containing different ratios of synthetic histone peptides. In addition to label-free quantification of histone peptides, EpiProfile is flexible and can quantify different types of isotopically labeled histone peptides. EpiProfile is unique in generating layouts (i.e. relative retention time) of histone peptides when compared with manual quantification of the data and other programs (such as Skyline), filling the need of an automatic and freely available tool to quantify labeled and non-labeled modified histone peptides. In summary, EpiProfile is a valuable nanoflow liquid chromatography coupled with high resolution tandem mass spectrometry-based quantification tool for histone peptides, which can also be adapted to analyze nonhistone protein samples. PMID:25805797

  12. Taylor Dispersion Analysis as a promising tool for assessment of peptide-peptide interactions.

    PubMed

    Høgstedt, Ulrich B; Schwach, Grégoire; van de Weert, Marco; Østergaard, Jesper

    2016-10-10

    Protein-protein and peptide-peptide (self-)interactions are of key importance in understanding the physiochemical behavior of proteins and peptides in solution. However, due to the small size of peptide molecules, characterization of these interactions is more challenging than for proteins. In this work, we show that protein-protein and peptide-peptide interactions can advantageously be investigated by measurement of the diffusion coefficient using Taylor Dispersion Analysis. Through comparison to Dynamic Light Scattering it was shown that Taylor Dispersion Analysis is well suited for the characterization of protein-protein interactions of solutions of α-lactalbumin and human serum albumin. The peptide-peptide interactions of three selected peptides were then investigated in a concentration range spanning from 0.5mg/ml up to 80mg/ml using Taylor Dispersion Analysis. The peptide-peptide interactions determination indicated that multibody interactions significantly affect the PPIs at concentration levels above 25mg/ml for the two charged peptides. Relative viscosity measurements, performed using the capillary based setup applied for Taylor Dispersion Analysis, showed that the viscosity of the peptide solutions increased with concentration. Our results indicate that a viscosity difference between run buffer and sample in Taylor Dispersion Analysis may result in overestimation of the measured diffusion coefficient. Thus, Taylor Dispersion Analysis provides a practical, but as yet primarily qualitative, approach to assessment of the colloidal stability of both peptide and protein formulations. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Space-based measurements of elemental abundances and their relation to solar abundances

    NASA Technical Reports Server (NTRS)

    Coplan, M. A.; Ogilvie, K. W.; Bochsler, P.; Geiss, J.

    1990-01-01

    The Ion Composition Instrument (ICI) aboard the ISEE-3/ICE spacecraft was in the solar wind continuously from August 1978 to December 1982. The results made it possible to establish long-term average solar wind abundance values for helium, oxygen, neon, silicon, and iron. The Charge-Energy-Mass instrument aboard the CCE spacecraft of the AMPTE mission has measured the abundance of these elements in the magnetosheath and has also added carbon, nitrogen, magnesium, and sulfur to the list. There is strong evidence that these magnetosheath abundances are representative of the solar wind. Other sources of solar wind abundances are Solar Energetic Particle experiments and Apollo lunar foils. When comparing the abundances from all of these sources with photospheric abundances, it is clear that helium is depleted in the solar wind while silicon and iron are enhanced. Solar wind abundances for carbon, nitrogen, oxygen, and neon correlate well with the photospheric values. The incorporation of minor ions into the solar wind appears to depend upon both the ionization times for the elements and the Coulomb drag exerted by the outflowing proton flux.

  14. Comparison of aldosterone synthesis in adrenal cells, effect of various AT1 receptor blockers with or without atrial natriuretic peptide.

    PubMed

    Miura, Shin-Ichiro; Nakayama, Asuka; Tomita, Sayo; Matsuo, Yoshino; Suematsu, Yasunori; Saku, Keijiro

    2015-01-01

    Bifunctional angiotensin II (Ang II) type 1 (AT1) receptor blockers (ARBs) that can block the activation of not only AT1 receptor, but also neprilysin, which metabolizes vasoactive peptides including atrial natriuretic peptide (ANP), are currently being developed. However, the usefulness of the inactivation of ANP in addition to the AT1 receptor with regard to aldosterone (Ald) synthesis is not yet clear. We evaluated the inhibitory effects of various ARBs combined with or without ANP on Ang II-induced adrenal Ald synthesis using a human adrenocortical cell line (NCI-H295R). Ang II increased Ald synthesis in a dose- and time-dependent manner. Ald synthesis induced by Ang II was completely blocked by azilsartan, but not PD123319 (AT2 receptor antagonist). CGP42112 AT2 receptor agonist did not affect Ald synthesis. While most ARBs block Ang II-induced Ald synthesis to different extents, azilsartan and olmesartan have similar blocking effects on Ald synthesis. The different effects of ARBs were particularly observed at 10(-7) and 10(-8 )M. ANP attenuated Ang II-induced Ald synthesis, and ANP-mediated attenuation of Ang II-induced Ald synthesis were blocked by inhibitors of G-protein signaling subtype 4 and protein kinase G. ANP (10(-8) and 10(-7 )M) without ARBs inhibited Ald synthesis, and the combination of ANP (10(-7 )M) and ARB (10(-8 )M) had an additive effect with respect to the inhibition of Ald synthesis. In conclusions, ARBs had differential effects on Ang II-induced Ald synthesis, and ANP may help to block Ald synthesis when the dose of ARB is not sufficient to block its secretion.

  15. Peptides and methods against diabetes

    DOEpatents

    Albertini, Richard J.; Falta, Michael T.

    2000-01-01

    This invention relates to methods of preventing or reducing the severity of diabetes. In one embodiment, the method involves administering to the individual a peptide having substantially the sequence of a on-conserved region sequence of a T cell receptor present on the surface of T cells mediating diabetes or a fragment thereof, wherein the peptide or fragment is capable of causing an effect on the immune system to regulate the T cells. In particular, the T cell receptor has the V.beta. regional V.beta.6 or V.beta.14. In another embodiment, the method involves gene therapy. The invention also relates to methods of diagnosing diabetes by determining the presence of diabetes predominant T cell receptors.

  16. Deuterium Abundance in Consciousness and Current Cosmology

    NASA Astrophysics Data System (ADS)

    Rauscher, Elizabeth A.

    We utilize the deuterium-hydrogen abundances and their role in setting limits on the mass and other conditions of cosmogenesis and cosmological evolution. We calculate the dependence of a set of physical variables such as density, temperature, energy mass, entropy and other physical variable parameters through the evolution of the universe under the Schwarzschild conditions as a function from early to present time. Reconciliation with the 3°K and missing mass is made. We first examine the Schwarzschild condition; second, the geometrical constraints of a multidimensional Cartesian space on closed cosmologies, and third we will consider the cosmogenesis and evolution of the universe in a multidimensional Cartesian space, obeying the Schwarzschild condition. Implications of this model for matter creation are made. We also examine experimental evidence for closed versus open cosmologies; x-ray detection of the "missing mass" density. Also the interstellar deuterium abundance, along with the value of the Hubble constant set a general criterion on the value of the curvature constant, k. Once the value of the Hubble constant, H is determined, the deuterium abundance sets stringent restrictions on the value of the curvature constant k by an detailed discussion is presented. The experimental evidences for the determination of H and the primary set of coupled equations to determine D abundance is given. 'The value of k for an open, closed, or flat universe will be discussed in terms of the D abundance which will affect the interpretation of the Schwarzschild, black hole universe. We determine cosmology solutions to Einstein's field obeying the Schwarzschild solutions condition. With this model, we can form a reconciliation of the black hole, from galactic to cosmological scale. Continuous creation occurs at the dynamic blackhole plasma field. We term this new model the multiple big bang or "little whimper model". We utilize the deuteriumhydrogen abundances and their role in

  17. Peptide stabilized amphotericin B nanodisks

    PubMed Central

    Tufteland, Megan; Pesavento, Joseph B.; Bermingham, Rachelle L.; Hoeprich, Paul D.; Ryan, Robert O.

    2007-01-01

    Nanometer scale apolipoprotein A-I stabilized phospholipid disk complexes (nanodisks; ND) have been formulated with the polyene antibiotic amphotericin B (AMB). The present studies were designed to evaluate if a peptide can substitute for the function of the apolipoprotein component of ND with respect to particle formation and stability. An 18-residue synthetic amphipathic α-helical peptide, termed 4F (Ac-D-W-F-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F-NH2), solubilized vesicles comprised of egg phosphatidylcholine (egg PC), dipentadecanoyl PC or dimyristoylphosphatidylcholine (DMPC) at rates greater than or equal to solubilization rates observed with human apolipoprotein A-I (apoA-I; 243 amino acids). Characterization studies revealed that interaction with DMPC induced a near doubling of 4F tryptophan fluorescence emission quantum yield (excitation 280 nm) and a ~7 nm blue shift in emission wavelength maximum. Inclusion of AMB in the vesicle substrate resulted in formation of 4F AMB-ND. Spectra of AMB containing particles revealed the antibiotic is a highly effective quencher of 4F tryptophan fluorescence emission, giving rise to a Ksv = 7.7 × 104. Negative stain electron microscopy revealed that AMB-ND prepared with 4F possessed a disk shaped morphology similar to ND prepared without AMB or prepared with apoA-I. In yeast and pathogenic fungi growth inhibition assays, 4F AMB-ND was as effective as apoA-I AMB-ND. The data indicate that AMB-ND generated using an amphipathic peptide in lieu of apoA-I form a discrete population of particles that possess potent biological activity. Given their intrinsic versatility, peptides may be preferred for scale up and clinical application of AMB-ND. PMID:17293004

  18. Enrichment and Analysis of Non-enzymatically Glycated Peptides: Boronate Affinity Chromatography Coupled with Electron Transfer Dissociation Mass Spectrometry

    PubMed Central

    Zhang, Qibin; Tang, Ning; Brock, Jonathan W. C.; Mottaz, Heather M.; Ames, Jennifer M.; Baynes, John W.; Smith, Richard D.; Metz, Thomas O.

    2008-01-01

    Non-enzymatic glycation of peptides and proteins by D-glucose has important implications in the pathogenesis of diabetes mellitus, particularly in the development of diabetic complications. However, no effective high-throughput methods exist for identifying proteins containing this low abundance post-translational modification in bottom-up proteomic studies. In this report, phenylboronate affinity chromatography was used in a two-step enrichment scheme to selectively isolate first glycated proteins and then glycated, tryptic peptides from human serum glycated in vitro. Enriched peptides were subsequently analyzed by alternating electron transfer dissociation (ETD) and collision induced dissociation (CID) tandem mass spectrometry. ETD fragmentation mode permitted identification of a significantly higher number of glycated peptides (87.6% of all identified peptides) versus CID mode (17.0% of all identified peptides), when utilizing enrichment on first the protein and then the peptide level. This study illustrates that phenylboronate affinity chromatography coupled with LC-MS/MS and using ETD as the fragmentation mode is an efficient approach for analysis of glycated proteins and may have broad application in studies of diabetes mellitus. PMID:17488106

  19. A differential protein solubility approach for the depletion of highly abundant proteins in plasma using ammonium sulfate.

    PubMed

    Bollineni, Ravi Chand; Guldvik, Ingrid J; Grönberg, Henrik; Wiklund, Fredrik; Mills, Ian G; Thiede, Bernd

    2015-12-21

    Depletion of highly abundant proteins is an approved step in blood plasma analysis by mass spectrometry (MS). In this study, we explored a precipitation and differential protein solubility approach as a fractionation strategy for abundant protein removal from plasma. Total proteins from plasma were precipitated with 90% saturated ammonium sulfate, followed by differential solubilization in 55% and 35% saturated ammonium sulfate solutions. Using a four hour liquid chromatography (LC) gradient and an LTQ-Orbitrap XL mass spectrometer, a total of 167 and 224 proteins were identified from the 55% and 35% ammonium sulfate fractions, whereas 235 proteins were found in the remaining protein fractions with at least two unique peptides. SDS-PAGE and exclusive total spectrum counts from LC-MS/MS analyses clearly showed that majority of the abundant plasma proteins were solubilized in 55% and 35% ammonium sulfate solutions, indicating that the remaining protein fraction is of potential interest for identification of less abundant plasma proteins. Serum albumin, serotransferrin, alpha-1-antitrypsin and transthyretin were the abundant proteins that were highly enriched in 55% ammonium sulfate fractions. Immunoglobulins, complement system proteins, and apolipoproteins were among other abundant plasma proteins that were enriched in 35% ammonium sulfate fractions. In the remaining protein fractions a total of 40 unique proteins were identified of which, 32 proteins were identified with at least 10 exclusive spectrum counts. According to PeptideAtlas, 9 of these 32 proteins were estimated to be present at low μg ml(-1) (0.12-1.9 μg ml(-1)) concentrations in the plasma, and 17 at low ng ml(-1) (0.1-55 ng ml(-1)) range.

  20. Coffee, hunger, and peptide YY.

    PubMed

    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 < 0.05). Caffeine in water had no effects on 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.

  1. Biopharmaceuticals: From peptide to drug

    NASA Astrophysics Data System (ADS)

    Hannappel, Margarete

    2017-08-01

    Biologics are therapeutic proteins or peptides that are produced by means of biological processes within living organisms and cells. They are highly specific molecules and play a crucial role as therapeutics for the treatment of severe and chronic diseases (e.g. cancer, rheumatoid arthritis, diabetes, autoimmune disorders). The development of new biologics and biologics-based drugs gains more and more importance in the fight against various diseases. A short overview on biotherapeutical drug development is given. Cone snails are a large group of poisonous, predatory sea snails with more than 700 species. They use a very powerful venom which rapidly inactivates and paralyzes their prey. Most bioactive venom components are small peptides (conotoxins, conopeptides) which are precisely directed towards a specific target (e.g. ion channel, receptors). Due to their small size, their precision and speed of action, naturally occurring cone snail venom peptides represent an attractive source for the identification and design of novel biological drug entities. The Jagna cone snail project is an encouraging initiative to map the ecological variety of cone snails around the island of Bohol (Philippines) and to conserve the biological information for potential future application.

  2. Colonic vascular conductance increased by Daikenchuto via calcitonin gene-related peptide and receptor-activity modifying protein 1.

    PubMed

    Kono, Toru; Koseki, Takashi; Chiba, Shinichi; Ebisawa, Yoshiaki; Chisato, Naoyuki; Iwamoto, Jun; Kasai, Shinichi

    2008-11-01

    Daikencyuto (DKT) is a traditional Japanese medicine (Kampo) and is a mixture of extract powders from dried Japanese pepper, processed ginger, ginseng radix, and maltose powder and has been used as the treatment of paralytic ileus. DKT may increase gastrointestinal motility by an up-regulation of the calcitonin gene-related peptide (CGRP). CGRP is also the most powerful vasoactive substance. In the present study, we investigated whether DKT has any effect on the colonic blood flow in rats. Experiments were performed on fasted anesthetized and artificially ventilated Wistar rats. Systemic mean arterial blood pressure and heart rate were recorded. Red blood cell flux in colonic blood flow was measured using noncontact laser tissue blood flowmetry, and colonic vascular conductance (CVC) was calculated as the ratio of flux to mean arterial blood pressure. We examined four key physiological mechanisms underlying the response using blocker drugs: CGRP1 receptor blocker (CGRP(8-37)), nitric oxide synthase inhibitor, vasoactive intestinal polypeptide (VIP) receptor blocker ([4-Cl-DPhe6, Leu17]-VIP), and substance P receptor blocker (spantide). Reverse transcription-polymerase chain reaction was used for the detection of mRNA of calcitonin receptor-like receptor, receptor-activity modifying protein 1, the component of CGRP 1 receptor and CGRP. After laparotomy, a cannula was inserted into the proximal colon to administer the DKT and to measure CVC at the distal colon. Intracolonal administration of DKT (10, 100, and 300 mg/kg) increased CVC (basal CVC, 0.10 mL/mmHg) from the first 15-min observation period (0.14, 0.17, and 0.17 mL/mmHg, respectively) and with peak response at either 45 min (0.17 mL/mmHg by 10 mg/kg), or 75 and 60 min (0.23 and 0.21 mL/mmHg by 100 and 300 mg/kg, respectively). CGRP(8-37) completely abolished the DKT-induced hyperemia, whereas nitric oxide synthase inhibitor partially attenuated the DKT-induced hyperemia. [4-Cl-DPhe6, Leu17]-VIP and spantide

  3. Chemical methods for peptide and protein production.

    PubMed

    Chandrudu, Saranya; Simerska, Pavla; Toth, Istvan

    2013-04-12

    Since the invention of solid phase synthetic methods by Merrifield in 1963, the number of research groups focusing on peptide synthesis has grown exponentially. However, the original step-by-step synthesis had limitations: the purity of the final product decreased with the number of coupling steps. After the development of Boc and Fmoc protecting groups, novel amino acid protecting groups and new techniques were introduced to provide high quality and quantity peptide products. Fragment condensation was a popular method for peptide production in the 1980s, but unfortunately the rate of racemization and reaction difficulties proved less than ideal. Kent and co-workers revolutionized peptide coupling by introducing the chemoselective reaction of unprotected peptides, called native chemical ligation. Subsequently, research has focused on the development of novel ligating techniques including the famous click reaction, ligation of peptide hydrazides, and the recently reported α-ketoacid-hydroxylamine ligations with 5-oxaproline. Several companies have been formed all over the world to prepare high quality Good Manufacturing Practice peptide products on a multi-kilogram scale. This review describes the advances in peptide chemistry including the variety of synthetic peptide methods currently available and the broad application of peptides in medicinal chemistry.

  4. Stability of peptide drugs in the colon.

    PubMed

    Wang, Jie; Yadav, Vipul; Smart, Alice L; Tajiri, Shinichiro; Basit, Abdul W

    2015-10-12

    This study was the first to investigate the colonic stability of 17 peptide molecules (insulin, calcitonin, glucagon, secretin, somatostatin, desmopressin, oxytocin, Arg-vasopressin, octreotide, ciclosporin, leuprolide, nafarelin, buserelin, histrelin, [D-Ser(4)]-gonadorelin, deslorelin, and goserelin) in a model of the large intestine using mixed human faecal bacteria. Of these, the larger peptides - insulin, calcitonin, somatostatin, glucagon and secretin - were metabolized rapidly, with complete degradation observed within 5 min. In contrast, a number of the smaller peptides - Arg-vasopressin, desmopressin, oxytocin, gonadorelin, goserelin, buserelin, leuprolide, nafarelin and deslorelin - degraded more slowly, while octreotide, histrelin and ciclosporin were seen to be more stable as compared to the other small peptides under the same conditions. Peptide degradation rate was directly correlated to peptide lipophilicity (logP); those peptides with a higher logP were more stable in the colonic model (R(2)=0.94). In the absence of human faecal bacteria, all peptides were stable. This study highlights the impact of the colonic environment - in particular, the gut microbiota - on the metabolism of peptide drugs, and identifies potential peptide candidates for drug delivery to the colon. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Deuterium Abundance in the Local Interstellar Medium

    NASA Technical Reports Server (NTRS)

    Ferlet, R.; Gry, C.; Vidal-Madjar, A.

    1984-01-01

    The present situation of deuterium abundance evaluation in interstellar space is discussed, and it is shown that it should be or = .00001 by studying in more detail lambda the Sco line of sight and by observing two NaI interstellar components toward that star, it can be shown that the D/H evaluation made toward lambda Sco is in fact related to the local interstellar medium (less than 10 pc from the Sun). Because this evaluation is also or = .00001 it is in striking contrast with the one made toward alpha Aur (D/H or = .000018 confirming the fact that the deuterium abundance in the local interstellar medium varies by at least a factor of two over few parsecs.

  6. Precision measures of the primordial deuterium abundance.

    NASA Astrophysics Data System (ADS)

    Cooke, R. J.; Pettini, M.; Jorgenson, R. A.; Murphy, M. T.; Steidel, C. C.

    Near-pristine damped Lyman-alpha systems (DLAs) are the ideal environments to measure the primordial abundance of deuterium. In this conference report, I summarise our ongoing research programme to obtain the most precise determination of the primordial deuterium abundance from five high redshift DLAs. From this sample, we derive (D/H)_p = (2.53±0.04)×105, corresponding to a baryon density 100 Omega_b ,0 h2 = 2.202±0.046 assuming the standard model of Big Bang Nucleosynthesis. This value is in striking agreement with that measured from the temperature fluctuations imprinted on the cosmic microwave background. Although we find no strong evidence for new physics beyond the standard model, this line of research shows great promise in the near-future, when the next generation 30+ m telescopes equipped with echelle spectrographs come online.

  7. Lithium Abundance in M3 Red Giant

    NASA Astrophysics Data System (ADS)

    Givens, Rashad; Pilachowski, Catherine A.

    2015-01-01

    We present the abundance of lithium in the red giant star vZ 1050 (SK 291) in the globular cluster M3. A previous survey of giants in the cluster showed that like IV-101, vZ 1050 displays a prominent Li I 6707 Å feature. vZ 1050 lies on the blue side of the red giant branch about 1.3 magnitudes above the level of the horizontal branch, and may be an asymptotic giant branch star. A high resolution spectrum of M3 vZ1050 was obtained with the ARC 3.5m telescope and the ARC Echelle Spectrograph (ARCES). Atmospheric parameters were determined using Fe I and Fe II lines from the spectrum using the MOOG spectral analysis program, and the lithium abundance was determined using spectrum synthesis.

  8. Attenuation of species abundance distributions by sampling

    PubMed Central

    Shimadzu, Hideyasu; Darnell, Ross

    2015-01-01

    Quantifying biodiversity aspects such as species presence/ absence, richness and abundance is an important challenge to answer scientific and resource management questions. In practice, biodiversity can only be assessed from biological material taken by surveys, a difficult task given limited time and resources. A type of random sampling, or often called sub-sampling, is a commonly used technique to reduce the amount of time and effort for investigating large quantities of biological samples. However, it is not immediately clear how (sub-)sampling affects the estimate of biodiversity aspects from a quantitative perspective. This paper specifies the effect of (sub-)sampling as attenuation of the species abundance distribution (SAD), and articulates how the sampling bias is induced to the SAD by random sampling. The framework presented also reveals some confusion in previous theoretical studies. PMID:26064626

  9. Revised Thorium Abundances for Lunar Red Spots

    NASA Technical Reports Server (NTRS)

    Hagerty, J. J.; Lawrence, D. J.; Elphic, R. C.; Feldman, W. C.; Vaniman, D. T.; Hawke, B. R.

    2005-01-01

    Lunar red spots are features on the nearside of the Moon that are characterized by high albedo and by a strong absorption in the ultraviolet. These red spots include the Gruithuisen domes, the Mairan domes, Hansteen Alpha, the southern portion of Montes Riphaeus, Darney Chi and Tau, Helmet, and an area near the Lassell crater. It has been suggested that many of the red spots are extrusive, nonmare, volcanic features that could be composed of an evolved lithlogy enriched in thorium. In fact, Hawke et al. used morphological characteristics to show that Hansteen Alpha is a nonmare volcanic construct. However, because the apparent Th abundances (6 - 7 ppm) were lower than that expected for evolved rock types, Hawke et al. concluded that Hansteen Alpha was composed of an unknown rock type. Subsequent studies by Lawrence et al. used improved knowledge of the Th spatial distribution for small area features on the lunar surface to revisit the interpretation of Th abundances at the Hansteen Alpha red spot. As part of their study, Lawrence et al. used a forward modeling technique to show that the Th abundance at Hansteen Alpha is not 6 ppm, but is more likely closer to 25 ppm, a value consistent with evolved lithologies. This positive correlation between the morphology and composition of Hansteen Alpha provides support for the presence of evolved lithologies on the lunar surface. It is possible, however, that Hansteen Alpha represents an isolated occurrence of non-mare volcanism. That is why we have chosen to use the forward modeling technique of Lawrence et al. to investigate the Th abundances at other lunar red spots, starting with the Gruithuisen domes. Additional information is included in the original extended abstract.

  10. Human Antimicrobial Peptides and Proteins

    PubMed Central

    Wang, Guangshun

    2014-01-01

    As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs) play a critical role in warding off invading microbial pathogens. In addition, AMPs can possess other biological functions such as apoptosis, wound healing, and immune modulation. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. Over 100 such peptides have been identified from a variety of tissues and epithelial surfaces, including skin, eyes, ears, mouths, gut, immune, nervous and urinary systems. These peptides vary from 10 to 150 amino acids with a net charge between −3 and +20 and a hydrophobic content below 60%. The sequence diversity enables human AMPs to adopt various 3D structures and to attack pathogens by different mechanisms. While α-defensin HD-6 can self-assemble on the bacterial surface into nanonets to entangle bacteria, both HNP-1 and β-defensin hBD-3 are able to block cell wall biosynthesis by binding to lipid II. Lysozyme is well-characterized to cleave bacterial cell wall polysaccharides but can also kill bacteria by a non-catalytic mechanism. The two hydrophobic domains in the long amphipathic α-helix of human cathelicidin LL-37 lays the basis for binding and disrupting the curved anionic bacterial membrane surfaces by forming pores or via the carpet model. Furthermore, dermcidin may serve as ion channel by forming a long helix-bundle structure. In addition, the C-type lectin RegIIIα can initially recognize bacterial peptidoglycans followed by pore formation in the membrane. Finally, histatin 5 and GAPDH(2-32) can enter microbial cells to exert their effects. It appears that granulysin enters cells and kills intracellular pathogens with the aid of pore-forming perforin. This arsenal of human defense proteins not only keeps us healthy but also inspires the development of a new generation of personalized medicine to

  11. A global database of ant species abundances

    USGS Publications Warehouse

    Gibb, Heloise; Dunn, Rob R.; Sanders, Nathan J.; Grossman, Blair F.; Photakis, Manoli; Abril, Silvia; Agosti, Donat; Andersen, Alan N.; Angulo, Elena; Armbrecht, Ingre; Arnan, Xavier; Baccaro, Fabricio B.; Bishop, Tom R.; Boulay, Raphael; Bruhl, Carsten; Castracani, Cristina; Cerda, Xim; Del Toro, Israel; Delsinne, Thibaut; Diaz, Mireia; Donoso, David A.; Ellison, Aaron M.; Enriquez, Martha L.; Fayle, Tom M.; Feener Jr., Donald H.; Fisher, Brian L.; Fisher, Robert N.; Fitpatrick, Matthew C.; Gomez, Cristanto; Gotelli, Nicholas J.; Gove, Aaron; Grasso, Donato A.; Groc, Sarah; Guenard, Benoit; Gunawardene, Nihara; Heterick, Brian; Hoffmann, Benjamin; Janda, Milan; Jenkins, Clinton; Kaspari, Michael; Klimes, Petr; Lach, Lori; Laeger, Thomas; Lattke, John; Leponce, Maurice; Lessard, Jean-Philippe; Longino, John; Lucky, Andrea; Luke, Sarah H.; Majer, Jonathan; McGlynn, Terrence P.; Menke, Sean; Mezger, Dirk; Mori, Alessandra; Moses, Jimmy; Munyai, Thinandavha Caswell; Pacheco, Renata; Paknia, Omid; Pearce-Duvet, Jessica; Pfeiffer, Martin; Philpott, Stacy M.; Resasco, Julian; Retana, Javier; Silva, Rogerio R.; Sorger, Magdalena D.; Souza, Jorge; Suarez, Andrew V.; Tista, Melanie; Vasconcelos, Heraldo L.; Vonshak, Merav; Weiser, Michael D.; Yates, Michelle; Parr, Catherine L.

    2017-01-01

    What forces structure ecological assemblages? A key limitation to general insights about assemblage structure is the availability of data that are collected at a small spatial grain (local assemblages) and a large spatial extent (global coverage). Here, we present published and unpublished data from 51,388 ant abundance and occurrence records of more than 2693 species and 7953 morphospecies from local assemblages collected at 4212 locations around the world. Ants were selected because they are diverse and abundant globally, comprise a large fraction of animal biomass in most terrestrial communities, and are key contributors to a range of ecosystem functions. Data were collected between 1949 and 2014, and include, for each geo-referenced sampling site, both the identity of the ants collected and details of sampling design, habitat type and degree of disturbance. The aim of compiling this dataset was to provide comprehensive species abundance data in order to test relationships between assemblage structure and environmental and biogeographic factors. Data were collected using a variety of standardised methods, such as pitfall and Winkler traps, and will be valuable for studies investigating large-scale forces structuring local assemblages. Understanding such relationships is particularly critical under current rates of global change. We encourage authors holding additional data on systematically collected ant assemblages, especially those in dry and cold, and remote areas, to contact us and contribute their data to this growing dataset.

  12. Abundance ratios in dwarf elliptical galaxies

    NASA Astrophysics Data System (ADS)

    Şen, Ş.; Peletier, R. F.; Boselli, A.; den Brok, M.; Falcón-Barroso, J.; Hensler, G.; Janz, J.; Laurikainen, E.; Lisker, T.; Mentz, J. J.; Paudel, S.; Salo, H.; Sybilska, A.; Toloba, E.; van de Ven, G.; Vazdekis, A.; Yesilyaprak, C.

    2018-04-01

    We determine abundance ratios of 37 dwarf ellipticals (dEs) in the nearby Virgo cluster. This sample is representative of the early-type population of galaxies in the absolute magnitude range -19.0 < Mr < -16.0. We analyse their absorption line-strength indices by means of index-index diagrams and scaling relations and use the stellar population models to interpret them. We present ages, metallicities, and abundance ratios obtained from these dEs within an aperture size of Re/8. We calculate [Na/Fe] from NaD, [Ca/Fe] from Ca4227, and [Mg/Fe] from Mgb. We find that [Na/Fe] is underabundant with respect to solar, whereas [Mg/Fe] is around solar. This is exactly opposite to what is found for giant ellipticals, but follows the trend with metallicity found previously for the Fornax dwarf NGC 1396. We discuss possible formation scenarios that can result in such elemental abundance patterns, and we speculate that dEs have disc-like star formation history (SFH) favouring them to originate from late-type dwarfs or small spirals. Na-yields appear to be very metal-dependent, in agreement with studies of giant ellipticals, probably due to the large dependence on the neutron-excess in stars. We conclude that dEs have undergone a considerable amount of chemical evolution, they are therefore not uniformly old, but have extended SFH, similar to many of the Local Group galaxies.

  13. The Coronal Abundance Anomalies of M Dwarfs

    NASA Astrophysics Data System (ADS)

    Wood, Brian E.; Laming, J. Martin; Karovska, Margarita

    2012-07-01

    We analyze Chandra X-ray spectra of the M0 V+M0 V binary GJ 338. As quantified by X-ray surface flux, these are the most inactive M dwarfs ever observed with X-ray grating spectroscopy. We focus on measuring coronal abundances, in particular searching for evidence of abundance anomalies related to first ionization potential (FIP). In the solar corona and wind, low-FIP elements are overabundant, which is the so-called FIP effect. For other stars, particularly very active ones, an "inverse FIP effect" is often observed, with low-FIP elements being underabundant. For both members of the GJ 338 binary, we find evidence for a modest inverse FIP effect, consistent with expectations from a previously reported correlation between spectral type and FIP bias. This amounts to strong evidence that all M dwarfs should exhibit the inverse FIP effect phenomenon, not just the active ones. We take the first step toward modeling the inverse FIP phenomenon in M dwarfs, building on past work that has demonstrated that MHD waves coursing through coronal loops can lead to a ponderomotive force that fractionates elements in a manner consistent with the FIP effect. We demonstrate that in certain circumstances this model can also lead to an inverse FIP effect, pointing the way to more detailed modeling of M dwarf coronal abundances in the future.

  14. A global database of ant species abundances.

    PubMed

    Gibb, Heloise; Dunn, Rob R; Sanders, Nathan J; Grossman, Blair F; Photakis, Manoli; Abril, Silvia; Agosti, Donat; Andersen, Alan N; Angulo, Elena; Armbrecht, Inge; Arnan, Xavier; Baccaro, Fabricio B; Bishop, Tom R; Boulay, Raphaël; Brühl, Carsten; Castracani, Cristina; Cerda, Xim; Del Toro, Israel; Delsinne, Thibaut; Diaz, Mireia; Donoso, David A; Ellison, Aaron M; Enriquez, Martha L; Fayle, Tom M; Feener, Donald H; Fisher, Brian L; Fisher, Robert N; Fitzpatrick, Matthew C; Gómez, Crisanto; Gotelli, Nicholas J; Gove, Aaron; Grasso, Donato A; Groc, Sarah; Guenard, Benoit; Gunawardene, Nihara; Heterick, Brian; Hoffmann, Benjamin; Janda, Milan; Jenkins, Clinton; Kaspari, Michael; Klimes, Petr; Lach, Lori; Laeger, Thomas; Lattke, John; Leponce, Maurice; Lessard, Jean-Philippe; Longino, John; Lucky, Andrea; Luke, Sarah H; Majer, Jonathan; McGlynn, Terrence P; Menke, Sean; Mezger, Dirk; Mori, Alessandra; Moses, Jimmy; Munyai, Thinandavha Caswell; Pacheco, Renata; Paknia, Omid; Pearce-Duvet, Jessica; Pfeiffer, Martin; Philpott, Stacy M; Resasco, Julian; Retana, Javier; Silva, Rogerio R; Sorger, Magdalena D; Souza, Jorge; Suarez, Andrew; Tista, Melanie; Vasconcelos, Heraldo L; Vonshak, Merav; Weiser, Michael D; Yates, Michelle; Parr, Catherine L

    2017-03-01

    What forces structure ecological assemblages? A key limitation to general insights about assemblage structure is the availability of data that are collected at a small spatial grain (local assemblages) and a large spatial extent (global coverage). Here, we present published and unpublished data from 51 ,388 ant abundance and occurrence records of more than 2,693 species and 7,953 morphospecies from local assemblages collected at 4,212 locations around the world. Ants were selected because they are diverse and abundant globally, comprise a large fraction of animal biomass in most terrestrial communities, and are key contributors to a range of ecosystem functions. Data were collected between 1949 and 2014, and include, for each geo-referenced sampling site, both the identity of the ants collected and details of sampling design, habitat type, and degree of disturbance. The aim of compiling this data set was to provide comprehensive species abundance data in order to test relationships between assemblage structure and environmental and biogeographic factors. Data were collected using a variety of standardized methods, such as pitfall and Winkler traps, and will be valuable for studies investigating large-scale forces structuring local assemblages. Understanding such relationships is particularly critical under current rates of global change. We encourage authors holding additional data on systematically collected ant assemblages, especially those in dry and cold, and remote areas, to contact us and contribute their data to this growing data set. © 2016 by the Ecological Society of America.

  15. 2015-2016 Palila abundance estimates

    USGS Publications Warehouse

    Camp, Richard J.; Brinck, Kevin W.; Banko, Paul C.

    2016-01-01

    The palila (Loxioides bailleui) population was surveyed annually during 1998−2016 on Mauna Kea Volcano to determine abundance, population trend, and spatial distribution. In the latest surveys, the 2015 population was estimated at 852−1,406 birds (point estimate: 1,116) and the 2016 population was estimated at 1,494−2,385 (point estimate: 1,934). Similar numbers of palila were detected during the first and subsequent counts within each year during 2012−2016; the proportion of the total annual detections in each count ranged from 46% to 56%; and there was no difference in the detection probability due to count sequence. Furthermore, conducting repeat counts improved the abundance estimates by reducing the width of the confidence intervals between 9% and 32% annually. This suggests that multiple counts do not affect bird or observer behavior and can be continued in the future to improve the precision of abundance estimates. Five palila were detected on supplemental survey stations in the Ka‘ohe restoration area, outside the core survey area but still within Palila Critical Habitat (one in 2015 and four in 2016), suggesting that palila are present in habitat that is recovering from cattle grazing on the southwest slope. The average rate of decline during 1998−2016 was 150 birds per year. Over the 18-year monitoring period, the estimated rate of change equated to a 58% decline in the population.

  16. How selection structures species abundance distributions

    PubMed Central

    Magurran, Anne E.; Henderson, Peter A.

    2012-01-01

    How do species divide resources to produce the characteristic species abundance distributions seen in nature? One way to resolve this problem is to examine how the biomass (or capacity) of the spatial guilds that combine to produce an abundance distribution is allocated among species. Here we argue that selection on body size varies across guilds occupying spatially distinct habitats. Using an exceptionally well-characterized estuarine fish community, we show that biomass is concentrated in large bodied species in guilds where habitat structure provides protection from predators, but not in those guilds associated with open habitats and where safety in numbers is a mechanism for reducing predation risk. We further demonstrate that while there is temporal turnover in the abundances and identities of species that comprise these guilds, guild rank order is conserved across our 30-year time series. These results demonstrate that ecological communities are not randomly assembled but can be decomposed into guilds where capacity is predictably allocated among species. PMID:22787020

  17. Impact of microencapsulated peptidase (Aspergillus oryzae) on cheddar cheese proteolysis and its biologically active peptide profile.

    PubMed

    Seneweera, Saman; Kailasapathy, Kaila

    2011-07-01

    We investigated the delivery of calcium-alginate encapsulated peptidase (Flavourzyme(®), Aspergillus oryzae) on proteolysis of Cheddar cheese. Physical and chemical characteristics such as moisture, pH and fat content were measured, and no differences were found between control and experimental cheese at day 0. SDS-PAGE analysis clearly showed that proteolysis of α and k casein was significantly accelerated after three months of maturity in the experimental cheese. A large number of low molecular weight peptides were found in the water soluble fraction of the experimental cheeses and some of these peptides were new. N-terminal amino acid sequence analysis identified these as P(1), Leu-Thu-Glu; P(3), Asp-Val-Pro-Ser-Glu) and relatively abundant stable peptides P(2), P(4), Arg-Pro-Lys-His-Pro-Ile; P(5), Arg-Pro-Lys-His-Pro-Ile-Lys and P(6). These peptides were mainly originated from αs1-CN and β-CN. Three of the identified peptides (P(1), P(2), P(3) and P(4)) are known to biologically active and P(1) and P(3) were only present in experimental cheese suggesting that experimental cheese has improved health benefits.

  18. Refining comparative proteomics by spectral counting to account for shared peptides and multiple search engines

    PubMed Central

    Chen, Yao-Yi; Dasari, Surendra; Ma, Ze-Qiang; Vega-Montoto, Lorenzo J.; Li, Ming

    2013-01-01

    Spectral counting has become a widely used approach for measuring and comparing protein abundance in label-free shotgun proteomics. However, when analyzing complex samples, the ambiguity of matching between peptides and proteins greatly affects the assessment of peptide and protein inventories, differentiation, and quantification. Meanwhile, the configuration of database searching algorithms that assign peptides to MS/MS spectra may produce different results in comparative proteomic analysis. Here, we present three strategies to improve comparative proteomics through spectral counting. We show that comparing spectral counts for peptide groups rather than for protein groups forestalls problems introduced by shared peptides. We demonstrate the advantage and flexibility of this new method in two datasets. We present four models to combine four popular search engines that lead to significant gains in spectral counting differentiation. Among these models, we demonstrate a powerful vote counting model that scales well for multiple search engines. We also show that semi-tryptic searching outperforms tryptic searching for comparative proteomics. Overall, these techniques considerably improve protein differentiation on the basis of spectral count tables. PMID:22552787

  19. Refining comparative proteomics by spectral counting to account for shared peptides and multiple search engines.

    PubMed

    Chen, Yao-Yi; Dasari, Surendra; Ma, Ze-Qiang; Vega-Montoto, Lorenzo J; Li, Ming; Tabb, David L

    2012-09-01

    Spectral counting has become a widely used approach for measuring and comparing protein abundance in label-free shotgun proteomics. However, when analyzing complex samples, the ambiguity of matching between peptides and proteins greatly affects the assessment of peptide and protein inventories, differentiation, and quantification. Meanwhile, the configuration of database searching algorithms that assign peptides to MS/MS spectra may produce different results in comparative proteomic analysis. Here, we present three strategies to improve comparative proteomics through spectral counting. We show that comparing spectral counts for peptide groups rather than for protein groups forestalls problems introduced by shared peptides. We demonstrate the advantage and flexibility of this new method in two datasets. We present four models to combine four popular search engines that lead to significant gains in spectral counting differentiation. Among these models, we demonstrate a powerful vote counting model that scales well for multiple search engines. We also show that semi-tryptic searching outperforms tryptic searching for comparative proteomics. Overall, these techniques considerably improve protein differentiation on the basis of spectral count tables.

  20. Insecticidal peptides from the theraposid spider Brachypelma albiceps: an NMR-based model of Ba2.

    PubMed

    Corzo, Gerardo; Bernard, Cedric; Clement, Herlinda; Villegas, Elba; Bosmans, Frank; Tytgat, Jan; Possani, Lourival D; Darbon, Herve; Alagón, Alejandro

    2009-08-01

    Soluble venom and purified fractions of the theraposid spider Brachypelma albiceps were screened for insecticidal peptides based on toxicity to crickets. Two insecticidal peptides, named Ba1 and Ba2, were obtained after the soluble venom was separated by high performance liquid chromatography and cation exchange chromatography. The two insecticidal peptides contain 39 amino acid residues and three disulfide bonds, and based on their amino acid sequence, they are highly identical to the insecticidal peptides from the theraposid spiders Aphonopelma sp. from the USA and Haplopelma huwenum from China indicating a relationship among these genera. Although Ba1 and Ba2 were not able to modify currents in insect and vertebrate cloned voltage-gated sodium ion channels, they have noteworthy insecticidal activities compared to classical arachnid insecticidal toxins indicating that they might target unknown receptors in insect species. The most abundant insecticidal peptide Ba2 was submitted to NMR spectroscopy to determine its 3-D structure; a remarkable characteristic of Ba2 is a cluster of basic residues, which might be important for receptor recognition.

  1. Using Peptide-Level Proteomics Data for Detecting Differentially Expressed Proteins.

    PubMed

    Suomi, Tomi; Corthals, Garry L; Nevalainen, Olli S; Elo, Laura L

    2015-11-06

    The expression of proteins can be quantified in high-throughput means using different types of mass spectrometers. In recent years, there have emerged label-free methods for determining protein abundance. Although the expression is initially measured at the peptide level, a common approach is to combine the peptide-level measurements into protein-level values before differential expression analysis. However, this simple combination is prone to inconsistencies between peptides and may lose valuable information. To this end, we introduce here a method for detecting differentially expressed proteins by combining peptide-level expression-change statistics. Using controlled spike-in experiments, we show that the approach of averaging peptide-level expression changes yields more accurate lists of differentially expressed proteins than does the conventional protein-level approach. This is particularly true when there are only few replicate samples or the differences between the sample groups are small. The proposed technique is implemented in the Bioconductor package PECA, and it can be downloaded from http://www.bioconductor.org.

  2. Ampulexins: A New Family of Peptides in Venom of the Emerald Jewel Wasp, Ampulex compressa.

    PubMed

    Moore, Eugene L; Arvidson, Ryan; Banks, Christopher; Urenda, Jean Paul; Duong, Elizabeth; Mohammed, Haroun; Adams, Michael E

    2018-03-27

    The parasitoid wasp Ampulex compressa injects venom directly into the brain and subesophageal ganglion of the cockroach Periplaneta americana, inducing a 7 to 10 day lethargy termed hypokinesia. Hypokinesia presents as a significant reduction in both escape response and spontaneous walking. We examined aminergic and peptidergic components of milked venom with HPLC and MALDI-TOF mass spectrometry. HPLC coupled with electrochemical detection confirmed the presence of dopamine in milked venom, while mass spectrometry revealed that the venom gland and venom sac have distinct peptide profiles, with milked venom predominantly composed of venom sac peptides. We isolated and characterized novel α-helical, amphipathic venom sac peptides that constitute a new family of venom toxins termed ampulexins. Injection of the most abundant venom peptide, ampulexin 1, into the subesophageal ganglion of cockroaches resulted in a short-term increase in escape threshold. Neither milked venom nor venom peptides interfered with growth of Escherichia coli or Bacillus thuringiensis on agar plates, and exposure to ampulexins or milked venom did not induce cell death in Chinese hamster ovary cells (CHO-K1) or Hi5 cells ( Trichoplusia ni).

  3. PECAN: Library Free Peptide Detection for Data-Independent Acquisition Tandem Mass Spectrometry Data

    PubMed Central

    Ting, Ying S.; Egertson, Jarrett D.; Bollinger, James G.; Searle, Brian C.; Payne, Samuel H.; Noble, William Stafford; MacCoss, Michael J.

    2017-01-01

    In mass spectrometry-based shogun proteomics, data-independent acquisition (DIA) is an emerging technique for unbiased and reproducible measurement of protein mixtures. Without targeting a specific precursor ion, DIA MS/MS spectra are often highly multiplexed, containing product ions from multiple co-fragmenting precursors. Thus, detecting peptides directly from DIA data is challenging; most DIA data analyses require spectral libraries. Here we present a new library-free, peptide-centric tool PECAN that detects peptides directly from DIA data. PECAN reports evidence of detection based on product ion scoring, enabling detection of low abundance analytes with poor precursor ion signal. We benchmarked PECAN with chromatographic peak picking accuracy and peptide detection capability. We further validated PECAN detection with data-dependent acquisition and targeted analyses. Last, we used PECAN to build a library from DIA data and to query sequence variants. Together, these results show that PECAN detects peptides robustly and accurately from DIA data without using a library. PMID:28783153

  4. Extensive characterization of peptides from Panax ginseng C. A. Meyer using mass spectrometric approach.

    PubMed

    Ye, Xueting; Zhao, Nan; Yu, Xi; Han, Xiaoli; Gao, Huiyuan; Zhang, Xiaozhe

    2016-11-01

    Panax ginseng is an important herb that has clear effects on the treatment of diverse diseases. Until now, the natural peptide constitution of this herb remains unclear. Here, we conduct an extensive characterization of Ginseng peptidome using MS-based data mining and sequencing. The screen on the charge states of precursor ions indicated that Ginseng is a peptide-rich herb in comparison of a number of commonly used herbs. The Ginseng peptides were then extracted and submitted to nano-LC-MS/MS analysis using different fragmentation modes, including CID, high-energy collisional dissociation, and electron transfer dissociation. Further database search and de novo sequencing allowed the identification of total 308 peptides, some of which might have important biological activities. This study illustrates the abundance and sequences of endogenous Ginseng peptides, thus providing the information of more candidates for the screening of active compounds for future biological research and drug discovery studies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Quantitation of peptides from non-invasive skin tapings using isotope dilution and tandem mass spectrometry.

    PubMed

    Reisdorph, Nichole; Armstrong, Michael; Powell, Roger; Quinn, Kevin; Legg, Kevin; Leung, Donald; Reisdorph, Rick

    2018-05-01

    Previous work from our laboratories utilized a novel skin taping method and mass spectrometry-based proteomics to discover clinical biomarkers of skin conditions; these included atopic dermatitis, Staphylococcus aureus colonization, and eczema herpeticum. While suitable for discovery purposes, semi-quantitative proteomics is generally time-consuming and expensive. Furthermore, depending on the method used, discovery-based proteomics can result in high variation and inadequate sensitivity to detect low abundant peptides. Therefore, we strove to develop a rapid, sensitive, and reproducible method to quantitate disease-related proteins from skin tapings. We utilized isotopically-labeled peptides and tandem mass spectrometry to obtain absolute quantitation values on 14 peptides from 7 proteins; these proteins had shown previous importance in skin disease. The method demonstrated good reproducibility, dynamic range, and linearity (R 2  > 0.993) when n = 3 standards were analyzed across 0.05-2.5 pmol. The method was used to determine if differences exist between skin proteins in a small group of atopic versus non-atopic individuals (n = 12). While only minimal differences were found, peptides were detected in all samples and exhibited good correlation between peptides for 5 of the 7 proteins (R 2  = 0.71-0.98). This method can be applied to larger cohorts to further establish the relationships of these proteins to skin disease. Copyright © 2017. Published by Elsevier B.V.

  6. Metastable Atom-Activated Dissociation Mass Spectrometry of Phosphorylated and Sulfonated Peptides in Negative Ion Mode

    NASA Astrophysics Data System (ADS)

    Cook, Shannon L.; Jackson, Glen P.

    2011-06-01

    The dissociation behavior of phosphorylated and sulfonated peptide anions was explored using metastable atom-activated dissociation mass spectrometry (MAD-MS) and collision-induced dissociation (CID). A beam of high kinetic energy helium (He) metastable atoms was exposed to isolated phosphorylated and sulfonated peptides in the 3- and 2- charge states. Unlike CID, where phosphate losses are dominant, the major dissociation channels observed using MAD were Cα - C peptide backbone cleavages and neutral losses of CO2, H2O, and [CO2 + H2O] from the charge reduced (oxidized) product ion, consistent with an electron detachment dissociation (EDD) mechanism such as Penning ionization. Regardless of charge state or modification, MAD provides ample backbone cleavages with little modification loss, which allows for unambiguous PTM site determination. The relative abundance of certain fragment ions in MAD is also demonstrated to be somewhat sensitive to the number and location of deprotonation sites, with backbone cleavage somewhat favored adjacent to deprotonated sites like aspartic acid residues. MAD provides a complementary dissociation technique to CID, ECD, ETD, and EDD for peptide sequencing and modification identification. MAD offers the unique ability to analyze highly acidic peptides that contain few to no basic amino acids in either negative or positive ion mode.

  7. Abundant Solar Nebula Solids in Comets

    NASA Technical Reports Server (NTRS)

    Messenger, S.; Keller, L. P.; Nakamura-Messenger, K.; Nguyen, A. N.; Clemett, S.

    2016-01-01

    Comets have been proposed to consist of unprocessed interstellar materials together with a variable amount of thermally annealed interstellar grains. Recent studies of cometary solids in the laboratory have shown that comets instead consist of a wide range of materials from across the protoplanetary disk, in addition to a minor complement of interstellar materials. These advances were made possible by the return of direct samples of comet 81P/Wild 2 coma dust by the NASA Stardust mission and recent advances in microscale analytical techniques. Isotopic studies of 'cometary' chondritic porous interplanetary dust particles (CP-IDPs) and comet 81P/Wild 2 Stardust samples show that preserved interstellar materials are more abundant in comets than in any class of meteorite. Identified interstellar materials include sub-micron-sized presolar silicates, oxides, and SiC dust grains and some fraction of the organic material that binds the samples together. Presolar grain abundances reach 1 weight percentage in the most stardust-rich CP-IDPs, 50 times greater than in meteorites. Yet, order of magnitude variations in presolar grain abundances among CP-IDPs suggest cometary solids experienced significant variations in the degree of processing in the solar nebula. Comets contain a surprisingly high abundance of nebular solids formed or altered at high temperatures. Comet 81P/Wild 2 samples include 10-40 micron-sized, refractory Ca- Al-rich inclusion (CAI)-, chondrule-, and ameboid olivine aggregate (AOA)-like materials. The O isotopic compositions of these refractory materials are remarkably similar to their meteoritic counterparts, ranging from 5 percent enrichments in (sup 16) O to near-terrestrial values. Comet 81P/Wild 2 and CP-IDPs also contain abundant Mg-Fe crystalline and amorphous silicates whose O isotopic compositions are also consistent with Solar System origins. Unlike meteorites, that are dominated by locally-produced materials, comets appear to be composed of

  8. Quantification of VGF- and pro-SAAS-derived peptides in endocrine tissues and the brain, and their regulation by diet and cold stress.

    PubMed

    Chakraborty, Tandra R; Tkalych, Oleg; Nanno, Daniela; Garcia, Angelo L; Devi, Lakshmi A; Salton, Stephen R J

    2006-05-17

    Two novel granin-like polypeptides, VGF and pro-SAAS, which are stored in and released from secretory vesicles and are expressed widely in nervous, endocrine, and neuroendocrine tissues, play roles in the regulation of body weight, feeding, and energy expenditure. Both VGF and pro-SAAS are cleaved into peptide fragments, several of which are biologically active. We utilized a highly sensitive and specific radioimmunoassay (RIA) to immunoreactive, pro-SAAS-derived PEN peptides, developed another against immunoreactive, VGF-derived AQEE30 peptides, and quantified these peptides in various mouse tissues and brain regions. Immunoreactive AQEE30 was most abundant in the pituitary, while brain levels were highest in hypothalamus, striatum, and frontal cortex. Immunoreactive PEN levels were highest in the pancreas and spinal cord, and in brain, PEN was most abundant in striatum, hippocampus, pons and medulla, and cortex. Since both peptides were expressed in hypothalamus, a region of the brain that controls feeding and energy expenditure, double label immunofluorescence studies were employed. These demonstrated that 42% of hypothalamic arcuate neurons coexpress VGF and SAAS peptides, and that the intracellular distributions of these peptides in arcuate neurons differed. By RIA, cold stress increased immunoreactive AQEE30 and PEN peptide levels in female but not male hypothalamus, while a high fat diet increased AQEE30 and PEN peptide levels in female but not male hippocampus. VGF and SAAS-derived peptides are therefore widely expressed in endocrine, neuroendocrine, and neural tissues, can be accurately quantified by RIA, and are differentially regulated in the brain by diet and cold stress.

  9. Manual method of visually identifying candidate signals for a targeted peptide.

    PubMed

    Filimonov, Aleksey; Kopylov, Arthur; Lisitsa, Andrey; Archakov, Alexander

    2018-04-15

    The purpose of this study is to improve peptide signal identification in groups of extracted ion chromatograms (XICs) obtained with the liquid chromatography-selected reaction monitoring (LC-SRM) technique and a triple quadrupole mass spectrometer (QqQ) operating in one of the supported multiple reaction monitoring (MRM) modes. The imperfection of quadrupole mass analyzers causes ion interference, which impedes the identification of peptide signals as chromatographic peak groups in relevant retention time intervals. To investigate this problem in depth, the QqQ conversion of the eluate into XIC groups was considered as the consecutive transformations of the particles' abundances as the corresponding functions of retention time. In this study, the hypothesis that, during this conversion, the same chromatographic profile should be preserved as an implicit sign in each chromatographic peak of the signal was confirmed for peptides. To examine chromatographic profiles, continuous transformations of XIC groups were derived and implemented in srm2prot Express software (s2pe, http://msr.ibmc.msk.ru/s2pe). Because of ion interference, several peptide-like signals may appear in one XIC group. Therefore, these signals must be considered candidates for a targeted peptide's signal and should be resolved after identification. The theoretical investigation of intensity functions as XICs that are not distorted by noise produced three rules for Identifying Candidate Signals for a targeted Peptide (ICSP, http://msr.ibmc.msk.ru/ICSP) that constitute the proposed manual visual method. We theoretically and experimentally compared this method with the conventional semiempirical intuitive technique and found that the former significantly streamlines peptide signal identification and avoids typical errors. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. New APETx-like peptides from sea anemone Heteractis crispa modulate ASIC1a channels.

    PubMed

    Kalina, Rimma; Gladkikh, Irina; Dmitrenok, Pavel; Chernikov, Oleg; Koshelev, Sergey; Kvetkina, Aleksandra; Kozlov, Sergey; Kozlovskaya, Emma; Monastyrnaya, Margarita

    2018-06-01

    Sea anemones are an abundant source of various biologically active peptides. The hydrophobic 20% ethanol fraction of tropical sea anemone Heteractis crispa was shown to contain at least 159 peptide compounds including neurotoxins, proteinase and α-amylase inhibitors, as well as modulators of acid-sensing ion channels (ASICs). The three new peptides, π-AnmTX Hcr 1b-2, -3, and -4 (41 aa) (short names Hcr 1b-2, -3, -4), identified by a combination of reversed-phase liquid chromatography and mass spectrometry were found to belong to the class 1b sea anemone neurotoxins. The amino acid sequences of these peptides were determined by Edman degradation and tandem mass spectrometry. The percent of identity of Hcr 1b-2, -3, and -4 with well-known ASIC3 inhibitors Hcr 1b-1 from H. crispa and APETx2 from Anthopleura elegantissima is 95-78% and 46-49%, respectively. Electrophysiological experiments on homomeric ASIC channels expressed in Xenopus laevis oocytes establish that these peptides are the first inhibitors of ASIC1a derived from sea anemone venom. The major peptide, Hcr 1b-2, inhibited both rASIC1a (IC 50 4.8 ± 0.3 μM; nH 0.92 ± 0.05) and rASIC3 (IC 50 15.9 ± 1.1 μM; nH 1.0 ± 0.05). The maximum inhibition at saturating peptide concentrations reached 64% and 81%, respectively. In the model of acid-induced muscle pain Hcr 1b-2 was also shown to exhibit an antihyperalgesic effect, significantly reducing of the pain threshold of experimental animals. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Beryllium and Boron abundances in population II stars

    NASA Technical Reports Server (NTRS)

    1995-01-01

    The scientific focus of this program was to undertake UV spectroscopic abundance analyses of extremely metal poor stars with attention to determining abundances of light elements such as beryllium and boron. The abundances are likely to reflect primordial abundances within the early galaxy and help to constrain models for early galactic nucleosynthesis. The general metal abundances of these stars are also important for understanding stellar evolution.

  12. Methionine peptide formation under primordial earth conditions.

    PubMed

    Li, Feng; Fitz, Daniel; Fraser, Donald G; Rode, Bernd M

    2008-01-01

    According to recent research on the origin of life it seems more and more likely that amino acids and peptides were among the first biomolecules formed on earth and that a peptide/protein world was thus a key starting point in evolution towards life. Salt-induced Peptide Formation (SIPF) has repeatedly been shown to be the most universal and plausible peptide-forming reaction currently known under prebiotic conditions and forms peptides from amino acids with the help of copper ions and sodium chloride. In this paper we present experimental results for salt-induced peptide formation from methionine. This is the first time that a sulphur-containing amino acid was investigated in this reaction. The possible catalytic effects of glycine and L-histidine in this reaction were also investigated and a possible distinction between the L- and D-forms of methionine was studied as well.

  13. Toward structure prediction of cyclic peptides.

    PubMed

    Yu, Hongtao; Lin, Yu-Shan

    2015-02-14

    Cyclic peptides are a promising class of molecules that can be used to target specific protein-protein interactions. A computational method to accurately predict their structures would substantially advance the development of cyclic peptides as modulators of protein-protein interactions. Here, we develop a computational method that integrates bias-exchange metadynamics simulations, a Boltzmann reweighting scheme, dihedral principal component analysis and a modified density peak-based cluster analysis to provide a converged structural description for cyclic peptides. Using this method, we evaluate the performance of a number of popular protein force fields on a model cyclic peptide. All the tested force fields seem to over-stabilize the α-helix and PPII/β regions in the Ramachandran plot, commonly populated by linear peptides and proteins. Our findings suggest that re-parameterization of a force field that well describes the full Ramachandran plot is necessary to accurately model cyclic peptides.

  14. Potent peptidic fusion inhibitors of influenza virus

    SciTech Connect

    Kadam, Rameshwar U.; Juraszek, Jarek; Brandenburg, Boerries

    Influenza therapeutics with new targets and mechanisms of action are urgently needed to combat potential pandemics, emerging viruses, and constantly mutating strains in circulation. We report here on the design and structural characterization of potent peptidic inhibitors of influenza hemagglutinin. The peptide design was based on complementarity-determining region loops of human broadly neutralizing antibodies against the hemagglutinin (FI6v3 and CR9114). The optimized peptides exhibit nanomolar affinity and neutralization against influenza A group 1 viruses, including the 2009 H1N1 pandemic and avian H5N1 strains. The peptide inhibitors bind to the highly conserved stem epitope and block the low pH–induced conformational rearrangementsmore » associated with membrane fusion. These peptidic compounds and their advantageous biological properties should accelerate the development of new small molecule– and peptide-based therapeutics against influenza virus.« less

  15. Hevein-Like Antimicrobial Peptides of Plants.

    PubMed

    Slavokhotova, A A; Shelenkov, A A; Andreev, Ya A; Odintsova, T I

    2017-12-01

    Plant antimicrobial peptides represent one of the evolutionarily oldest innate immunity components providing the first line of host defense to pathogen attacks. This review is dedicated to a small, currently actively studied family of hevein-like peptides that can be found in various monocot and dicot plants. The review thoroughly describes all known peptides belonging to this family including data on their structures, functions, and antimicrobial activity. The main features allowing to assign these peptides to a separate family are given, and the specific characteristics of each peptide are described. Further, the mode of action for hevein-like peptides, their role in plant immune system, and the applications of these molecules in biotechnology and medicine are considered.

  16. Natriuretic peptides: Diagnostic and therapeutic use

    PubMed Central

    Pandit, Kaushik; Mukhopadhyay, Pradip; Ghosh, Sujoy; Chowdhury, Subhankar

    2011-01-01

    Natriuretic peptides (NPs) are hormones which are mainly secreted from heart and have important natriuretic and kaliuretic properties. There are four different groups NPs identified till date [atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), C-type natriuretic peptide (CNP) and dendroaspis natriuretic peptide, a D-type natriuretic peptide (DNP)], each with its own characteristic functions. The N-terminal part of the prohormone of BNP, NT-proBNP, is secreted alongside BNP and has been documented to have important diagnostic value in heart failure. NPs or their fragments have been subjected to scientific observation for their diagnostic value and this has yielded important epidemiological data for interpretation. However, little progress has been made in harnessing the therapeutic potential of these cardiac hormones. PMID:22145138

  17. Synthesis of peptide .alpha.-thioesters

    DOEpatents

    Camarero, Julio A [Livermore, CA; Mitchell, Alexander R [Livermore, CA; De Yoreo, James J [Clayton, CA

    2008-08-19

    Disclosed herein is a new method for the solid phase peptide synthesis (SPPS) of C-terminal peptide .alpha. thioesters using Fmoc/t-Bu chemistry. This method is based on the use of an aryl hydrazine linker, which is totally stable to conditions required for Fmoc-SPPS. When the peptide synthesis has been completed, activation of the linker is achieved by mild oxidation. The oxidation step converts the acyl-hydrazine group into a highly reactive acyl-diazene intermediate which reacts with an .alpha.-amino acid alkylthioester (H-AA-SR) to yield the corresponding peptide .alpha.-thioester in good yield. A variety of peptide thioesters, cyclic peptides and a fully functional Src homology 3 (SH3) protein domain have been successfully prepared.

  18. Relative Abundance of Integral Plasma Membrane Proteins in Arabidopsis Leaf and Root Tissue Determined by Metabolic Labeling and Mass Spectrometry

    PubMed Central

    Bernfur, Katja; Larsson, Olaf; Larsson, Christer; Gustavsson, Niklas

    2013-01-01

    Metabolic labeling of proteins with a stable isotope (15N) in intact Arabidopsis plants was used for accurate determination by mass spectrometry of differences in protein abundance between plasma membranes isolated from leaves and roots. In total, 703 proteins were identified, of which 188 were predicted to be integral membrane proteins. Major classes were transporters, receptors, proteins involved in membrane trafficking and cell wall-related proteins. Forty-one of the integral proteins, including nine of the 13 isoforms of the PIP (plasma membrane intrinsic protein) aquaporin subfamily, could be identified by peptides unique to these proteins, which made it possible to determine their relative abundance in leaf and root tissue. In addition, peptides shared between isoforms gave information on the proportions of these isoforms. A comparison between our data for protein levels and corresponding data for mRNA levels in the widely used database Genevestigator showed an agreement for only about two thirds of the proteins. By contrast, localization data available in the literature for 21 of the 41 proteins show a much better agreement with our data, in particular data based on immunostaining of proteins and GUS-staining of promoter activity. Thus, although mRNA levels may provide a useful approximation for protein levels, detection and quantification of isoform-specific peptides by proteomics should generate the most reliable data for the proteome. PMID:23990937

  19. Use of galerina marginata genes and proteins for peptide production

    SciTech Connect

    Hallen-Adams, Heather E.; Scott-Craig, John S.; Walton, Jonathan D.

    The present invention relates to compositions and methods comprising genes and peptides associated with cyclic peptides and cyclic peptide production in mushrooms. In particular, the present invention relates to using genes and proteins from Galerina species encoding peptides specifically relating to amatoxins in addition to proteins involved with processing cyclic peptide toxins. In a preferred embodiment, the present invention also relates to methods for making small peptides and small cyclic peptides including peptides similar to amanitin. Further, the present inventions relate to providing kits for making small peptides.

  20. Use of Galerina marginata genes and proteins for peptide production

    SciTech Connect

    Hallen-Adams, Heather E.; Scott-Craig, John S.; Walton, Jonathan D.

    The present invention relates to compositions and methods comprising genes and peptides associated with cyclic peptides and cyclic peptide production in mushrooms. In particular, the present invention relates to using genes and proteins from Galerina species encoding peptides specifically relating to amatoxins in addition to proteins involved with processing cyclic peptide toxins. In a preferred embodiment, the present invention also relates to methods for making small peptides and small cyclic peptides including peptides similar to amanitin. Further, the present inventions relate to providing kits for making small peptides.