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Sample records for endogenous compounds including

  1. Endogenous compounds labeled with radionuclides of short half-life-some perspectives

    DEFF Research Database (Denmark)

    Roland Långström, Bengt; Karimi, F; Watanabe, Y

    2013-01-01

    In the article, the strategy and synthesis of some endogenous compounds labeled mainly with (11) C are presented. There are some examples illustrating how endogenous labeled compounds in connection with positron emission tomography have unique properties to describe various biological processes......, and a few examples of the use of tracers labeled with (13) N and (15) O are also discussed. Labeled endogenous compounds may be an important asset to describe the conditions and the status of biological systems and might therefore be a key for the future search of individualized medicine....

  2. Clinical breath analysis: Discriminating between human endogenous compounds and exogenous (environmental) chemical confounders

    Science.gov (United States)

    Volatile organic compounds (VOCs) in exhaled breath originate from current or previous environmental exposures (exogenous compounds) and internal metabolic anabolic and catabolic) production (endogenous compounds). The origins of certain VOCs in breath presumed to be endogenous ...

  3. Partial purification of endogenous digitalis-like compound(s) in cord blood

    Energy Technology Data Exchange (ETDEWEB)

    Balzan, S.; Ghione, S.; Biver, P.; Gazzetti, P.; Montali, U. (C.N.R. Institute of Clinical Physiology, Pisa (Italy))

    1991-02-01

    Increasing evidence indicates the presence of endogenous digitalis-like compound(s) in human body fluids. In this preliminary report, we describe a study of the partial purification by HPLC of these compounds in the plasma of neonates (who have particularly high concentrations of this substance) and adults. Plasma samples from neonates (cord blood) and adults, lyophilized and extracted with methanol, were applied on a 300 x 3.9 mm C18 Nova Pak column and eluted with a mobile phase of acetonitrile/methanol/water (17/17/66 or 14/14/72 by vol) and, after 30 min, with 100% methanol. We assayed eluted fractions for inhibitory activity of 86Rb uptake and for digoxin-like immunoreactivity. The elution profile revealed a first peak of inhibitory activity of 86Rb uptake at the beginning of the chromatography; another peak was eluted with the 100% methanol. The two peaks also cross-reacted with antidigoxin antibodies. Because the second peak could possibly reflect the nonspecific interference of various lipophilic compounds, we focused our attention on the first peak. For these fractions dose-response curves for 86Rb uptake and for displacement of digoxin were parallel, respectively, to those of ouabain and digoxin, suggesting similarities of digoxin-like immunoreactive substance to cardiac glycosides. Similar chromatographic profiles were also obtained for plasma from adults, suggesting that the endogenous glycoside-like compound(s) in the neonate may be the same as those in the adult.

  4. Changes in endogenous bioactive compounds of Korean native chicken meat at different ages and during cooking.

    Science.gov (United States)

    Jayasena, Dinesh D; Jung, Samooel; Bae, Young Sik; Kim, Sun Hyo; Lee, Soo Kee; Lee, Jun Heon; Jo, Cheorun

    2014-07-01

    This study aimed to examine the effect of bird age on the contents of endogenous bioactive compounds, including carnosine, anserine, creatine, betaine, and carnitine, in meat from a certified meat-type commercial Korean native chicken strain (KNC; Woorimatdag). Additionally, the effects of the meat type (breast or leg meat) and the state of the meat (raw or cooked) were examined. Cocks of KNC were raised under similar standard commercial conditions at a commercial chicken farm. At various ages (10, 11, 12, 13, and 14 wk), breast and leg meats from a total of 10 birds from each age group were obtained. Raw and cooked meat samples were then prepared separately and analyzed for bioactive compounds. The age of the KNC had a significant effect only on the betaine content. The breast meat of KNC had higher amounts of carnosine and anserine but had lower amounts of betaine and carnitine than the leg meat (P cooking (P cooking, whereas breast meat showed almost complete retention of betaine and carnitine. The results of this study provide useful and rare information regarding the presence, amounts, and determinants of endogenous bioactive compounds in KNC meat, which can be useful for selection and breeding programs, and also for popularizing indigenous chicken meat. © 2014 Poultry Science Association Inc.

  5. Endogenous Locus Reporter Assays.

    Science.gov (United States)

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

    2018-01-01

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

  6. Endogenous versus exogenous exposure to N-nitroso compounds and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST) study.

    NARCIS (Netherlands)

    Jakszyn, Paula; Bingham, Sheila A; Pera, Guillem; Agudo, Antonio; Luben, Robert; Welch, Ailsa; Boeing, Heiner; Giudice, Giuseppe del; Palli, Domenico; Saieva, Calogero; Krogh, Vittorio; Sacerdote, Carlotta; Tumino, Rosario; Panico, Salvatore; Berglund, Göran; Simán, Henrik; Hallmans, Göran; Sanchez, María José; Larrañaga, Nerea; Barricarte, Aurelio; Chirlaque, María-Dolores; Quirós, José Ramón; Key, Timothy J; Allen, Naomi E; Lund, Eiliv; Carneiro, Fátima; Linseisen, Jakob; Nagel, Gabriele; Overvad, Kim; Tjønneland, Anne; Olsen, Anja; Bueno-de-Mesquita, H Bas; Ocké, Marga C; Peeters, Petra H M; Numans, Mattijs E; Clavel-Chapelon, Françoise; Trichopoulou, Antonia; Fenger, Claus; Stenling, Roger; Ferrari, Pietro; Jenab, Mazda; Norat, Teresa; Riboli, Elio; González, Carlos Alberto

    2006-01-01

    The risk of gastric cancer (GC) associated with dietary intake of nitrosodimethylamine (NDMA) and endogenous formation of nitroso compounds (NOCs) was investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC). The study included 521,457 individuals and 314 incident

  7. Endogenous versus exogenous exposure to N-Nitroso compounds and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST) study.

    NARCIS (Netherlands)

    Jakszyn, P.; Bingham, S.; Pera, G.; Agudo, A.; Luben, R.; Welch, A.; Boeing, H.; Giudice, G. del; Palli, D.; Saieva, C.; Krogh, V.; Sacerdote, C.; Tumino, R.; Panico, S.; Berglund, G.; Simán, H.; Hallmans, G.; Sanchez, M.J.; Larrañaga, N.; Barricarte, A.; Chirlaque, M.D.; Quirós, J.R.; Key, T.J.; Allen, N.; Lund, E.; Carneiro, F.; Linseisen, J.; Nagel, G.; Overvad, K.; Tjønneland, A.; Olsen, A.; Bueno-de-Mesquita, H.B.; Ocké, M.O.; Peeters, P.H.M.; Numans, M.E.; Clavel-Chapelon, F.; Trichopoulou, A.; Fenger, C.; Stenling, R.; Ferrari, P.; Jenab, M.; Norat, T.; Riboli, E.; Gonzalez, C.A.

    The risk of gastric cancer (GC) associated with dietary intake of Nitrosodimethylamine (NDMA) and endogenous formation of Nitroso compounds (NOCs) was investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC). The study included 521,457 individuals and 314 incident

  8. Effect of Aging and Surface Interactions on the Diffusion of Endogenous Compounds in Latent Fingerprints Studied by Mass Spectrometry Imaging.

    Science.gov (United States)

    O'Neill, Kelly C; Lee, Young Jin

    2018-05-01

    The ability to determine the age of fingerprints would be immeasurably beneficial in criminal investigations. We explore the possibility of determining the age of fingerprints by analyzing various compounds as they diffuse from the ridges to the valleys of fingerprints using matrix-assisted laser desorption/ionization mass spectrometry imaging. The diffusion of two classes of endogenous fingerprint compounds, fatty acids and triacylglycerols (TGs), was studied in fresh and aged fingerprints on four surfaces. We expected higher molecular weight TGs would diffuse slower than fatty acids and allow us to determine the age of older fingerprints. However, we found interactions between endogenous compounds and the surface have a much stronger impact on diffusion than molecular weight. For example, diffusion of TGs is faster on hydrophilic plain glass or partially hydrophilic stainless steel surfaces, than on a hydrophobic Rain-x treated surface. This result further complicates utilizing a diffusion model to age fingerprints. © 2017 American Academy of Forensic Sciences.

  9. Addressing the need for biomarker liquid chromatography/mass spectrometry assays: a protocol for effective method development for the bioanalysis of endogenous compounds in cerebrospinal fluid.

    Science.gov (United States)

    Benitex, Yulia; McNaney, Colleen A; Luchetti, David; Schaeffer, Eric; Olah, Timothy V; Morgan, Daniel G; Drexler, Dieter M

    2013-08-30

    Research on disorders of the central nervous system (CNS) has shown that an imbalance in the levels of specific endogenous neurotransmitters may underlie certain CNS diseases. These alterations in neurotransmitter levels may provide insight into pathophysiology, but can also serve as disease and pharmacodynamic biomarkers. To measure these potential biomarkers in vivo, the relevant sample matrix is cerebrospinal fluid (CSF), which is in equilibrium with the brain's interstitial fluid and circulates through the ventricular system of the brain and spinal cord. Accurate analysis of these potential biomarkers can be challenging due to low CSF sample volume, low analyte levels, and potential interferences from other endogenous compounds. A protocol has been established for effective method development of bioanalytical assays for endogenous compounds in CSF. Database searches and standard-addition experiments are employed to qualify sample preparation and specificity of the detection thus evaluating accuracy and precision. This protocol was applied to the study of the histaminergic neurotransmitter system and the analysis of histamine and its metabolite 1-methylhistamine in rat CSF. The protocol resulted in a specific and sensitive novel method utilizing pre-column derivatization ultra high performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS), which is also capable of separating an endogenous interfering compound, identified as taurine, from the analytes of interest. Copyright © 2013 John Wiley & Sons, Ltd.

  10. Endogenous and Exogenous Natural Adjuvants for Vaccine Development.

    Science.gov (United States)

    Bolhassani, Azam; Talebi, Somayeh; Anvar, Ali

    2017-01-01

    Objective & Background: Various adjuvants are usually co-injected with an antigen for stimulation of effective immune responses. Adjuvants are able to elicit innate immune responses at the injection site. Depending on the activated type of innate responses, adjuvants can modify the quality and quantity of adaptive immune responses. Their mechanisms of action in vaccine development include: a) enhancement of the total antibody titers; b) reduction of the antigen dose; c) induction of potent cell-mediated immunity; d) increase in the speed and duration of the protective response; e) stimulation of mucosal immunity; and f) cross-protection. Up to now, different exogenous adjuvants have been identified to boost immune responses including inorganic compounds, mineral oil, bacterial products, non-bacterial organics, detergents or Quil A, plant saponins, Freund's complete or incomplete adjuvants, and delivery systems. However, some immune responses can be generated in the absence of the exogenous adjuvants. Indeed, endogenous adjuvants released from the cells were known as the danger signals and immunogenic compounds. Several main endogenous adjuvants contain cytokines, chemokines, alarmins, dendritic cells (DCs), toll like receptor (TLR) ligands or agonists, and antibodies. In this review, the immune activities of the natural adjuvants especially endogenous adjuvants and their mechanisms of action are discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Electrolyte solutions including a phosphoranimine compound, and energy storage devices including same

    Science.gov (United States)

    Klaehn, John R.; Dufek, Eric J.; Rollins, Harry W.; Harrup, Mason K.; Gering, Kevin L.

    2017-09-12

    An electrolyte solution comprising at least one phosphoranimine compound and a metal salt. The at least one phosphoranimine compound comprises a compound of the chemical structure ##STR00001## where X is an organosilyl group or a tert-butyl group and each of R.sup.1, R.sup.2, and R.sup.3 is independently selected from the group consisting of an alkyl group, an aryl group, an alkoxy group, or an aryloxy group. An energy storage device including the electrolyte solution is also disclosed.

  12. A potential role for endogenous proteins as sacrificial sunscreens and antioxidants in human tissues

    OpenAIRE

    Sarah A. Hibbert; Rachel E.B. Watson; Neil K. Gibbs; Patrick Costello; Clair Baldock; Anthony S. Weiss; Christopher E.M. Griffiths; Michael J. Sherratt

    2015-01-01

    Excessive ultraviolet radiation (UVR) exposure of the skin is associated with adverse clinical outcomes. Although both exogenous sunscreens and endogenous tissue components (including melanins and tryptophan-derived compounds) reduce UVR penetration, the role of endogenous proteins in absorbing environmental UV wavelengths is poorly defined. Having previously demonstrated that proteins which are rich in UVR-absorbing amino acid residues are readily degraded by broadband UVB-radiation (contain...

  13. MDR1 P-glycoprotein transports endogenous opioid peptides

    NARCIS (Netherlands)

    Oude Elferink, R. P.; Zadina, J.

    2001-01-01

    MDR1 P-glycoprotein is generally regarded as an efflux pump for amphipathic toxic compounds. The question remains, however, whether certain endogenous compounds are also substrates for this transporter. Certain peptides have been shown to interact with MDR1 Pgp as well and we have therefore

  14. Endogenous antipyretics.

    Science.gov (United States)

    Roth, Joachim

    2006-09-01

    The febrile increase of body temperature is regarded as a component of the complex host response to infection or inflammation that accompanies the activation of the immune system. Late phases of fever appear mediated by pro-inflammatory cytokines called endogenous pyrogens. The rise of body temperature is beneficial because it accelerates several components of the activated immune system. To prevent an excessive and dangerous rise of body temperature the febrile response is controlled, limited in strength and duration, and sometimes even prevented by the actions of endogenous antipyretic substances liberated systemically or within the brain during fever. In most cases the antipyretic effects are achieved by an inhibitory influence on the formation or action of endogenous pyrogens, or by effects on neuronal thermoregulatory circuits that are activated during fever. Endogenous antipyretic substances include steroid hormones, neuropeptides, cytokines and other molecules. It is the purpose of this review to consider the current state in the research on endogenous antipyretic systems.

  15. Mycobacterium tuberculosis has diminished capacity to counteract redox stress induced by elevated levels of endogenous superoxide.

    Science.gov (United States)

    Tyagi, Priyanka; Dharmaraja, Allimuthu T; Bhaskar, Ashima; Chakrapani, Harinath; Singh, Amit

    2015-07-01

    Mycobacterium tuberculosis (Mtb) has evolved protective and detoxification mechanisms to maintain cytoplasmic redox balance in response to exogenous oxidative stress encountered inside host phagocytes. In contrast, little is known about the dynamic response of this pathogen to endogenous oxidative stress generated within Mtb. Using a noninvasive and specific biosensor of cytoplasmic redox state of Mtb, we for first time discovered a surprisingly high sensitivity of this pathogen to perturbation in redox homeostasis induced by elevated endogenous reactive oxygen species (ROS). We synthesized a series of hydroquinone-based small molecule ROS generators and found that ATD-3169 permeated mycobacteria to reliably enhance endogenous ROS including superoxide radicals. When Mtb strains including multidrug-resistant (MDR) and extensively drug-resistant (XDR) patient isolates were exposed to this compound, a dose-dependent, long-lasting, and irreversible oxidative shift in intramycobacterial redox potential was detected. Dynamic redox potential measurements revealed that Mtb had diminished capacity to restore cytoplasmic redox balance in comparison with Mycobacterium smegmatis (Msm), a fast growing nonpathogenic mycobacterial species. Accordingly, Mtb strains were extremely susceptible to inhibition by ATD-3169 but not Msm, suggesting a functional linkage between dynamic redox changes and survival. Microarray analysis showed major realignment of pathways involved in redox homeostasis, central metabolism, DNA repair, and cell wall lipid biosynthesis in response to ATD-3169, all consistent with enhanced endogenous ROS contributing to lethality induced by this compound. This work provides empirical evidence that the cytoplasmic redox poise of Mtb is uniquely sensitive to manipulation in steady-state endogenous ROS levels, thus revealing the importance of targeting intramycobacterial redox metabolism for controlling TB infection. Copyright © 2015 The Authors. Published by

  16. Classical endocannabinoid-like compounds and their regulation by nutrients

    DEFF Research Database (Denmark)

    Kleberg, Karen; Hassing, Helle A.; Hansen, Harald S.

    2014-01-01

    Endocannabinoid-like compounds are structurally related to the true endocannabinoids but do not contain highly unsaturated fatty acids, and they do not bind the cannabinoid receptors. The classical endocannabinoid-like compounds include N-acylethanolamines and 2-monoacylglycerols......, which are particularly interesting in a nutritional and metabolic context. Exogenously supplied oleoylethanolamide, palmitoylethanolamide, and linoleoylethanolamide have anorexic effects, and the endogenous formation of these N-acylethanolamines in the small intestine may serve an important role...

  17. 1-Methyl-beta-carboline (harmane), a potent endogenous inhibitor of benzodiazepine receptor binding.

    Science.gov (United States)

    Rommelspacher, H; Nanz, C; Borbe, H O; Fehske, K J; Müller, W E; Wollert, U

    1980-10-01

    The interaction of several beta-carbolines with specific [3H]-flunitrazepam binding to benzodiazepine receptors in rat brain membranes was investigated. Out of the investigated compounds, harmane and norharmane were the most potent inhibitors of specific [3H]-flunitrazepam binding, with IC50-values in the micromolar range. All other derivatives, including harmine, harmaline, and several tetrahydroderivatives were at least ten times less potent. Harmane has been previously found in rat brain and human urine, so it is the most potent endogenous inhibitor of specific [3H]-flunitrazepam binding known so far, with a several fold higher affinity for the benzodiazepine receptor than inosine and hypoxanthine. Thus, we suggest that harmane or other related beta-carbolines could be potential candidates as endogenous ligands of the benzodiazepine receptor.

  18. Environmental toxin acrolein alters levels of endogenous lipids, including TRP agonists: A potential mechanism for headache driven by TRPA1 activation

    Directory of Open Access Journals (Sweden)

    Emma Leishman

    2017-01-01

    Full Text Available Exposure to airborne toxins can trigger headaches, but the mechanisms are not well understood. Some environmental toxins, such as acrolein, activate transient receptor potential ankyrin 1 (TRPA1, a receptor involved in pain sensation that is highly expressed in the trigeminovascular system. It has been shown in rat models that repeated exposure to acrolein induces trigeminovascular sensitization to both TRPA1 and TRP vanilloid 1 (TRPV1 agonists, a phenomenon linked to headache. In this study, we test the hypothesis that the sensitization of trigeminovascular responses in rats after acrolein exposure via inhalation is associated with changes in levels of endogenous lipids, including TRPV1 agonists, in the trigeminal ganglia, trigeminal nucleus, and cerebellum. Lipidomics analysis of 80 lipids was performed on each tissue after acute acrolein, chronic acrolein, or room air control. Both acute and chronic acrolein exposure drove widespread alterations in lipid levels. After chronic acrolein exposure, levels of all 6 N-acyl ethanolamines in the screening library, including the endogenous cannabinoid and TRPV1 agonist, N-arachidonoyl ethanolamine, were elevated in trigeminal tissue and in the cerebellum. This increase in TRPV1 ligands by acrolein exposure may indicate further downstream signaling, in that we also show here that a combination of these TRPV1 endogenous agonists increases the potency of the individual ligands in TRPV1-HEK cells. In addition to these TRPV1 agonists, 3 TRPV3 antagonists, 4 TRPV4 agonists, and 25 orphan lipids were up and down regulated after acrolein exposure. These data support the hypothesis that lipid signaling may represent a mechanism by which repeated exposure to the TRPA1 agonist and environmental toxin, acrolein, drives trigeminovascular sensitization. Keywords: Lipidomics, Endogenous cannabinoid, TRPA1, TRPV1, Lipoamine, Acrolein, Migraine

  19. Endogenous Pyrogen Physiology.

    Science.gov (United States)

    Beisel, William R.

    1980-01-01

    Discusses the physiology of endogenous pyrogen (EP), the fever-producing factor of cellular origin. Included are: its hormone-like role, its molecular nature, bioassay procedures, cellular production and mechanisms of EP action. (SA)

  20. Effect of temperature on the floral scent emission and endogenous volatile profile of Petunia axillaris.

    Science.gov (United States)

    Sagae, Masanori; Oyama-Okubo, Naomi; Ando, Toshio; Marchesi, Eduardo; Nakayama, Masayoshi

    2008-01-01

    The floral scent emission and endogenous level of its components in Petunia axillaris under different conditions (20, 25, 30, and 35 degrees C) were investigated under the hypothesis that floral scent emission would be regulated by both metabolic and vaporization processes. The total endogenous amount of scent components decreased as the temperature increased, the total emission showing a peak at 30 degrees C. This decrease in endogenous amount was compensated for by increased vaporization, resulting in an increase of floral scent emission from 20 degrees C to 30 degrees C. The ambient temperature differently and independently influenced the metabolism and vaporization of the scent compounds, and differences in vapor pressure among the scent compounds were reduced as the temperature increased. These characteristics suggest the operation of an unknown regulator to change the vaporization of floral scent.

  1. Development and validation of a GC-C-IRMS method for the confirmation analysis of pseudo-endogenous glucocorticoids in doping control.

    Science.gov (United States)

    de la Torre, Xavier; Curcio, Davide; Colamonici, Cristiana; Molaioni, Francesco; Cilia, Marta; Botrè, Francesco

    2015-01-01

    Glucocorticoids are included in the S9 section of the World Anti-doping Agency (WADA) prohibited list international standard. Some among them are pseudo-endogenous steroids, like cortisol and cortisone, which present the same chemical structure as endogenously produced steroids. We are proposing an analytical method based on gas chromatography coupled to isotope ratio mass spectrometry (GC-C-IRMS) which allows discrimination between endogenous and synthetic origin of the urinary metabolites of the pseudo-endogenous glucocorticoids. A preliminary purification treatment by high-performance liquid chromatography (HPLC) of the target compounds (TC) (i.e., cortisol, tetrahydrocortisone (THE) 5α-tetrahydrocortisone (aTHE), tetrahydrocortisol (THF), and 5α-tetrahydrocortisol (aTHF)) allows collection of extracts with adequate purity for the subsequent analysis by IRMS. A population of 40 urine samples was analyzed for the TC and for the endogenous reference compounds (ERC: i.e., 11-desoxy-tetrahydrocortisol (THS) or pregnanediol). For each sample, the difference between the delta values of the ERCs and TCs (Δδ values) were calculated and based on that, some decision limits for atypical findings are proposed. The limits are below 3% units except for cortisol. The fit to purpose of the method has been confirmed by the analysis of urine samples collected in two patients under treatment with 25 mg of cortisone acetate (p.o). The samples showed Δδ values higher than 3 for at least 24 h following administration depending on the TC considered. The method can easily be integrated into existing procedures already used for the HPLC purification and IRMS analysis of pseudo-endogenous steroids with androgenic/anabolic activity. Copyright © 2015 John Wiley & Sons, Ltd.

  2. Endogenous hallucinogens as ligands of the trace amine receptors: a possible role in sensory perception.

    Science.gov (United States)

    Wallach, J V

    2009-01-01

    While the endogenous hallucinogens, N,N-dimethyltryptamine, 5-hydroxy-N,N-dimethyl-tryptamine and 5-methoxy-N,N-dimethyltryptamine, have been acknowledged as naturally occurring components of the mammalian body for decades, their biological function remains as elusive now as it was at the time of their discovery. The recent discovery of the trace amine associated receptors and the activity of DMT and other hallucinogenic compounds at these receptor sites leads to the hypothesis that the endogenous hallucinogens act as neurotransmitters of a subclass of these trace amine receptors. Additionally, while activity at the serotonin 5-HT2A receptor has been proposed as being responsible for the hallucinogenic affects of administered hallucinogens, in their natural setting the 5-HT2A receptor may not interact with the endogenous hallucinogens at all. Additionally 5-HT2A agonist activity is unable to account for the visual altering effects of many of the administered hallucinogens; these effects may be mediated by one of the endogenous hallucinogen trace amine receptors rather than the serotonin 5-HT2A receptor. Therefore, activity at the trace amine receptors, in addition to serotonin receptors, may play a large role in the sensory altering effects of administered hallucinogens and the trace amine receptors along with their endogenous hallucinogen ligands may serve an endogenous role in mediating sensory perception in the mammalian central nervous system. Thus the theory proposed states that these compounds act as true endogenous hallucinogenic transmitters acting in regions of the central nervous system involved in sensory perception.

  3. Are human endogenous retroviruses triggers of autoimmune diseases?

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  4. Are endogenous feline leukemia viruses really endogenous?

    Science.gov (United States)

    Stewart, H; Jarrett, O; Hosie, M J; Willett, B J

    2011-10-15

    Full length endogenous feline leukemia virus (FeLV) proviruses exist within the genomes of many breeds of domestic cat raising the possibility that they may also exist in a transmissible exogenous form. Such viruses would share receptor usage with the recombinant FeLV-B subgroup, a viral subgroup that arises in vivo by recombination between exogenous subgroup A virus (FeLV-A) and endogenous FeLV. Accordingly, all isolates of FeLV-B made to date have contained a "helper" FeLV-A, consistent with their recombinatorial origin. In order to assess whether endogenous viruses are transmitted between cats, we examined primary isolates of FeLV for which the viral subgroup had been determined for the presence of a subgroup B virus that lacked an FeLV-A. Here we describe the identification of two primary field isolates of FeLV (2518 and 4314) that appeared to contain subgroup B virus only by classical interference assays, raising the possibility of between-host transmission of endogenous FeLV. Sequencing of the env gene and U3 region of the 3' long terminal repeat (LTR) confirmed that both viral genomes contained endogenous viral env genes. However the viral 3' LTRs appeared exogenous in origin with a putative 3' recombination breakpoint residing at the 3' end of the env gene. Further, the FeLV-2518 virions also co-packaged a truncated FeLV-A genome containing a defective env gene, termed FeLV-2518(A) whilst no helper subgroup A viral genome was detected in virions of FeLV-4314. The acquisition of an exogenous LTR by the endogenous FeLV in 4314 may have allowed a recombinant FeLV variant to outgrow an exogenous FeLV-A virus that was presumably present during first infection. Given time, a similar evolution may also occur within the 2518 isolate. The data suggest that endogenous FeLVs may be mobilised by acquisition of exogenous LTRs yielding novel viruses that type biologically as FeLV-B. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Therapeutic targeting strategies using endogenous cells and proteins.

    Science.gov (United States)

    Parayath, Neha N; Amiji, Mansoor M

    2017-07-28

    Targeted drug delivery has become extremely important in enhancing efficacy and reducing the toxicity of therapeutics in the treatment of various disease conditions. Current approaches include passive targeting, which relies on naturally occurring differences between healthy and diseased tissues, and active targeting, which utilizes various ligands that can recognize targets expressed preferentially at the diseased site. Clinical translation of these mechanisms faces many challenges including the immunogenic and toxic effects of these non-natural systems. Thus, use of endogenous targeting systems is increasingly gaining momentum. This review is focused on strategies for employing endogenous moieties, which could serve as safe and efficient carriers for targeted drug delivery. The first part of the review involves cells and cellular components as endogenous carriers for therapeutics in multiple disease states, while the second part discusses the use of endogenous plasma components as endogenous carriers. Further understanding of the biological tropism with cells and proteins and the newer generation of delivery strategies that exploits these endogenous approaches promises to provide better solutions for site-specific delivery and could further facilitate clinical translations. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Effects of toxic compounds in Montipora capitata on exogenous and endogenous zooxanthellae performance and fertilization success.

    Directory of Open Access Journals (Sweden)

    Mary Hagedorn

    Full Text Available Studies have identified chemicals within the stony coral genus Montipora that have significant biological activities. For example, Montiporic acids A and B and other compounds have been isolated from the adult tissue and eggs of Montipora spp. and have displayed antimicrobial activity and cytotoxicity in cultured cells. The ecological role of these toxic compounds is currently unclear. This study examines the role these toxins play in reproduction. Toxins were found in the eggs and larvae of the coral Montipora capitata. Releasing these toxins by crushing both the eggs and larvae resulted in irreversible inhibition of photosynthesis in endogenous and exogenous zooxanthellae within minutes. Moreover, these toxins were stable, as frozen storage of eggs and larvae did not affect toxicity. Photosynthetic competency of Porites compressa zooxanthellae treated with either frozen or fresh, crushed eggs was inhibited similarly (P > 0.05, ANCOVA. Addition of toxic eggs plugs to live P. compressa fragments caused complete tissue necrosis under the exposed area on the fragments within 1 week. Small volumes of M. capitata crushed eggs added to sperm suspensions reduced in vitro fertilization success by killing the sperm. After 30 min, untreated sperm maintained 90 ± 1.9% SEM motility while those treated with crushed eggs were rendered immotile, 4 ± 1.4% SEM. Flow cytometry indicated membrane disruption of the immotile sperm. Fertilization success using untreated sperm was 79 ± 4% SEM, whereas the success rate dropped significantly after exposure to the crushed eggs, 1.3 ± 0% SEM. Unlike the eggs and the larvae, M. capitata sperm did not reduce the photosynthetic competency of P. compressa zooxanthellae, suggesting the sperm was nontoxic. The identity of the toxins, cellular mechanism of action, advantage of the toxins for M. capitata and their role on the reef are still unknown.

  7. Effects of toxic compounds in Montipora capitata on exogenous and endogenous zooxanthellae performance and fertilization success.

    Science.gov (United States)

    Hagedorn, Mary; Farrell, Ann; Carter, Virginia; Zuchowicz, Nikolas; Johnston, Erika; Padilla-Gamiño, Jacqueline; Gunasekera, Sarath; Paul, Valerie

    2015-01-01

    Studies have identified chemicals within the stony coral genus Montipora that have significant biological activities. For example, Montiporic acids A and B and other compounds have been isolated from the adult tissue and eggs of Montipora spp. and have displayed antimicrobial activity and cytotoxicity in cultured cells. The ecological role of these toxic compounds is currently unclear. This study examines the role these toxins play in reproduction. Toxins were found in the eggs and larvae of the coral Montipora capitata. Releasing these toxins by crushing both the eggs and larvae resulted in irreversible inhibition of photosynthesis in endogenous and exogenous zooxanthellae within minutes. Moreover, these toxins were stable, as frozen storage of eggs and larvae did not affect toxicity. Photosynthetic competency of Porites compressa zooxanthellae treated with either frozen or fresh, crushed eggs was inhibited similarly (P > 0.05, ANCOVA). Addition of toxic eggs plugs to live P. compressa fragments caused complete tissue necrosis under the exposed area on the fragments within 1 week. Small volumes of M. capitata crushed eggs added to sperm suspensions reduced in vitro fertilization success by killing the sperm. After 30 min, untreated sperm maintained 90 ± 1.9% SEM motility while those treated with crushed eggs were rendered immotile, 4 ± 1.4% SEM. Flow cytometry indicated membrane disruption of the immotile sperm. Fertilization success using untreated sperm was 79 ± 4% SEM, whereas the success rate dropped significantly after exposure to the crushed eggs, 1.3 ± 0% SEM. Unlike the eggs and the larvae, M. capitata sperm did not reduce the photosynthetic competency of P. compressa zooxanthellae, suggesting the sperm was nontoxic. The identity of the toxins, cellular mechanism of action, advantage of the toxins for M. capitata and their role on the reef are still unknown.

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

    OpenAIRE

    Cozzi, Guido

    2017-01-01

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

  9. Endogenous mitigation of H2S inside of the landfills.

    Science.gov (United States)

    Fang, Yuan; Zhong, Zhong; Shen, Dongsheng; Du, Yao; Xu, Jing; Long, Yuyang

    2016-02-01

    Vast quantities of hydrogen sulfide (H2S) emitted from landfill sites require urgent disposal. The current study focused on source control and examined the migration and conversion behavior of sulfur compounds in two lab-scale simulated landfills with different operation modes. It aimed to explore the possible strategies and mechanisms for H2S endogenous mitigation inside of landfills during decomposition. It was found that the strength of H2S emissions from the landfill sites was dependent on the municipal solid waste (MSW) degradation speed and vertical distribution of sulfide. Leachate recirculation can shorten both the H2S influence period and pollution risk to the surrounding environment. H2S endogenous mitigation may be achieved by chemical oxidation, biological oxidation, adsorption, and/or precipitation in different stages. Migration and conversion mainly affected H2S release behavior during the initial stabilization phase in the landfill. Microbial activities related to sulfur, nitrogen, and iron can further promote H2S endogenous mitigation during the high reducing phase. Thus, H2S endogenous mitigation can be effectively enhanced via control of the aforementioned processes.

  10. Factors that influence the volatile organic compound content in human breath

    NARCIS (Netherlands)

    Blanchet, L.; Smolinska, Agnieszka; Baranska, Agnieszka; Tigchelaar-Feenstra, E.; Swertz, M.; Zhernakova, A.; Dallinga, J. W.; Wijmenga, C.; van Schooten, Frederik J.

    Background. Thousands of endogenous and exogenous volatile organic compounds (VOCs) are excreted in each breath. Inflammatory and deviant metabolic processes affect the level of endogeneous VOCs, which can serve as specific biomarkers for clinical diagnosis and disease monitoring. Important issues

  11. On the role of endogenous serotin in the radioprotective action of some aminothiols

    International Nuclear Information System (INIS)

    Sverdlov, A.G.; Pavlova, L.M.

    1977-01-01

    It has been studied whether there is a correlation of the radioprotective effect of cystamine (50 and 150 mg/kg by base) and its analogue, N',N'-tetramethyl cystamine (130 mg/kg by base), with the ability of these compounds to rise the endogenous serotonin content of radiosensitive organs 20 and 60 minutes after intraperitoneal administration to mice. The ability of sulphur-containing radioprotectors does not necessarily correlate with their preventive properties: an ineffective radioprotector analogue, N',N'-tetramethyl cystamine, has the same effect on the endogeneous serotonin level as the protector itself

  12. Induction of conidiation by endogenous volatile compounds in Trichoderma spp.

    Science.gov (United States)

    Nemcovic, Marek; Jakubíková, Lucia; Víden, Ivan; Farkas, Vladimír

    2008-07-01

    Light and starvation are two principal environmental stimuli inducing conidiation in the soil micromycete Trichoderma spp. We observed that volatiles produced by conidiating colonies of Trichoderma spp. elicited conidiation in colonies that had not been induced previously by exposure to light. The inducing effect of volatiles was both intra- and interspecific. Chemical profiles of the volatile organic compounds (VOCs) produced by the nonconidiated colonies grown in the dark and by the conidiating colonies were compared using solid-phase microextraction of headspace samples followed by tandem GC-MS. The conidiation was accompanied by increased production of eight-carbon compounds 1-octen-3-ol and its analogs 3-octanol and 3-octanone. When vapors of these compounds were applied individually to dark-grown colonies, they elicited their conidiation already at submicromolar concentrations. It is concluded that the eight-carbon VOCs act as signaling molecules regulating development and mediating intercolony communication in Trichoderma.

  13. Contagion risk in endogenous financial networks

    International Nuclear Information System (INIS)

    Li, Shouwei; Sui, Xin

    2016-01-01

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

  14. Degradation of exogenous caffeine by Populus alba and its effects on endogenous caffeine metabolism.

    Science.gov (United States)

    Pierattini, Erika C; Francini, Alessandra; Raffaelli, Andrea; Sebastiani, Luca

    2016-04-01

    This is the first study reporting the presence of endogenous caffeine, theobromine, and theophylline in all organs of poplar plants. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was used in order to evaluate the uptake, translocation, and metabolism of caffeine-(trimethyl-(13)C) in Populus alba L. Villafranca clone grown in hydroponic conditions. We investigated the remediation of caffeine since it is one of the most widely consumed drugs and it is frequently detected in wastewater treatment plant effluents, surface water, and groundwater worldwide. Our results demonstrated that poplar can absorb and degrade exogenous caffeine without negative effects on plant health. Data showed that concentrations of all endogenous compounds varied depending on caffeine-(trimethyl-(13)C) treatments. In particular, in control conditions, endogenous caffeine, theobromine, and theophylline were mainly distributed in roots. On the other hand, once caffeine-(trimethyl-(13)C) was provided, this compound and its dimethy-(13)C metabolites are mainly localized at leaf level. In conclusion, our results support the possible use of Villafranca clone in association with other water treatment systems in order to complete the process of caffeine remediation.

  15. "The Lower Threshold" phenomenon in tumor cells toward endogenous digitalis-like compounds: Responsible for tumorigenesis?

    Directory of Open Access Journals (Sweden)

    Heidrun Weidemann

    2012-01-01

    Full Text Available Since their first discovery as potential anti-cancer drugs decades ago, there is increasing evidence that digitalis-like compounds (DLC have anti-tumor effects. Less is known about endogenous DLC (EDLC metabolism and regulation. As stress hormones synthesized in and secreted from the adrenal gland, they likely take part in the hypothalamo-pituitary-adrenal (HPA axis. In a previous study, we revealed reduced EDLC concentrations in plasma and organs from immune-compromised animals and proposed that a similar situation of a deregulated HPA axis with "adrenal EDLF exhaustion" may contribute to tumorigenesis in chronic stress situations. Here, we put forward the hypothesis that a lowered EDLC response threshold of tumor cells as compared with normal cells increases the risk of tumorigenesis, especially in those individuals with reduced EDLC plasma concentrations after chronic stress exposure. We will evaluate this hypothesis by (a summarizing the effects of different DLC concentrations on tumor as compared with normal cells and (b reviewing some essential differences in the Na/K-ATPase of tumor as compared with normal cells (isoform pattern, pump activity, mutations of other signalosome receptors. We will conclude that (1 tumor cells, indeed, seem to have their individual "physiologic" EDLC response range that already starts at pmolar levels and (2 that individuals with markedly reduced (pmolar EDLC plasma levels are predisposed to cancer because these EDLC concentrations will predominantly stimulate the proliferation of tumor cells. Finally, we will summarize preliminary results from our department supporting this hypothesis.

  16. Endogenous fertility and development traps with endogenous lifetime

    OpenAIRE

    Fanti, Luciano; Gori, Luca

    2010-01-01

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

  17. Further comparisons of endogenous pyrogens and leukocytic endogenous mediators.

    Science.gov (United States)

    Kampschmidt, R F; Upchurch, H F; Worthington, M L

    1983-07-01

    It was recently shown (Murphy et al., Infect. Immun. 34:177-183), that rabbit macrophages produce two biochemically and immunologically distinct endogenous pyrogens. One of these has or copurifies with substances having a molecular weight of 13,000 and a pI of 7.3. This protein was produced by blood monocytes or inflammatory cells elicited in 16-h rabbit peritoneal exudates. These acute peritoneal exudates were produced by the intraperitoneal injection of large volumes of saline containing shellfish glycogen. When the leukocytes in these exudates were washed and incubated at 37 degrees C in saline, they released an endogenous pyrogen. The injection of this pyrogen into rabbits, rats, or mice caused the biological manifestations which have been attributed to leukocytic endogenous mediator. These effects were increases in blood neutrophils, the lowering of plasma iron and zinc levels, and the increased synthesis of the acute-phase proteins. The other rabbit endogenous pyrogen seems to be a family of proteins with isoelectric points between 4.5 and 5.0. These proteins are produced by macrophages in the lung, liver, or in chronic peritoneal exudates. In these experiments, the lower-isoelectric-point endogenous pyrogens were produced by macrophages from the peritoneal cavity of rabbits that had been injected 4 days earlier with 50 ml of light mineral oil. These rabbit pyrogens were found to have leukocytic endogenous mediator activity in mice but to be completely inactive in rats. When injected into rabbits, these proteins produced fever, lowered plasma iron, increased blood neutrophils, but failed to elevate plasma fibrinogen.

  18. [The endogenous opioid system and drug addiction].

    Science.gov (United States)

    Maldonado, R

    2010-01-01

    Drug addiction is a chronic brain disorder leading to complex adaptive changes within the brain reward circuits. Several neurotransmitters, including the endogenous opioid system are involved in these changes. The opioid system plays a pivotal role in different aspects of addiction. Thus, opioid receptors and endogenous opioid peptides are largely distributed in the mesolimbic system and modulate dopaminergic activity within the reward circuits. Opioid receptors and peptides are selectively involved in several components of the addictive processes induced by opioids, cannabinoids, psychostimulants, alcohol and nicotine. This review is focused on the contribution of each component of the endogenous opioid system in the addictive properties of the different drugs of abuse. Copyright 2010 Elsevier Masson SAS. All rights reserved.

  19. Role of Endogenous and Exogenous Tocopherols in the Lipid Stability of Marine Oil Systems: A Review

    Directory of Open Access Journals (Sweden)

    Guadalupe Miroslava Suárez-Jiménez

    2016-11-01

    Full Text Available In marine organisms primarily intended for human consumption, the quality of the muscle and the extracted oils may be affected by lipid oxidation during storage, even at low temperatures. This has led to a search for alternatives to maintain quality. In this sense, antioxidant compounds have been used to prevent such lipid deterioration. Among the most used compounds are tocopherols, which, due to their natural origin, have become an excellent alternative to prevent or retard lipid oxidation and maintain the quality of marine products. Tocopherols as antioxidants have been studied both exogenously and endogenously. Exogenous tocopherols are often used by incorporating them into plastic packaging films or adding them directly to fish oil. It has been observed that exogenous tocopherols incorporated in low concentrations maintain the quality of both muscle and the extracted oils during food storage. However, it has been reported that tocopherols applied at higher concentrations act as a prooxidant molecule, probably because their reactions with singlet oxygen may generate free radicals and cause the oxidation of polyunsaturated fatty acids in fish oils. However, when tocopherols are included in a fish diet (endogenous tocopherols, the antioxidant effect on the muscle lipids is more effective due to their incorporation into the membrane lipids, which can help extend the shelf life of seafood by reducing the lipid deterioration that occurs due to antioxidant synergy with other phenolic compounds used supplements in fish muscle. This review focuses on the most important studies in this field and highlights the potential of using tocopherols as antioxidants in marine oils.

  20. Role of Endogenous and Exogenous Tocopherols in the Lipid Stability of Marine Oil Systems: A Review

    Science.gov (United States)

    Suárez-Jiménez, Guadalupe Miroslava; López-Saiz, Carmen María; Ramírez-Guerra, Hugo Enrique; Ezquerra-Brauer, Josafat Marina; Ruiz-Cruz, Saul; Torres-Arreola, Wilfrido

    2016-01-01

    In marine organisms primarily intended for human consumption, the quality of the muscle and the extracted oils may be affected by lipid oxidation during storage, even at low temperatures. This has led to a search for alternatives to maintain quality. In this sense, antioxidant compounds have been used to prevent such lipid deterioration. Among the most used compounds are tocopherols, which, due to their natural origin, have become an excellent alternative to prevent or retard lipid oxidation and maintain the quality of marine products. Tocopherols as antioxidants have been studied both exogenously and endogenously. Exogenous tocopherols are often used by incorporating them into plastic packaging films or adding them directly to fish oil. It has been observed that exogenous tocopherols incorporated in low concentrations maintain the quality of both muscle and the extracted oils during food storage. However, it has been reported that tocopherols applied at higher concentrations act as a prooxidant molecule, probably because their reactions with singlet oxygen may generate free radicals and cause the oxidation of polyunsaturated fatty acids in fish oils. However, when tocopherols are included in a fish diet (endogenous tocopherols), the antioxidant effect on the muscle lipids is more effective due to their incorporation into the membrane lipids, which can help extend the shelf life of seafood by reducing the lipid deterioration that occurs due to antioxidant synergy with other phenolic compounds used supplements in fish muscle. This review focuses on the most important studies in this field and highlights the potential of using tocopherols as antioxidants in marine oils. PMID:27886145

  1. Endogenous Lunar Volatiles

    Science.gov (United States)

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

    2018-04-01

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

  2. Effects of Methyl Jasmonate on the Composition of Volatile Compounds in Pyropia yezoensis

    Science.gov (United States)

    He, Lihong; Wang, Liang; Wang, Linfang; Shen, Songdong

    2018-04-01

    Volatile organic compounds in marine algae have been reported to comprise characteristic flavor of algae and play an important role in their growth, development and defensive response. Yet their biogeneration remain largely unknown. Here we studied the composition of volatile compouds in Pyropia yezoensis and their variations in response to methyl jasmonate (MeJA) and diethyldithiocarbamic acid (DIECA) treatment using gas chromatography-mass spectrometry (GC-MS). A total of 44 compounds belonging to the following chemical classes (n) were identified, including aldehydes (11), alcohols (8), acids and esters (6), alkanes (5), ketones (5), alkenes (3), and S- or N-containing miscellaneous compounds (6). External treatment with plant hormone MeJA increased the content of 1-dodecanol, 4-heptenal, and 2-propenoic acid-2-methyl dodecylester, but decreased the content of phytol, 3-heptadecene, 2-pentadecanone, and isophytol. When pretreated with DIECA, an inhibitor of the octadecanoid pathway leading to the biosynthesis of endogeneous jasmonates and some secondary metabolites, phytol and isophytol were increased, while 4-heptenal, 1-dodecanol, and 2-propenoic acid-2-methyl dodecylester were decreased, both of which were negatively correlated with their variations under MeJA treatment. Collectively, these results suggest that MeJA does affect the volatile composition of P. yezoensis, and the octadecanoid pathway together with endogenous jasmonate pathway may be involved in the biosynthesis of volatile compounds, thereby providing some preliminary envision on the composition and biogeneration of volatile compounds in P. yezoensis.

  3. Endogenous Digitalis-like Factors: An Overview of the History

    Directory of Open Access Journals (Sweden)

    Vardaman eBuckalew

    2015-04-01

    Full Text Available The sodium pump is a ubiquitous cell surface enzyme, a Na, K ATPase, which maintains ion gradients between cells and the extracellular fluid (ECF. The extracellular domain of this enzyme contains a highly conserved binding site, a receptor for a plant derived family of compounds, the digitalis glycosides. These compounds inhibit the enzyme and are used in the treatment of congestive heart failure, and certain cardiac arrhythmias. The highly conserved nature of this enzyme and its digitalis receptor led to early suggestions that endogenous regulators might exist. Recent examination of this hypothesis emerged from research in two separate areas: the regulation of ECF volume by a natriuretic hormone (NH, and the regulation of peripheral vascular resistance by a circulating inhibitor of vascular Na, K ATPase. These two areas merged with the hypothesis that NH and the vascular Na, K ATPase inhibitor were in fact the same entity, and that it played a causative role in the pathophysiology of certain types of hypertension. The possibility that multiple endogenous digitalis-like factors (EDLFs exist emerged from efforts to characterize the circulating enzyme inhibitory activity. In this review, the development of this field from its beginnings is traced, the current status of the structure of EDLFs is briefly discussed, and areas for future development are suggested. Key Words: natriuretic hormone, digitalis-like factor, hypertension, Na, K ATPase, ouabain, marinobufagenin, bufodienolides, cardenolides

  4. The epigenetic alterations of endogenous retroelements in aging.

    Science.gov (United States)

    Cardelli, Maurizio

    2018-02-16

    Endogenous retroelements, transposons that mobilize through RNA intermediates, include some of the most abundant repetitive sequences of the human genome, such as Alu and LINE-1 sequences, and human endogenous retroviruses. Recent discoveries demonstrate that these mobile genetic elements not only act as intragenomic parasites, but also exert regulatory roles in living cells. The risk of genomic instability represented by endogenous retroelements is normally counteracted by a series of epigenetic control mechanisms which include, among the most important, CpG DNA methylation. Indeed, most of the genomic CpG sites subjected to DNA methylation in the nuclear DNA are carried by these repetitive elements. As other parts of the genome, endogenous retroelements and other transposable elements are subjected to deep epigenetic alterations during aging, repeatedly observed in the context of organismal and cellular senescence, in human and other species. This review summarizes the current status of knowledge about the epigenetic alterations occurring in this large, non-genic portion of the genome in aging and age-related conditions, with a focus on the causes and the possible functional consequences of these alterations. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Endogenous opiates and behavior: 2014.

    Science.gov (United States)

    Bodnar, Richard J

    2016-01-01

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

  6. The Endogenous Exposome

    Science.gov (United States)

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

    2014-01-01

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

  7. Production of endogenous pyrogen.

    Science.gov (United States)

    Dinarello, C A

    1979-01-01

    The production and release of endogenous pyrogen by the host is the first step in the pathogenesis of fever. Endogenous pyrogen is a low-molecular-weight protein released from phagocytic leukocytes in response to several substances of diverse nature. Some of these agents stimulate production of endogenous pyrogen because they are toxic; others act as antigens and interact with either antibody or sensitized lymphocytes in order to induce its production. Some tumors of macrophage origin produce the molecule spontaneously. Whatever the mechanism involved, endogenous pyrogen is synthesized following transcription of new DNA and translation of mRNA into new protein. Once synthesis is completed, the molecule is released without significant intracellular storage. Recent evidence suggests that following release, molecular aggregates form which are biologically active. In its monomer form, endogenous pyrogen is a potent fever-producing substance and mediates fever by its action on the thermoregulatory center.

  8. Endogenous antispermatogenic agents: prospects for male contraception.

    Science.gov (United States)

    Ewing, L L; Robaire, B

    1978-01-01

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

  9. In situ tissue regeneration: chemoattractants for endogenous stem cell recruitment.

    Science.gov (United States)

    Vanden Berg-Foels, Wendy S

    2014-02-01

    Tissue engineering uses cells, signaling molecules, and/or biomaterials to regenerate injured or diseased tissues. Ex vivo expanded mesenchymal stem cells (MSC) have long been a cornerstone of regeneration therapies; however, drawbacks that include altered signaling responses and reduced homing capacity have prompted investigation of regeneration based on endogenous MSC recruitment. Recent successful proof-of-concept studies have further motivated endogenous MSC recruitment-based approaches. Stem cell migration is required for morphogenesis and organogenesis during development and for tissue maintenance and injury repair in adults. A biomimetic approach to in situ tissue regeneration by endogenous MSC requires the orchestration of three main stages: MSC recruitment, MSC differentiation, and neotissue maturation. The first stage must result in recruitment of a sufficient number of MSC, capable of effecting regeneration, to the injured or diseased tissue. One of the challenges for engineering endogenous MSC recruitment is the selection of effective chemoattractant(s). The objective of this review is to synthesize and evaluate evidence of recruitment efficacy by reported chemoattractants, including growth factors, chemokines, and other more recently appreciated MSC chemoattractants. The influence of MSC tissue sources, cell culture methods, and the in vitro and in vivo environments is discussed. This growing body of knowledge will serve as a basis for the rational design of regenerative therapies based on endogenous MSC recruitment. Successful endogenous MSC recruitment is the first step of successful tissue regeneration.

  10. Comparative study of 5-fluorouracil and its derivative, N1-(2'-tetrahydrofuryl)-5-fluorouracil on endogenous colony forming units in spleens of mice

    International Nuclear Information System (INIS)

    Ueno, Yori

    1976-01-01

    The effect of intraperitoneal injection of N 1 -(2'-tetrahydrofuryl)-5-fluorouracil (FT-207) which is metabolized to 5-fluorouracil (5-FU) in vivo, on endogeneous colony forming units in the spleen (endogeneous CFU-s) was observed and compared with that of 5-FU. The 8 x 10 -4 m eqv of FT-207 injected in mice 20 minutes before x-rays irradiation of 450 rads suppressed the endogeneous CFU-s count to about 60% and about 5.5 x 10 -5 m eqv of 5-FU had the same effect. The suppression of FT-207 continued over 120 minutes and increased gradually. The effect of 5-FU was strong shortly after the injection but faded out for 120 minutes. FT-207 had almost no effect on the recovery constant (Blair) of endogeneous CFU-s for 3 days, whereas 5-FU reduced seriously, especially for the first 2 days. The differences in the effects of both compounds could not be explained on the base of the only differences in the metabolism of both compounds. (auth.)

  11. Biopsychosocial Factors Associated with Prurigo Nodularis in Endogenous Eczema.

    Science.gov (United States)

    Oh, Choon Chiat; Li, Huihua; Lee, Wellington; Tey, Hong Liang

    2015-01-01

    Prurigo nodularis is a dermatological manifestation secondary to chronic scratching or picking on focal areas of the skin. Its pathogenesis remains poorly understood, and limited data has indicated its association with psychological factors. To determine the biological, psychological and social factors associated with the occurrence of prurigo nodularis in patients with underlying endogenous eczema. A prospective case-control questionnaire -based study on patients with endogenous eczema, with and without prurigo nodules, was performed. The Impact of Skin Disease on Daily Life questionnaire was used to assess dimensions of physical functioning, including extent and severity of skin disease, itch, pain, fatigue and scratching, as well as dimensions of psychological and social functioning, including mood, illness cognition, disease-related impact, stigmatization and social support. Thirty-six cases and 47 controls were recruited. Patients with endogenous eczema and prurigo nodules indicated a higher itch score on the visual analog scale over the previous 4 weeks compared to those without prurigo nodules (p=0.0292). There were no significant differences between the 2 groups in the scores reflecting the other parameters of physical, psychological and social functioning. In patients with endogenous eczema, those with prurigo nodules experience a greater itch intensity compared to those without prurigo nodules. There were no other physical, psychological and social factors that were found to be associated with the occurrence of prurigo nodules in endogenous eczema.

  12. Stimulating endogenous cardiac regeneration

    Directory of Open Access Journals (Sweden)

    Amanda eFinan

    2015-09-01

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

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

    OpenAIRE

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

    2007-01-01

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

  14. Dietary N-nitroso compounds, endogenous nitrosation, and the risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study.

    Science.gov (United States)

    Keszei, András P; Goldbohm, R Alexandra; Schouten, Leo J; Jakszyn, Paula; van den Brandt, Piet A

    2013-01-01

    Dietary N-nitroso compounds and endogenous nitrosation are important carcinogenic factors, but human evidence of their role is scarce for esophageal cancer and inconsistent for gastric cancer. We studied the relation between risks of esophageal and gastric cancer subtypes and dietary intake of N-nitrosodimethylamine, heme iron, nitrite, and nitrate in the Netherlands Cohort Study. A total of 120,852 men and women aged 55-69 y were recruited in 1986, and diet, based on a 150-item food-frequency questionnaire, and other risk factors were assessed. The cohort was followed for 16.3 y, and 110 esophageal squamous cell carcinoma (ESCC), 151 esophageal adenocarcinoma, 166 gastric cardia adenocarcinoma, and 497 gastric noncardia adenocarcinoma (GNCA) cases were analyzed along with 4032 subcohort members in a case-cohort analysis. Positive associations were observed between N-nitrosodimethylamine intake and ESCC risk (HR for 0.1-μg/d increase in intake: 1.15; 95% CI: 1.05, 1.25; P-trend = 0.01 based on tertiles of intake) and GNCA risk (1.06; 95% CI: 1.01, 1.10; P-trend = 0.09) in men. ESCC risk was associated with nitrite intake (HR for 0.1-mg/d increase: 1.19; 95% CI: 1.05, 1.36; P-trend = 0.06) and heme-iron intake (HR for 1-mg/d increase: 1.83; 95% CI: 0.98, 3.39; P-trend = 0.03). Among women, exposure levels were lower, and we found no convincing positive associations. These results suggest that N-nitroso compounds may influence the risk of ESCC in men, but there are no clear associations for other esophageal and gastric subtypes.

  15. Tissue-specific tagging of endogenous loci in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Kate Koles

    2016-01-01

    Full Text Available Fluorescent protein tags have revolutionized cell and developmental biology, and in combination with binary expression systems they enable diverse tissue-specific studies of protein function. However these binary expression systems often do not recapitulate endogenous protein expression levels, localization, binding partners and/or developmental windows of gene expression. To address these limitations, we have developed a method called T-STEP (tissue-specific tagging of endogenous proteins that allows endogenous loci to be tagged in a tissue specific manner. T-STEP uses a combination of efficient CRISPR/Cas9-enhanced gene targeting and tissue-specific recombinase-mediated tag swapping to temporally and spatially label endogenous proteins. We have employed this method to GFP tag OCRL (a phosphoinositide-5-phosphatase in the endocytic pathway and Vps35 (a Parkinson's disease-implicated component of the endosomal retromer complex in diverse Drosophila tissues including neurons, glia, muscles and hemocytes. Selective tagging of endogenous proteins allows, for the first time, cell type-specific live imaging and proteomics in complex tissues.

  16. Endogenous Prospect Theory

    OpenAIRE

    Schmidt, Ulrich; Zank, Horst

    2010-01-01

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

  17. Isobutanol production in Synechocystis PCC 6803 using heterologous and endogenous alcohol dehydrogenases

    Directory of Open Access Journals (Sweden)

    Rui Miao

    2017-12-01

    Full Text Available Isobutanol is a flammable compound that can be used as a biofuel due to its high energy density and suitable physical and chemical properties. In this study, we examined the capacity of engineered strains of Synechocystis PCC 6803 containing the α-ketoisovalerate decarboxylase from Lactococcus lactis and different heterologous and endogenous alcohol dehydrogenases (ADH for isobutanol production. A strain expressing an introduced kivd without any additional copy of ADH produced 3 mg L−1 OD750−1 isobutanol in 6 days. After the cultures were supplemented with external addition of isobutyraldehyde, the substrate for ADH, 60.8 mg L−1 isobutanol was produced after 24 h when OD750 was 0.8. The in vivo activities of four different ADHs, two heterologous and two putative endogenous in Synechocystis, were examined and the Synechocystis endogenous ADH encoded by slr1192 showed the highest efficiency for isobutanol production. Furthermore, the strain overexpressing the isobutanol pathway on a self-replicating vector with the strong Ptrc promoter showed significantly higher gene expression and isobutanol production compared to the corresponding strains expressing the same operon introduced on the genome. Hence, this study demonstrates that Synechocystis endogenous AHDs have a high capacity for isobutanol production, and identifies kivd encoded α-ketoisovalerate decarboxylase as one of the likely bottlenecks for further isobutanol production.

  18. Fanconi anemia proteins and endogenous stresses

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-07-31

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

  19. Fanconi anemia proteins and endogenous stresses

    International Nuclear Information System (INIS)

    Pang Qishen; Andreassen, Paul R.

    2009-01-01

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

  20. Endogenous viral elements in animal genomes.

    Directory of Open Access Journals (Sweden)

    Aris Katzourakis

    2010-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Laura eFont

    2013-07-01

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

  2. Novel endogenous angiogenesis inhibitors and their therapeutic potential.

    Science.gov (United States)

    Rao, Nithya; Lee, Yu Fei; Ge, Ruowen

    2015-10-01

    Angiogenesis, the formation of new blood vessels from the pre-existing vasculature is essential for embryonic development and tissue homeostasis. It also plays critical roles in diseases such as cancer and retinopathy. A delicate balance between pro- and anti-angiogenic factors ensures normal physiological homeostasis. Endogenous angiogenesis inhibitors are proteins or protein fragments that are formed in the body and have the ability to limit angiogenesis. Many endogenous angiogenesis inhibitors have been discovered, and the list continues to grow. Endogenous protein/peptide inhibitors are relatively less toxic, better tolerated and have a lower risk of drug resistance, which makes them attractive as drug candidates. In this review, we highlight ten novel endogenous protein angiogenesis inhibitors discovered within the last five years, including ISM1, FKBPL, CHIP, ARHGAP18, MMRN2, SOCS3, TAp73, ZNF24, GPR56 and JWA. Although some of these proteins have been well characterized for other biological functions, we focus on their new and specific roles in angiogenesis inhibition and discuss their potential for therapeutic application.

  3. Endogenous network of firms and systemic risk

    Science.gov (United States)

    Ma, Qianting; He, Jianmin; Li, Shouwei

    2018-02-01

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

  4. On the origins of endogenous thoughts.

    Science.gov (United States)

    Tillas, Alexandros

    2017-05-01

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

  5. Dynamic equilibrium of endogenous selenium nanoparticles in selenite-exposed cancer cells: a deep insight into the interaction between endogenous SeNPs and proteins.

    Science.gov (United States)

    Bao, Peng; Chen, Song-Can; Xiao, Ke-Qing

    2015-12-01

    Elemental selenium (Se) was recently found to exist as endogenous nanoparticles (i.e., SeNPs) in selenite-exposed cancer cells. By sequestrating critical intracellular proteins, SeNPs appear capable of giving rise to multiple cytotoxicity mechanisms including inhibition of glycolysis, glycolysis-dependent mitochondrial dysfunction, microtubule depolymerization and inhibition of autophagy. In this work, we reveal a dynamic equilibrium of endogenous SeNP assembly and disassembly in selenite-exposed H157 cells. Endogenous SeNPs are observed both in the cytoplasm and in organelles. There is an increase in endogenous SeNPs between 24 h and 36 h, and a decrease between 36 h and 72 h according to transmission electron microscopy results and UV-Vis measurements. These observations imply that elemental Se in SeNPs could be oxidized back into selenite by scavenging superoxide radicals and ultimately re-reduced into selenide; then the assembly and disassembly of SeNPs proceed simultaneously with the sequestration and release of SeNP high-affinity proteins. There is also a possibility that the reduction of elemental Se to selenide pathway may lie in selenite-exposed cancer cells, which results in the assembly and disassembly of endogenous SeNPs. Genome-wide expression analysis results show that endogenous SeNPs significantly altered the expression of 504 genes, compared to the control. The endogenous SeNPs induced mitochondrial impairment and decreasing of the annexin A2 level can lead to inhibition of cancer cell invasion and migration. This dynamic flux of endogenous SeNPs amplifies their cytotoxic potential in cancer cells, thus provide a starting point to design more efficient intracellular self-assembling systems for overcoming multidrug resistance.

  6. Habits, aspirations and endogenous fertility

    OpenAIRE

    Luciano Fanti

    2012-01-01

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

  7. Gamma-hydroxybutyric acid endogenous production and post-mortem behaviour - the importance of different biological matrices, cut-off reference values, sample collection and storage conditions.

    Science.gov (United States)

    Castro, André L; Dias, Mário; Reis, Flávio; Teixeira, Helena M

    2014-10-01

    Gamma-Hydroxybutyric Acid (GHB) is an endogenous compound with a story of clinical use, since the 1960's. However, due to its secondary effects, it has become a controlled substance, entering the illicit market for recreational and "dance club scene" use, muscle enhancement purposes and drug-facilitated sexual assaults. Its endogenous context can bring some difficulties when interpreting, in a forensic context, the analytical values achieved in biological samples. This manuscript reviewed several crucial aspects related to GHB forensic toxicology evaluation, such as its post-mortem behaviour in biological samples; endogenous production values, whether in in vivo and in post-mortem samples; sampling and storage conditions (including stability tests); and cut-off reference values evaluation for different biological samples, such as whole blood, plasma, serum, urine, saliva, bile, vitreous humour and hair. This revision highlights the need of specific sampling care, storage conditions, and cut-off reference values interpretation in different biological samples, essential for proper practical application in forensic toxicology. Copyright © 2014 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  8. Host-virus interactions of mammalian endogenous retroviruses

    OpenAIRE

    Farkašová, Helena

    2017-01-01

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

  9. Endogenous Monetary Policy Regime Change

    OpenAIRE

    Troy Davig; Eric M. Leeper

    2006-01-01

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

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

    Science.gov (United States)

    Arjan-Odedra, Shetal; Swanson, Chad M; Sherer, Nathan M; Wolinsky, Steven M; Malim, Michael H

    2012-06-22

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

  11. Chemical Atherogenesis: Role of Endogenous and Exogenous Poisons in Disease Development

    Directory of Open Access Journals (Sweden)

    Matthew K. Ross

    2014-01-01

    Full Text Available Chemical atherogenesis is an emerging field that describes how environmental pollutants and endogenous toxins perturb critical pathways that regulate lipid metabolism and inflammation, thus injuring cells found within the vessel wall. Despite growing awareness of the role of environmental pollutants in the development of cardiovascular disease, the field of chemical atherogenesis can broadly include both exogenous and endogenous poisons and the study of molecular, biochemical, and cellular pathways that become dysregulated during atherosclerosis. This integrated approach is logical because exogenous and endogenous toxins often share the same mechanism of toxicity. Chemical atherogenesis is a truly integrative discipline because it incorporates concepts from several different fields, including biochemistry, chemical biology, pharmacology, and toxicology. This review will provide an overview of this emerging research area, focusing on cellular and animal models of disease.

  12. Chemical Atherogenesis: Role of Endogenous and Exogenous Poisons in Disease Development.

    Science.gov (United States)

    Ross, Matthew K; Matthews, Anberitha T; Mangum, Lee C

    Chemical atherogenesis is an emerging field that describes how environmental pollutants and endogenous toxins perturb critical pathways that regulate lipid metabolism and inflammation, thus injuring cells found within the vessel wall. Despite growing awareness of the role of environmental pollutants in the development of cardiovascular disease, the field of chemical atherogenesis can broadly include both exogenous and endogenous poisons and the study of molecular, biochemical, and cellular pathways that become dysregulated during atherosclerosis. This integrated approach is logical because exogenous and endogenous toxins often share the same mechanism of toxicity. Chemical atherogenesis is a truly integrative discipline because it incorporates concepts from several different fields, including biochemistry, chemical biology, pharmacology, and toxicology. This review will provide an overview of this emerging research area, focusing on cellular and animal models of disease.

  13. Staphylococcal endogenous endophthalmitis in association with pyogenic vertebral osteomyelitis.

    Science.gov (United States)

    Steeples, L R; Jones, N P

    2016-01-01

    PURPOSE To describe pyogenic vertebral osteomyelitis as a rare infection associated with endogenous endophthalmitis.METHODS A retrospective review of three patients with endogenous endophthalmitis and sepsis due to underlying Staphylococcal vertebral osteomyelitis presenting during a 21-month time period. The ophthalmic and systemic features and management and outcomes are presented.RESULTS One patient developed unilateral endophthalmitis with cervical spine osteomyelitis, Staphylococcus aureus being isolated from blood cultures. The second presented with bilateral endophthalmitis with disseminated Methicillin-resistant S. aureus (MRSA) infection, with thoracic and lumbar discitis and para-spinal abscesses. MRSA was cultured from vitreous, blood, and synovial fluid. Both patients received prolonged courses of intravenous antibiotics. Intravitreal antibiotic therapy was used in the second patient. Excellent visual and systemic outcomes were achieved in both cases with no ocular complications. The third patient developed lumbar osteomyelitis following spinal surgery and presented with disseminated S. aureus sepsis including unilateral endogenous endophthalmitis. Despite systemic antibiotics and intensive care the patient died.CONCLUSIONS Endogenous endophthalmitis should be suspected in septic patients developing eye symptoms. Endogenous endophthalmitis with staphylococcal bone infection is a rare but serious condition. Osteomyelitis should be considered as an infective source in any such patient reporting bone pain or reduced spinal mobility. Prompt investigation and treatment can achieve favourable visual and systemic outcomes.

  14. ENDOGENEITY OF INDONESIAN MONEY SUPPLY

    Directory of Open Access Journals (Sweden)

    Meutia Safrina Rachma

    2011-09-01

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

  15. Occurrence of indole compounds in some vegetables : toxicological implications of nitrosation with emphasis on mutagenicity

    NARCIS (Netherlands)

    Tiedink, H.G.M.

    1991-01-01

    From the introduction to the chemistry, occurrence and formation of N-nitroso compounds (NOC) (Chapter 1), it can be concluded that human exposure to these potent carcinogenic compounds is mainly through the endogenous nitrosation of dietary precursors. Vegetables are the major source of

  16. Non-invasive method for quantitative evaluation of exogenous compound deposition on skin.

    Science.gov (United States)

    Stamatas, Georgios N; Wu, Jeff; Kollias, Nikiforos

    2002-02-01

    Topical application of active compounds on skin is common to both pharmaceutical and cosmetic industries. Quantification of the concentration of a compound deposited on the skin is important in determining the optimum formulation to deliver the pharmaceutical or cosmetic benefit. The most commonly used techniques to date are either invasive or not easily reproducible. In this study, we have developed a noninvasive alternative to these techniques based on spectrofluorimetry. A mathematical model based on diffusion approximation theory is utilized to correct fluorescence measurements for the attenuation caused by endogenous skin chromophore absorption. The limitation is that the compound of interest has to be either fluorescent itself or fluorescently labeled. We used the method to detect topically applied salicylic acid. Based on the mathematical model a calibration curve was constructed that is independent of endogenous chromophore concentration. We utilized the method to localize salicylic acid in epidermis and to follow its dynamics over a period of 3 d.

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

    Science.gov (United States)

    2012-01-01

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

  18. Role of endogenous thiols in protection

    Science.gov (United States)

    Vos, O.

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

  19. Further identification of endogenous gibberellins in the shoots of pea, line G2

    International Nuclear Information System (INIS)

    Halinska, A.; Davies, P.J.; Lee, J.W.; Zhu, Yuxian

    1989-01-01

    To interpret the metabolism of radiolabeled gibberellins A 12 -aldehyde and A 12 in shoots of pea (Pisum sativum L.), the identity of the radiolabeled peaks has to be determined and the endogenous presence of the gibberellins demonstrated. High specific activity [ 14 C]GA 12 and [ 14 C]GA 12 -aldehyde were synthesized using a pumpkin endosperm enzyme preparation, and purified by high performance liquid chromatography (HPLC). [ 14 C]GA 12 was supplied to upper shoots of pea, line G2, to produce radiolabeled metabolites on the 13-OH pathway. Endogenous compounds copurifying with the [ 14 C]GAs on HPLC were analyzed by gas chromatography-mass spectrometry. The endogenous presence of GA 53 , GA 44 , GA 19 and GA 20 was demonstrated and their HPLC peak identity ascertained. The 14 C was progressively diluted in GAs further down the pathway, proportional to the levels found in the tissue and inversely proportional to the speed of metabolism, ranging from 63% in GA 53 to 4% in GA 20 . Calculated levels of GA 20 , GA 19 , GA 44 , and GA 53 were 42, 8, 10, and 0.5 nanograms/gram, respectively

  20. REFERENCE MODELS OF ENDOGENOUS ECONOMIC GROWTH

    OpenAIRE

    GEAMĂNU MARINELA

    2012-01-01

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

  1. ENDOGENEITY OF INDONESIAN MONEY SUPPLY

    OpenAIRE

    Rachma, Meutia Safrina

    2011-01-01

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

  2. Endogeneity Of Indonesian Money Supply

    OpenAIRE

    Rachma, Meutia Safrina

    2010-01-01

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

  3. Specificity of carboxylesterase protection against the toxicity of organophosphorus compounds. (Reannouncement with new availability information)

    Energy Technology Data Exchange (ETDEWEB)

    Maxwell, D.M.

    1992-12-31

    The ability of endogenous carboxylesterase (CaE) to protect against the lethal effects of a variety of organophosphorus (OP) compounds was examined in rats. The in vivo protection provided by endogenous CaE was measured by the difference in the LD50 values of OP compounds in controlrats and rats whose CaE activity had been inhibited by sc injection with2 mg/kg of 2-(O cresyl)-4H-1,3,2-benzodi oxaphosphorin-2-oxide. Endogenous CaE provided significant protection against the in vivo toxicity of soman, sarin, tabun, and paraoxon, but not against dichlorvos, diisopropyl fluorophosphate, or ethoxymethyl-S-2- (DIISOPROPYLAMINO)ETHYL THIOPHOSPHONATE (VX). The relationship between the in vivo CaE protection against OP compounds and their relative reactivities with CaE and acetylcholinesterase (AChE) was evaluated by measuring the in vitro bimolecular rate constants (ki) for inhibition of plasma CaE and brain AChE. Except for VX, ki values for CaE inhibition varied <10-fold while ki values for AChE inhibition varied 105-fold. Chemical warfare agents, Nerve agents, Organophosphoruscompound soman, VX, Carboxylesterase, Protection, Pretreatment.

  4. Effects of Endogenous Formaldehyde in Nasal Tissues on Inhaled Formmaldehyde Dosimetry Predictions in the Rat, Monkey, and Human Nasal Passages

    Science.gov (United States)

    ABSTRACT Formaldehyde, a nasal carcinogen, is also an endogenous compound that is present in all living cells. Due to its high solubility and reactivity, quantitative risk estimates for inhaled formaldehyde rely on internal dose calculations in the upper respiratory tract which ...

  5. Endogenous small RNAs and antibacterial immunity in plants.

    Science.gov (United States)

    Jin, Hailing

    2008-08-06

    Small RNAs are non-coding regulatory RNA molecules that control gene expression by mediating mRNA degradation, translational inhibition, or chromatin modification. Virus-derived small RNAs induce silencing of viral RNAs and are essential for antiviral defense in both animal and plant systems. The role of host endogenous small RNAs on antibacterial immunity has only recently been recognized. Host disease resistance and defense responses are achieved by activation and repression of a large array of genes. Certain endogenous small RNAs in plants, including microRNAs (miRNAs) and small interfering RNAs (siRNAs), are induced or repressed in response to pathogen attack and subsequently regulate the expression of genes involved in disease resistance and defense responses by mediating transcriptional or post-transcriptional gene silencing. Thus, these small RNAs play an important role in gene expression reprogramming in plant disease resistance and defense responses. This review focuses on the recent findings of plant endogenous small RNAs in antibacterial immunity.

  6. Cytokines as endogenous pyrogens.

    Science.gov (United States)

    Dinarello, C A

    1999-03-01

    Cytokines are pleiotropic molecules mediating several pathologic processes. Long before the discovery of cytokines as immune system growth factors or as bone marrow stimulants, investigators learned a great deal about cytokines when they studied them as the endogenous mediators of fever. The terms "granulocytic" or "endogenous pyrogen" were used to describe substances with the biologic property of fever induction. Today, we recognize that pyrogenicity is a fundamental biologic property of several cytokines and hence the clinically recognizeable property of fever links host perturbations during disease with fundamental perturbations in cell biology. In this review, the discoveries made on endogenous pyrogens are revisited, with insights into the importance of the earlier work to the present-day understanding of cytokines in health and in disease.

  7. Hepatoprotective Activity of a Complex Compound of 5-Hydroxy-6-Methyluracil and Succinic Acid in Experimental Peritonitis

    Directory of Open Access Journals (Sweden)

    D. A. Yenikeyev

    2008-01-01

    Full Text Available Objective: to evaluate the hepatoprotective efficacy of a complex compound of 5-hydroxy-6-methyluracil and succinic acid in experimental peritonitis. Materials and methods. Experiments were carried out on 48 male albino rats in which peritonitis was simulated via intraperitoneal administration of 7% fecal suspension in a dose of 0.6 ml per 100 g bodyweight. The rate of free radical oxidation processes, the activity of antioxidative protection, the degree of endogenous intoxication and cytolytic syndrome, and the effect of the test compound on these parameters were estimated in the experiment. Results. With the development of an abdominal inflammatory process, there were increases in rates of endogenous intoxication and free radical oxidation (FRO, a change in the activity of antioxidative protection enzymes, and a reduction in the levels of ceruloplasmin and sulfahydryl groups. The complex compound, that comprised 5-hydroxy-6-methyluracil and succinic acid used as monotherapy, reduced the degree of endogenous intoxication, FRO, and lipid peroxidation-antioxidative defense system imbalance. Conclusion. The experimental data suggest that the use of the complex compound containing succinic acid and 5-hydroxy-6-methy-luracil is pathogenetically warranted. Key words: peritonitis, lipid peroxidation, antioxidants, succinic acid, pyrim-idine derivatives.

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

    African Journals Online (AJOL)

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

  9. Endogenous growth and the environment

    NARCIS (Netherlands)

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

    2001-01-01

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

  10. Endogenous growth and environmental policy

    NARCIS (Netherlands)

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

    2001-01-01

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

  11. Endogen endoftalmitis som første kliniske manifestation af aortaklapendokarditis

    DEFF Research Database (Denmark)

    Rudbæk, Torsten; Haastrup, Peter; Frydkjær-Olsen, Ulrik

    2012-01-01

    Infectious endocarditis is considered one of the most severe infections in the Western world. Complications include septic embolism, for example to the brain or the eye. Endogeneous endophthalmitis is a rare but severe eye disease. It is important to remember that clinical signs from the eye can...... be the first manifestation of systemic disease. We present a case report of an 81-year-old woman with endogenous endophthalmitis as the first clinical manifestation of infectious endocarditis....

  12. Endogenous pyrogen-like substance produced by reptiles.

    Science.gov (United States)

    Bernheim, H A; Kluger, M J

    1977-06-01

    1. Injection of lizards (Dipsosaurus dorsalis) with rabbit endogenous pyrogen led to a fever. Injections with denatured endogenous pyrogen did not affect body temperature. 2. Injection of lizards with lizard endogenous pyrogen led to a fever of short duration, while injection of denatured lizard endogenous pyrogen produced no change in body temperature. 3. These data support the hypothesis that the febrile mechanism observed in the higher vertebrates has its origins in some primitive vertebrate.

  13. Controlling for endogeneity in attributable costs of vancomycin-resistant enterococci from a Canadian hospital.

    Science.gov (United States)

    Lloyd-Smith, Patrick

    2017-12-01

    Decisions regarding the optimal provision of infection prevention and control resources depend on accurate estimates of the attributable costs of health care-associated infections. This is challenging given the skewed nature of health care cost data and the endogeneity of health care-associated infections. The objective of this study is to determine the hospital costs attributable to vancomycin-resistant enterococci (VRE) while accounting for endogeneity. This study builds on an attributable cost model conducted by a retrospective cohort study including 1,292 patients admitted to an urban hospital in Vancouver, Canada. Attributable hospital costs were estimated with multivariate generalized linear models (GLMs). To account for endogeneity, a control function approach was used. The analysis sample included 217 patients with health care-associated VRE. In the standard GLM, the costs attributable to VRE are $17,949 (SEM, $2,993). However, accounting for endogeneity, the attributable costs were estimated to range from $14,706 (SEM, $7,612) to $42,101 (SEM, $15,533). Across all model specifications, attributable costs are 76% higher on average when controlling for endogeneity. VRE was independently associated with increased hospital costs, and controlling for endogeneity lead to higher attributable cost estimates. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  14. The Endogenous Feedback Network

    DEFF Research Database (Denmark)

    Augustenborg, Claudia Carrara

    2010-01-01

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

  15. A New Nanobody-Based Biosensor to Study Endogenous PARP1 In Vitro and in Live Human Cells

    Science.gov (United States)

    Nüske, Stefan; Scholz, Armin M.; Bogner, Jacqueline; Ruf, Benjamin; Zolghadr, Kourosh; Drexler, Sophie E.; Drexler, Guido A.; Girst, Stefanie; Greubel, Christoph; Reindl, Judith; Siebenwirth, Christian; Romer, Tina; Friedl, Anna A.; Rothbauer, Ulrich

    2016-01-01

    Poly(ADP-ribose) polymerase 1 (PARP1) is a key player in DNA repair, genomic stability and cell survival and it emerges as a highly relevant target for cancer therapies. To deepen our understanding of PARP biology and mechanisms of action of PARP1-targeting anti-cancer compounds, we generated a novel PARP1-affinity reagent, active both in vitro and in live cells. This PARP1-biosensor is based on a PARP1-specific single-domain antibody fragment (~ 15 kDa), termed nanobody, which recognizes the N-terminus of human PARP1 with nanomolar affinity. In proteomic approaches, immobilized PARP1 nanobody facilitates quantitative immunoprecipitation of functional, endogenous PARP1 from cellular lysates. For cellular studies, we engineered an intracellularly functional PARP1 chromobody by combining the nanobody coding sequence with a fluorescent protein sequence. By following the chromobody signal, we were for the first time able to monitor the recruitment of endogenous PARP1 to DNA damage sites in live cells. Moreover, tracing of the sub-nuclear translocation of the chromobody signal upon treatment of human cells with chemical substances enables real-time profiling of active compounds in high content imaging. Due to its ability to perform as a biosensor at the endogenous level of the PARP1 enzyme, the novel PARP1 nanobody is a unique and versatile tool for basic and applied studies of PARP1 biology and DNA repair. PMID:26950694

  16. A New Nanobody-Based Biosensor to Study Endogenous PARP1 In Vitro and in Live Human Cells.

    Directory of Open Access Journals (Sweden)

    Andrea Buchfellner

    Full Text Available Poly(ADP-ribose polymerase 1 (PARP1 is a key player in DNA repair, genomic stability and cell survival and it emerges as a highly relevant target for cancer therapies. To deepen our understanding of PARP biology and mechanisms of action of PARP1-targeting anti-cancer compounds, we generated a novel PARP1-affinity reagent, active both in vitro and in live cells. This PARP1-biosensor is based on a PARP1-specific single-domain antibody fragment (~ 15 kDa, termed nanobody, which recognizes the N-terminus of human PARP1 with nanomolar affinity. In proteomic approaches, immobilized PARP1 nanobody facilitates quantitative immunoprecipitation of functional, endogenous PARP1 from cellular lysates. For cellular studies, we engineered an intracellularly functional PARP1 chromobody by combining the nanobody coding sequence with a fluorescent protein sequence. By following the chromobody signal, we were for the first time able to monitor the recruitment of endogenous PARP1 to DNA damage sites in live cells. Moreover, tracing of the sub-nuclear translocation of the chromobody signal upon treatment of human cells with chemical substances enables real-time profiling of active compounds in high content imaging. Due to its ability to perform as a biosensor at the endogenous level of the PARP1 enzyme, the novel PARP1 nanobody is a unique and versatile tool for basic and applied studies of PARP1 biology and DNA repair.

  17. A New Nanobody-Based Biosensor to Study Endogenous PARP1 In Vitro and in Live Human Cells.

    Science.gov (United States)

    Buchfellner, Andrea; Yurlova, Larisa; Nüske, Stefan; Scholz, Armin M; Bogner, Jacqueline; Ruf, Benjamin; Zolghadr, Kourosh; Drexler, Sophie E; Drexler, Guido A; Girst, Stefanie; Greubel, Christoph; Reindl, Judith; Siebenwirth, Christian; Romer, Tina; Friedl, Anna A; Rothbauer, Ulrich

    2016-01-01

    Poly(ADP-ribose) polymerase 1 (PARP1) is a key player in DNA repair, genomic stability and cell survival and it emerges as a highly relevant target for cancer therapies. To deepen our understanding of PARP biology and mechanisms of action of PARP1-targeting anti-cancer compounds, we generated a novel PARP1-affinity reagent, active both in vitro and in live cells. This PARP1-biosensor is based on a PARP1-specific single-domain antibody fragment (~ 15 kDa), termed nanobody, which recognizes the N-terminus of human PARP1 with nanomolar affinity. In proteomic approaches, immobilized PARP1 nanobody facilitates quantitative immunoprecipitation of functional, endogenous PARP1 from cellular lysates. For cellular studies, we engineered an intracellularly functional PARP1 chromobody by combining the nanobody coding sequence with a fluorescent protein sequence. By following the chromobody signal, we were for the first time able to monitor the recruitment of endogenous PARP1 to DNA damage sites in live cells. Moreover, tracing of the sub-nuclear translocation of the chromobody signal upon treatment of human cells with chemical substances enables real-time profiling of active compounds in high content imaging. Due to its ability to perform as a biosensor at the endogenous level of the PARP1 enzyme, the novel PARP1 nanobody is a unique and versatile tool for basic and applied studies of PARP1 biology and DNA repair.

  18. A Derivatization and Validation Strategy for Determining the Spatial Localization of Endogenous Amine Metabolites in Tissues using MALDI Imaging Mass Spectrometry

    Science.gov (United States)

    Manier, M. Lisa; Spraggins, Jeffrey M.; Reyzer, Michelle L.; Norris, Jeremy L.; Caprioli, Richard M.

    2014-01-01

    Imaging mass spectrometry (IMS) studies increasingly focus on endogenous small molecular weight metabolites and consequently bring special analytical challenges. Since analytical tissue blanks do not exist for endogenous metabolites, careful consideration must be given to confirm molecular identity. Here we present approaches for the improvement in detection of endogenous amine metabolites such as amino acids and neurotransmitters in tissues through chemical derivatization and matrix-assisted laser desorption/ionization (MALDI) IMS. Chemical derivatization with 4-hydroxy-3-methoxycinnamaldehyde (CA) was used to improve sensitivity and specificity. CA was applied to the tissue via MALDI sample targets precoated with a mixture of derivatization reagent and ferulic acid (FA) as a MALDI matrix. Spatial distributions of chemically derivatized endogenous metabolites in tissue were determined by high-mass resolution and MSn imaging mass spectrometry. We highlight an analytical strategy for metabolite validation whereby tissue extracts are analyzed by high-performance liquid chromatography (HPLC)-MS/MS to unambiguously identify metabolites and distinguish them from isobaric compounds. PMID:25044893

  19. Avian endogenous provirus (ev-3) env gene sequencing: implication for pathogenic retrovirus origination.

    Science.gov (United States)

    Tikhonenko, A T; Lomovskaya, O L

    1990-02-01

    The avian endogenous env gene product blocks the surface receptor and, as a result, cells become immune to related exogenous retroviruses. On the other hand, the same sequence can be included in the pathogenic retrovirus genome, as shown by oligonucleotide mapping. However, since the complete env gene sequence was not known, the comparison of genomic nucleotide sequences was not possible. Therefore an avian endogenous provirus with an intact env gene was cloned from a chicken gene bank and the regions coding for the C terminus of the gp85 and gp37 proteins were sequenced. Comparison of this sequence with those of other retroviruses proved that one of the pathogenic viruses associated with osteopetrosis is a cross between avian endogenous virus and Rous sarcoma virus. Retroviruses and, especially, endogenous retroviruses are traditionally of the most developed models of viral carcinogenesis. Many endogenous retroviruses are implicated in neoplastic transformation of the cell. For instance, endogenous mouse mammary tumor virus of some inbred lines appears to be the only causative agent in these mammary cancers. Other even nonpathogenic murine endogenous retroviruses are involved in the origination of MCF-type recombinant acute leukosis viruses. Some endogenous retroviruses are implicated in the transduction or activation of cellular protooncogenes. Our interest in endogenous viruses is based on their ability to make cells resistant to exogenous retroviruses. Expression of their major envelope glycoprotein leads to cellular surface receptor blockage and imparts immunity to infection by the related leukemia retroviruses. This problem is quite elaborated for chicken endogenous virus RAV-O (7-9).(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Endogenous Lunar Volatiles

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2013-03-01

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

  2. Endogenous Opiates and Behavior: 2006

    Science.gov (United States)

    Bodnar, Richard J.

    2009-01-01

    This paper is the twenty-ninth consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning thirty years of research. It summarizes papers published during 2006 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurological disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17). PMID:17949854

  3. Endogenous opiates and behavior: 2012.

    Science.gov (United States)

    Bodnar, Richard J

    2013-12-01

    This paper is the thirty-fifth consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2012 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17). Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Studies on endogenous circulating calcium entry blocker and stimulator

    International Nuclear Information System (INIS)

    Pang, P.K.T.; Yang, M.C.M.

    1986-01-01

    Several synthetic compounds have been studied extensively for their calcium entry blockade and stimulation in smooth muscles. It is hypothesized that there should be endogenous substances which control calcium entry into cells. We recently investigated the effect of some vasoactive hormones on calcium entry. Our studies on rat tail artery helical strip showed that the in vitro vasoconstriction produced by arginine vasopressin (AVP) decreased stepwise with decreasing concentration of both calcium. After exposure of the tail artery to calcium-free Ringer's solution for 1 minute or longer, the tissue lost its ability to respond to AVP. Subsequent addition of calcium to the medium produced immediate contraction. Measurements of low affinity lanthanum resistant pool of calcium with 45 Ca showed that AVP increased calcium uptake by tail artery in a dose-dependent manner. In another study rat tail artery helical strip indicated that the vasorelaxing action of parathyroid hormone (PTH) was related to an inhibition of calcium uptake. AVP or 60 mM potassium chloride increased the low affinity lanthanum resistant pool of calcium in rate tail artery and PTH inhibited the increase. In conclusion, AVP and PTH may behave like endogenous calcium entry stimulator and inhibitor respectively in vascular tissues

  5. On the classification and evolution of endogenous retrovirus: human endogenous retroviruses may not be 'human' after all.

    Science.gov (United States)

    Escalera-Zamudio, Marina; Greenwood, Alex D

    2016-01-01

    Retroviruses, as part of their replication cycle, become integrated into the genome of their host. When this occurs in the germline the integrated proviruses can become an endogenous retrovirus (ERV) which may eventually become fixed in the population. ERVs are present in the genomes of all vertebrates including humans, where more than 50 groups of human endogenous retrovirus (HERVs) have been described within the last 30 years. Despite state-of-the-art genomic tools available for retroviral discovery and the large number of retroviral sequences described to date, there are still gaps in understanding retroviral macroevolutionary patterns and host-retrovirus interactions and a lack of a coherent systematic classification particularly for HERVs. Here, we discuss the current knowledge on ERV (and HERV) classification, distribution and origins focusing on the role of cross-species transmission in retroviral diversity. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  6. Synthetic mRNA devices that detect endogenous proteins and distinguish mammalian cells.

    Science.gov (United States)

    Kawasaki, Shunsuke; Fujita, Yoshihiko; Nagaike, Takashi; Tomita, Kozo; Saito, Hirohide

    2017-07-07

    Synthetic biology has great potential for future therapeutic applications including autonomous cell programming through the detection of protein signals and the production of desired outputs. Synthetic RNA devices are promising for this purpose. However, the number of available devices is limited due to the difficulty in the detection of endogenous proteins within a cell. Here, we show a strategy to construct synthetic mRNA devices that detect endogenous proteins in living cells, control translation and distinguish cell types. We engineered protein-binding aptamers that have increased stability in the secondary structures of their active conformation. The designed devices can efficiently respond to target proteins including human LIN28A and U1A proteins, while the original aptamers failed to do so. Moreover, mRNA delivery of an LIN28A-responsive device into human induced pluripotent stem cells (hiPSCs) revealed that we can distinguish living hiPSCs and differentiated cells by quantifying endogenous LIN28A protein expression level. Thus, our endogenous protein-driven RNA devices determine live-cell states and program mammalian cells based on intracellular protein information. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  7. Determination of endogenous inflammation-related lipid mediators in ischemic stroke rats using background subtracting calibration curves by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Yang, Yang; Zhong, Qisheng; Mo, Canlong; Zhang, Hao; Zhou, Ting; Tan, Wen

    2017-11-01

    Accurate and reliable quantification of endogenous lipid mediators in complex biological samples is a daunting challenge. In this study, a robust and direct endogenous quantitative method using background subtracting calibration curves by liquid chromatography-tandem mass spectrometry was first developed for the determination of endogenous lipid mediators in ischemic stroke rats. Absolute quantification without surrogate matrix could be achieved by using background subtracting calibration curves, which were corrected and verified from standard curves constructed on original matrix. The recoveries of this method were in the range of 50.3-98.3%, the precision with the relative standard deviation was less than 13.8%, and the accuracy with the relative error was within ± 15.0%. In addition, background subtracting calibration curves were further verified by validation factors ranging from 90.3 to 110.9%. This validated method has been successfully applied to the analysis of seven endogenous inflammation-related lipid mediators in the brain tissues of ischemic stroke rats. The results indicated that prostaglandins as inflammatory factors and some lipid mediators with neuroprotective effects increased apparently (p endogenous compounds in the complex biological samples. Graphical abstract The analysis procedure of determining endogenous inflammation-related lipid mediators using BSCC by LC-MS/MS.

  8. Neuronal Rat Brain Damage Caused by Endogenous and Exogenous Hyperthermia

    Directory of Open Access Journals (Sweden)

    Mustafa Aydın

    2012-03-01

    Full Text Available OBJECTIVE: Hyperthermia may induce pathologic alterations within body systems and organs including brain. In this study, neuronal effects of endogenous and exogenous hyperthermia (41°C were studied in rats. METHODS: The endogenous hyperthermia (41°C was induced by lipopolysaccharide and the exogenous by an (electric heater. Possible neuronal damage was evaluated by examining healthy, apoptotic and necrotic cells, and heat shock proteins (HSP 27, HSP 70 in the cerebral cortex, cerebellum and hypothalamus RESULTS: At cellular level, when all neuronal tissues are taken into account; (i a significant increase in the necrotic cells was observed in the both groups (p0.05. CONCLUSION: The neural tissue of brain can show different degree of response to hyperthermia. But we can conclude that endogenous hyperthermia is more harmful to central nervous system than exogenous hyperthermia

  9. Endogenous lentivirus in Malayan colugo (Galeopterus variegatus), a close relative of primates.

    Science.gov (United States)

    Hron, Tomáš; Fábryová, Helena; Pačes, Jan; Elleder, Daniel

    2014-10-04

    A significant fraction of mammalian genomes is composed of endogenous retroviral (ERV) sequences that are formed by germline infiltration of various retroviruses. In contrast to other retroviral genera, lentiviruses only rarely form ERV copies. We performed a computational search aimed at identification of novel endogenous lentiviruses in vertebrate genomes. Using the in silico strategy, we have screened 104 publicly available vertebrate genomes for the presence of endogenous lentivirus sequences. In addition to the previously described cases, the search revealed the presence of endogenous lentivirus in the genome of Malayan colugo (Galeopterus variegatus). At least three complete copies of this virus, denoted ELVgv, were detected in the colugo genome, and approximately one hundred solo LTR sequences. The assembled consensus sequence of ELVgv had typical lentivirus genome organization including three predicted accessory genes. Phylogenetic analysis placed this virus as a distinct subgroup within the lentivirus genus. The time of insertion into the dermopteran lineage was estimated to be more than thirteen million years ago. We report the discovery of the first endogenous lentivirus in the mammalian order Dermoptera, which is a taxon close to the Primates. Lentiviruses have infiltrated the mammalian germline several times across millions of years. The colugo virus described here represents possibly the oldest documented endogenization event and its discovery can lead to new insights into lentivirus evolution. This is also the first report of an endogenous lentivirus in an Asian mammal, indicating a long-term presence of this retrovirus family in Asian continent.

  10. Endogenous phosphorus excretion by sheep fed hydrolyzed sugarcane bagasse, lucerne hay and citrus pulp

    International Nuclear Information System (INIS)

    Dias, R.S.; Roque, A.P.; Vitti, D.M.S.S.

    2006-01-01

    The objective of this study was to determine endogenous phosphorus excretion in sheep fed with different diets. Sixteen male growing sheep, received a basic diet with: 42% hydrolyzed sugarcane bagasse (HSB), 45% lucerne hay (LH) plus 14% hydrolyzed sugarcane bagasse, and 30% citrus pulp (CTP) plus 40% hydrolyzed sugarcane bagasse. A dose of 7.7 MBq 32 P was injected into the left jugular vein of each animal. The P endogenous fecal losses were: 1.69, 2.50, 2.33 and 1.45 g/animal for treatments HSB, LH, and CTP respectively (P>0.05). The type of diet influenced slight endogenous P excretion but altered excretion of P in urine. Endogenous P excreted in feces (P F ) comes mainly from saliva and represents an important loss of P. The estimation of net requirements of phosphorus (P) for ruminants includes endogenous losses, which is also essential for calculating true absorption of this mineral. Physical structure of the feed may influence endogenous losses, altering the metabolism of P and also the demand of this mineral, therefore being important to know how different feeds affect endogenous P losses. (author)

  11. A turn-on fluorescent probe for endogenous formaldehyde in the endoplasmic reticulum of living cells

    Science.gov (United States)

    Tang, Yonghe; Ma, Yanyan; Xu, An; Xu, Gaoping; Lin, Weiying

    2017-06-01

    As the simplest aldehyde compounds, formaldehyde (FA) is implicated in nervous system diseases and cancer. Endoplasmic reticulum is an organelle that plays important functions in living cells. Accordingly, the development of efficient methods for FA detection in the endoplasmic reticulum (ER) is of great biomedical importance. In this work, we developed the first ER-targeted fluorescent FA probe Na-FA-ER. The detection is based on the condensation reaction of the hydrazine group and FA to suppress the photo-induced electron transfer (PET) pathway, resulting in a fluorescence increase. The novel Na-FA-ER showed high sensitivity to FA. In addition, the Na-FA-ER enabled the bio-imaging of exogenous and endogenous FA in living HeLa cells. Most significantly, the new Na-FA-ER was employed to visualize the endogenous FA in the ER in living cells for the first time.

  12. Proteomics investigation of endogenous S-nitrosylation in Arabidopsis

    International Nuclear Information System (INIS)

    Fares, Abasse; Rossignol, Michel; Peltier, Jean-Benoît

    2011-01-01

    Highlights: ► Identification and quantification of nitrosothiols. ► A first dataset of endogenously nitrosylated cysteines in Arabidopsis cells. ► Nitrosothiols display apolar motifs not located in close vicinity of cysteines. ► Salt stress alters the endogenous nitrosylation of specific cysteines in Arabidopsis. -- Abstract: S-Nitrosylation emerges as an important protein modification in many processes. However, most data were obtained at the protein level after addition of a NO donor, particularly in plants where information about the cysteines nitrosylated in these proteins is scarce. An adapted work-flow, combining the classical biotin switch method and labeling with isotope-coded affinity tags (ICAT), is proposed. Without addition of NO donor, a total of 53 endogenous nitrosocysteines was identified in Arabidopsis cells, in proteins belonging to all cell territories, including membranes, and covering a large panel of functions. This first repertoire of nitrosothiols in plants enabled also preliminary structural description. Three apolar motifs, not located in close vicinity of cysteines and accounting for half the dataset, were detected and are proposed to complement nitrosylation prediction algorithms, poorly trained with plant data to date. Analysis of changes induced by a brief salt stress showed that NaCl modified the nitrosylation level of a small proportion of endogenously nitrosylated proteins and did not concern all nitrosothiols in these proteins. The possible role of some NO targets in the response to salt stress was discussed.

  13. Non-targeted, high resolution mass spectrometry strategy for simultaneous monitoring of xenobiotics and endogenous compounds in green sea turtles on the Great Barrier Reef.

    Science.gov (United States)

    Heffernan, Amy L; Gómez-Ramos, Maria M; Gaus, Caroline; Vijayasarathy, Soumini; Bell, Ian; Hof, Christine; Mueller, Jochen F; Gómez-Ramos, Maria J

    2017-12-01

    Chemical contamination poses a threat to ecosystem, biota and human health, and identifying these hazards is a complex challenge. Traditional hazard identification relies on a priori-defined targets of limited chemical scope, and is generally inappropriate for exploratory studies such as explaining toxicological effects in environmental systems. Here we present a non-target high resolution mass spectrometry environmental monitoring study with multivariate statistical analysis to simultaneously detect biomarkers of exposure (e.g. xenobiotics) and biomarkers of effect in whole turtle blood. Borrowing the concept from clinical chemistry, a case-control sampling approach was used to investigate the potential influence of xenobiotics of anthropogenic origin on free-ranging green sea turtles (Chelonia mydas) from a remote, offshore 'control' site; and two coastal 'case' sites influenced by urban/industrial and agricultural activities, respectively, on the Great Barrier Reef in North Queensland, Australia. Multiple biomarkers of exposure, including sulfonic acids (n=9), a carbamate insecticide metabolite, and other industrial chemicals; and five biomarkers of effect (lipid peroxidation products), were detected in case sites. Additionally, two endogenous biomarkers of neuroinflammation and oxidative stress were identified, and showed moderate-to-strong correlations with clinical measures of inflammation and liver dysfunction. Our data filtering strategy overcomes limitations of traditional a priori selection of target compounds, and adds to the limited environmental xenobiotic metabolomics literature. To our knowledge this is the first case-control study of xenobiotics in marine megafauna, and demonstrates the utility of green sea turtles to link internal and external exposure, to explain potential toxicological effects in environmental systems. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Analysis of volatile compounds by open-air ionization mass spectrometry.

    Science.gov (United States)

    Meher, Anil Kumar; Chen, Yu-Chie

    2017-05-08

    This study demonstrates a simple method for rapid and in situ identification of volatile and endogenous compounds in culinary spice samples through mass spectrometry (MS). This method only requires a holder for solid spice sample (2-3 mm) that is placed close to a mass spectrometer inlet, which is applied with a high voltage. Volatile species responsible for the aroma of the spice samples can be readily detected by the mass spectrometer. Sample pretreatment is not required prior to MS analysis, and no solvent was used during MS analysis. The high voltage applied to the inlet of the mass spectrometer induces the ionization of volatile compounds released from the solid spice samples. Furthermore, moisture in the air also contributes to the ionization of volatile compounds. Dried spices including cinnamon and cloves are used as the model sample to demonstrate this straightforward MS analysis, which can be completed within few seconds. Furthermore, we also demonstrate the suitability of the current method for rapid screening of cinnamon quality through detection of the presence of a hepatotoxic agent, i.e. coumarin. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Accurate quantification of endogenous androgenic steroids in cattle's meat by gas chromatography mass spectrometry using a surrogate analyte approach

    International Nuclear Information System (INIS)

    Ahmadkhaniha, Reza; Shafiee, Abbas; Rastkari, Noushin; Kobarfard, Farzad

    2009-01-01

    Determination of endogenous steroids in complex matrices such as cattle's meat is a challenging task. Since endogenous steroids always exist in animal tissues, no analyte-free matrices for constructing the standard calibration line will be available, which is crucial for accurate quantification specially at trace level. Although some methods have been proposed to solve the problem, none has offered a complete solution. To this aim, a new quantification strategy was developed in this study, which is named 'surrogate analyte approach' and is based on using isotope-labeled standards instead of natural form of endogenous steroids for preparing the calibration line. In comparison with the other methods, which are currently in use for the quantitation of endogenous steroids, this approach provides improved simplicity and speed for analysis on a routine basis. The accuracy of this method is better than other methods at low concentration and comparable to the standard addition at medium and high concentrations. The method was also found to be valid according to the ICH criteria for bioanalytical methods. The developed method could be a promising approach in the field of compounds residue analysis

  16. Revealing of endogenous Marinobufagin by an ultra-specific and sensitive UHPLC-MS/MS assay in pregnant women.

    Science.gov (United States)

    Lenaerts, Charline; Bond, Liz; Tuytten, Robin; Blankert, Bertrand

    2018-09-01

    Marinobufagenin (MBG) is a bufadienolide cardiac inotrope implicated in volume expansion-mediated hypertensive states including essential hypertension and preeclampsia (PE). Endogenous MBG is an inhibitor of the α1-isoform of Na + ,K + -ATPase with vasoconstrictive and cardiotonic properties, causing hypertension and natriuresis. Elevated endogenous MBG-like material levels have been described by immunoassays in salt-sensitive pregnant and preeclamptic rats as well as in preeclamptic human patients. The rise of endogenous MBG-like material appears prior the development of the main symptoms of PE, leading us to consider MBG as one of the potential biomarkers for PE. The weak specificity and the high variability of the published immunoassays gives no certification about endogenous MBG existence. This led us to set-up a highly specific and sensitive analytical method to detect MBG in plasma at low levels relying on liquid chromatography combined to mass spectrometry (UHPLC-MS/MS) with recording of 7 highly specific MRM transitions for MBG. Pure MBG standard used in the method development was obtained by purification from the Bufo marinus toad venom. d 3 -25-hydroxyvitamin D3 was used as internal standard. An increasing organic gradient with mobile phase A and B composed of 97:3 (v/v) H 2 O: MeOH and 50:45:5 (v/v/v) MeOH:IPA:H 2 O at pH 4.5 respectively was used on a Pursuit 3 PFP column (100 mm × 3 mm; 3 µm) to allow elution and separation of the plasmatic compounds. Chromatographic analyses of plasma samples were preceded by a precipitation of proteins pretreatment. The developed UHPLC-MS/MS assay has been applied to early-pregnant women plasma samples allowing us to investigate MBG plasma levels. Thanks to the high specificity of the assay we were able to authenticate and certify the presence of endogenous MBG in early-pregnant women plasma with the use of the 7 selected specific mass transitions. These pioneering preliminary results are giving a

  17. Ciliary neurotrophic factor is an endogenous pyrogen.

    Science.gov (United States)

    Shapiro, L; Zhang, X X; Rupp, R G; Wolff, S M; Dinarello, C A

    1993-09-15

    Fever is initiated by the action of polypeptide cytokines called endogenous pyrogens, which are produced by the host during inflammation, trauma, or infection and which elevate the thermoregulatory set point in the hypothalamus. Ciliary neurotrophic factor (CNTF) supports the differentiation and survival of central and peripheral neurons. We describe the activity of CNTF as intrinsically pyrogenic in the rabbit. CNTF induced a monophasic fever which rose rapidly (within the first 12 min) following intravenous injection; CNTF fever was blocked by pretreatment with indomethacin. The fever induced by CNTF was not due to contaminating endotoxins. Increasing doses of CNTF resulted in prolongation of the fever, suggesting the subsequent induction of additional endogenous pyrogenic activity. After passive transfer of plasma obtained during CNTF-induced fever, endogenous pyrogen activity was not present in the circulation; CNTF also did not induce the endogenous pyrogens interleukin 1, tumor necrosis factor, or interleukin 6 in vitro. Nevertheless, a second endogenous pyrogen may originate within the central nervous system following the systemic injection of CNTF. Of the four endogenous pyrogens described to date (interleukin 1, tumor necrosis factor, interferon, and interleukin 6), CNTF, like interleukin 6, utilizes the cell-surface gp 130 signal-transduction apparatus.

  18. MRE: a web tool to suggest foreign enzymes for the biosynthesis pathway design with competing endogenous reactions in mind

    KAUST Repository

    Kuwahara, Hiroyuki; Alazmi, Meshari; Cui, Xuefeng; Gao, Xin

    2016-01-01

    To rationally design a productive heterologous biosynthesis system, it is essential to consider the suitability of foreign reactions for the specific endogenous metabolic infrastructure of a host. We developed a novel web server, called MRE, which, for a given pair of starting and desired compounds in a given chassis organism, ranks biosynthesis routes from the perspective of the integration of new reactions into the endogenous metabolic system. For each promising heterologous biosynthesis pathway, MRE suggests actual enzymes for foreign metabolic reactions and generates information on competing endogenous reactions for the consumption of metabolites. These unique, chassis-centered features distinguish MRE from existing pathway design tools and allow synthetic biologists to evaluate the design of their biosynthesis systems from a different angle. By using biosynthesis of a range of high-value natural products as a case study, we show that MRE is an effective tool to guide the design and optimization of heterologous biosynthesis pathways. The URL of MRE is http://www.cbrc.kaust.edu.sa/mre/.

  19. MRE: a web tool to suggest foreign enzymes for the biosynthesis pathway design with competing endogenous reactions in mind

    KAUST Repository

    Kuwahara, Hiroyuki

    2016-04-29

    To rationally design a productive heterologous biosynthesis system, it is essential to consider the suitability of foreign reactions for the specific endogenous metabolic infrastructure of a host. We developed a novel web server, called MRE, which, for a given pair of starting and desired compounds in a given chassis organism, ranks biosynthesis routes from the perspective of the integration of new reactions into the endogenous metabolic system. For each promising heterologous biosynthesis pathway, MRE suggests actual enzymes for foreign metabolic reactions and generates information on competing endogenous reactions for the consumption of metabolites. These unique, chassis-centered features distinguish MRE from existing pathway design tools and allow synthetic biologists to evaluate the design of their biosynthesis systems from a different angle. By using biosynthesis of a range of high-value natural products as a case study, we show that MRE is an effective tool to guide the design and optimization of heterologous biosynthesis pathways. The URL of MRE is http://www.cbrc.kaust.edu.sa/mre/.

  20. Fluconazole-Pyridoxine Bis-Triazolium Compounds with Potent Activity against Pathogenic Bacteria and Fungi Including Their Biofilm-Embedded Forms

    Directory of Open Access Journals (Sweden)

    Marsel R. Garipov

    2017-01-01

    Full Text Available Two novel quaternary ammonium salts, bis-triazolium derivatives of fluconazole and pyridoxine, were synthesized by reaction of fluconazole with pyridoxine-based synthetic intermediates. The leading compound demonstrated pronounced antimycotic and antibacterial in vitro activity, comparable to or exceeding that of the reference antifungal (fluconazole, terbinafine and antibacterial/antiseptic (miramistin, benzalkonium chloride agents. In contrast to many antimicrobials, the leading compound was also active against biofilm-embedded staphylococci and Escherichia coli. While no biofilm structure destruction occurred, all compounds were able to diffuse into the matrix and reduce the number of colony-forming units by three orders of magnitude at 16 × MBC. The leading compound was significantly less toxic than miramistin and benzalkonium chloride and more toxic than the reference antifungal drugs. The obtained results make the described chemotype a promising starting point for the development of new broad-spectrum antimicrobial therapies with powerful effect on fungal and bacterial pathogens including their biofilm-embedded forms.

  1. Comparison of Active Vitamin D Compounds and a Calcimimetic in Mineral Homeostasis

    OpenAIRE

    Nguyen-Yamamoto, Loan; Bolivar, Isabel; Strugnell, Stephen A.; Goltzman, David

    2010-01-01

    The differential effects between cinacalcet and active vitamin D compounds on parathyroid function, mineral metabolism, and skeletal function are incompletely understood. Here, we studied cinacalcet and active vitamin D compounds in mice expressing the null mutation for Cyp27b1, which encodes 25-hydroxyvitamin D-1α-hydroxylase, thereby lacking endogenous 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Vehicle-treated mice given high dietary calcium had hypocalcemia, hypophosphatemia, and marked secon...

  2. A validated LC-MS/MS method for the quantitative measurement of creatinine as an endogenous biomarker in human plasma.

    Science.gov (United States)

    Zhao, Yue; Liu, Guowen; Angeles, Aida; Christopher, Lisa J; Wang, Zhaoqing; Arnold, Mark E; Shen, Jim X

    2016-10-01

    Creatinine is an endogenous compound generated from creatine by normal muscular metabolism. It is an important indicator of renal function and the serum level is routinely monitored in clinical labs. Results & methodology: Surrogate analyte (d3-creatinine) was used for calibration standard and quality control preparation and the relative instrument response ratio between creatinine and d3-creatinine was used to calculate the endogenous creatinine concentrations. A fit-for-purpose strategy of using a surrogate analyte and authentic matrix was adopted for this validation. The assay was the first human plasma assay using such strategy and was successfully applied to a clinical study to confirm a transient elevation of creatinine observed using an existing clinical assay.

  3. Parvovirus-derived endogenous viral elements in two South American rodent genomes.

    Science.gov (United States)

    Arriagada, Gloria; Gifford, Robert J

    2014-10-01

    We describe endogenous viral elements (EVEs) derived from parvoviruses (family Parvoviridae) in the genomes of the long-tailed chinchilla (Chinchilla lanigera) and the degu (Octodon degus). The novel EVEs include dependovirus-related elements and representatives of a clearly distinct parvovirus lineage that also has endogenous representatives in marsupial genomes. In the degu, one dependovirus-derived EVE was found to carry an intact reading frame and was differentially expressed in vivo, with increased expression in the liver. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  4. Interaction between endogenous and exogenous orienting in crossmodal attention.

    Science.gov (United States)

    Chen, Xiaoxi; Chen, Qi; Gao, Dingguo; Yue, Zhenzhu

    2012-08-01

    Using a cue-target paradigm, we investigated the interaction between endogenous and exogenous orienting in cross-modal attention. A peripheral (exogenous) cue was presented after a central (endogenous) cue with a variable time interval. The endogenous and exogenous cues were presented in one sensory modality (auditory in Experiment 1 and visual in Experiment 2) whereas the target was presented in another modality. Both experiments showed a significant endogenous cuing effect (longer reaction times in the invalid condition than in the valid condition). However, exogenous cuing produced a facilitatory effect in both experiments in response to the target when endogenous cuing was valid, but it elicited a facilitatory effect in Experiment 1 and an inhibitory effect in Experiment 2 when endogenous cuing was invalid. These findings indicate that endogenous and exogenous cuing can co-operate in orienting attention to the crossmodal target. Moreover, the interaction between endogenous and exogenous orienting of attention is modulated by the modality between the cue and the target. © 2012 The Authors. Scandinavian Journal of Psychology © 2012 The Scandinavian Psychological Associations.

  5. Endogenous price flexibility and optimal monetary policy

    OpenAIRE

    Ozge Senay; Alan Sutherland

    2014-01-01

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

  6. Endogenous money: the evolutionary versus revolutionary views

    OpenAIRE

    Louis-Philippe Rochon; Sergio Rossi

    2013-01-01

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

  7. Analysis of multiple quaternary ammonium compounds in the brain using tandem capillary column separation and high resolution mass spectrometric detection.

    Science.gov (United States)

    Falasca, Sara; Petruzziello, Filomena; Kretz, Robert; Rainer, Gregor; Zhang, Xiaozhe

    2012-06-08

    Endogenous quaternary ammonium compounds are involved in various physiological processes in the central nervous system. In the present study, eleven quaternary ammonium compounds, including acetylcholine, choline, carnitine, acetylcarnitine and seven other acylcarnitines of low polarity, were analyzed from brain extracts using a two dimension capillary liquid chromatography-Fourier transform mass spectrometry method. To deal with their large difference in hydrophobicities, tandem coupling between reversed phase and hydrophilic interaction chromatography columns was used to separate all the targeted quaternary ammonium compounds. Using high accuracy mass spectrometry in selected ion monitoring mode, all the compounds could be detected from each brain sample with high selectivity. The developed method was applied for the relative quantification of these quaternary ammonium compounds in three different brain regions of tree shrews: prefrontal cortex, striatum, and hippocampus. The comparative analysis showed that quaternary ammonium compounds were differentially distributed across the three brain areas. The analytical method proved to be highly sensitive and reliable for simultaneous determination of all the targeted analytes from brain samples. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Endogeneity of Money Supply: Evidence From Turkey

    Directory of Open Access Journals (Sweden)

    Oguzhan Cepni

    2017-02-01

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

  9. Endogenous Peer Effects: Fact or Fiction?

    Science.gov (United States)

    Yeung, Ryan; Nguyen-Hoang, Phuong

    2016-01-01

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

  10. Characterizing endogenous and oxidative low molecular weight flavor/aroma compounds in fresh squeezed/blended pomegranate juice.

    Science.gov (United States)

    Little published information exists regarding flavor and aroma compounds in pomegranate (Punica granatum) juices. Although, arils have fruity and sweet characteristics, we found no publications describing volatile and semi-volatile compounds responsible for their typical flavor. Only two reports w...

  11. Simulation of Injection Molding Process Including Mold Filling and Compound Curing

    Directory of Open Access Journals (Sweden)

    Mohamad Reza Erfanian

    2012-12-01

    Full Text Available The present work reports and discusses the results of a 3D simulation of the injection molding process of a rubber compound that includes the mold flling stage and  material curing, using the computer code is developed in “UDF” part of the Fluent 6.3 CAE software. The data obtained from a rheometer (MDR 2000 is used to characterize the rubber material in order to fnd the cure model parameters which exist in curing model. Because of non-newtonian behavior of rubber, in this work the non-newtonian model for viscosity was used and viscosity parameters were computed by mean of viscometry test by RPA. After calculation of the physical and curing properties, vulcanization process was simulated for a complex rubber article with non-uniform thickness by solving the continuity, momentum, energy and curing process equations. Predicted flling and curing time in a complex and 3D rubber part is compared with experimentally measured data which confrmed  the accuracy and applicability of the method.

  12. Acute myocardial infarction without significant coronary stenoses associated with endogenous subclinical hyperthyroidism.

    Science.gov (United States)

    Patanè, Salvatore; Marte, Filippo; Sturiale, Mauro

    2012-04-05

    Subclinical hyperthyroidism is an increasingly recognized entity that is defined as a normal serum free thyroxine and free triiodothyronine levels with a thyroid-stimulating hormone level suppressed below the normal range and usually undetectable. It has been reported that subclinical hyperthyroidism is not associated with coronary heart disease or mortality from cardiovascular causes but it is sufficient to induce arrhythmias including atrial fibrillation and atrial flutter. Nowadays, there is growing interest regarding endogenous sublinical hyperthyroidism and the cardiovascular system. We present a case of acute myocardial infarction without significant coronary stenoses in a 75-year-old Italian woman with endogenous subclinical hyperthyroidism. Also this case focuses attention on the importance of a correct evaluation of endogenous subclinical hyperthyroidism. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

  13. Accurate quantification of endogenous androgenic steroids in cattle's meat by gas chromatography mass spectrometry using a surrogate analyte approach

    Energy Technology Data Exchange (ETDEWEB)

    Ahmadkhaniha, Reza; Shafiee, Abbas [Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14174 (Iran, Islamic Republic of); Rastkari, Noushin [Center for Environmental Research, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Kobarfard, Farzad [Department of Medicinal Chemistry, School of Pharmacy, Shaheed Beheshti University of Medical Sciences, Tavaneer Ave., Valieasr St., Tehran (Iran, Islamic Republic of)], E-mail: farzadkf@yahoo.com

    2009-01-05

    Determination of endogenous steroids in complex matrices such as cattle's meat is a challenging task. Since endogenous steroids always exist in animal tissues, no analyte-free matrices for constructing the standard calibration line will be available, which is crucial for accurate quantification specially at trace level. Although some methods have been proposed to solve the problem, none has offered a complete solution. To this aim, a new quantification strategy was developed in this study, which is named 'surrogate analyte approach' and is based on using isotope-labeled standards instead of natural form of endogenous steroids for preparing the calibration line. In comparison with the other methods, which are currently in use for the quantitation of endogenous steroids, this approach provides improved simplicity and speed for analysis on a routine basis. The accuracy of this method is better than other methods at low concentration and comparable to the standard addition at medium and high concentrations. The method was also found to be valid according to the ICH criteria for bioanalytical methods. The developed method could be a promising approach in the field of compounds residue analysis.

  14. Effect of processed and red meat on endogenous nitrosation and DNA damage.

    Science.gov (United States)

    Joosen, Annemiek M C P; Kuhnle, Gunter G C; Aspinall, Sue M; Barrow, Timothy M; Lecommandeur, Emmanuelle; Azqueta, Amaya; Collins, Andrew R; Bingham, Sheila A

    2009-08-01

    Haem in red meat (RM) stimulates the endogenous production of mutagenic nitroso compounds (NOC). Processed (nitrite-preserved red) meat additionally contains high concentrations of preformed NOC. In two studies, of a fresh RM versus a vegetarian (VEG) diet (six males and six females) and of a nitrite-preserved red meat (PM) versus a VEG diet (5 males and 11 females), we investigated whether processing of meat might increase colorectal cancer risk by stimulating nitrosation and DNA damage. Meat diets contained 420 g (males) or 366 g (females) meat/per day. Faecal homogenates from day 10 onwards were analysed for haem and NOC and associated supernatants for genotoxicity. Means are adjusted for differences in male to female ratios between studies. Faecal NOC concentrations on VEG diets were low (2.6 and 3.5 mmol/g) but significantly higher on meat diets (PM 175 +/- 19 nmol/g versus RM 185 +/- 22 nmol/g; P = 0.75). The RM diet resulted in a larger proportion of nitrosyl iron (RM 78% versus PM 54%; P meat diets (P Meats cured with nitrite have the same effect as fresh RM on endogenous nitrosation but show increased FW-induced oxidative DNA damage.

  15. An endogenous aryl hydrocarbon receptor ligand acts on dendritic cells and T cells to suppress experimental autoimmune encephalomyelitis

    Science.gov (United States)

    Quintana, Francisco J.; Murugaiyan, Gopal; Farez, Mauricio F.; Mitsdoerffer, Meike; Tukpah, Ann-Marcia; Burns, Evan J.; Weiner, Howard L.

    2010-01-01

    The ligand-activated transcription factor aryl hydrocarbon receptor (AHR) participates in the differentiation of FoxP3+ Treg, Tr1 cells, and IL-17–producing T cells (Th17). Most of our understanding on the role of AHR on the FoxP3+ Treg compartment results from studies using the toxic synthetic chemical 2,3,7,8-tetrachlorodibenzo-p-dioxin. Thus, the physiological relevance of AHR signaling on FoxP3+ Treg in vivo is unclear. We studied mice that carry a GFP reporter in the endogenous foxp3 locus and a mutated AHR protein with reduced affinity for its ligands, and found that AHR signaling participates in the differentiation of FoxP3+ Treg in vivo. Moreover, we found that treatment with the endogenous AHR ligand 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) given parenterally or orally induces FoxP3+ Treg that suppress experimental autoimmune encephalomyelitis. ITE acts not only on T cells, but also directly on dendritic cells to induce tolerogenic dendritic cells that support FoxP3+ Treg differentiation in a retinoic acid-dependent manner. Thus, our work demonstrates that the endogenous AHR ligand ITE promotes the induction of active immunologic tolerance by direct effects on dendritic and T cells, and identifies nontoxic endogenous AHR ligands as potential unique compounds for the treatment of autoimmune disorders. PMID:21068375

  16. 59 eyes with endogenous endophthalmitis

    DEFF Research Database (Denmark)

    Bjerrum, Søren Solborg; la Cour, Morten

    2017-01-01

    BACKGROUND: To study the epidemiology of patients with endogenous endophthalmitis in Denmark. MATERIAL AND METHODS: Retrospective and prospective case series of 59 eyes in patients with endogenous endophthalmitis in Denmark between 2000 and 2016. RESULTS: The age of the patients ranged from 28 to......, the visual outcome and the mortality of the patients. The epidemiology of the disease is very different in Scandinavia compared to Asia. The visual prognosis remains grave and the majority of the eyes lose useful vision....

  17. Independent effects of endogenous and exogenous attention in touch.

    Science.gov (United States)

    Jones, Alexander; Forster, Bettina

    2013-12-01

    Endogenous and exogenous attention in touch have typically been investigated separately. Here we use a double-cueing paradigm manipulating both types of orienting in each trial. Bilateral endogenous cues induced long-lasting facilitation of endogenous attention up to 2 s. However, the exogenous cue only elicited an effect at short intervals. Our results favour a supramodal account of attention and this study provides new insight into how endogenous and exogenous attention operates in the tactile modality.

  18. Endogenous inhibition of somatic pain is impaired in girls with irritable bowel syndrome compared with healthy girls

    Science.gov (United States)

    Endogenous pain inhibition is often deficient in adults with chronic pain conditions including irritable bowel syndrome (IBS). It is unclear whether deficiencies in pain inhibition are present in young children with IBS. The present study compared endogenous pain inhibition, somatic pain threshold, ...

  19. Endogenous morphine-6-glucuronide (M6G) is present in the plasma of patients: validation of a specific anti-M6G antibody for clinical and basic research.

    Science.gov (United States)

    Laux-Biehlmann, Alexis; Chung, Hélène; Mouheiche, Jinane; Vérièpe, Julie; Delalande, François; Lamshöft, Marc; Welters, Ingeborg D; Soldevila, Stéphanie; Bazin, Hervé; Lamarque, Laurent; Van Dorsselaer, Alain; Poisbeau, Pierrick; Schneider, Francis; Goumon, Yannick; Garnero, Patrick

    2014-01-01

    Endogenous morphine and its derivatives (morphine-6-glucuronide [M6G]; morphine-3-glucuronide [M3G]) are formed by mammalian cells from dopamine. Changes in the concentrations of endogenous morphine have been demonstrated in several pathologies (sepsis, Parkinson's disease, etc.), and they might be relevant as pathological markers. While endogenous morphine levels are detectable using enzyme-linked immunosorbant assay (ELISA), mass spectrometry (MS) analysis was, so far, the only approach to detect and quantify M6G. This study describes the preparation of a specific anti-M6G rabbit polyclonal antibody and its validation. The specificity of this antibody was assessed against 30 morphine-related compounds. Then, a M6G-specific ELISA-assay was tested to quantify M6G in the plasma of healthy donors, morphine-treated, and critically ill patients. The antibody raised against M6G displays a strong affinity for M6G, codeine-6-glucuronide, and morphine-3-6-glucuronide, whereas only weak cross-reactivities were observed for the other compounds. Both M6G-ELISA and LC-MS/MS approaches revealed the absence of M6G in the plasma of healthy donors (controls, n = 8). In all positive donors treated with morphine-patch (n = 5), M6G was detected using both M6G-ELISA and LC-MS/MS analysis. Finally, in a study on critically ill patients with circulating endogenous morphine (n = 26), LC-MS/MS analysis revealed that 73% of the positive-patients (19 of 26), corresponding to high M6G-levels in M6G-ELISA, contained M6G. In conclusion, we show that endogenous M6G can be found at higher levels than morphine in the blood of morphine-naive patients. With respect to the interest of measuring endogenous M6G in pathologies, we provide evidences that our ELISA procedure represents a powerful tool as it can easily and specifically detect endogenous M6G levels. © 2013 International Union of Biochemistry and Molecular Biology.

  20. Endogenous versus exogenous shocks in systems with memory

    Science.gov (United States)

    Sornette, D.; Helmstetter, A.

    2003-02-01

    Systems with long-range persistence and memory are shown to exhibit different precursory as well as recovery patterns in response to shocks of exogenous versus endogenous origins. By endogenous, we envision either fluctuations resulting from an underlying chaotic dynamics or from a stochastic forcing origin which may be external or be an effective coarse-grained description of the microscopic fluctuations. In this scenario, endogenous shocks result from a kind of constructive interference of accumulated fluctuations whose impacts survive longer than the large shocks themselves. As a consequence, the recovery after an endogenous shock is in general slower at early times and can be at long times either slower or faster than after an exogenous perturbation. This offers the tantalizing possibility of distinguishing between an endogenous versus exogenous cause of a given shock, even when there is no “smoking gun”. This could help in investigating the exogenous versus self-organized origins in problems such as the causes of major biological extinctions, of change of weather regimes and of the climate, in tracing the source of social upheaval and wars, and so on. Sornette et al., Volatility fingerprints of large stocks: endogenous versus exogenous, cond-mat/0204626 has already shown how this concept can be applied concretely to differentiate the effects on financial markets of the 11 September 2001 attack or of the coup against Gorbachev on 19 August 1991 (exogenous) from financial crashes such as October 1987 (endogenous).

  1. Origin of ores of endogeneous uranium ore deposits

    International Nuclear Information System (INIS)

    Kasanskij, V.I.; Laverov, N.P.; Tugarinov, A.I.

    1976-01-01

    The consideration mainly includes those endogenous uranium ore deposits of which more exact data are available, such as precambrian ones in areas of proto-activated old platforms, deposits of palaeozoic fold areas, and mesozoic deposits in areas of tectonic-magnetic activation. Their genesis and typical characters are mentioned and conclusions on the general distribution of the deposits are drawn. (author)

  2. Borderline Personality Disorder: A Dysregulation of the Endogenous Opioid System?

    Science.gov (United States)

    Bandelow, Borwin; Schmahl, Christian; Falkai, Peter; Wedekind, Dirk

    2010-01-01

    The neurobiology of borderline personality disorder (BPD) remains unclear. Dysfunctions of several neurobiological systems, including serotoninergic, dopaminergic, and other neurotransmitter systems, have been discussed. Here we present a theory that alterations in the sensitivity of opioid receptors or the availability of endogenous opioids…

  3. Measurement of endogenous allergens in genetically modified soybeans--short communication.

    Science.gov (United States)

    Ladics, Gregory S; Budziszewski, Gregory J; Herman, Rod A; Herouet-Guicheney, Corinne; Joshi, Saurabh; Lipscomb, Elizabeth A; McClain, Scott; Ward, Jason M

    2014-10-01

    The measurement of endogenous allergens is required by the European Commission (EC) as part of the compositional analysis for GM products from host plants that are common causes of food allergy, such as soybean (EC Implementing Regulation No. 503/2013). In each case, the EC Implementing Regulation indicates that analysis be conducted on identified allergens as specified in the Organization of Economic Cooperation and Development (OECD) consensus documents on compositional considerations for new plant varieties. This communication discusses the methods available to measure endogenous allergens as well as the endogenous soybean allergens that should be analyzed. It is suggested herein that in conjunction with the 2012 OECD consensus document on soybean, any list of soybean allergens should be based on clinically relevant data among publicly available allergen databases and peer-reviewed scientific publications, and the ability to measure the identified allergen. Based on a detailed analysis of the scientific literature, the following key points are recommended: (1) the acceptance of serum-free, quantitative analytical method data as an alternative to traditional IgE reactivity qualitative or semi-quantitative data for evaluation of endogenous soybean allergen content; (2) eight of the 15 potential allergens listed in the OECD soybean consensus document (Gly m 3, Gly m 4, Gly m Bd28K, Gly m Bd30K, Gly m 5, Gly m 6, Gly m 8, and Kunitz trypsin inhibitor) have both appropriate supporting clinical data and sufficient sequence information to be evaluated in comparative endogenous soybean allergen studies; and (3) the remaining seven proteins (Gly m 1, Gly m 2, unknown 50kDa protein, unknown 39kDa protein, P-22-25, lipoxygenase and lectin) lack sufficient data for clear classification as confirmed allergens and/or available sequence information and should not be currently included in the measurement of endogenous soybean allergens in the compositional analysis for the EU

  4. Endogenous allergens and compositional analysis in the allergenicity assessment of genetically modified plants.

    Science.gov (United States)

    Fernandez, A; Mills, E N C; Lovik, M; Spoek, A; Germini, A; Mikalsen, A; Wal, J M

    2013-12-01

    Allergenicity assessment of genetically modified (GM) plants is one of the key pillars in the safety assessment process of these products. As part of this evaluation, one of the concerns is to assess that unintended effects (e.g. over-expression of endogenous allergens) relevant for the food safety have not occurred due to the genetic modification. Novel technologies are now available and could be used as complementary and/or alternative methods to those based on human sera for the assessment of endogenous allergenicity. In view of these developments and as a step forward in the allergenicity assessment of GM plants, it is recommended that known endogenous allergens are included in the compositional analysis as additional parameters to be measured. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Methylated DNA Immunoprecipitation Analysis of Mammalian Endogenous Retroviruses.

    Science.gov (United States)

    Rebollo, Rita; Mager, Dixie L

    2016-01-01

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

  6. International Environmental Agreements with Endogenous or Exogenous Risk

    OpenAIRE

    Fuhai Hong; Larry Karp

    2014-01-01

    We examine the effect of endogenous and exogenous risk on the equilibrium (expected) membership of an International Environmental Agreement when countries are risk averse. Endogenous risk arises when countries use mixed rather than pure strategies at the participation game, and exogenous risk arises from the inherent uncertainty about the costs and benefits of increased abate- ment. Under endogenous risk, an increase in risk aversion increases expected participation. Under exogenous risk and ...

  7. Importance of Endogenous Fibrinolysis in Platelet Thrombus Formation.

    Science.gov (United States)

    Gue, Ying X; Gorog, Diana A

    2017-08-25

    The processes of thrombosis and coagulation are finely regulated by endogenous fibrinolysis maintaining healthy equilibrium. When the balance is altered in favour of platelet activation and/or coagulation, or if endogenous fibrinolysis becomes less efficient, pathological thrombosis can occur. Arterial thrombosis remains a major cause of morbidity and mortality in the world despite advances in medical therapies. The role endogenous fibrinolysis in the pathogenesis of arterial thrombosis has gained increasing attention in recent years as it presents novel ways to prevent and treat existing diseases. In this review article, we discuss the role of endogenous fibrinolysis in platelet thrombus formation, methods of measurement of fibrinolytic activity, its role in predicting cardiovascular diseases and clinical outcomes and future directions.

  8. Uncertainty and endogenous technical change in climate policy models

    International Nuclear Information System (INIS)

    Baker, Erin; Shittu, Ekundayo

    2008-01-01

    Until recently endogenous technical change and uncertainty have been modeled separately in climate policy models. In this paper, we review the emerging literature that considers both these elements together. Taken as a whole the literature indicates that explicitly including uncertainty has important quantitative and qualitative impacts on optimal climate change technology policy. (author)

  9. Bilateral endogenous Fusarium solani endophthalmitis in a liver-transplanted patient

    DEFF Research Database (Denmark)

    Jørgensen, Jesper Skovlund; Prause, Jan Ulrik; Kiilgaard, Jens Folke

    2014-01-01

    Endogenous Fusarium endophthalmitis is a rare disease predominantly described in immunocompromised patients often due to leukemia. We report a case of bilateral endogenous Fusarium solani endophthalmitis in a liver-transplanted patient.......Endogenous Fusarium endophthalmitis is a rare disease predominantly described in immunocompromised patients often due to leukemia. We report a case of bilateral endogenous Fusarium solani endophthalmitis in a liver-transplanted patient....

  10. Feeding Releases Endogenous Opioids in Humans.

    Science.gov (United States)

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

    2017-08-23

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

  11. The Endogenous-Exogenous Partition in Attribution Theory

    Science.gov (United States)

    Kruglanski, Arie W.

    1975-01-01

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

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

    Directory of Open Access Journals (Sweden)

    OSMAN DEMİR

    2013-06-01

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

  13. Endogenous biotin expression in renal and testicular tumours and literature review.

    Science.gov (United States)

    Fahmy, Nader; Woo, Mark; Alameldin, Mona; Lee, Joe King; MacDonald, Kyle; Goneau, Lee W; Cadieux, Peter; Burton, Jeremy; Pautler, Stephen

    2014-07-01

    The aim of this study was to examine endogenous biotin levels in tumour specimens collected from patients with renal and testicular tumours and compare them to the surrounding non-neoplastic surgical margin. Frozen samples were obtained from the Ontario Tumour Bank. Renal and testicular tumour tissue were included in this study. Normal tissue from the negative surgical margins of each tumour served as a control. Biotin detection in tissue specimens was determined using immunohistochemistry (IHC). Specimens collected from 56 patients (36 men and 20 women) were included in this study. Histopathology of the 52 renal tumours included 31 (60%) conventional type RCC, 5 (10%) chromophobe RCC, 5 (10%) papillary RCC, 1 (2%) oncocytoma and 10 (19%) upper tract urothelial carcinoma (UC). The 4 testicular tumours included 1 seminomatous (25%) germ cell tumour and 3 (75%) non seminomatous germ cell tumours. No biotin signal was perceived in all tested tumour samples. Endogenous biotin expression was detected in the matching non-neoplastic surgical margin of tested renal tissues. This lack of staining may prove to be a valuable tool in future studies.

  14. Endogenous Cartilage Repair by Recruitment of Stem Cells.

    Science.gov (United States)

    Im, Gun-Il

    2016-04-01

    Articular cartilage has a very limited capacity for repair after injury. The adult body has a pool of stem cells that are mobilized during injury or disease. These cells exist inside niches in bone marrow, muscle, adipose tissue, synovium, and other connective tissues. A method that mobilizes this endogenous pool of stem cells will provide a less costly and less invasive alternative if these cells successfully regenerate defective cartilage. Traditional microfracture procedures employ the concept of bone marrow stimulation to regenerate cartilage. However, the regenerated tissue usually is fibrous cartilage, which has very poor mechanical properties compared to those of normal hyaline cartilage. A method that directs the migration of a large number of autologous mesenchymal stem cells toward injury sites, retains these cells around the defects, and induces chondrogenic differentiation that would enhance success of endogenous cartilage repair. This review briefly summarizes chemokines and growth factors that induce recruitment, proliferation, and differentiation of endogenous progenitor cells, endogenous cell sources for regenerating cartilage, scaffolds for delivery of bioactive factors, and bioadhesive materials that are necessary to bring about endogenous cartilage repair.

  15. Endogeneity of Money Supply: Evidence From Turkey

    OpenAIRE

    Oguzhan Cepni; Ibrahim Ethem Guney

    2017-01-01

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

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

    African Journals Online (AJOL)

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

  17. Increasing Goat Productivity Through the Improvement of Endogenous Secretion of Pregnant Hormones Using Follicle Stimulating Hormone

    Directory of Open Access Journals (Sweden)

    Andriyanto Andriyanto

    2011-05-01

    Full Text Available Abstract. Previous studies reported that the improvement of endogenous estrogen and progesterone secretions during gestation improved fetal prenatal growth, birth weight, mammary gland growth and development, milk production, litter size, pre- and post-weaning growths. An experiment was conducted to apply the improvement of endogenous secretion of pregnant hormones during pregnancy to increase goat productivity. Thirty-six female ettawah-cross does were divided into 2 groups. Group 1 (control: 18 does included does without improvement of endogenous secretion of pregnant hormones and Group 2 (treatment: 18 does included does with improvement of endogenous secretion of pregnant hormones using follicle stimulating hormones to stimulate super ovulation. The application of this technology increased total offspring born (control: 25 offspring; treatment: 42 offspring, average litter size (control: 1.88; treatment: 2.33, offspring birth weight (control: 2.85±0.50 kg; treatment: 3.82±0.40 kg, and does milk production (control: 1.36±0.34 L/does/day; treatment: 2.10±0.21 L/does/day. Offspring born to does with improved endogenous secretion of pregnant hormones had better weaning weight (control: 11.17±1.99 kg/offspring; treatment: 14.5±1.11 kg/offspring. At weaning period, does with improved endogenous secretion of pregnant hormones produced offspring with total weaning weight twice as heavy as control does (control: 189.9 kg; treatment: 403.6 kg. By a simple calculation of economic analysis, this technology application could increase gross revenue per does until weaning by Rp. 432.888,89. It was concluded that this technology is economically feasible to be applied in small-scale farm. Key Words: follicle stimulating hormone, pregnant hormones, endogenous secretion, super ovulation, ettawah-cross does

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

    Science.gov (United States)

    McKillip, Jack

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

  19. P-wave dispersion in endogenous and exogenous subclinical hyperthyroidism.

    Science.gov (United States)

    Gen, R; Akbay, E; Camsari, A; Ozcan, T

    2010-02-01

    The aim of this study was to measure maximum P wave duration (Pmax) and P wave dispersion (PWD), which can be indicators for the risk of paroxysmal atrial fibrillation when increased, and to reveal their relationship with thyroid hormone levels in patients with endogenous and exogenous subclinical hyperthyroidism. Seventy-one patients with sublinical thyrotoxicosis (34 endogenous, 37 exogenous) and 69 healthy individuals were enrolled in the study. Pmax and minimum P wave duration (Pmin) on electrocardiogram recordings were measured and PWD was calculated as Pmax-Pmin. Pmax (pendogenous subclinical hyperthyroidism compared with the control group. Pmax (pexogenous subclinical thyrotoxicosis compared with the control group. Pmax (p=0.710) and PWD (p=0.127) were not significantly different in patients with endogenous subclinical hyperthyroidism compared with exogenous subclinical hyperthyroid patients. Pmax and PWD negatively associated with TSH in endogenous and exogenous subclinical hyperthyroidism. In the present study, we observed that Pmax and PWD were longer in patients with endogenous and exogenous subclinical hyperthyroidism. Lack of a difference in Pmax and PWD between patients with endogenous and exogenous subclinical hyperthyroidism seems to support the idea that hormone levels rather than the etiology of thyrotoxicosis affect the heart.

  20. Carbon monoxide: from toxin to endogenous modulator of cardiovascular functions

    Directory of Open Access Journals (Sweden)

    R.A. Johnson

    1999-01-01

    Full Text Available Carbon monoxide (CO is a pollutant commonly recognized for its toxicological attributes, including CNS and cardiovascular effects. But CO is also formed endogenously in mammalian tissues. Endogenously formed CO normally arises from heme degradation in a reaction catalyzed by heme oxygenase. While inhibitors of endogenous CO production can raise arterial pressure, heme loading can enhance CO production and lead to vasodepression. Both central and peripheral tissues possess heme oxygenases and generate CO from heme, but the inability of heme substrate to cross the blood brain barrier suggests the CNS heme-heme oxygenase-CO system may be independent of the periphery. In the CNS, CO apparently acts in the nucleus tractus solitarii (NTS promoting changes in glutamatergic neurotransmission and lowering blood pressure. At the periphery, the heme-heme oxygenase-CO system can affect cardiovascular functions in a two-fold manner; specifically: 1 heme-derived CO generated within vascular smooth muscle (VSM can promote vasodilation, but 2 its actions on the endothelium apparently can promote vasoconstriction. Thus, it seems reasonable that the CNS-, VSM- and endothelial-dependent actions of the heme-heme oxygenase-CO system may all affect cardiac output and vascular resistance, and subsequently blood pressure.

  1. Endogene CGRP

    OpenAIRE

    Höfer, Martina

    2010-01-01

    Hintergrund und Ziele Die vorliegende tierexperimentelle Arbeit beschäftigt sich mit der Frage, welche Rolle endogenes Calcitonin-gene related peptide (CGRP) in der Niere spielt. Hierbei untersuchten wir die renale CGRP Freisetzung aus renalen Afferenzen in vitro anhand von gesunden Tieren und einem pathologischen Modell der Glomerulonephritis. Man weiß bereits, dass sowohl sympathische als auch primär sensorische Neuronen die Entzündung und die Immunantwort in der Peripherie regulieren (68)....

  2. Endogenous Money Supply and Money Demand

    OpenAIRE

    Woon Gyu Choi; Seonghwan Oh

    2000-01-01

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

  3. Optimized endogenous post-stratification in forest inventories

    Science.gov (United States)

    Paul L. Patterson

    2012-01-01

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

  4. Characterization of Macrophage Endogenous S-Nitrosoproteome Using a Cysteine-Specific Phosphonate Adaptable Tag in Combination with TiO2 Chromatography.

    Science.gov (United States)

    Ibáñez-Vea, María; Huang, Honggang; Martínez de Morentin, Xabier; Pérez, Estela; Gato, Maria; Zuazo, Miren; Arasanz, Hugo; Fernández-Irigoyen, Joaquin; Santamaría, Enrique; Fernandez-Hinojal, Gonzalo; Larsen, Martin R; Escors, David; Kochan, Grazyna

    2018-03-02

    Protein S-nitrosylation is a cysteine post-translational modification mediated by nitric oxide. An increasing number of studies highlight S-nitrosylation as an important regulator of signaling involved in numerous cellular processes. Despite the significant progress in the development of redox proteomic methods, identification and quantification of endogeneous S-nitrosylation using high-throughput mass-spectrometry-based methods is a technical challenge because this modification is highly labile. To overcome this drawback, most methods induce S-nitrosylation chemically in proteins using nitrosylating compounds before analysis, with the risk of introducing nonphysiological S-nitrosylation. Here we present a novel method to efficiently identify endogenous S-nitrosopeptides in the macrophage total proteome. Our approach is based on the labeling of S-nitrosopeptides reduced by ascorbate with a cysteine specific phosphonate adaptable tag (CysPAT), followed by titanium dioxide (TiO 2 ) chromatography enrichment prior to nLC-MS/MS analysis. To test our procedure, we performed a large-scale analysis of this low-abundant modification in a murine macrophage cell line. We identified 569 endogeneous S-nitrosylated proteins compared with 795 following exogenous chemically induced S-nitrosylation. Importantly, we discovered 579 novel S-nitrosylation sites. The large number of identified endogenous S-nitrosylated peptides allowed the definition of two S-nitrosylation consensus sites, highlighting protein translation and redox processes as key S-nitrosylation targets in macrophages.

  5. Two-stage residual inclusion estimation: addressing endogeneity in health econometric modeling.

    Science.gov (United States)

    Terza, Joseph V; Basu, Anirban; Rathouz, Paul J

    2008-05-01

    The paper focuses on two estimation methods that have been widely used to address endogeneity in empirical research in health economics and health services research-two-stage predictor substitution (2SPS) and two-stage residual inclusion (2SRI). 2SPS is the rote extension (to nonlinear models) of the popular linear two-stage least squares estimator. The 2SRI estimator is similar except that in the second-stage regression, the endogenous variables are not replaced by first-stage predictors. Instead, first-stage residuals are included as additional regressors. In a generic parametric framework, we show that 2SRI is consistent and 2SPS is not. Results from a simulation study and an illustrative example also recommend against 2SPS and favor 2SRI. Our findings are important given that there are many prominent examples of the application of inconsistent 2SPS in the recent literature. This study can be used as a guide by future researchers in health economics who are confronted with endogeneity in their empirical work.

  6. SwePep, a database designed for endogenous peptides and mass spectrometry.

    Science.gov (United States)

    Fälth, Maria; Sköld, Karl; Norrman, Mathias; Svensson, Marcus; Fenyö, David; Andren, Per E

    2006-06-01

    A new database, SwePep, specifically designed for endogenous peptides, has been constructed to significantly speed up the identification process from complex tissue samples utilizing mass spectrometry. In the identification process the experimental peptide masses are compared with the peptide masses stored in the database both with and without possible post-translational modifications. This intermediate identification step is fast and singles out peptides that are potential endogenous peptides and can later be confirmed with tandem mass spectrometry data. Successful applications of this methodology are presented. The SwePep database is a relational database developed using MySql and Java. The database contains 4180 annotated endogenous peptides from different tissues originating from 394 different species as well as 50 novel peptides from brain tissue identified in our laboratory. Information about the peptides, including mass, isoelectric point, sequence, and precursor protein, is also stored in the database. This new approach holds great potential for removing the bottleneck that occurs during the identification process in the field of peptidomics. The SwePep database is available to the public.

  7. Differential diagnosis algorithm of endogenous catatonia, catatonia-morphic and catatonia-mimicking states

    Directory of Open Access Journals (Sweden)

    D. N. Safonov

    2017-08-01

    Full Text Available Subject relevance. The process of mental pathology pathomorphosis leads to the polymorphism of its clinical manifestations and, as a consequence – to difficulties in identification and differential diagnosis. The solution to this problem is in the adaption of diagnostic methodology to clinical realities by including into their structure instruments formed basing on pathomorphosis factors and trends. In this perspective, the most prominent example is endogenous catatonia, which in the academic tradition is conventionally affiliated with the form of schizophrenia with the same name. According to the classical understanding, endogenous catatonia, or, in the narrow sense – catatonic syndrome, is a group of intermittent motor disorders, arranged with polymorphic shell constellation of neuropsychiatric manifestations. The aim is to develop pathomorphosis adapted clinical algorithm of endogenous catatonia differential diagnostics. Materials and methods: 236 patients of Zaporizhzhia Regional Psychiatric Clinic were examined. Patients were divided into groups due to their mental disorders: – core group: patients with elements of endogenous catatonia in the structure of different clinical forms of schizophrenia (there were 144 patients in this group; – comparison group #1: 69 patients with late neurotropic effects of neuroleptic therapy (LNENT; – comparison group #2: 103 patients with catatonia-morphic dissociative disorders (CDD; – comparison group #3: 90 patients with organic catatonic disorder (OrCD; Results. Using Bush-Francis Catatonia Rating scale as an instrument of clinical analysis and statistical research of results with A. Wald’s sequential analysis (modificated by E. V. Gubler an algorithm of differential diagnostics of endogenus catatonia which includes 3 steps of Recognition Scale for Endogenous Catatonia is developed. Conclusion. Designed scales have a number of categorical differences from existing analogues, foremost by

  8. Endogenous zinc excretion in relation to various levels of dietary zinc intake in the mink (Mustela vison)

    International Nuclear Information System (INIS)

    Mejborn, H.

    1990-01-01

    Endogenous zinc excretion was studied in adult male mink fed experimental diets for 73 d, including a collection period from d 69 to 73. Dietary zinc levels were 2.8, 26 or 121 mg/kg wet weight. In accordance with the results of a methodological study, also reported here, the animals had an intramuscular injection of 65ZnCl2 12 d before the start of the collection period. Total fecal (endogenous + unabsorbed) zinc excretion for d 69-73 in the three groups was 2.3, 20.4 and 91.0 mg. The endogenous zinc excretion was 1.3, 2.0 and 6.4 mg, corresponding to 80.8, 10.6 and 6.4% of the zinc intake. Thus, the endogenous excretion was mainly important for the zinc homeostasis at low zinc intake, whereas at high intake the homeostasis was regulated via absorption from the digestive tract. The overall conclusion of the experiment was that mink are comparable to other species (including man) in regard to mechanisms controlling zinc homeostasis

  9. Endogenous opioids regulate moment-to-moment neuronal communication and excitability

    Science.gov (United States)

    Winters, Bryony L.; Gregoriou, Gabrielle C.; Kissiwaa, Sarah A.; Wells, Oliver A.; Medagoda, Danashi I.; Hermes, Sam M.; Burford, Neil T.; Alt, Andrew; Aicher, Sue A.; Bagley, Elena E.

    2017-01-01

    Fear and emotional learning are modulated by endogenous opioids but the cellular basis for this is unknown. The intercalated cells (ITCs) gate amygdala output and thus regulate the fear response. Here we find endogenous opioids are released by synaptic stimulation to act via two distinct mechanisms within the main ITC cluster. Endogenously released opioids inhibit glutamate release through the δ-opioid receptor (DOR), an effect potentiated by a DOR-positive allosteric modulator. Postsynaptically, the opioids activate a potassium conductance through the μ-opioid receptor (MOR), suggesting for the first time that endogenously released opioids directly regulate neuronal excitability. Ultrastructural localization of endogenous ligands support these functional findings. This study demonstrates a new role for endogenously released opioids as neuromodulators engaged by synaptic activity to regulate moment-to-moment neuronal communication and excitability. These distinct actions through MOR and DOR may underlie the opposing effect of these receptor systems on anxiety and fear. PMID:28327612

  10. Endogenous Phenolics in Hulls and Cotyledons of Mustard and Canola: A Comparative Study on Its Sinapates and Antioxidant Capacity

    OpenAIRE

    Mayengbam, Shyamchand; Aachary, Ayyappan; Thiyam-Holländer, Usha

    2014-01-01

    Endogenous sinapic acid (SA), sinapine (SP), sinapoyl glucose (SG) and canolol (CAN) of canola and mustard seeds are the potent antioxidants in various lipid-containing systems. The study investigated these phenolic antioxidants using different fractions of canola and mustard seeds. Phenolic compounds were extracted from whole seeds and their fractions: hulls and cotyledons, using 70% methanol by the ultrasonication method and quantified using HPLC-DAD. The major phenolics from both hulls and...

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

    Science.gov (United States)

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

    2018-03-01

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

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

    Science.gov (United States)

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

    2016-12-01

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

  13. Endogene opioider og deres terapeutiske anvendelse i smertebehandling

    DEFF Research Database (Denmark)

    Juul, A; Pedersen, A T

    1990-01-01

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

  14. Endogenous vs. exogenous regulations in the commons

    DEFF Research Database (Denmark)

    Abatayo, Anna Lou; Lynham, John

    2016-01-01

    It is widely believed that there is strong experimental evidence to support the idea that exogenously imposed regulations crowd out the intrinsic motivations of common pool resource (CPR) users to refrain from over-harvesting. We introduce a novel experimental design that attempts to disentangle...... potential confounds in previous experiments. A key feature of our experimental design is to have the exact same regulations chosen endogenously as those that are imposed exogenously. When we compare the same regulations chosen endogenously to those externally imposed, we observe no differences in extraction...... endogenous regulations with communication and exogenous regulations without communication. Our results suggest that externally imposed regulations do not crowd out intrinsic motivations in the lab and they confirm that communication facilitates cooperation to reduce extraction....

  15. Exercise induced asthma and endogenous opioids.

    Science.gov (United States)

    Gaillard, R C; Bachman, M; Rochat, T; Egger, D; de Haller, R; Junod, A F

    1986-01-01

    Concentrations of endogenous opioid peptides in the plasma are increased during exercise and these substances have been implicated in the pathogenesis of asthma induced by chloropropramide and alcohol in diabetic patients. This work was undertaken to determine whether exercise induced asthma might be mediated by endogenous opioids. Plasma beta endorphin, met-enkephalin, and adrenocorticotrophic hormone (ACTH) concentrations were measured in five asthmatic patients and five normal volunteers breathing cold air during exercise. In four of the patients the effect of an infusion of naloxone on FEV1 was also measured during exercise induced asthma. Exercise produced acute bronchoconstriction in all asthmatics, characterised by a fall in FEV1; whereas no change occurred in normal subjects. There was no difference in plasma met-enkephalin, beta endorphin, and ACTH concentration between the two groups. Infusion of naloxone neither prevented nor worsened exercise induced asthma. These data suggest that endogenous opioids probably do not play a part in the development of exercise induced asthma. PMID:2944240

  16. Odd-Z Transactinide Compound Nucleus Reactions Including the Discovery of 260Bh

    International Nuclear Information System (INIS)

    Nelson, Sarah L; Nelson, Sarah L

    2008-01-01

    Several reactions producing odd-Z transactinide compound nuclei were studied with the 88-Inch Cyclotron and the Berkeley Gas-Filled Separator at the Lawrence Berkeley National Laboratory. The goal was to produce the same compound nucleus at or near the same excitation energy with similar values of angular momentum via different nuclear reactions. In doing so, it can be determined if there is a preference in entrance channel, because under these experimental conditions the survival portion of Swiatecki, Siwek-Wilcznska, and Wilczynski's 'Fusion By Diffusion' model is nearly identical for the two reactions. Additionally, because the same compound nucleus is produced, the exit channel is the same. Four compound nuclei were examined in this study: 258Db, 262Bh, 266Mt, and 272Rg. These nuclei were produced by using very similar heavy-ion induced-fusion reactions which differ only by one proton in the projectile or target nucleus (e.g.: 50Ti + 209Bi vs. 51V + 208Pb). Peak 1n exit channel cross sections were determined for each reaction in each pair, and three of the four pairs; cross sections were identical within statistical uncertainties. This indicates there is not an obvious preference of entrance channel in these paired reactions. Charge equilibration immediately prior to fusion leading to a decreased fusion barrier is the likely cause of this phenomenon. In addition to this systematic study, the lightest isotope of element 107, bohrium, was discovered in the 209Bi(52Cr,n) reaction. 260Bh was found to decay by emission of a 10.16 MeV alpha particle with a half-life of 35 ms. The cross section is 59 pb at an excitation energy of 15.0 MeV. The effect of the N = 152 shell is also seen in this isotope's alpha particle energy, the first evidence of such an effect in Bh. All reactions studied are also compared to model predictions by Swiatecki, Siwek-Wilcznska, and Wilczynski's 'Fusion By Diffusion' theory

  17. The human endogenous circadian system causes greatest platelet activation during the biological morning independent of behaviors.

    Directory of Open Access Journals (Sweden)

    Frank A J L Scheer

    Full Text Available Platelets are involved in the thromboses that are central to myocardial infarctions and ischemic strokes. Such adverse cardiovascular events have day/night patterns with peaks in the morning (~9 AM, potentially related to endogenous circadian clock control of platelet activation. The objective was to test if the human endogenous circadian system influences (1 platelet function and (2 platelet response to standardized behavioral stressors. We also aimed to compare the magnitude of any effects on platelet function caused by the circadian system with that caused by varied standardized behavioral stressors, including mental arithmetic, passive postural tilt and mild cycling exercise.We studied 12 healthy adults (6 female who lived in individual laboratory suites in dim light for 240 h, with all behaviors scheduled on a 20-h recurring cycle to permit assessment of endogenous circadian function independent from environmental and behavioral effects including the sleep/wake cycle. Circadian phase was assessed from core body temperature. There were highly significant endogenous circadian rhythms in platelet surface activated glycoprotein (GP IIb-IIIa, GPIb and P-selectin (6-17% peak-trough amplitudes; p ≤ 0.01. These circadian peaks occurred at a circadian phase corresponding to 8-9 AM. Platelet count, ATP release, aggregability, and plasma epinephrine also had significant circadian rhythms but with later peaks (corresponding to 3-8 PM. The circadian effects on the platelet activation markers were always larger than that of any of the three behavioral stressors.These data demonstrate robust effects of the endogenous circadian system on platelet activation in humans--independent of the sleep/wake cycle, other behavioral influences and the environment. The 9 AM timing of the circadian peaks of the three platelet surface markers, including platelet surface activated GPIIb-IIIa, the final common pathway of platelet aggregation, suggests that endogenous

  18. Endogenous and exogenously-induced immunomodulation of tumour-host responsiveness

    Directory of Open Access Journals (Sweden)

    Richard J. Ablin

    1987-01-01

    Full Text Available In spite of the availability of multiple effector mechanisms of the immune system to combat tumour growth and metastases, their impairment frequently accompanies the appearance of cancer. Factors contributing to this impairment may be related to properties of the host and/or the tumour itself and may be with respect to their origin -endogenous or exogenour. Based on the unique biological behavior of prostate cancer (PCa, and its apparent escape from immune surveillance in the presence of tumour immuno genicity, continuing investigation of endogenous and exogenous factors thought to be relevant to its pathogenesis have been made. For this purpose further studies of the suggested role of human seminal plasma (SePl and the synthetic oestrogen, diethylstiboestrol (DES, as representative endogenous and exogenous immunomodulatory factors (IMF of tumour-host responsiveness, together with evaluation of human prostatic tissue extracts and leuprolide (the luteinizing-hormone-releasing-hormone proposed as an alternate to DES therapy have been made by evaluating their effect on the lytic activity of natural killer (NK cells. SePl and prostate extracts significantly suppressed NK cell lysis. Physicochemical studies suggest SePl and prostate IMF to be associated with high and low molecular weight macromolecules; and implicate the participation of transglutaminase and prostaglandins. Comparative study of therapeutic levels of DES vs. leuprolide on NK cell lysis demonstrated significant suppression by DES vs. a negligible effect of leuprolide. Metastases are highly prevalent in PCa, and contribute significantly to its morbidity and mortality. Further knowledge of the range of effects of endogenous and exogenous IMF on effector mechanisms of tumour-host responsiveness, to include suppression of NK cells, and elucidation of their nature, may contribute toward our understanding of the unique biological behavior of tumours of the prostate, in addition to

  19. Endogenous Cortical Oscillations Constrain Neuromodulation by Weak Electric Fields

    Science.gov (United States)

    Schmidt, Stephen L.; Iyengar, Apoorva K.; Foulser, A. Alban; Boyle, Michael R.; Fröhlich, Flavio

    2014-01-01

    Background Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation modality that may modulate cognition by enhancing endogenous neocortical oscillations with the application of sine-wave electric fields. Yet, the role of endogenous network activity in enabling and shaping the effects of tACS has remained unclear. Objective We combined optogenetic stimulation and multichannel slice electrophysiology to elucidate how the effect of weak sine-wave electric field depends on the ongoing cortical oscillatory activity. We hypothesized that the structure of the response to stimulation depended on matching the stimulation frequency to the endogenous cortical oscillation. Methods We studied the effect of weak sine-wave electric fields on oscillatory activity in mouse neocortical slices. Optogenetic control of the network activity enabled the generation of in vivo like cortical oscillations for studying the temporal relationship between network activity and sine-wave electric field stimulation. Results Weak electric fields enhanced endogenous oscillations but failed to induce a frequency shift of the ongoing oscillation for stimulation frequencies that were not matched to the endogenous oscillation. This constraint on the effect of electric field stimulation imposed by endogenous network dynamics was limited to the case of weak electric fields targeting in vivo-like network dynamics. Together, these results suggest that the key mechanism of tACS may be enhancing but not overriding of intrinsic network dynamics. Conclusion Our results contribute to understanding the inconsistent tACS results from human studies and propose that stimulation precisely adjusted in frequency to the endogenous oscillations is key to rational design of non-invasive brain stimulation paradigms. PMID:25129402

  20. Mobilization of endogenous retroviruses in mice after infection with an exogenous retrovirus.

    Science.gov (United States)

    Evans, Leonard H; Alamgir, A S M; Owens, Nick; Weber, Nick; Virtaneva, Kimmo; Barbian, Kent; Babar, Amenah; Malik, Frank; Rosenke, Kyle

    2009-03-01

    Mammalian genomes harbor a large number of retroviral elements acquired as germ line insertions during evolution. Although many of the endogenous retroviruses are defective, several contain one or more intact viral genes that are expressed under certain physiological or pathological conditions. This is true of the endogenous polytropic retroviruses that generate recombinant polytropic murine leukemia viruses (MuLVs). In these recombinants the env gene sequences of exogenous ecotropic MuLVs are replaced with env gene sequences from an endogenous polytropic retrovirus. Although replication-competent endogenous polytropic retroviruses have not been observed, the recombinant polytropic viruses are capable of replicating in numerous species. Recombination occurs during reverse transcription of a virion RNA heterodimer comprised of an RNA transcript from an endogenous polytropic virus and an RNA transcript from an exogenous ecotropic MuLV RNA. It is possible that homodimers corresponding to two full-length endogenous RNA genomes are also packaged. Thus, infection by an exogenous virus may result not only in recombination with endogenous sequences, but also in the mobilization of complete endogenous retrovirus genomes via pseudotyping within exogenous retroviral virions. We report that the infection of mice with an ecotropic virus results in pseudotyping of intact endogenous viruses that have not undergone recombination. The endogenous retroviruses infect and are integrated into target cell genomes and subsequently replicate and spread as pseudotyped viruses. The mobilization of endogenous retroviruses upon infection with an exogenous retrovirus may represent a major interaction of exogenous retroviruses with endogenous retroviruses and may have profound effects on the pathogenicity of retroviral infections.

  1. Endogenous Vascular Endothelial Growth Factor-A (VEGF-A) Maintains Endothelial Cell Homeostasis by Regulating VEGF Receptor-2 Transcription*

    Science.gov (United States)

    E, Guangqi; Cao, Ying; Bhattacharya, Santanu; Dutta, Shamit; Wang, Enfeng; Mukhopadhyay, Debabrata

    2012-01-01

    Vascular endothelial growth factor A (VEGF-A) is one of the most important factors controlling angiogenesis. Although the functions of exogenous VEGF-A have been widely studied, the roles of endogenous VEGF-A remain unclear. Here we focused on the mechanistic functions of endogenous VEGF-A in endothelial cells. We found that it is complexed with VEGF receptor 2 (VEGFR-2) and maintains a basal expression level for VEGFR-2 and its downstream signaling activation. Endogenous VEGF-A also controls expression of key endothelial specific genes including VEGFR-2, Tie-2, and vascular endothelial cadherin. Of importance, endogenous VEGF-A differs from exogenous VEGF-A by regulating VEGFR-2 transcription through mediation of FoxC2 binding to the FOX:ETS motif, and the complex formed by endogenous VEGF-A with VEGFR-2 is localized within the EEA1 (early endosome antigen 1) endosomal compartment. Taken together, our results emphasize the importance of endogenous VEGF-A in endothelial cells by regulating key vascular proteins and maintaining the endothelial homeostasis. PMID:22167188

  2. Endogenous fields enhanced stochastic resonance in a randomly coupled neuronal network

    International Nuclear Information System (INIS)

    Deng, Bin; Wang, Lin; Wang, Jiang; Wei, Xi-le; Yu, Hai-tao

    2014-01-01

    Highlights: • We study effects of endogenous fields on stochastic resonance in a neural network. • Stochastic resonance can be notably enhanced by endogenous field feedback. • Endogenous field feedback delay plays a vital role in stochastic resonance. • The parameters of low-passed filter play a subtle role in SR. - Abstract: Endogenous field, evoked by structured neuronal network activity in vivo, is correlated with many vital neuronal processes. In this paper, the effects of endogenous fields on stochastic resonance (SR) in a randomly connected neuronal network are investigated. The network consists of excitatory and inhibitory neurons and the axonal conduction delays between neurons are also considered. Numerical results elucidate that endogenous field feedback results in more rhythmic macroscope activation of the network for proper time delay and feedback coefficient. The response of the network to the weak periodic stimulation can be notably enhanced by endogenous field feedback. Moreover, the endogenous field feedback delay plays a vital role in SR. We reveal that appropriately tuned delays of the feedback can either induce the enhancement of SR, appearing at every integer multiple of the weak input signal’s oscillation period, or the depression of SR, appearing at every integer multiple of half the weak input signal’s oscillation period for the same feedback coefficient. Interestingly, the parameters of low-passed filter which is used in obtaining the endogenous field feedback signal play a subtle role in SR

  3. A potential role for endogenous proteins as sacrificial sunscreens and antioxidants in human tissues

    Directory of Open Access Journals (Sweden)

    Sarah A. Hibbert

    2015-08-01

    Full Text Available Excessive ultraviolet radiation (UVR exposure of the skin is associated with adverse clinical outcomes. Although both exogenous sunscreens and endogenous tissue components (including melanins and tryptophan-derived compounds reduce UVR penetration, the role of endogenous proteins in absorbing environmental UV wavelengths is poorly defined. Having previously demonstrated that proteins which are rich in UVR-absorbing amino acid residues are readily degraded by broadband UVB-radiation (containing UVA, UVB and UVC wavelengths here we hypothesised that UV chromophore (Cys, Trp and Tyr content can predict the susceptibility of structural proteins in skin and the eye to damage by physiologically relevant doses (up to 15.4 J/cm2 of solar UVR (95% UVA, 5% UVB. We show that: i purified suspensions of UV-chromophore-rich fibronectin dimers, fibrillin microfibrils and β- and γ-lens crystallins undergo solar simulated radiation (SSR-induced aggregation and/or decomposition and ii exposure to identical doses of SSR has minimal effect on the size or ultrastructure of UV chromophore-poor tropoelastin, collagen I, collagen VI microfibrils and α-crystallin. If UV chromophore content is a factor in determining protein stability in vivo, we would expect that the tissue distribution of Cys, Trp and Tyr-rich proteins would correlate with regional UVR exposure. From bioinformatic analysis of 244 key structural proteins we identified several biochemically distinct, yet UV chromophore-rich, protein families. The majority of these putative UV-absorbing proteins (including the late cornified envelope proteins, keratin associated proteins, elastic fibre-associated components and β- and γ-crystallins are localised and/or particularly abundant in tissues that are exposed to the highest doses of environmental UVR, specifically the stratum corneum, hair, papillary dermis and lens. We therefore propose that UV chromophore-rich proteins are localised in regions of high UVR

  4. A potential role for endogenous proteins as sacrificial sunscreens and antioxidants in human tissues.

    Science.gov (United States)

    Hibbert, Sarah A; Watson, Rachel E B; Gibbs, Neil K; Costello, Patrick; Baldock, Clair; Weiss, Anthony S; Griffiths, Christopher E M; Sherratt, Michael J

    2015-08-01

    Excessive ultraviolet radiation (UVR) exposure of the skin is associated with adverse clinical outcomes. Although both exogenous sunscreens and endogenous tissue components (including melanins and tryptophan-derived compounds) reduce UVR penetration, the role of endogenous proteins in absorbing environmental UV wavelengths is poorly defined. Having previously demonstrated that proteins which are rich in UVR-absorbing amino acid residues are readily degraded by broadband UVB-radiation (containing UVA, UVB and UVC wavelengths) here we hypothesised that UV chromophore (Cys, Trp and Tyr) content can predict the susceptibility of structural proteins in skin and the eye to damage by physiologically relevant doses (up to 15.4 J/cm(2)) of solar UVR (95% UVA, 5% UVB). We show that: i) purified suspensions of UV-chromophore-rich fibronectin dimers, fibrillin microfibrils and β- and γ-lens crystallins undergo solar simulated radiation (SSR)-induced aggregation and/or decomposition and ii) exposure to identical doses of SSR has minimal effect on the size or ultrastructure of UV chromophore-poor tropoelastin, collagen I, collagen VI microfibrils and α-crystallin. If UV chromophore content is a factor in determining protein stability in vivo, we would expect that the tissue distribution of Cys, Trp and Tyr-rich proteins would correlate with regional UVR exposure. From bioinformatic analysis of 244 key structural proteins we identified several biochemically distinct, yet UV chromophore-rich, protein families. The majority of these putative UV-absorbing proteins (including the late cornified envelope proteins, keratin associated proteins, elastic fibre-associated components and β- and γ-crystallins) are localised and/or particularly abundant in tissues that are exposed to the highest doses of environmental UVR, specifically the stratum corneum, hair, papillary dermis and lens. We therefore propose that UV chromophore-rich proteins are localised in regions of high UVR exposure

  5. Endogenous Generalized Weights under DEA Control

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

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

  6. Evaluation by mass fragmentography of metabolic pathways of endogenous and exogenous compounds in eukaryote cell cultures

    International Nuclear Information System (INIS)

    Padieu, P.; Maume, B.F.

    1977-01-01

    Carbon-14 labelled compounds in cell cultures are used to establish the interconnections between different metabolic pathways as well as the competitive action of effectors on these different pathways. Analysis was performed by the GC-MS combination. Identification was carried out by comparison with the mass spectra of d9-TMS, 35 Cl-TMS and 37 Cl-TMS derivatizations of the culture extracts. Examples are given of the metabolic study of hormonal steroids and of safrale, a carcinogenic compound, by differentiated eukaryotic cells in cultures from the rat

  7. Endogenous Turnover of Cyanogenic Glycosides in Plants

    DEFF Research Database (Denmark)

    Picmanova, Martina

    , there is strong evidence that CNglcs serve a no less significant purpose as a transport and storage form of reduced nitrogen which may be remobilized and recycled to balance the needs of primary metabolism during certain developmental events. Reduced nitrogen from CNglcs may be recovered either via HCN refixation...... revealed the formation of glycosides of amides, carboxylic acids and "anitriles", including their di- and triglycosides, evidently derived from CNglcs. Based on results common to the three phylogenetically unrelated plant species, a recycling endogenous turnover pathway for CNglcs was suggested in which...

  8. How Stock Markets Development Affect Endogenous Growth Theory

    Directory of Open Access Journals (Sweden)

    Najeb Masoud

    2013-10-01

    Full Text Available This paper can bedescribed as a significant exploratory study that will provide a significantcontribution to knowledge to consider crucial issues which need to be barriersto understanding or a temptation/ requirement to judge some practices as‘better’ than others for stock market development effective approach andimplement successful stock market performance and economic growth. Recentanalysis of the link between financial development and growth, gained frominsights acquired as a result of using the technique of endogenous growthmodels, has illustrated that growth without exogenous technical progress andthat growth rates could be related to technology, income distribution andinstitutional arrangements. This provides the theoretical background thatempirical studies have lacked; illustrating that financial intermediationaffects the level of economic growth. Resulting models have provided newimpetus to empirical research of the effects of financial development. Thebirth of the new endogenous growth theory has facilitated the development ofimproved growth models where the long-term rate could be affected by a numberof elements. These included technology, education and health policies in theprocess of economic development, capital accumulation, government policies andinstitutional activities in the role of financial development in economicgrowth.

  9. A comparative assessment of endogenous water institutional change

    Science.gov (United States)

    Pande, Saket; Ersten, Maurits

    2013-04-01

    This paper builds the theory of endogenous institutional change, first proposed by Greif and Laitin (2004), for water scarce regions in context of water institutions. The current emphasis on environmental change, including hydrological change, largely ignores the adaptation of human societies to change. Humans have mostly been considered as boundary conditions or parameters of the dynamics of hydrological change and are not considered as conduits of feedbacks. Nonetheless, the dynamical representation of hydrological change with feedbacks between various components of a system is assuring since it is reminiscent of processual ecological anthropology(Orlove, 1980), except that individual decision making is absent. This paper proposes to consider selected dryland basins of the world, to conceptualize proxies of water relevant socio-economic organisation, such as spatial scales of upstream-downstream cooperation in water use, synthesized over time and then proposes a comparative assessment to test regularities predicted by an extension of river game theory (Ambec and Ehlers, 2008; van der Brink et al, 2012) to endogenous institutional change. References: Orlove, B. S. (1980). Ecological Anthropology. Annual Review of Anthropology, Vol. 9 (1980), pp. 235-273. Greif. A. and D. D. Laitin (2004). A Theory of Endogenous Institutional Change. American Political Science Review, Vol. 98, No. 4 November 2004. Ambec, S. and L. Ehlers (2008). Sharing a river amongst satiable agents. Games and Economic Behavior, 64, 35-50. Van der Brink, G. van der Laan and N. Moes (2012). Fair agreements for sharing international rivers with multiple springs and externalities. Journal of Environmental Economics and Management, 63, 388-403.

  10. Invasive fungal infections in endogenous Cushing's syndrome

    Science.gov (United States)

    Scheffel, Rafael Selbach; Dora, José Miguel; Weinert, Letícia Schwerz; Aquino, Valério; Maia, Ana Luiza; Canani, Luis Henrique; Goldani, Luciano Z.

    2010-01-01

    Cushing's syndrome is a condition characterized by elevated cortisol levels that can result from either augmented endogenous production or exogenous administration of corticosteroids. The predisposition to fungal infections among patients with hypercortisolemia has been noted since Cushing's original description of the disease. We describe here a patient with endogenous Cushing's syndrome secondary to an adrenocortical carcinoma, who developed concomitant disseminated cryptococcosis and candidiasis in the course of his disease. PMID:24470886

  11. Short-term exposure to the organotin compound triphenyltin modulates esterified steroid levels in females of Marisa cornuarietis.

    Science.gov (United States)

    Lyssimachou, Angeliki; Bachmann, J; Porte, C

    2008-08-29

    Long-term exposures to organotin compounds have shown alterations on endogenous steroid levels in gastropods together with the development of imposex. However, information regarding short-term effects of these compounds on the endocrine system of gastropods is lacking. This work aimed at investigating those responses in the ramshorn snail Marisa cornuarietis by looking at both endogenous levels of free and esterified steroids and the metabolism of the androgen precursor androstenedione by digestive gland/gonad microsomal fractions. One-week exposure to the organotin compound triphenyltin (TPT) led to a significant increase in esterified testosterone (60-85%) and a decrease in esterified estradiol (50-84%) in females, but had no effect on males. The observed alterations in esterified steroids were not directly related to changes in P450 aromatase activity that remained unchanged in exposed females. The enzymes involved in the metabolism of the androgen precursor androstenedione, namely 17beta-hydroxysteroid dehydrogenases and 5alpha-reductases, were not significantly altered by TPT exposure, suggesting that such enzymes are not primary targets of TPT in M. cornuarietis. Additional studies are needed to fully understand the significance of the observed alterations in females and their potential relationship with the development of imposex.

  12. Odd-Z Transactinide Compound Nucleus Reactions Including the Discovery of 260Bh

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, Sarah L. [Univ. of California, Berkeley, CA (United States)

    2008-01-01

    Several reactions producing odd-Z transactinide compound nuclei were studiedwith the 88-Inch Cyclotron and the Berkeley Gas-Filled Separator at the Lawrence Berkeley National Laboratory. The goal was to produce the same compound nucleus ator near the same excitation energy with similar values of angular momentum via differentnuclear reactions. In doing so, it can be determined if there is a preference in entrancechannel, because under these experimental conditions the survival portion of Swiatecki, Siwek-Wilcznska, and Wilczynski's"Fusion By Diffusion" model is nearly identical forthe two reactions. Additionally, because the same compound nucleus is produced, theexit channel is the same. Four compound nuclei were examined in this study: 258Db, 262Bh, 266Mt, and 272Rg. These nuclei were produced by using very similar heavy-ion induced-fusion reactions which differ only by one proton in the projectile or target nucleus (e.g.: 50Ti + 209Bi vs. 51V + 208Pb). Peak 1n exit channel cross sections were determined for each reaction in each pair, and three of the four pairs' cross sections were identical within statistical uncertainties. This indicates there is not an obvious preference of entrancechannel in these paired reactions. Charge equilibration immediately prior to fusionleading to a decreased fusion barrier is the likely cause of this phenomenon. In addition to this systematic study, the lightest isotope of element 107, bohrium, was discovered in the 209Bi(52Cr,n) reaction. 260Bh was found to decay by emission of a 10.16 MeV alpha particle with a half-life of 35$+19\\atop{-9}$ ms. The cross section is 59 pb at an excitation energy of 15.0 MeV. The effect of the N = 152 shell is also seen in this isotope's alpha particle energy, the first evidence of such an effect in Bh. All reactions studied are also compared to model predictions by Swiatecki

  13. The endogenous opioid system: a common substrate in drug addiction.

    Science.gov (United States)

    Trigo, José Manuel; Martin-García, Elena; Berrendero, Fernando; Robledo, Patricia; Maldonado, Rafael

    2010-05-01

    Drug addiction is a chronic brain disorder leading to complex adaptive changes within the brain reward circuits that involve several neurotransmitters. One of the neurochemical systems that plays a pivotal role in different aspects of addiction is the endogenous opioid system (EOS). Opioid receptors and endogenous opioid peptides are largely distributed in the mesolimbic system and modulate dopaminergic activity within these reward circuits. Chronic exposure to the different prototypical drugs of abuse, including opioids, alcohol, nicotine, psychostimulants and cannabinoids has been reported to produce significant alterations within the EOS, which seem to play an important role in the development of the addictive process. In this review, we will describe the adaptive changes produced by different drugs of abuse on the EOS, and the current knowledge about the contribution of each component of this neurobiological system to their addictive properties.

  14. [Research progress of intervertebral disc endogenous stem cells for intervertebral disc regeneration].

    Science.gov (United States)

    Liang, Hang; Deng, Xiangyu; Shao, Zengwu

    2017-10-01

    To summarize the research progress of intervertebral disc endogenous stem cells for intervertebral disc regeneration and deduce the therapeutic potential of endogenous repair for intervertebral disc degeneration. The original articles about intervertebral disc endogenous stem cells for intervertebral disc regeneration were extensively reviewed; the reparative potential in vivo and the extraction and identification in vitro of intervertebral disc endogenous stem cells were analyzed; the prospect of endogenous stem cells for intervertebral disc regeneration was predicted. Stem cell niche present in the intervertebral discs, from which stem cells migrate to injured tissues and contribute to tissues regeneration under certain specific microenvironment. Moreover, the migration of stem cells is regulated by chemokines system. Tissue specific progenitor cells have been identified and successfully extracted and isolated. The findings provide the basis for biological therapy of intervertebral disc endogenous stem cells. Intervertebral disc endogenous stem cells play a crucial role in intervertebral disc regeneration. Therapeutic strategy of intervertebral disc endogenous stem cells is proven to be a promising biological approach for intervertebral disc regeneration.

  15. Endogenous Retroviruses in the Genomics Era.

    Science.gov (United States)

    Johnson, Welkin E

    2015-11-01

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

  16. Exogenous and endogenous spatial attention effects on visuospatial working memory.

    Science.gov (United States)

    Botta, Fabiano; Santangelo, Valerio; Raffone, Antonino; Lupiáñez, Juan; Belardinelli, Marta Olivetti

    2010-08-01

    In this study, we investigate how exogenous and endogenous orienting of spatial attention affect visuospatial working memory (VSWM). Specifically, we focused on two attentional effects and their consequences on storage in VSWM, when exogenous (Experiment 1) or endogenous (Experiment 2) orienting cues were used. The first effect, known as the meridian effect, is given by a decrement in behavioural performance when spatial cues and targets are presented in locations separated by vertical and/or horizontal meridians. The second effect, known as the distance effect, is given by a decrement in the orienting effects as a function of the spatial distance between cues and targets. Our results revealed a dissociation between exogenous and endogenous orienting mechanisms in terms of both meridian and distance effects. We found that meridian crossing affects performance only when endogenous cues were used. Specifically, VSWM performance with endogenous cueing depended more on the number of meridian crossings than on distance between cue and target. By contrast, a U-shaped distance dependency was observed using exogenous cues. Our findings therefore suggest that exogenous and endogenous orienting mechanisms lead to different forms of attentional bias for storage in VSWM.

  17. Sucessfull management of bilateral presumed Candida endogenous endophtalmitis following pancreatitis

    Directory of Open Access Journals (Sweden)

    Ricardo Evangelista Marrocos de Aragão

    2016-06-01

    Full Text Available ABSTRACT Endogenous endophthalmitis is a rare, and frequently devastating, ophthalmic disease. It occurs mostly in immunocompromised patients, or those with diabetes mellitus, cancer or intravenous drugs users. Candida infection is the most common cause of endogenous endophthalmitis. Ocular candidiasis develops within days to weeks of fungemia. The association of treatment for pancreatitis with endophthalmitis is unusual. Treatment with broad-spectrum antibiotics and total parenteral nutrition may explain endogenous endophthalmitis. We report the case of a patient with pancreatitis treated with broad-spectrum antibiotics and total parenteral nutrition who developed bilateral presumed Candida endogenous endophthalmitis that was successfully treated with vitrectomy and intravitreal amphotericin B.

  18. Alpha Power Modulates Perception Independently of Endogenous Factors

    Directory of Open Access Journals (Sweden)

    Sasskia Brüers

    2018-04-01

    Full Text Available Oscillations are ubiquitous in the brain. Alpha oscillations in particular have been proposed to play an important role in sensory perception. Past studies have shown that the power of ongoing EEG oscillations in the alpha band is negatively correlated with visual outcome. Moreover, it also co-varies with other endogenous factors such as attention, vigilance, or alertness. In turn, these endogenous factors influence visual perception. Therefore, it remains unclear how much of the relation between alpha and perception is indirectly mediated by such endogenous factors, and how much reflects a direct causal influence of alpha rhythms on sensory neural processing. We propose to disentangle the direct from the indirect causal routes by introducing modulations of alpha power, independently of any fluctuations in endogenous factors. To this end, we use white-noise sequences to constrain the brain activity of 20 participants. The cross-correlation between the white-noise sequences and the concurrently recorded EEG reveals the impulse response function (IRF, a model of the systematic relationship between stimulation and brain response. These IRFs are then used to reconstruct rather than record the brain activity linked with new random sequences (by convolution. Interestingly, this reconstructed EEG only contains information about oscillations directly linked to the white-noise stimulation; fluctuations in attention and other endogenous factors may still modulate brain alpha rhythms during the task, but our reconstructed EEG is immune to these factors. We found that the detection of near-perceptual threshold targets embedded within these new white-noise sequences depended on the power of the ~10 Hz reconstructed EEG over parieto-occipital channels. Around the time of presentation, higher power led to poorer performance. Thus, fluctuations in alpha power, induced here by random luminance sequences, can directly influence perception: the relation between

  19. Role of endogenous substances in enhancing radioresistance background

    International Nuclear Information System (INIS)

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

    1979-01-01

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

  20. Neurobiological mechanisms involved in nicotine dependence and reward: participation of the endogenous opioid system

    Science.gov (United States)

    Berrendero, Fernando; Robledo, Patricia; Trigo, José Manuel; Martín-García, Elena; Maldonado, Rafael

    2010-01-01

    Nicotine is the primary component of tobacco that maintains the smoking habit and develops addiction. The adaptive changes of nicotinic acetylcholine receptors produced by repeated exposure to nicotine play a crucial role in the establishment of dependence. However, other neurochemical systems also participate in the addictive effects of nicotine including glutamate, cannabinoids, GABA and opioids. This review will cover the involvement of these neurotransmitters in nicotine addictive properties, with a special emphasis on the endogenous opioid system. Thus, endogenous enkephalins and beta-endorphins acting on mu-opioid receptors are involved in nicotine rewarding effects, whereas opioid peptides derived from prodynorphin participate in nicotine aversive responses. An upregulation of mu-opioid receptors has been reported after chronic nicotine treatment that could counteract the development of nicotine tolerance, whereas the downregulation induced on kappa-opioid receptors seems to facilitate nicotine tolerance. Endogenous enkephalins acting on mu-opioid receptors also play a role in the development of physical dependence to nicotine. In agreement with these actions of the endogenous opioid system, the opioid antagonist naltrexone has shown to be effective for smoking cessation in certain subpopulations of smokers. PMID:20170672

  1. An endogenous standard, radioisotopic ratio method in NAA

    International Nuclear Information System (INIS)

    Byrne, A.R.; Dermelj, M.

    1997-01-01

    A derivative form of NAA is proposed which is based on the use of an endogenous internal standard of already known concentration in the sample. If a comparator with a known ratio of the determinand and endogenous standard are co-irradiated with the sample, the determinand concentration is derived in terms of the endogenous standard concentration and the activity ratios of the two induced nuclides in the sample and comparator. As well as eliminating the sample mass and greatly reducing errors caused by pulse pile-up and geometrical differences, it was shown that in the radiochemical mode, if the endogenous standard is chosen so that the induced activity is radioisotopic with that from the determinand, the radiochemical yield is also eliminated and the risk non-achievement of isotopic exchange greatly reduced. The method is demonstrated with good results on reference materials for the determination of I, Mn and Ni. The advantages and disadvantages of this approach are discussed. It is suggested that it may be of application in quality control and in extending the range of certified elements in reference materials. (author)

  2. Evolution of endogenous analgesia

    NARCIS (Netherlands)

    Niesters, Marieke

    2014-01-01

    Endogenous pain modulation is a complex phenomenon involved in the perception of pain. It consists of top-down inhibitory and facilitatory pathways that originate at higher sites within the central nervous system and converge at dorsal horn neurons in the spinal cord, to modulate incoming afferent

  3. Recent advances in matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) for in situ analysis of endogenous molecules in plants.

    Science.gov (United States)

    Qin, Liang; Zhang, Yawen; Liu, Yaqin; He, Huixin; Han, Manman; Li, Yanyan; Zeng, Maomao; Wang, Xiaodong

    2018-04-17

    Mass spectrometry imaging (MSI) as a label-free and powerful imaging technique enables in situ evaluation of a tissue metabolome and/or proteome, becoming increasingly popular in the detection of plant endogenous molecules. The characterization of structure and spatial information of endogenous molecules in plants are both very important aspects to better understand the physiological mechanism of plant organism. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a commonly-used tissue imaging technique, which requires matrix to assist in situ detection of a variety of molecules on the surface of a tissue section. In previous studies, MALDI-MSI was mostly used for the detection of molecules from animal tissue sections, compared to plant samples due to cell structural limitations, such as plant cuticles, epicuticular waxes, and cell walls. Despite the enormous progress that has been made in tissue imaging, there is still a challenge for MALDI-MSI suitable for the imaging of endogenous compounds in plants. This review summarises the recent advances in MALDI-MSI, focusing on the application of in situ detection of endogenous molecules in different plant organs, i.e. root, stem, leaf, flower, fruit, and seed. Further improvements on instrumentation sensitivity, matrix selection, image processing and sample preparation will expand the application of MALDI-MSI in plant research. Copyright © 2018 John Wiley & Sons, Ltd.

  4. Effects physiopathological of secondary compounds in monogastric feeding

    Directory of Open Access Journals (Sweden)

    Lozada-Salcedo Euclides Efraín

    2017-04-01

    Full Text Available The high nutritious value which they contribute to the originating products nonconventional of legumes in the nutrition animal cannot be used in their totality due to the compound presence secondary also denominated antinutricionales factors, such that structurally contain a great variety of biologically active substances that according to its nature and concentration is those that limits their use due to the injurious effects that produce in the monogastric animals since they do not count on the protection that offers the ruminal bacterial flora as in the case of the ruminants. With this investigation one looks for to analyze in detailed form the adverse effects that cause tannins, inhibitors of protease, lectins, vicina and convicina, oligosaccharides, saponins, fítico acid, L-Drug, in the diverse physiological, metabolic processes and enzymatic since they interfere in the digestibility of the nutrients, block the mineral use, they promote the lost one of endogenous protein, exacerbate the neurotransmission in the nervous system, alter the immunological system, digestive upheavals, produces anatomical damages and structural, they slow down the growth of the animals specially when its consumption is in intensive form, by such reason is essential to know the dynamics of these compounds to be able to a great extent take advantage of the nutritious quality the seeds in the different production systems when including them in balanced diets.

  5. Demonstration of endogenous imipramine like material in rat brain

    International Nuclear Information System (INIS)

    Rehavi, M.; Ventura, I.; Sarne, Y.

    1985-01-01

    The extraction and partial purification of an endogenous imipramine-like material from rat brain is described. The endogenous factor obtained after gel filtration and silica chromatography inhibits [ 3 H] imipramine specific binding and mimics the inhibitory effect of imipramine on [ 3 H] serotonin uptake in both brain and platelet preparations. The effects of the endogenous material are dose-dependent and it inhibits [ 3 H] imipramine binding in a competitive fashion. The factor is unevenly distributed in the brain with high concentration in the hypothalamus and low concentration in the cerebellum

  6. Differences between the release of radiolabelled and endogenous dopamine from superfused rat brain slices: effects of depolarizing stimuli, amphetamine and synthesis inhibition

    International Nuclear Information System (INIS)

    Herdon, H.; Strupish, J.; Nahorski, S.R.

    1985-01-01

    Direct comparisons between radiolabelled and endogenous dopamine (DA) release from superfused rat brain slices have been made. Striatal slices were prelabelled with [ 3 H]dopamine ([ 3 H]DA), then superfused at 0.5 ml/min and the released catecholamines analyzed by HPLC with electrochemical detection and radioactivity present in superfusate fractions also counted. The studies indicate that labelled and endogenous amine release do not always occur in parallel, and that major causes of discrepancy between them may include the presence of a large newly-synthesized component in endogenous release and the uneven distribution of labelled amine within endogenous releasable pools. The results also suggest that the prelabelling process itself may alter the pools contributing to subsequent endogenous release. (Auth.)

  7. Differences between endogenous and exogenous emotion inhibition in the human brain.

    Science.gov (United States)

    Kühn, Simone; Haggard, Patrick; Brass, Marcel

    2014-05-01

    The regulation of emotions is an integral part of our mental health. It has only recently been investigated using brain imaging techniques. In most studies, participants are instructed by a cue to inhibit a specific emotional reaction. The aim of the present study was to investigate the alternative situation where a person decides to inhibit an emotion as an act of endogenous self-control. Healthy participants viewed highly arousing pictures with negative valence. In the endogenous condition, participants could freely choose on each trial to inhibit or feel the emotions elicited by the picture. In an exogenous condition, a visual cue instructed them to either feel or inhibit the emotion elicited by the picture. Participants' subjective ratings of intensity of experienced emotion showed an interaction effect between source of control (endogenous/exogenous) and feel/inhibit based on a stronger modulation between feel and inhibition for the endogenous compared to the exogenous condition. Endogenous inhibition of emotions was associated with dorso-medial prefrontal cortex activation, whereas exogenous inhibition was found associated with lateral prefrontal cortex activation. Thus, the brain regions for both endogenous and exogenous inhibition of emotion are highly similar to those for inhibition of motor actions in Brass and Haggard (J Neurosci 27:9141-9145, 2007), Kühn et al. (Hum Brain Mapp 30:2834-2843, 2009). Functional connectivity analyses showed that dorsofrontomedial cortex exerts greater control onto pre-supplementary motor area during endogenous inhibition compared to endogenous feel. This functional dissociation between an endogenous, fronto-medial and an exogenous, fronto-lateral inhibition centre has important implications for our understanding of emotion regulation in health and psychopathology.

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

    OpenAIRE

    Palley, Thomas I.

    2013-01-01

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

  9. ENDOGENOUS ANALGESIA, DEPENDENCE, AND LATENT PAIN SENSITIZATION

    Science.gov (United States)

    Taylor, Bradley K; Corder, Gregory

    2015-01-01

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

  10. Multiple groups of endogenous epsilon-like retroviruses conserved across primates.

    Science.gov (United States)

    Brown, Katherine; Emes, Richard D; Tarlinton, Rachael E

    2014-11-01

    Several types of cancer in fish are caused by retroviruses, including those responsible for major outbreaks of disease, such as walleye dermal sarcoma virus and salmon swim bladder sarcoma virus. These viruses form a phylogenetic group often described as the epsilonretrovirus genus. Epsilon-like retroviruses have become endogenous retroviruses (ERVs) on several occasions, integrating into germ line cells to become part of the host genome, and sections of fish and amphibian genomes are derived from epsilon-like retroviruses. However, epsilon-like ERVs have been identified in very few mammals. We have developed a pipeline to screen full genomes for ERVs, and using this pipeline, we have located over 800 endogenous epsilon-like ERV fragments in primate genomes. Genomes from 32 species of mammals and birds were screened, and epsilon-like ERV fragments were found in all primate and tree shrew genomes but no others. These viruses appear to have entered the genome of a common ancestor of Old and New World monkeys between 42 million and 65 million years ago. Based on these results, there is an ancient evolutionary relationship between epsilon-like retroviruses and primates. Clearly, these viruses had the potential to infect the ancestors of primates and were at some point a common pathogen in these hosts. Therefore, this result raises questions about the potential of epsilonretroviruses to infect humans and other primates and about the evolutionary history of these retroviruses. Epsilonretroviruses are a group of retroviruses that cause several important diseases in fish. Retroviruses have the ability to become a permanent part of the DNA of their host by entering the germ line as endogenous retroviruses (ERVs), where they lose their infectivity over time but can be recognized as retroviruses for millions of years. Very few mammals are known to have epsilon-like ERVs; however, we have identified over 800 fragments of endogenous epsilon-like ERVs in the genomes of all major

  11. Concise classification of the genomic porcine endogenous retroviral gamma1 load to defined lineages.

    Science.gov (United States)

    Klymiuk, Nikolai; Wolf, Eckhard; Aigner, Bernhard

    2008-02-05

    We investigated the infection history of porcine endogenous retroviruses (PERV) gamma1 by analyzing published env and LTR sequences. PERV sequences from various breeds, porcine cell lines and infected human primary cells were included in the study. We identified a considerable number of retroviral lineages indicating multiple independent colonization events of the porcine genome. A recent boost of the proviral load in an isolated pig herd and exclusive occurrence of distinct lineages in single studies indicated the ongoing colonization of the porcine genome with endogenous retroviruses. Retroviral recombination between co-packaged genomes was a general factor for PERV gamma1 diversity which indicated the simultaneous expression of different proviral loci over a period of time. In total, our detailed description of endogenous retroviral lineages is the prerequisite for breeding approaches to minimize the infectious potential of porcine tissues for the subsequent use in xenotransplantation.

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  13. Effect of endogenous and exogenous enzymatic treatment of green vanilla beans on extraction of vanillin and main aromatic compounds.

    Science.gov (United States)

    Pardío, Violeta T; Flores, Argel; López, Karla M; Martínez, David I; Márquez, Ofelia; Waliszewski, Krzysztof N

    2018-06-01

    Endogenous and exogenous enzymatic hydrolysis carried out to obtain vanilla extracts with higher concentrations of vanillin using green vanilla beans. Sequences initiated with freezing of green vanilla beans at - 1 °C for 24 h, followed by endogenous hydrolysis under optimal β-glucosidase activity at 4.2 and 35 °C for 96 h, exogenous hydrolysis with Crystalzyme PML-MX at pH 5.0 and 40 °C for 72 h, and ethanol extraction at 40% (v v -1 ) for 30 days. In the proposed method, 200 g of fresh green vanilla beans with 84% moisture (32 g dry base) were used to obtain a liter of single fold vanilla extract. This method allowed the release of 82.57% of the theoretically available vanillin from its precursor glucovanillin with 5.78 g 100 g -1 green vanilla beans (dry base). Vanillic acid, p -hydroxybenzaldehyde and vanillyl alcohol were also released and found in commercial and enzymatic extracts. Glucovanillin was detected in commercial and traditional extracts but was absent in enzymatic extracts, indicating incomplete hydrolysis during the curing process. An in vitro assay was conducted to determine if the presence of peroxidase during hydrolysis might affect overall vanillin concentration. Results showed that POD can use vanillin as a substrate under conditions similar to those in which hydrolysis was conducted (pH 5.0 and 50 °C), possibly explaining why vanillin concentration was not complete at the end of the process.

  14. Standardized Competencies for Parenteral Nutrition Order Review and Parenteral Nutrition Preparation, Including Compounding: The ASPEN Model.

    Science.gov (United States)

    Boullata, Joseph I; Holcombe, Beverly; Sacks, Gordon; Gervasio, Jane; Adams, Stephen C; Christensen, Michael; Durfee, Sharon; Ayers, Phil; Marshall, Neil; Guenter, Peggi

    2016-08-01

    Parenteral nutrition (PN) is a high-alert medication with a complex drug use process. Key steps in the process include the review of each PN prescription followed by the preparation of the formulation. The preparation step includes compounding the PN or activating a standardized commercially available PN product. The verification and review, as well as preparation of this complex therapy, require competency that may be determined by using a standardized process for pharmacists and for pharmacy technicians involved with PN. An American Society for Parenteral and Enteral Nutrition (ASPEN) standardized model for PN order review and PN preparation competencies is proposed based on a competency framework, the ASPEN-published interdisciplinary core competencies, safe practice recommendations, and clinical guidelines, and is intended for institutions and agencies to use with their staff. © 2016 American Society for Parenteral and Enteral Nutrition.

  15. Exogenic and endogenic Europa minerals

    Science.gov (United States)

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

    2016-12-01

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

  16. Unemployment and endogenous growth

    NARCIS (Netherlands)

    van Schaik, A.B.T.M.; de Groot, H.L.F.

    1995-01-01

    In this paper we develop a two-sector endogenous growth model with a dual labour market, based on efficiency wages. Growth is driven by intentional R&D performed in the high-tech and high-wage sector. It is examined how a change in rivalry among firms affects simultaneously growth and unemployment.

  17. Endogenous scheduling preferences and congestion

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; Small, Kenneth

    2017-01-01

    We consider the timing of activities through a dynamic model of commuting with congestion, in which workers care solely about leisure and consumption. Implicit preferences for the timing of the commute form endogenously due to temporal agglomeration economies. Equilibrium exists uniquely and is i......We consider the timing of activities through a dynamic model of commuting with congestion, in which workers care solely about leisure and consumption. Implicit preferences for the timing of the commute form endogenously due to temporal agglomeration economies. Equilibrium exists uniquely...... and is indistinguishable from that of a generalized version of the classical Vickrey bottleneck model, based on exogenous trip-timing preferences, but optimal policies differ: the Vickrey model will misstate the benefits of a capacity increase, it will underpredict the benefits of congestion pricing, and pricing may make...

  18. Structural analysis of protein-ligand interactions: the binding of endogenous compounds and of synthetic drugs.

    Science.gov (United States)

    Gallina, Anna M; Bork, Peer; Bordo, Domenico

    2014-02-01

    The large number of macromolecular structures deposited with the Protein Data Bank (PDB) describing complexes between proteins and either physiological compounds or synthetic drugs made it possible a systematic analysis of the interactions occurring between proteins and their ligands. In this work, the binding pockets of about 4000 PDB protein-ligand complexes were investigated and amino acid and interaction types were analyzed. The residues observed with lowest frequency in protein sequences, Trp, His, Met, Tyr, and Phe, turned out to be the most abundant in binding pockets. Significant differences between drug-like and physiological compounds were found. On average, physiological compounds establish with respect to drugs about twice as many hydrogen bonds with protein atoms, whereas drugs rely more on hydrophobic interactions to establish target selectivity. The large number of PDB structures describing homologous proteins in complex with the same ligand made it possible to analyze the conservation of binding pocket residues among homologous protein structures bound to the same ligand, showing that Gly, Glu, Arg, Asp, His, and Thr are more conserved than other amino acids. Also in the cases in which the same ligand is bound to unrelated proteins, the binding pockets showed significant conservation in the residue types. In this case, the probability of co-occurrence of the same amino acid type in the binding pockets could be up to thirteen times higher than that expected on a random basis. The trends identified in this study may provide an useful guideline in the process of drug design and lead optimization. Copyright © 2014 John Wiley & Sons, Ltd.

  19. Some observations about the endogenous money theory

    OpenAIRE

    Bertocco Giancarlo

    2006-01-01

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

  20. CITROBACTER ENDOGENOUS ENDOPHTHALMITIS: A CASE REPORT AND REVIEW OF THE LITERATURE.

    Science.gov (United States)

    Wong, Daniel H T; Liu, Candice C H; Tong, Justin M K; Luk, Wei-Kwang; Li, Kenneth K W

    2017-11-16

    We present a case of endogenous endophthalmitis because of an unusual bacterium, Citrobacter koseri. A 57-year-old woman without previous history of eye surgery or trauma presented with diabetic ketoacidosis and a painful right eye with the reduction of vision. C. koseri was identified in blood culture; thus, a diagnosis of right eye endogenous endophthalmitis was made. Intravenous and intravitreal antibiotics were both started, and vitreous culture further confirmed C. koseri as the causative organism. Computed tomography of the abdomen and pelvis revealed a right C-shaped perinephric abscess, which was drained under ultrasound guidance. Because of rapid progression to corneal melting, evisceration was performed. Cases of endogenous endophthalmitis caused by Citrobacter are very limited, and a review of all published cases in the English literature and the present case revealed that endogenous Citrobacter endophthalmitis arose almost entirely from Citrobacter renal infection. Early recognition and drainage of renal abscess may lower the chance of uncontrolled infection and endogenous spread to the eyes. Despite prompt and intensive treatment, the clinical outcome of Citrobacter endogenous endophthalmitis seems to be poor.

  1. Strategies for the photo-control of endogenous protein activity.

    Science.gov (United States)

    Brechun, Katherine E; Arndt, Katja M; Woolley, G Andrew

    2017-08-01

    Photo-controlled or 'optogenetic' effectors interfacing with endogenous protein machinery allow the roles of endogenous proteins to be probed. There are two main approaches being used to develop optogenetic effectors: (i) caging strategies using photo-controlled conformational changes, and (ii) protein relocalization strategies using photo-controlled protein-protein interactions. Numerous specific examples of these approaches have been reported and efforts to develop general methods for photo-control of endogenous proteins are a current focus. The development of improved screening and selection methods for photo-switchable proteins would advance the field. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Endogenous lung regeneration: potential and limitations.

    Science.gov (United States)

    Rock, Jason; Königshoff, Melanie

    2012-12-15

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

  3. Endogenous versus Exogenous Growth Factor Regulation of Articular Chondrocytes

    Science.gov (United States)

    Shi, Shuiliang; Chan, Albert G.; Mercer, Scott; Eckert, George J.; Trippel, Stephen B.

    2014-01-01

    Anabolic growth factors that regulate the function of articular chondrocytes are candidates for articular cartilage repair. Such factors may be delivered by pharmacotherapy in the form of exogenous proteins, or by gene therapy as endogenous proteins. It is unknown whether delivery method influences growth factor effectiveness in regulating articular chondrocyte reparative functions. We treated adult bovine articular chondrocytes with exogenous recombinant insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1), or with the genes encoding these growth factors for endogenous production. Treatment effects were measured as change in chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression. We found that IGF-I stimulated chondrocyte biosynthesis similarly when delivered by either exogenous or endogenous means. In contrast, exogenous TGF-ß1 stimulated these reparative functions, while endogenous TGF-ß1 had little effect. Endogenous TGF-ß1 became more bioactive following activation of the transgene protein product. These data indicate that effective mechanisms of growth factor delivery for articular cartilage repair may differ for different growth factors. In the case of IGF-I, gene therapy or protein therapy appear to be viable options. In contrast, TGF-ß1 gene therapy may be constrained by a limited ability of chondrocytes to convert latent complexes to an active form. PMID:24105960

  4. Development of a keratinocyte-based screening model for antipsoriatic drugs using green fluorescent protein under the control of an endogenous promoter.

    Science.gov (United States)

    Pol, Arno; van Ruissen, Fred; Schalkwijk, Joost

    2002-08-01

    Inflamed epidermis (psoriasis, wound healing, ultraviolet-irradiated skin) harbors keratinocytes that are hyperproliferative and display an abnormal differentiation program. A distinct feature of this so-called regenerative maturation pathway is the expression of proteins such as the cytokeratins CK6, CK16, and CK17 and the antiinflammatory protein SKALP/elafin. These proteins are absent in normal skin but highly induced in lesional psoriatic skin. Expression of these genes can be used as a surrogate marker for psoriasis in drug-screening procedures of large compound libraries. The aim of this study was to develop a keratinocyte cell line that contained a reporter gene under the control of a psoriasis-associated endogenous promoter and demonstrate its use in an assay suitable for screening. We generated a stably transfected keratinocyte cell line that expresses enhanced green fluorescent protein (EGFP), under the control of a 0.8-kb fragment derived from the promoter of the SKALP/elafin gene, which confers high levels of tissue-specific expression at the mRNA level. Induction of the SKALP promoter by tumor necrosis factor-alpha resulted in increased expression levels of the secreted SKALP-EGFP fusion protein as assessed by direct readout of fluorescence and fluorescence polarization in 96-well cell culture plates. The fold stimulation of the reporter gene was comparable to that of the endogenous SKALP gene as assessed by enzyme-linked immunosorbent assay. Although the dynamic range of the screening system is limited, the small standard deviation yields a Z factor of 0.49. This indicates that the assay is suitable as a high-throughput screen, and provides proof of the concept that a secreted EGFP fusion protein under the control of a physiologically relevant endogenous promoter can be used as a fluorescence-based high-throughput screen for differentiation-modifying or antiinflammatory compounds that act via the keratinocyte.

  5. Slow Replication Fork Velocity of Homologous Recombination-Defective Cells Results from Endogenous Oxidative Stress

    Science.gov (United States)

    Magdalou, Indiana; Machon, Christelle; Dardillac, Elodie; Técher, Hervé; Guitton, Jérôme; Debatisse, Michelle; Lopez, Bernard S.

    2016-01-01

    Replications forks are routinely hindered by different endogenous stresses. Because homologous recombination plays a pivotal role in the reactivation of arrested replication forks, defects in homologous recombination reveal the initial endogenous stress(es). Homologous recombination-defective cells consistently exhibit a spontaneously reduced replication speed, leading to mitotic extra centrosomes. Here, we identify oxidative stress as a major endogenous source of replication speed deceleration in homologous recombination-defective cells. The treatment of homologous recombination-defective cells with the antioxidant N-acetyl-cysteine or the maintenance of the cells at low O2 levels (3%) rescues both the replication fork speed, as monitored by single-molecule analysis (molecular combing), and the associated mitotic extra centrosome frequency. Reciprocally, the exposure of wild-type cells to H2O2 reduces the replication fork speed and generates mitotic extra centrosomes. Supplying deoxynucleotide precursors to H2O2-exposed cells rescued the replication speed. Remarkably, treatment with N-acetyl-cysteine strongly expanded the nucleotide pool, accounting for the replication speed rescue. Remarkably, homologous recombination-defective cells exhibit a high level of endogenous reactive oxygen species. Consistently, homologous recombination-defective cells accumulate spontaneous γH2AX or XRCC1 foci that are abolished by treatment with N-acetyl-cysteine or maintenance at 3% O2. Finally, oxidative stress stimulated homologous recombination, which is suppressed by supplying deoxynucleotide precursors. Therefore, the cellular redox status strongly impacts genome duplication and transmission. Oxidative stress should generate replication stress through different mechanisms, including DNA damage and nucleotide pool imbalance. These data highlight the intricacy of endogenous replication and oxidative stresses, which are both evoked during tumorigenesis and senescence initiation

  6. Slow Replication Fork Velocity of Homologous Recombination-Defective Cells Results from Endogenous Oxidative Stress.

    Directory of Open Access Journals (Sweden)

    Therese Wilhelm

    2016-05-01

    Full Text Available Replications forks are routinely hindered by different endogenous stresses. Because homologous recombination plays a pivotal role in the reactivation of arrested replication forks, defects in homologous recombination reveal the initial endogenous stress(es. Homologous recombination-defective cells consistently exhibit a spontaneously reduced replication speed, leading to mitotic extra centrosomes. Here, we identify oxidative stress as a major endogenous source of replication speed deceleration in homologous recombination-defective cells. The treatment of homologous recombination-defective cells with the antioxidant N-acetyl-cysteine or the maintenance of the cells at low O2 levels (3% rescues both the replication fork speed, as monitored by single-molecule analysis (molecular combing, and the associated mitotic extra centrosome frequency. Reciprocally, the exposure of wild-type cells to H2O2 reduces the replication fork speed and generates mitotic extra centrosomes. Supplying deoxynucleotide precursors to H2O2-exposed cells rescued the replication speed. Remarkably, treatment with N-acetyl-cysteine strongly expanded the nucleotide pool, accounting for the replication speed rescue. Remarkably, homologous recombination-defective cells exhibit a high level of endogenous reactive oxygen species. Consistently, homologous recombination-defective cells accumulate spontaneous γH2AX or XRCC1 foci that are abolished by treatment with N-acetyl-cysteine or maintenance at 3% O2. Finally, oxidative stress stimulated homologous recombination, which is suppressed by supplying deoxynucleotide precursors. Therefore, the cellular redox status strongly impacts genome duplication and transmission. Oxidative stress should generate replication stress through different mechanisms, including DNA damage and nucleotide pool imbalance. These data highlight the intricacy of endogenous replication and oxidative stresses, which are both evoked during tumorigenesis and

  7. Slow Replication Fork Velocity of Homologous Recombination-Defective Cells Results from Endogenous Oxidative Stress.

    Science.gov (United States)

    Wilhelm, Therese; Ragu, Sandrine; Magdalou, Indiana; Machon, Christelle; Dardillac, Elodie; Técher, Hervé; Guitton, Jérôme; Debatisse, Michelle; Lopez, Bernard S

    2016-05-01

    Replications forks are routinely hindered by different endogenous stresses. Because homologous recombination plays a pivotal role in the reactivation of arrested replication forks, defects in homologous recombination reveal the initial endogenous stress(es). Homologous recombination-defective cells consistently exhibit a spontaneously reduced replication speed, leading to mitotic extra centrosomes. Here, we identify oxidative stress as a major endogenous source of replication speed deceleration in homologous recombination-defective cells. The treatment of homologous recombination-defective cells with the antioxidant N-acetyl-cysteine or the maintenance of the cells at low O2 levels (3%) rescues both the replication fork speed, as monitored by single-molecule analysis (molecular combing), and the associated mitotic extra centrosome frequency. Reciprocally, the exposure of wild-type cells to H2O2 reduces the replication fork speed and generates mitotic extra centrosomes. Supplying deoxynucleotide precursors to H2O2-exposed cells rescued the replication speed. Remarkably, treatment with N-acetyl-cysteine strongly expanded the nucleotide pool, accounting for the replication speed rescue. Remarkably, homologous recombination-defective cells exhibit a high level of endogenous reactive oxygen species. Consistently, homologous recombination-defective cells accumulate spontaneous γH2AX or XRCC1 foci that are abolished by treatment with N-acetyl-cysteine or maintenance at 3% O2. Finally, oxidative stress stimulated homologous recombination, which is suppressed by supplying deoxynucleotide precursors. Therefore, the cellular redox status strongly impacts genome duplication and transmission. Oxidative stress should generate replication stress through different mechanisms, including DNA damage and nucleotide pool imbalance. These data highlight the intricacy of endogenous replication and oxidative stresses, which are both evoked during tumorigenesis and senescence initiation

  8. Expression and function of endogenous retroviruses in the placenta.

    Science.gov (United States)

    Denner, Joachim

    2016-01-01

    Although the expression of endogenous retroviruses in the placenta of numerous species was observed a long time ago, their physiological function during gestation was demonstrated only very recently. Expression of retroviral envelope proteins, also called syncytins, in the placenta allows generation of the multinuclear syncytiotrophoblast as an outer cellular layer of the placenta by fusion of the trophoblast cells. This fusion process is crucial for the development of the placenta and for successful pregnancy. It is still unclear whether the immunosuppressive properties of the transmembrane envelope protein of the endogenous retroviruses expressed in the placenta contribute to immunosuppression to prevent the rejection of the semiallotransplant embryo. The presence of placenta cells expressing retroviral envelope proteins surrounded by immune cells deep in the maternal tissue supports an immunosuppressive function. It is important to emphasize that during evolution different species utilized ('enslaved') different endogenous retroviruses and that two or more endogenous retroviruses are involved in placentogenesis in each species. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  9. School system evaluation by value added analysis under endogeneity.

    Science.gov (United States)

    Manzi, Jorge; San Martín, Ernesto; Van Bellegem, Sébastien

    2014-01-01

    Value added is a common tool in educational research on effectiveness. It is often modeled as a (prediction of a) random effect in a specific hierarchical linear model. This paper shows that this modeling strategy is not valid when endogeneity is present. Endogeneity stems, for instance, from a correlation between the random effect in the hierarchical model and some of its covariates. This paper shows that this phenomenon is far from exceptional and can even be a generic problem when the covariates contain the prior score attainments, a typical situation in value added modeling. Starting from a general, model-free definition of value added, the paper derives an explicit expression of the value added in an endogeneous hierarchical linear Gaussian model. Inference on value added is proposed using an instrumental variable approach. The impact of endogeneity on the value added and the estimated value added is calculated accurately. This is also illustrated on a large data set of individual scores of about 200,000 students in Chile.

  10. Innate heart regeneration: endogenous cellular sources and exogenous therapeutic amplification.

    Science.gov (United States)

    Malliaras, Konstantinos; Vakrou, Styliani; Kapelios, Chris J; Nanas, John N

    2016-11-01

    The -once viewed as heretical- concept of the adult mammalian heart as a dynamic organ capable of endogenous regeneration has recently gained traction. However, estimated rates of myocyte turnover vary wildly and the underlying mechanisms of cardiac plasticity remain controversial. It is still unclear whether the adult mammalian heart gives birth to new myocytes through proliferation of resident myocytes, through cardiomyogenic differentiation of endogenous progenitors or through both mechanisms. In this review, the authors discuss the cellular origins of postnatal mammalian cardiomyogenesis and touch upon therapeutic strategies that could potentially amplify innate cardiac regeneration. The adult mammalian heart harbors a limited but detectable capacity for spontaneous endogenous regeneration. During normal aging, proliferation of pre-existing cardiomyocytes is the dominant mechanism for generation of new cardiomyocytes. Following myocardial injury, myocyte proliferation increases modestly, but differentiation of endogenous progenitor cells appears to also contribute to cardiomyogenesis (although agreement on the latter point is not universal). Since cardiomyocyte deficiency underlies almost all types of heart disease, development of therapeutic strategies that amplify endogenous regeneration to a clinically-meaningful degree is of utmost importance.

  11. Social Laughter Triggers Endogenous Opioid Release in Humans.

    Science.gov (United States)

    Manninen, Sandra; Tuominen, Lauri; Dunbar, Robin I; Karjalainen, Tomi; Hirvonen, Jussi; Arponen, Eveliina; Hari, Riitta; Jääskeläinen, Iiro P; Sams, Mikko; Nummenmaa, Lauri

    2017-06-21

    The size of human social networks significantly exceeds the network that can be maintained by social grooming or touching in other primates. It has been proposed that endogenous opioid release after social laughter would provide a neurochemical pathway supporting long-term relationships in humans (Dunbar, 2012), yet this hypothesis currently lacks direct neurophysiological support. We used PET and the μ-opioid-receptor (MOR)-specific ligand [ 11 C]carfentanil to quantify laughter-induced endogenous opioid release in 12 healthy males. Before the social laughter scan, the subjects watched laughter-inducing comedy clips with their close friends for 30 min. Before the baseline scan, subjects spent 30 min alone in the testing room. Social laughter increased pleasurable sensations and triggered endogenous opioid release in thalamus, caudate nucleus, and anterior insula. In addition, baseline MOR availability in the cingulate and orbitofrontal cortices was associated with the rate of social laughter. In a behavioral control experiment, pain threshold-a proxy of endogenous opioidergic activation-was elevated significantly more in both male and female volunteers after watching laughter-inducing comedy versus non-laughter-inducing drama in groups. Modulation of the opioidergic activity by social laughter may be an important neurochemical pathway that supports the formation, reinforcement, and maintenance of human social bonds. SIGNIFICANCE STATEMENT Social contacts are vital to humans. The size of human social networks significantly exceeds the network that can be maintained by social grooming in other primates. Here, we used PET to show that endogenous opioid release after social laughter may provide a neurochemical mechanism supporting long-term relationships in humans. Participants were scanned twice: after a 30 min social laughter session and after spending 30 min alone in the testing room (baseline). Endogenous opioid release was stronger after laughter versus the

  12. Altered consciousness states and endogenous psychoses: a common molecular pathway?

    Science.gov (United States)

    Ciprian-Ollivier, J; Cetkovich-Bakmas, M G

    1997-12-19

    Interest in the role of indolamines in the pathogenesis of psychoses has been renewed in recent years by the development of atypical antipsychotic drugs such as clozapine, olanzapine, and risperidone, which act on serotonin receptors. Discovery of the hallucinogenic compounds called methylated indolealkyalamines (MIAs) (e.g. N,N-dimethylserotonin, or bufotenin, and N,N-dimethyltryptamine, or DMT) led proponents of the transmethylation hypothesis of schizophrenia to theorize that through some inborn error of metabolism, serotonin or tryptamine might undergo the addition of extra methyl radicals, thereby forming MIAs with hallucinogenic properties. Various studies have attempted to detect the excretion of MIAs, especially DMT, in the body fluids of psychotic patients and normal controls. Some of these studies have demonstrated elevated MIA concentrations in psychotic patients, including those with schizophrenia, compared with normal persons, and others have not. A number of variables may account for these contradictory findings. The mechanism whereby the beverage ayahuasca, which is used in certain cure and divination rituals in the Amazon Basin, exerts its hallucinogenic effects may serve as a model to explain the mechanism underlying hallucinogenic symptoms in schizophrenia and may lend support to the transmethylation hypothesis. Certain studies suggest that specific perceptual disturbances manifested by schizophrenic patients could contribute to progressive deterioration and negative symptomatology. All these findings point to the need for further study of the neurophysiology of MIAs and their pathogenetic role in endogenous psychoses.

  13. Mapping absolute tissue endogenous fluorophore concentrations with chemometric wide-field fluorescence microscopy

    Science.gov (United States)

    Xu, Zhang; Reilley, Michael; Li, Run; Xu, Min

    2017-06-01

    We report chemometric wide-field fluorescence microscopy for imaging the spatial distribution and concentration of endogenous fluorophores in thin tissue sections. Nonnegative factorization aided by spatial diversity is used to learn both the spectral signature and the spatial distribution of endogenous fluorophores from microscopic fluorescence color images obtained under broadband excitation and detection. The absolute concentration map of individual fluorophores is derived by comparing the fluorescence from "pure" fluorophores under the identical imaging condition following the identification of the fluorescence species by its spectral signature. This method is then demonstrated by characterizing the concentration map of endogenous fluorophores (including tryptophan, elastin, nicotinamide adenine dinucleotide, and flavin adenine dinucleotide) for lung tissue specimens. The absolute concentrations of these fluorophores are all found to decrease significantly from normal, perilesional, to cancerous (squamous cell carcinoma) tissue. Discriminating tissue types using the absolute fluorophore concentration is found to be significantly more accurate than that achievable with the relative fluorescence strength. Quantification of fluorophores in terms of the absolute concentration map is also advantageous in eliminating the uncertainties due to system responses or measurement details, yielding more biologically relevant data, and simplifying the assessment of competing imaging approaches.

  14. Endogenous induced technical change and the costs of Kyoto

    International Nuclear Information System (INIS)

    Buonanno, Paolo; Carraro, Carlo; Galeotti, M.

    2001-09-01

    Many predictions and conclusions in the climate change literature have been made and drawn on the basis of theoretical analyses and quantitative models that are either static or that allow for simple forms of changes in technology, often along exogenously given time paths. It is therefore not clear a priori whether those conclusions and policy recipes still hold in the more realistic case of endogenously evolving technologies. In this paper, a quantitative tool with the features of an endogenous growth model is presented, which also accounts for the possibility that technical change can be induced by environmental policy measures. Both the output production technology and the emission-output ratio depend upon the stock of knowledge, which accumulates through R and D activities. R and D is thus an additional policy variable that comes into play along with pollution abatement and capital investment. Two versions of this climate model are studied, one with endogenous technical change but exogenous environmental technical change (i.e. no induced technical change) and the other with both endogenous and induced technical change. Hence, in both models technical change evolves endogenously as far as the production technology is concerned, but endogenous environmental (or induced) technical change is only accounted for in the second version. Finally, a third version of the model also captures technological spillover effects. As an application, the three versions of the model are simulated allowing for trade of pollution permits as specified in the Kyoto Protocol and assessing the implications in terms of cost efficiency, economic growth and R and D efforts of the three different specifications of technical change

  15. A panel Granger-causality test of endogenous vs. exogenous growth

    OpenAIRE

    Jochen Hartwig

    2009-01-01

    The paper proposes a new test of endogenous vs. exogenous growth theories based on the Granger-causality methodology and applies it to a panel of 20 OECD countries. The test yields divergent evidence with respect to physical and human capital. For physical capital, the test results favor Solow-type exogenous growth theory over AK-type endogenous growth models. On the other hand, the test results lend support to human capital oriented endogenous growth models - like the Uzawa-Lucas model - rat...

  16. Amplification and chromosomal dispersion of human endogenous retroviral sequences

    International Nuclear Information System (INIS)

    Steele, P.E.; Martin, M.A.; Rabson, A.B.; Bryan, T.; O'Brien, S.J.

    1986-01-01

    Endogenous retroviral sequences have undergone amplification events involving both viral and flanking cellular sequences. The authors cloned members of an amplified family of full-length endogenous retroviral sequences. Genomic blotting, employing a flanking cellular DNA probe derived from a member of this family, revealed a similar array of reactive bands in both humans and chimpanzees, indicating that an amplification event involving retroviral and associated cellular DNA sequences occurred before the evolutionary separation of these two primates. Southern analyses of restricted somatic cell hybrid DNA preparations suggested that endogenous retroviral segments are widely dispersed in the human genome and that amplification and dispersion events may be linked

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

    Science.gov (United States)

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

    2002-01-01

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

  18. Structural Analysis of Silicic Lavas Reveals the Importance of Endogenous Flow During Emplacement

    Science.gov (United States)

    Andrews, G. D.; Martens, A.; Isom, S.; Maxwell, A.; Brown, S. R.

    2017-12-01

    Recent observations of silicic lava flows in Chile strongly suggest sustained, endogeneous flow beneath an insulating carapace, where the flow advances through breakouts at the flow margin. New mapping of vertical exposures around the margin of Obsidian Dome, California, has identified discreet lobe structures in cross-section, suggesting that flow-front breakouts occured there during emplacement. The flow lobes are identified through structural measurements of flow-banding orientation and the stretching directions of vesicles. Newly acquired lidar of the Inyo Domes, including Obsidian Dome, is being analyzed to better understand the patterns of folding on the upper surface of the lavas, and to test for fold vergence patterns that may distinguish between endogenous and exogenous flow.

  19. The emerging functionality of endogenous lectins: A primer to the concept and a case study on galectins including medical implications.

    Science.gov (United States)

    Gabius, Hans-Joachim; Wu, Albert M

    2006-01-01

    Biochemistry textbooks commonly make it appear that it is a foregone conclusion that the hardware of biological information storage and transfer is confined to nucleotides and amino acids, the letters of the genetic code. However, the remarkable talents of a third class of biomolecules are often overlooked. For example, one of them far surpasses the building blocks of nucleic acids and proteins in terms of theoretical coding capacity by oligomer formation. Although often exclusively assigned to duties in energy metabolism, carbohydrates as part of cellular glycoconjugates (glycoproteins, proteoglycans, glycolipids) have, in fact, other important tasks. Currently, they are increasingly gaining recognition as an operative high-density information coding system. An elaborate enzymatic machinery enables cells to be versatile enough to produce a glycan profile (glycome) that is as characteristic as a fingerprint. Moreover, swift modifications during dynamic processes, such as differentiation or malignant transformation, are readily possible. The translation of the information presented in oligosaccharide determinants to biological responses is carried out by lectins. Recognition of foreign glycosignatures in innate immunity, regulation of cell-cell/matrix interactions, cell migration or growth, and intra- and intercellular glycan routing etc represent physiologically far-reaching lectin-carbohydrate functionality. The classification of endogenous lectins is guided by sequence alignments and conservation of distinct structural traits. For example, a jelly-roll-like folding pattern and maintenance of key residue positioning involved in stacking and C-H/pi-interactions as well as directional hydrogen bonds to the 1-galactoside ligands are common denominators among galectins. Biochemical and biophysical studies are beginning to unravel the intricacies of the selection of a limited set of endogenous ligands, such as certain integrins or ganglioside GM1, and combined with

  20. Testing R&D-Based Endogenous Growth Models

    DEFF Research Database (Denmark)

    Kruse-Andersen, Peter Kjær

    2017-01-01

    R&D-based growth models are tested using US data for the period 1953-2014. A general growth model is developed which nests the model varieties of interest. The model implies a cointegrating relationship between multifactor productivity, research intensity, and employment. This relationship...... is estimated using cointegrated VAR models. The results provide evidence against the widely used fully endogenous variety and in favor of the semi-endogenous variety. Forecasts based on the empirical estimates suggest that the slowdown in US productivity growth will continue. Particularly, the annual long...

  1. Acute Consumption of Flavan-3-ol-Enriched Dark Chocolate Affects Human Endogenous Metabolism.

    Science.gov (United States)

    Ostertag, Luisa M; Philo, Mark; Colquhoun, Ian J; Tapp, Henri S; Saha, Shikha; Duthie, Garry G; Kemsley, E Kate; de Roos, Baukje; Kroon, Paul A; Le Gall, Gwénaëlle

    2017-07-07

    Flavan-3-ols and methylxanthines have potential beneficial effects on human health including reducing cardiovascular risk. We performed a randomized controlled crossover intervention trial to assess the acute effects of consumption of flavan-3-ol-enriched dark chocolate, compared with standard dark chocolate and white chocolate, on the human metabolome. We assessed the metabolome in urine and blood plasma samples collected before and at 2 and 6 h after consumption of chocolates in 42 healthy volunteers using a nontargeted metabolomics approach. Plasma samples were assessed and showed differentiation between time points with no further separation among the three chocolate treatments. Multivariate statistics applied to urine samples could readily separate the postprandial time points and distinguish between the treatments. Most of the markers responsible for the multivariate discrimination between the chocolates were of dietary origin. Interestingly, small but significant level changes were also observed for a subset of endogenous metabolites. 1 H NMR revealed that flavan-3-ol-enriched dark chocolate and standard dark chocolate reduced urinary levels of creatinine, lactate, some amino acids, and related degradation products and increased the levels of pyruvate and 4-hydroxyphenylacetate, a phenolic compound of bacterial origin. This study demonstrates that an acute chocolate intervention can significantly affect human metabolism.

  2. DMPD: Macrophage activation by endogenous danger signals. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18161744 Macrophage activation by endogenous danger signals. Zhang X, Mosser DM. J ...Pathol. 2008 Jan;214(2):161-78. (.png) (.svg) (.html) (.csml) Show Macrophage activation by endogenous dange...r signals. PubmedID 18161744 Title Macrophage activation by endogenous danger signals. Authors Zhang X, Moss

  3. Genome-wide analysis of potential cross-reactive endogenous allergens in rice (Oryza sativa L.

    Directory of Open Access Journals (Sweden)

    Fang Chao Zhu

    2015-01-01

    Full Text Available The proteins in the food are the source of common allergic components to certain patients. Current lists of plant endogenous allergens were based on the medical/clinical reports as well as laboratory results. Plant genome sequences made it possible to predict and characterize the genome-wide of putative endogenous allergens in rice (Oryza sativa L.. In this work, we identified and characterized 122 candidate rice allergens including the 22 allergens in present databases. Conserved domain analysis also revealed 37 domains among rice allergens including one novel domain (histidine kinase-, DNA gyrase B-, and HSP90-like ATPase, PF13589 adding to the allergen protein database. Phylogenetic analysis of the allergens revealed the diversity among the Prolamin superfamily and DnaK protein family, respectively. Additionally, some allergens proteins clustered on the rice chromosome might suggest the molecular function during the evolution.

  4. Immunolocalization of endogenous indole-3-acetic acid and abscisic acid in the shoot internodes of Fargesia yunnanensis bamboo during development

    Science.gov (United States)

    Shuguang Wang; Yongpeng Ma; Chengbin Wan; Chungyun Hse; Todd F. Shupe; Yujun Wang; Changming. Wang

    2016-01-01

    The Bambusoideae subfamily includes the fastest-growing plants worldwide, as a consequence of fast internode elongation. However, few studies have evaluated the temporal and spatial distribution of endogenous hormones during internode elongation. In this paper, endogenous indole-3-acetic acid (IAA) and abscisic acid (ABA) were detected in different developmental...

  5. Use of isotope ratio mass spectrometry to differentiate between endogenous steroids and synthetic homologues in cattle: A review

    International Nuclear Information System (INIS)

    Janssens, Geert; Courtheyn, Dirk; Mangelinckx, Sven; Prévost, Stéphanie; Bichon, Emmanuelle; Monteau, Fabrice; De Poorter, Geert; De Kimpe, Norbert; Le Bizec, Bruno

    2013-01-01

    Graphical abstract: Scheme: Representation of the observed isotope ratios and the relation to exogenous and endogenous natural steroids. AS stands for “amount of steroid”. Highlights: ► The difference between endogenous and exogenous steroids is thoroughly laid out. ► Factors influencing the carbon ratio and the use of Δ 13 C-values are explained. ► Implementation of GC/C/IRMS to detect steroid abuse in cattle is reviewed. ► Alternative methods and upcoming techniques are discussed. ► The differences and similarities with sports doping control are highlighted. -- Abstract: Although substantial technical advances have been achieved during the past decades to extend and facilitate the analysis of growth promoters in cattle, the detection of abuse of synthetic analogs of naturally occurring hormones has remained a challenging issue. When it became clear that the exogenous origin of steroid hormones could be traced based on the 13 C/ 12 C isotope ratio of the substances, GC/C/IRMS has been successfully implemented to this aim since the end of the past century. However, due to the costly character of the instrumental setup, the susceptibility of the equipment to errors and the complex and time consuming sample preparation, this method is up until now only applied by a limited number of laboratories. In this review, the general principles as well as the practical application of GC/C/IRMS to differentiate between endogenous steroids and exogenously synthesized homologous compounds in cattle will be discussed in detail, and will be placed next to other existing and to be developed methods based on isotope ratio mass spectrometry. Finally, the link will be made with the field of sports doping, where GC/C/IRMS has been established within the World Anti-Doping Agency (WADA) approved methods as the official technique to differentiate between exogenous and endogenous steroids over the past few years

  6. Re-education begins at home: an overview of the discovery of in vivo-active small molecule modulators of endogenous stem cells.

    Science.gov (United States)

    Um, JungIn; Lee, Ji-Hyung; Jung, Da-Woon; Williams, Darren R

    2018-04-01

    Degenerative diseases, such as Alzheimer's disease, heart disease and arthritis cause great suffering and are major socioeconomic burdens. An attractive treatment approach is stem cell transplantation to regenerate damaged or destroyed tissues. However, this can be problematic. For example, donor cells may not functionally integrate into the host tissue. An alternative methodology is to deliver bioactive agents, such as small molecules, directly into the diseased tissue to enhance the regenerative potential of endogenous stem cells. Areas covered: In this review, the authors discuss the necessity of developing these small molecules to treat degenerative diseases and survey progress in their application as therapeutics. They describe both the successes and caveats of developing small molecules that target endogenous stem cells to induce tissue regeneration. This article is based on literature searches which encompass databases for biomedical research and clinical trials. These small molecules are also categorized per their target disease and mechanism of action. Expert opinion: The development of small molecules targeting endogenous stem cells is a high-profile research area. Some compounds have made the successful transition to the clinic. Novel approaches, such as modulating the stem cell niche or targeted delivery to disease sites, should increase the likelihood of future successes in this field.

  7. Spatial orienting around the fovea: exogenous and endogenous cueing effects.

    Science.gov (United States)

    Yang, Taoxi; Zhang, Jiyuan; Bao, Yan

    2015-09-01

    The effect of covert attention in perifoveal and peripheral locations has been studied extensively. However, it is less clear whether attention operates similarly in the foveal area itself. The present study aims to investigate whether the attentional orienting elicited by an exogenous or endogenous cue can operate within the foveal area and whether attentional orienting operates similarly between foveal and perifoveal regions. By manipulating exogenous orienting in Experiment 1 and endogenous orienting in Experiment 2, we observed both forms of cueing in the foveal area. Specifically, we observed a larger exogenous cue-induced inhibitory effect (i.e., inhibition of return effect) and a similar endogenous cue-elicited facilitatory effect for the perifoveal relative to the foveal targets. We conclude that exogenous and endogenous orienting subject to two independent attentional systems with distinct modulation patterns in the foveal area.

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

    Science.gov (United States)

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

    2012-01-01

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

  9. Endogenous Information, Risk Characterization, and the Predictability of Average Stock Returns

    Directory of Open Access Journals (Sweden)

    Pradosh Simlai

    2012-09-01

    Full Text Available In this paper we provide a new type of risk characterization of the predictability of two widely known abnormal patterns in average stock returns: momentum and reversal. The purpose is to illustrate the relative importance of common risk factors and endogenous information. Our results demonstrates that in the presence of zero-investment factors, spreads in average momentum and reversal returns correspond to spreads in the slopes of the endogenous information. The empirical findings support the view that various classes of firms react differently to volatility risk, and endogenous information harbor important sources of potential risk loadings. Taken together, our results suggest that returns are influenced by random endogenous information flow, which is asymmetric in nature, and can be used as a performance attribution factor. If one fails to incorporate the existing asymmetric endogenous information hidden in the historical behavior, any attempt to explore average stock return predictability will be subject to an unquantified specification bias.

  10. Do endogenous and exogenous action control compete for perception?

    Science.gov (United States)

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

    2012-04-01

    Human actions are guided either by endogenous action plans or by external stimuli in the environment. These two types of action control seem to be mediated by neurophysiologically and functionally distinct systems that interfere if an endogenously planned action suddenly has to be performed in response to an exogenous stimulus. In this case, the endogenous representation has to be deactivated first to give way to the exogenous system. Here we show that interference of endogenous and exogenous action control is not limited to motor-related aspects but also affects the perception of action-related stimuli. Participants associated two actions with contingent sensory effects in learning blocks. In subsequent test blocks, preparing one of these actions specifically impaired responding to the associated effect in an exogenous speeded detection task, yielding a blindness-like effect for arbitrary, learned action effects. In accordance with the theory of event coding, this finding suggests that action planning influences perception even in the absence of any physical similarities between action and to-be-perceived stimuli.

  11. Endogenous opioid peptides as neurotransmitters in the rat hippocampus

    International Nuclear Information System (INIS)

    Neumaier, J.F.

    1989-01-01

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

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

    Science.gov (United States)

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

    2015-08-01

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

  13. Stochastic Stability of Endogenous Growth: Theory and Applications

    OpenAIRE

    Boucekkine, Raouf; Pintus, Patrick; Zou, Benteng

    2015-01-01

    We examine the issue of stability of stochastic endogenous growth. First, stochastic stability concepts are introduced and applied to stochastic linear homogenous differen- tial equations to which several stochastic endogenous growth models reduce. Second, we apply the mathematical theory to two models, starting with the stochastic AK model. It’s shown that in this case exponential balanced paths, which characterize optimal trajectories in the absence of uncertainty, are not robust to uncerta...

  14. Monopoly Insurance and Endogenous Information

    DEFF Research Database (Denmark)

    Lagerlöf, Johan N. M.; Schottmüller, Christoph

    2018-01-01

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

  15. Endogenous growth theory and regional development policy

    Directory of Open Access Journals (Sweden)

    Cvetanović Slobodan

    2015-01-01

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

  16. Gut luminal endogenous protein: implications for the determination of ileal amino acid digestibility in humans.

    Science.gov (United States)

    Moughan, Paul J; Rutherfurd, Shane M

    2012-08-01

    The true ileal digestibility assay provides the most informative measure of digestibility to assess bioavailability of amino acids in foods for humans. To determine 'true' estimates of ileal amino acid digestibility, requires that endogenous amino acids present in digesta at the terminal ileum be quantified. The amounts of endogenous amino acids in ileal digesta can be determined after feeding an animal or human a protein-free diet (traditional approach) or by various methods after giving a protein-containing diet. When the protein-free method has been applied with adult human subjects an overall mean value (three separate studies) for endogenous ileal nitrogen flow of 800 mg N/d has been reported. This value is considerably lower than a comparable value obtained after feeding protein of 1852 mg N/d (mean of four separate studies), and thus endogenous ileal N and amino acids should be measured under conditions of protein alimentation. There is some confusion concerning the terminology used to define digestibility, with the term "true" digestibility having different adopted meanings. Here, true amino acid digestibility is defined as apparent amino acid digestibility corrected for the basal amino acid losses determined after giving either a protein-free or a protein-containing diet. Basal losses should be determined at a defined dry-matter and protein intake. The protein-free diet approach to determining endogenous amino acids is considered unphysiological and basal losses refer to ileal endogenous amino acid flows associated with digesta dry-matter flow, and not including "specific" effects of dietary factors such as non starch polysaccharides and anti nutritional factors. Arguments are advanced that the enzyme hydrolysed protein/ultra filtration method may be suitable for routine application with a cannulated pig model, to obtain physiologically-valid basal estimates of ileal endogenous amino acids to allow calculation of true ileal amino acid digestibility in the

  17. Fast quantification of endogenous carbohydrates in plasma using hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry.

    Science.gov (United States)

    Zhu, Bangjie; Liu, Feng; Li, Xituo; Wang, Yan; Gu, Xue; Dai, Jieyu; Wang, Guiming; Cheng, Yu; Yan, Chao

    2015-01-01

    Endogenous carbohydrates in biosamples are frequently highlighted as the most differential metabolites in many metabolomics studies. A simple, fast, simultaneous quantitative method for 16 endogenous carbohydrates in plasma has been developed using hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry. In order to quantify 16 endogenous carbohydrates in plasma, various conditions, including columns, chromatographic conditions, mass spectrometry conditions, and plasma preparation methods, were investigated. Different conditions in this quantified analysis were performed and optimized. The reproducibility, precision, recovery, matrix effect, and stability of the method were verified. The results indicated that a methanol/acetonitrile (50:50, v/v) mixture could effectively and reproducibly precipitate rat plasma proteins. Cold organic solvents coupled with vortex for 1 min and incubated at -20°C for 20 min were the most optimal conditions for protein precipitation and extraction. The results, according to the linearity, recovery, precision, matrix effect, and stability, showed that the method was satisfactory in the quantification of endogenous carbohydrates in rat plasma. The quantified analysis of endogenous carbohydrates in rat plasma performed excellently in terms of sensitivity, high throughput, and simple sample preparation, which met the requirement of quantification in specific expanded metabolomic studies after the global metabolic profiling research. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Profiling of the Major Phenolic Compounds and Their Biosynthesis Genes in Sophora flavescens Aiton

    Directory of Open Access Journals (Sweden)

    Jeongyeo Lee

    2018-01-01

    Full Text Available Sophorae Radix (Sophora flavescens Aiton has long been used in traditional medicine in East Asia due to the various biological activities of its secondary metabolites. Endogenous contents of phenolic compounds (phenolic acid, flavonol, and isoflavone and the main bioactive compounds of Sophorae Radix were analyzed based on the qualitative HPLC analysis and evaluated in different organs and at different developmental stages. In total, 11 compounds were detected, and the composition of the roots and aerial parts (leaves, stems, and flowers was significantly different. trans-Cinnamic acid and p-coumaric acid were observed only in the aerial parts. Large amounts of rutin and maackiain were detected in the roots. Four phenolic acid compounds (benzoic acid, caffeic acid, ferulic acid, and chlorogenic acid and four flavonol compounds (kaempferol, catechin hydrate, epicatechin, and rutin were higher in aerial parts than in roots. To identify putative genes involved in phenolic compounds biosynthesis, a total of 41 transcripts were investigated. Expression patterns of these selected genes, as well as the multiple isoforms for the genes, varied by organ and developmental stage, implying that they are involved in the biosynthesis of various phenolic compounds both spatially and temporally.

  19. Evaluating the performance of simple estimators for probit models with two dummy endogenous regressors

    DEFF Research Database (Denmark)

    Holm, Anders; Nielsen, Jacob Arendt

    2013-01-01

    This study considers the small sample performance of approximate but simple two-stage estimators for probit models with two endogenous binary covariates. Monte Carlo simulations showthat all the considered estimators, including the simulated maximum-likelihood (SML) estimation, of the trivariate ...

  20. Design, Synthesis, and in Vitro Pharmacology of New Radiolabeled γ-Hydroxybutyric Acid Analogues Including Photolabile Analogues with Irreversible Binding to the High-Affinity γ-Hydroxybutyric Acid Binding Sites

    DEFF Research Database (Denmark)

    Sabbatini, Paola; Wellendorph, Petrine; Høg, Signe

    2010-01-01

    γ-Hydroxybutyric acid (GHB) is a psychotropic compound endogenous to the brain. Despite its potential physiological significance, the complete molecular mechanisms of action remain unexplained. To facilitate the isolation and identification of the high-affinity GHB binding site, we herein report ...

  1. Derivation of endogenous equivalent values to support risk assessment and risk management decisions for an endogenous carcinogen: Ethylene oxide.

    Science.gov (United States)

    Kirman, C R; Hays, S M

    2017-12-01

    An approach is presented for ethylene oxide (EO) to derive endogenous equivalent (EE) values, which are endogenous levels normally found within the body expressed in terms of exogenous exposures. EE values can be used to support risk assessment and risk management decisions for chemicals such as EO that have both endogenous and exogenous exposure pathways. EE values were derived using a meta-analysis of data from the published literature characterizing the distribution for an EO biomarker of exposure, hemoglobin N-(2-hydroxyethyl)-valine (HEV), in unexposed populations. These levels are compared to the those reported in exposed populations (smokers, workers). Correlation between the biomarker of exposure and external exposures of EO were applied to this distribution to determine corresponding EE values, which range from 0.13 to 6.9 ppb for EO in air. These values are orders of magnitude higher than risk-based concentration values derived for EO using default methods, and are provided as a pragmatic, data-driven alternative approach to managing the potential risks from exogenous exposures to EO. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Thermodynamic clarification of interaction between antiseptic compounds and lipids consisting of stratum corneum

    International Nuclear Information System (INIS)

    Aki, Hatsumi; Kawasaki, Yuhsuke

    2004-01-01

    The interactions of antiseptic compounds with quaternary ammonium, such as benzalkonium chloride (BC), benzethonium chloride (BZC), dodecyldiaminoethyl-glycine hydrochloride (AEG), and chlorhexidine gluconate (CHG), with components of the stratum corneum were investigated by isothermal titration calorimetry at pH 7.5 and 25 deg. C. The different mechanisms for their permeation to stratum corneum were clarified. Cationic surfactants of BC and BZC bound to cholesterol and cholesterol sulfate with high affinity (10 5 -10 6 M -1 ) to extract endogenous cholesterol and its derivatives from the stratum corneum and penetrated via an intercellular route. CHG also bound to cholesterol and accumulated in the stratum corneum without removing endogenous cholesterol. On the other hand, an amphoteric surfactant of AEG seemed to be incorporated into the lipid bilayer and bound to ceramide with its polar end close to the lipid polar heads by hydrophobic interaction

  3. Endogenous versus exogenous growth factor regulation of articular chondrocytes.

    Science.gov (United States)

    Shi, Shuiliang; Chan, Albert G; Mercer, Scott; Eckert, George J; Trippel, Stephen B

    2014-01-01

    Anabolic growth factors that regulate the function of articular chondrocytes are candidates for articular cartilage repair. Such factors may be delivered by pharmacotherapy in the form of exogenous proteins, or by gene therapy as endogenous proteins. It is unknown whether delivery method influences growth factor effectiveness in regulating articular chondrocyte reparative functions. We treated adult bovine articular chondrocytes with exogenous recombinant insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1), or with the genes encoding these growth factors for endogenous production. Treatment effects were measured as change in chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression. We found that IGF-I stimulated chondrocyte biosynthesis similarly when delivered by either exogenous or endogenous means. In contrast, exogenous TGF-β1 stimulated these reparative functions, while endogenous TGF-β1 had little effect. Endogenous TGF-β1 became more bioactive following activation of the transgene protein product. These data indicate that effective mechanisms of growth factor delivery for articular cartilage repair may differ for different growth factors. In the case of IGF-I, gene therapy or protein therapy appear to be viable options. In contrast, TGF-β1 gene therapy may be constrained by a limited ability of chondrocytes to convert latent complexes to an active form. Published 2013 by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. This article is a U.S. Government work and is in the public domain in the USA.

  4. Endogeneity in Strategy-Performance Analysis

    DEFF Research Database (Denmark)

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

    2018-01-01

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

  5. Endogeneously arising network allocation rules

    NARCIS (Netherlands)

    Slikker, M.

    2006-01-01

    In this paper we study endogenously arising network allocation rules. We focus on three allocation rules: the Myerson value, the position value and the component-wise egalitarian solution. For any of these three rules we provide a characterization based on component efficiency and some balanced

  6. Endogenous Protection Derived from Activin A/Smads Transduction Loop Stimulated via Ischemic Injury in PC12 Cells

    OpenAIRE

    Mang, Jing; Mei, Chun-Li; Wang, Jiao-Qi; Li, Zong-Shu; Chu, Ting-Ting; He, Jin-Ting; Xu, Zhong-Xin

    2013-01-01

    Activin A (ActA), a member of transforming growth factor-beta (TGF-b) super- family, affects many cellular processes, including ischemic stroke. Though the neuroprotective effects of exogenous ActA on oxygen-glucose deprivation (OGD) injury have already been reported by us, the endogenous role of ActA remains poorly understood. To further define the role and mechanism of endogenous ActA and its signaling in response to acute ischemic damage, we used an OGD model in PC12 cells to simulate isch...

  7. DMPD: Endogenous ligands of Toll-like receptors. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15178705 Endogenous ligands of Toll-like receptors. Tsan MF, Gao B. J Leukoc Biol. ...2004 Sep;76(3):514-9. Epub 2004 Jun 3. (.png) (.svg) (.html) (.csml) Show Endogenous ligands of Toll-like re...ceptors. PubmedID 15178705 Title Endogenous ligands of Toll-like receptors. Authors Tsan MF, Gao B. Publicat

  8. Endogenous 24S-hydroxycholesterol modulates NMDAR-mediated function in hippocampal slices.

    Science.gov (United States)

    Sun, Min-Yu; Izumi, Yukitoshi; Benz, Ann; Zorumski, Charles F; Mennerick, Steven

    2016-03-01

    N-methyl-D-aspartate receptors (NMDARs), a major subtype of glutamate receptors mediating excitatory transmission throughout the central nervous system (CNS), play critical roles in governing brain function and cognition. Because NMDAR dysfunction contributes to the etiology of neurological and psychiatric disorders including stroke and schizophrenia, NMDAR modulators are potential drug candidates. Our group recently demonstrated that the major brain cholesterol metabolite, 24S-hydroxycholesterol (24S-HC), positively modulates NMDARs when exogenously administered. Here, we studied whether endogenous 24S-HC regulates NMDAR activity in hippocampal slices. In CYP46A1(-/-) (knockout; KO) slices where endogenous 24S-HC is greatly reduced, NMDAR tone, measured as NMDAR-to-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) excitatory postsynaptic current (EPSC) ratio, was reduced. This difference translated into more NMDAR-driven spiking in wild-type (WT) slices compared with KO slices. Application of SGE-301, a 24S-HC analog, had comparable potentiating effects on NMDAR EPSCs in both WT and KO slices, suggesting that endogenous 24S-HC does not saturate its NMDAR modulatory site in ex vivo slices. KO slices did not differ from WT slices in either spontaneous neurotransmission or in neuronal intrinsic excitability, and exhibited LTP indistinguishable from WT slices. However, KO slices exhibited higher resistance to persistent NMDAR-dependent depression of synaptic transmission induced by oxygen-glucose deprivation (OGD), an effect restored by SGE-301. Together, our results suggest that loss of positive NMDAR tone does not elicit compensatory changes in excitability or transmission, but it protects transmission against NMDAR-mediated dysfunction. We expect that manipulating this endogenous NMDAR modulator may offer new treatment strategies for neuropsychiatric dysfunction. Copyright © 2016 the American Physiological Society.

  9. An endogenous model of the credit network

    Science.gov (United States)

    He, Jianmin; Sui, Xin; Li, Shouwei

    2016-01-01

    In this paper, an endogenous credit network model of firm-bank agents is constructed. The model describes the endogenous formation of firm-firm, firm-bank and bank-bank credit relationships. By means of simulations, the model is capable of showing some obvious similarities with empirical evidence found by other scholars: the upper-tail of firm size distribution can be well fitted with a power-law; the bank size distribution can be lognormally distributed with a power-law tail; the bank in-degrees of the interbank credit network as well as the firm-bank credit network fall into two-power-law distributions.

  10. [Mechanisms of leukocyte formation of endogenous pyrogen].

    Science.gov (United States)

    Rybakina, E G; Sorokin, A V

    1982-06-01

    A study was made of the kinetics of endogenous pyrogen production by rabbit blood and exudate leukocytes and possible role played by the products of activated leukocytes in autoregulation of the process. It was established that accumulation of endogenous pyrogen in the cell precedes its release by stimulated cells. Then the processes of active pyrogen formation and release gel interdependent: pyrogen formed releases from the cell; the lowering of pyrogen concentration in the cell is accompanied by the decrease of its content in the medium. No stimulating effect of the products activated during leukocyte inflammation on pyrogen formation by blood leukocytes was discovered.

  11. Quantitative regularities of development of endogenous infection in irradiated organism

    International Nuclear Information System (INIS)

    Mal'tsev, V.N.

    1979-01-01

    A statistical analysis of data from the literature and the author's own experimental results are reviewed to show the functional relationships between the radiation dose and the development of endogenous infection in irradiated organisms. A direct linear dependence was found between the dose of radiation and the severity of endogenous infection at doses causing death from the ''bone marrow'' syndrome in acute radiation sickness. In case of death from the ''intestinal'' syndrome, an inverse linear dependence can be observed between the radiation dose and the culture yield of microbes from internal organs. In this case, the pathological effect on the organism is due to bacterial endotoxins formed during the disintegration of microbial cells in the organism. Endogenous infection and endotoxinaemia essentially aggravate the progress of acute radiation disease. The importance of endogenous infection for the death of the organism is minimized in irradiation at doses causing death ''under the ray''. (author)

  12. Endogenous opioids encode relative taste preference.

    Science.gov (United States)

    Taha, Sharif A; Norsted, Ebba; Lee, Lillian S; Lang, Penelope D; Lee, Brian S; Woolley, Joshua D; Fields, Howard L

    2006-08-01

    Endogenous opioid signaling contributes to the neural control of food intake. Opioid signaling is thought to regulate palatability, the reward value of a food item as determined by orosensory cues such as taste and texture. The reward value of a food reflects not only these sensory properties but also the relative value of competing food choices. In the present experiment, we used a consummatory contrast paradigm to manipulate the relative value of a sucrose solution for two groups of rats. Systemic injection of the nonspecific opioid antagonist naltrexone suppressed sucrose intake; for both groups, however, this suppression was selective, occurring only for the relatively more valuable sucrose solution. Our results indicate that endogenous opioid signaling contributes to the encoding of relative reward value.

  13. [Mechanisms of endogenous drug resistance acquisition by spontaneous chromosomal gene mutation].

    Science.gov (United States)

    Fukuda, H; Hiramatsu, K

    1997-05-01

    Endogenous resistance in bacteria is caused by a change or loss of function and generally genetically recessive. However, this type of resistance acquisition are now prevalent in clinical setting. Chromosomal genes that afford endogenous resistance are the genes correlated with the target of the drug, the drug inactivating enzymes, and permeability of the molecules including the antibacterial agents. Endogenous alteration of the drug target are mediated by the spontaneous mutation of their structural gene. This mutation provides much lower affinity of the drugs for the target. Gene expression of the inactivating enzymes, such as class C beta-lactamase, is generally regulated by regulatory genes. Spontaneous mutations in the regulatory genes cause constitutive enzyme production and provides the resistant to the agent which is usually stable for such enzymes. Spontaneous mutation in the structural gene gives the enzyme extra-spectrum substrate specificity, like ESBL (Extra-Spectrum-beta-Lactamase). Expression of structural genes encoding the permeability systems are also regulated by some regulatory genes. The spontaneous mutation of the regulatory genes reduce an amount of porin protein. This mutation causes much lower influx of the drug in the cell. Spontaneous mutation in promoter region of the structural gene of efflux protein was observed. This mutation raised the gene transcription and overproduced efflux protein. This protein progresses the drug efflux from the cell.

  14. Invasive fungal infections in endogenous Cushing’s syndrome

    Directory of Open Access Journals (Sweden)

    Rafael Selbach Scheffel

    2010-06-01

    Full Text Available Cushing’s syndrome is a condition characterized by elevated cortisol levels that can result from either augmented endogenous production or exogenous administration of corticosteroids. The predisposition to fungal infections among patients with hypercortisolemia has been noted since Cushing’s original description of the disease. We describe here a patient with endo-genous Cushing’s syndrome secondary to an adrenocortical carcinoma, who developed concomitant disseminated cryptococcosis and candidiasis in the course of his disease.

  15. A General Outlook to the Endogenous Money Theory

    OpenAIRE

    ÖZGÜR, Gökçer

    2008-01-01

    The purpose of this study is to shed light on theorigins of the endogenous money theory and analyze the currentdebates on this topic. Endogenous money approach depends on a fundamental postulate: As banks meet the credit needs ofnon-financial businesses, new deposits emerge in the banking sector. Similarly,as the necessary reserves found for these new deposits the broad money expandsas well. Even though the central bank can intervene into this process it cannotfully control it. There...

  16. EXOGENOUS OR ENDOGENOUS MONEY SUPPLY: EVIDENCE FROM AUSTRALIA

    OpenAIRE

    ZATUL E. BADARUDIN; AHMED M. KHALID; MOHAMED ARIFF

    2012-01-01

    This paper investigates the nature of money supply in Australia over two separate monetary policy regimes: monetary and inflation targeting. The post-Keynesian theory on endogenous money was tested with the aim of investigating whether endogenous money supply, if it did exist, followed the accomodationist, structuralist or liquidity preference viewpoints. Data used are quarterly series from 1977 to 2007 and we used vector error-correction model for long-run and short-run causality tests. We f...

  17. Nitric oxide synthesis and biological functions of nitric oxide released from ruthenium compounds

    Directory of Open Access Journals (Sweden)

    A.C. Pereira

    2011-09-01

    Full Text Available During three decades, an enormous number of studies have demonstrated the critical role of nitric oxide (NO as a second messenger engaged in the activation of many systems including vascular smooth muscle relaxation. The underlying cellular mechanisms involved in vasodilatation are essentially due to soluble guanylyl-cyclase (sGC modulation in the cytoplasm of vascular smooth cells. sGC activation culminates in cyclic GMP (cGMP production, which in turn leads to protein kinase G (PKG activation. NO binds to the sGC heme moiety, thereby activating this enzyme. Activation of the NO-sGC-cGMP-PKG pathway entails Ca2+ signaling reduction and vasodilatation. Endothelium dysfunction leads to decreased production or bioavailability of endogenous NO that could contribute to vascular diseases. Nitrosyl ruthenium complexes have been studied as a new class of NO donors with potential therapeutic use in order to supply the NO deficiency. In this context, this article shall provide a brief review of the effects exerted by the NO that is enzymatically produced via endothelial NO-synthase (eNOS activation and by the NO released from NO donor compounds in the vascular smooth muscle cells on both conduit and resistance arteries, as well as veins. In addition, the involvement of the nitrite molecule as an endogenous NO reservoir engaged in vasodilatation will be described.

  18. Endogenous pain modulation in chronic orofacial pain: a systematic review and meta-analysis.

    Science.gov (United States)

    Moana-Filho, Estephan J; Herrero Babiloni, Alberto; Theis-Mahon, Nicole R

    2018-06-15

    Abnormal endogenous pain modulation was suggested as a potential mechanism for chronic pain, ie, increased pain facilitation and/or impaired pain inhibition underlying symptoms manifestation. Endogenous pain modulation function can be tested using psychophysical methods such as temporal summation of pain (TSP) and conditioned pain modulation (CPM), which assess pain facilitation and inhibition, respectively. Several studies have investigated endogenous pain modulation function in patients with nonparoxysmal orofacial pain (OFP) and reported mixed results. This study aimed to provide, through a qualitative and quantitative synthesis of the available literature, overall estimates for TSP/CPM responses in patients with OFP relative to controls. MEDLINE, Embase, and the Cochrane databases were searched, and references were screened independently by 2 raters. Twenty-six studies were included for qualitative review, and 22 studies were included for meta-analysis. Traditional meta-analysis and robust variance estimation were used to synthesize overall estimates for standardized mean difference. The overall standardized estimate for TSP was 0.30 (95% confidence interval: 0.11-0.49; P = 0.002), with moderate between-study heterogeneity (Q [df = 17] = 41.8, P = 0.001; I = 70.2%). Conditioned pain modulation's estimated overall effect size was large but above the significance threshold (estimate = 1.36; 95% confidence interval: -0.09 to 2.81; P = 0.066), with very large heterogeneity (Q [df = 8] = 108.3, P pain facilitation and trend for pain inhibition impairment in patients with nonparoxysmal OFP.

  19. Native Fluorescence Detection Methods, Devices, and Systems for Organic Compounds

    Science.gov (United States)

    Hug, William F. (Inventor); Bhartia, Rohit (Inventor); Reid, Ray D. (Inventor); Lane, Arthur L. (Inventor)

    2018-01-01

    Naphthalene, benzene, toluene, xylene, and other volatile organic compounds VOCs have been identified as serious health hazards. Embodiments of the invention are directed to methods and apparatus for near-real-time in-situ detection and accumulated dose measurement of exposure to naphthalene vapor and other hazardous gaseous VOCs. The methods and apparatus employ excitation of fluorophors native or endogenous to compounds of interest using light sources emitting in the ultraviolet below 300 nm and measurement of native fluorescence emissions in distinct wavebands above the excitation wavelength. The apparatus of some embodiments are cell-phone-sized sensor/dosimeter "badges" to be worn by personnel potentially exposed to hazardous VOCs. The badge sensor of some embodiments provides both real time detection and data logging of exposure to naphthalene or other VOCs of interest from which both instantaneous and accumulated dose can be determined.

  20. Symptomless endophytic fungi suppress endogenous levels of salicylic acid and interact with the jasmonate-dependent indirect defense traits of their host, lima bean (Phaseolus lunatus).

    Science.gov (United States)

    Navarro-Meléndez, Ariana L; Heil, Martin

    2014-07-01

    Symptomless ‘type II’ fungal endophytes colonize their plant host horizontally and exert diverse effects on its resistance phenotype. Here, we used wild Lima bean (Phaseolus lunatus) plants that were experimentally colonized with one of three strains of natural endophytes (Bartalinia pondoensis, Fusarium sp., or Cochliobolus lunatus) to investigate the effects of fungal colonization on the endogenous levels of salicylic acid (SA) and jasmonic acid (JA) and on two JA-dependent indirect defense traits. Colonization with Fusarium sp. enhanced JA levels in intact leaves, whereas B. pondoensis suppressed the induction of endogenous JA in mechanically damaged leaves. Endogenous SA levels in intact leaves were significantly decreased by all strains and B. pondoensis and Fusarium sp. decreased SA levels after mechanical damage. Colonization with Fusarium sp. or C. lunatus enhanced the number of detectable volatile organic compounds (VOCs) emitted from intact leaves, and all three strains enhanced the relative amount of several VOCs emitted from intact leaves as well as the number of detectable VOCs emitted from slightly damaged leaves. All three strains completely suppressed the induced secretion of extrafloral nectar (EFN) after the exogenous application of JA. Symptomless endophytes interact in complex and strain-specific ways with the endogenous levels of SA and JA and with the defense traits that are controlled by these hormones. These interactions can occur both upstream and downstream of the defense hormones.

  1. Endogenizing Prospect Theory's Reference Point

    OpenAIRE

    Ulrich Schmidt; Horst Zank

    2010-01-01

    In previous models of (cumulative) prospect theory reference-dependence of preferences is imposed beforehand and the location of the reference point is exogenously determined. This note provides a foundation of prospect theory, where reference-dependence is derived from preference conditions and a unique reference point arises endogenously.

  2. The role of human endogenous retroviruses in brain development and function.

    Science.gov (United States)

    Mortelmans, Kristien; Wang-Johanning, Feng; Johanning, Gary L

    2016-01-01

    Endogenous retroviral sequences are spread throughout the genome of all humans, and make up about 8% of the genome. Despite their prevalence, the function of human endogenous retroviruses (HERVs) in humans is largely unknown. In this review we focus on the brain, and evaluate studies in animal models that address mechanisms of endogenous retrovirus activation in the brain and central nervous system (CNS). One such study in mice found that TRIM28, a protein critical for mouse early development, regulates transcription and silencing of endogenous retroviruses in neural progenitor cells. Another intriguing finding in human brain cells and mouse models was that endogenous retrovirus HERV-K appears to be protective against neurotoxins. We also report on studies that associate HERVs with human diseases of the brain and CNS. There is little doubt of an association between HERVs and a number of CNS diseases. However, a cause and effect relationship between HERVs and these diseases has not yet been established. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  3. Endogenous cueing attenuates object substitution masking.

    Science.gov (United States)

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

    2010-07-01

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

  4. The search for an endogenous activator.

    Science.gov (United States)

    Gekowski, K. M.; Atkins, E.

    1985-01-01

    Certain febrile diseases are unaccompanied by infection or apparent hypersensitivity. In myocardial infarction or pulmonary embolism, for example, fever has been attributed to inflammation and/or tissue necrosis. Exogenous (microbial) pyrogens stimulate both human and animal monocytes/macrophages to produce endogenous pyrogen (EP) in vitro. To determine if plasma and cellular endogeneous mediators (EMs) of inflammation induced EP production, human mononuclear cells (M/L) were incubated for 18 hours with varying amounts of EM and the supernates assayed for EP in rabbits. Neutrophils (PMNs), which do not generate EP and yet are a feature of acute inflammation, were tested. Neither viable, phorbol myristic acetate-stimulated PMNs nor sonicated PMNs, red blood cells, or M/L stimulated human monocytes to produce EP. Human C3b and C5a, which mediate phagocytosis and chemotaxis, respectively, were also inactive. Despite its chemoattractant properties, the synthetic peptide FMLP failed to induce EP release. Since Poly I:Poly C (PIC: a synthetic, double-stranded RNA) is a potent pyrogen in rabbits, we investigated PIC, as well as a native, single-stranded RNA (from E. coli) and DNA (from calf thymus). None was active in vitro, and only PIC caused fever when given to rabbits intravenously. In summary, we have been unable to find an endogenous activator of EP from human monocytes to explain fevers associated with inflammation alone. PMID:3875936

  5. Analysis of eleven phenolic compounds including novel p-coumaroyl derivatives in lettuce (Lactuca sativa L.) by ultra-high-performance liquid chromatography with photodiode array and mass spectrometry detection.

    Science.gov (United States)

    Ribas-Agustí, Albert; Gratacós-Cubarsí, Marta; Sárraga, Carmen; García-Regueiro, José-Antonio; Castellari, Massimo

    2011-01-01

    Lettuce is a widely consumed vegetable and a good source of phenolic compounds. Several factors (genetic, agronomical and environmental) can influence the lettuce composition; their effects are not completely defined and more studies are needed on this topic. To develop an improved ultra-high-performance liquid chromatography (UHPLC) method to quantify the main target intact phenolic compounds in lettuce. UHPLC identification of the compounds was supported by PAD spectra and MS(n) analyses. Quantification was carried out by PAD, by creating matrix-matched calibration curves at the specific wavelength for each compound. Sample pretreatment was simplified, with neither purification nor hydrolysis steps. Chromatographic conditions were chosen to minimise matrix interferences and to give a suitable separation of the major phenolic compounds within 27 min. The method allowed the quantification of 11 intact phenolic compounds in Romaine lettuces, including phenolic acids (caffeoyl and p-coumaroyl esters) and flavonoids (quercetin glycosides). Four p-coumaroyl esters were tentatively identified and quantified for the first time in lettuce. The main intact phenolic compounds, including four novel p-coumaroyl esters, were simultaneously quantified in lettuce with optimal performances and a reduced total time of analysis. These findings make headway in the understanding of the lettuce phytochemicals with potential nutritional relevance. Copyright © 2011 John Wiley & Sons, Ltd.

  6. Expanded metabolomics approach to profiling endogenous carbohydrates in the serum of ovarian cancer patients.

    Science.gov (United States)

    Cheng, Yu; Li, Li; Zhu, Bangjie; Liu, Feng; Wang, Yan; Gu, Xue; Yan, Chao

    2016-01-01

    We applied hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry to the quantitative analysis of serum from 58 women, including ovarian cancer patients, ovarian benign tumor patients, and healthy controls. All of these ovarian cancer and ovarian benign tumor patients have elevated cancer antigen 125, which makes them clinically difficult to differentiate the malignant from the benign. All of the 16 endogenous carbohydrates were quantitatively detected in the human sera, of which, eight endogenous carbohydrates were significantly different (P-value carbohydrates in the expanded metabolomics approach after the global metabolic profiling are characterized and are potential biomarkers for the early diagnosis of ovarian cancer. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Identification of endogenous flurophores in the layered retina

    Science.gov (United States)

    Xu, Gaixia; Chen, Danni; Sun, Yiwen; Qu, Junle; Lin, Ziyang; Ding, Zhihua; Niu, Hanben

    2007-05-01

    In this paper, we measured and analyzed the characteristic of endogenous fluorophores in porcine layered retina by using advanced fluorescence spectroscopy and microscopy imaging technology. It was found that there were obvious contrasts corresponding to the different layers of retina, which may be important for fundus disease diagnosis. The retinal pigment epithelium cells exhibited strong autofluorescence with as emission peak of 600+/-10nm when excited with 860-nm light. The emission peak of photoreceptors was at 652+/-5nm, and the emission peak of retinal vessels layer was weak and at 640~700nm, when excited with 488-nm light. Autofluorescence images of three layers of retina were obtained using the same setup. We concluded that the main endogenous fluorophore in PRE was lipofuscin and that in retinal vessels was porphyrin. What's more, the FMHW (full width at half. maximum) of retinal fluorescence spectrum was broad, which suggested that there wasn't only one endogenous fluorophores of tissues excited.

  8. Induced pluripotency with endogenous and inducible genes

    International Nuclear Information System (INIS)

    Duinsbergen, Dirk; Eriksson, Malin; Hoen, Peter A.C. 't; Frisen, Jonas; Mikkers, Harald

    2008-01-01

    The recent discovery that two partly overlapping sets of four genes induce nuclear reprogramming of mouse and even human cells has opened up new possibilities for cell replacement therapies. Although the combination of genes that induce pluripotency differs to some extent, Oct4 and Sox2 appear to be a prerequisite. The introduction of four genes, several of which been linked with cancer, using retroviral approaches is however unlikely to be suitable for future clinical applications. Towards developing a safer reprogramming protocol, we investigated whether cell types that express one of the most critical reprogramming genes endogenously are predisposed to reprogramming. We show here that three of the original four pluripotency transcription factors (Oct4, Klf4 and c-Myc or MYCER TAM ) induced reprogramming of mouse neural stem (NS) cells exploiting endogenous SoxB1 protein levels in these cells. The reprogrammed neural stem cells differentiated into cells of each germ layer in vitro and in vivo, and contributed to mouse development in vivo. Thus a combinatorial approach taking advantage of endogenously expressed genes and inducible transgenes may contribute to the development of improved reprogramming protocols

  9. Endogenous analgesic effect of pregabalin: A double-blind and randomized controlled trial.

    Science.gov (United States)

    Sugimine, S; Saito, S; Araki, T; Yamamoto, K; Obata, H

    2017-07-01

    Conditioned pain modulation (CPM) is widely used to measure endogenous analgesia, and a recent study indicated that drugs that act on endogenous analgesia are more effective in individuals with lower CPM. Recent animal studies have indicated that pregabalin activates endogenous analgesia by stimulating the descending pain inhibitory system. The present study examined whether the analgesic effect of pregabalin is greater in individuals with lower original endogenous analgesia using CPM. Fifty-nine healthy subjects were randomly assigned to either a pregabalin group or a placebo group, and 50 of them completed the study. CPM was measured before and after pregabalin or placebo administration. The correlation of initial CPM to change in CPM was compared between the pregabalin and placebo groups. Initial CPM was significantly correlated with the change in CPM in the pregabalin group (r = -0.73, p CPM significantly affected the change in CPM in the pregabalin group but not in the placebo group (pregabalin group: adj R 2  = 0.51, p CPM) was stronger for subjects with lower original endogenous analgesia, suggesting that the mechanism of pregabalin involves the improvement of endogenous analgesia. © 2017 European Pain Federation - EFIC®.

  10. Two endogenous substrates for polyphenoloxidase in pericarp tissues of postharvest rambutan fruit.

    Science.gov (United States)

    Sun, Jian; Su, Weiqiang; Peng, Hongxiang; Zhu, Jianhua; Xu, Liangxiong; Bruñá, Nuria Martí

    2010-08-01

    The catalytic oxidation of phenolic substrates by polyphenoloxidase (PPO) causes pericarp browning of postharvest rambutan fruit. In the present study, PPO and its endogenous substrates were extracted from rambutan pericarp tissues (RPT). The substrate extracts were sequentially partitioned with ethyl acetate and n-butanol. The analysis of total phenolic content showed that the most phenolic compounds were distributed in ethyl acetate fraction. By high-performance liquid chromatography (HPLC), (-)-epicatechin (EC) and proanthocyanidin A2 (PA2) were identified from this fraction. After reacting with rambutan PPO, EC turned brown rapidly within 10 min, indicating that it was a significant endogenous substrate. Although PA2 could also be oxidized by the PPO, it turned brown very slowly. In addition, because EC and PA2 were continually catalyzed into browning products by PPO during storage of the fruit at 4 and 25 degrees C, their contents in RPT gradually declined with the extended storage time. It was further observed that both substrate contents in rambutan fruit storing at 25 degrees C decreased more rapidly than that storing at 4 degrees C, suggesting that low temperature inhibited the catalytic oxidation of substrates so as to slow down pericarp browning. Practical Application: Pericarp browning is a serious problem to storage and transport of harvested rambutan fruit. A generally accepted opinion on the browning mechanism is the oxidation of phenolic substrates by PPO. Ascertaining PPO substrates will effectively help us to control enzymatic reaction by chemical methods so as to delay or even prevent pericarp browning of harvested rambutan fruit.

  11. Animal spirits, competitive markets, and endogenous growth

    Science.gov (United States)

    Miyazaki, Kenji

    2013-10-01

    This paper uses a simple model with an endogenous discount rate and linear technology to investigate whether a competitive equilibrium has a higher balanced growth path (BGP) than the social planning solution and whether the BGP is determinate or indeterminate. The implications are as follows. To start with, people with an instinct to compare themselves with others possess an endogenous discount rate. In turn, this instinct affects the economic growth rate in a competitive market economy. The competitive market economy also sometimes achieves higher economic growth than a social planning economy. However, the outcomes of market economy occasionally fluctuate because of the presence of the self-fulfilling prophecy or animal spirits.

  12. A comparative analysis of property of lychee polyphenoloxidase using endogenous and exogenous substrates.

    Science.gov (United States)

    Sun, Jian; Shi, John; Zhao, Mouming; Xue, Sophia Jun; Ren, Jiaoyan; Jiang, Yueming

    2008-06-01

    Lychee polyphenoloxidase (PPO) was extracted and partially purified using ammonium sulphate precipitation and dialysis. The comparative analysis of PPO property was performed using its endogenous substrate (-)-epicatechin and exogenous substrate catechol. The pH optima for activity and activation temperature profiles of lychee PPO were very different when the enzyme reacted with endogenous and exogenous substrates. The addition of ethylenediaminetetraacetic acid disodium salt into the endogenous or exogenous substrate-enzyme system exhibited the same lowest inhibition of the PPO activity. However, l-cysteine was most effective in inhibiting enzymatic activity in the endogenous substrate-enzyme system while ascorbic acid was the best inhibitor in the exogenous substrate-enzyme system. Fe(2+) greatly accelerated the enzymatic reaction between endogenous substrate and PPO, but Cu(2+) exerted the same effect on the reaction between exogenous substrate and PPO. Based on the kinetic analysis, lychee PPO could strongly bind endogenous substrate but it possessed a higher catalytic efficiency to exogenous substrate. Copyright © 2007 Elsevier Ltd. All rights reserved.

  13. Endogenous induced technical change and the costs of Kyoto

    International Nuclear Information System (INIS)

    Buonanno, Paolo; Carraro, Carlo; Galeotti, Marzio

    2003-01-01

    We present a model for climate change policy analysis which accounts for the possibility that technology evolves endogenously and that technical change can be induced by environmental policy measures. Both the output production technology and the emission-output ratio depend upon a stock of knowledge, which accumulates through R and D activities. Two versions of this model are studied, one with endogenous technical change but exogenous environmental technical change and the other with both endogenous and induced technical change. A third version also captures technological spillover effects. As an application, the model is simulated allowing for trade of pollution permits as specified in the Kyoto Protocol and assessing the implications in terms of cost efficiency, economic growth and R and D efforts of the three different specifications of technical change

  14. Selection of Suitable Endogenous Reference Genes for Relative Copy Number Detection in Sugarcane

    Directory of Open Access Journals (Sweden)

    Bantong Xue

    2014-05-01

    Full Text Available Transgene copy number has a great impact on the expression level and stability of exogenous gene in transgenic plants. Proper selection of endogenous reference genes is necessary for detection of genetic components in genetically modification (GM crops by quantitative real-time PCR (qPCR or by qualitative PCR approach, especially in sugarcane with polyploid and aneuploid genomic structure. qPCR technique has been widely accepted as an accurate, time-saving method on determination of copy numbers in transgenic plants and on detection of genetically modified plants to meet the regulatory and legislative requirement. In this study, to find a suitable endogenous reference gene and its real-time PCR assay for sugarcane (Saccharum spp. hybrids DNA content quantification, we evaluated a set of potential “single copy” genes including P4H, APRT, ENOL, CYC, TST and PRR, through qualitative PCR and absolute quantitative PCR. Based on copy number comparisons among different sugarcane genotypes, including five S. officinarum, one S. spontaneum and two S. spp. hybrids, these endogenous genes fell into three groups: ENOL-3—high copy number group, TST-1 and PRR-1—medium copy number group, P4H-1, APRT-2 and CYC-2—low copy number group. Among these tested genes, P4H, APRT and CYC were the most stable, while ENOL and TST were the least stable across different sugarcane genotypes. Therefore, three primer pairs of P4H-3, APRT-2 and CYC-2 were then selected as the suitable reference gene primer pairs for sugarcane. The test of multi-target reference genes revealed that the APRT gene was a specific amplicon, suggesting this gene is the most suitable to be used as an endogenous reference target for sugarcane DNA content quantification. These results should be helpful for establishing accurate and reliable qualitative and quantitative PCR analysis of GM sugarcane.

  15. Endogenous Money, Non-neutrality and Interest-sensitivity in the Theory of Long Period Unemployment

    OpenAIRE

    Peter Docherty

    2006-01-01

    This paper investigates the role played by endogenous money in models with interest-sensitive expenditures. In particular, it examines the impact of endogenous money on a baseline neoclassical model arguing against the frequently asserted claim that traditional neoclassical macroeconomics is compatible with endogenous money. It demonstrates firstly that endogenous money is a sufficient condition to render unstable a neoclassical model characterised by interest-sensitive expenditures, full emp...

  16. Endogenous reward mechanisms and their importance in stress reduction, exercise and the brain.

    Science.gov (United States)

    Esch, Tobias; Stefano, George B

    2010-06-30

    Stress can facilitate disease processes and causes strain on the health care budgets. It is responsible or involved in many human ailments of our time, such as cardiovascular illnesses, particularly related to the psychosocial stressors of daily life, including work. Besides pharmacological or clinical medical treatment options, behavioral stress reduction is much-needed. These latter approaches rely on an endogenous healing potential via life-style modification. Hence, research has suggested different ways and approaches to self-treat stress or buffer against stressors and their impacts. These self-care-centred approaches are sometimes referred to as mind-body medicine or multi-factorial stress management strategies. They consist of various cognitive behavioral techniques, as well as relaxation exercises and nutritional counselling. However, a critical and consistent element of modern effective stress reduction strategies are exercise practices. With regard to underlying neurobiological mechanisms of stress relief, reward and motivation circuitries that are imbedded in the limbic regions of the brain are responsible for the autoregulatory and endogenous processing of stress. Exercise techniques clearly have an impact upon these systems. Thereby, physical activities have a potential to increase mood, i.e., decrease psychological distress by pleasure induction. For doing so, neurobiological signalling molecules such as endogenous morphine and coupled nitric oxide pathways get activated and finely tuned. Evolutionarily, the various activities and autoregulatory pathways are linked together, which can also be demonstrated by the fact that dopamine is endogenously converted into morphine which itself leads to enhanced nitric oxide release by activation of constitutive nitric oxide synthase enzymes. These molecules and mechanisms are clearly stress-reducing.

  17. Thermodynamic clarification of interaction between antiseptic compounds and lipids consisting of stratum corneum

    Energy Technology Data Exchange (ETDEWEB)

    Aki, Hatsumi; Kawasaki, Yuhsuke

    2004-06-24

    The interactions of antiseptic compounds with quaternary ammonium, such as benzalkonium chloride (BC), benzethonium chloride (BZC), dodecyldiaminoethyl-glycine hydrochloride (AEG), and chlorhexidine gluconate (CHG), with components of the stratum corneum were investigated by isothermal titration calorimetry at pH 7.5 and 25 deg. C. The different mechanisms for their permeation to stratum corneum were clarified. Cationic surfactants of BC and BZC bound to cholesterol and cholesterol sulfate with high affinity (10{sup 5}-10{sup 6} M{sup -1}) to extract endogenous cholesterol and its derivatives from the stratum corneum and penetrated via an intercellular route. CHG also bound to cholesterol and accumulated in the stratum corneum without removing endogenous cholesterol. On the other hand, an amphoteric surfactant of AEG seemed to be incorporated into the lipid bilayer and bound to ceramide with its polar end close to the lipid polar heads by hydrophobic interaction.

  18. A generalized endogenous grid method for discrete-continuous choice

    OpenAIRE

    John Rust; Bertel Schjerning; Fedor Iskhakov

    2012-01-01

    This paper extends Carroll's endogenous grid method (2006 "The method of endogenous gridpoints for solving dynamic stochastic optimization problems", Economic Letters) for models with sequential discrete and continuous choice. Unlike existing generalizations, we propose solution algorithm that inherits both advantages of the original method, namely it avoids all root finding operations, and also efficiently deals with restrictions on the continuous decision variable. To further speed up the s...

  19. Gut Microbial Glycerol Metabolism as an Endogenous Acrolein Source

    OpenAIRE

    Zhang, Jianbo; Sturla, Shana; Lacroix, Christophe; Schwab, Clarissa

    2018-01-01

    ABSTRACT Acrolein is a highly reactive electrophile causing toxic effects, such as DNA and protein adduction, oxidative stress, endoplasmic reticulum stress, immune dysfunction, and membrane damage. This Opinion/Hypothesis provides an overview of endogenous and exogenous acrolein sources, acrolein’s mode of action, and its metabolic fate. Recent reports underpin the finding that gut microbial glycerol metabolism leading to the formation of reuterin is an additional source of endogenous acrole...

  20. Endogenous enzymes, heat, and pH affect flavone profiles in parsley (Petroselinum crispum var. neapolitanum) and celery (Apium graveolens) during juice processing.

    Science.gov (United States)

    Hostetler, Gregory L; Riedl, Ken M; Schwartz, Steven J

    2012-01-11

    Flavones are abundant in parsley and celery and possess unique anti-inflammatory properties in vitro and in animal models. However, their bioavailability and bioactivity depend in part on the conjugation of sugars and other functional groups to the flavone core. The effects of juice extraction, acidification, thermal processing, and endogenous enzymes on flavone glycoside profile and concentration in both parsley and celery were investigated. Parsley yielded 72% juice with 64% of the total flavones extracted, whereas celery yielded 79% juice with 56% of flavones extracted. Fresh parsley juice averaged 281 mg flavones/100 g and fresh celery juice, 28.5 mg/100 g. Flavones in steamed parsley and celery were predominantly malonyl apiosylglucoside conjugates, whereas those in fresh samples were primarily apiosylglucoside conjugates; this was apparently the result of endogenous malonyl esterases. Acidification and thermal processing of celery converted flavone apiosylglucosides to flavone glucosides, which may affect the intestinal absorption and metabolism of these compounds.

  1. Recruiting endogenous stem cells: a novel therapeutic approach for erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Zhong-Cheng Xin

    2016-01-01

    Full Text Available Transplanted stem cells (SCs, owing to their regenerative capacity, represent one of the most promising methods to restore erectile dysfunction (ED. However, insufficient source, invasive procedures, ethical and regulatory issues hamper their use in clinical applications. The endogenous SCs/progenitor cells resident in organ and tissues play critical roles for organogenesis during development and for tissue homeostasis in adulthood. Even without any therapeutic intervention, human body has a robust self-healing capability to repair the damaged tissues or organs. Therefore, SCs-for-ED therapy should not be limited to a supply-side approach. The resident endogenous SCs existing in patients could also be a potential target for ED therapy. The aim of this review was to summarize contemporary evidence regarding: (1 SC niche and SC biological features in vitro; (2 localization and mobilization of endogenous SCs; (3 existing evidence of penile endogenous SCs and their possible mode of mobilization. We performed a search on PubMed for articles related to these aspects in a wide range of basic studies. Together, numerous evidences hold the promise that endogenous SCs would be a novel therapeutic approach for the therapy of ED.

  2. Measuring endogenous 5-HT release by emission tomography: promises and pitfalls

    DEFF Research Database (Denmark)

    Paterson, Louise M; Tyacke, Robin J; Nutt, David J

    2010-01-01

    Molecular in vivo neuroimaging techniques can be used to measure regional changes in endogenous neurotransmitters, evoked by challenges that alter synaptic neurotransmitter concentration. This technique has most successfully been applied to the study of endogenous dopamine release using positron......, with reference to the dopaminergic system. Studies that aim to image acute, endogenous 5-HT release or depletion at 5-HT receptor targets are summarised, with particular attention to studies in humans. Radiotracers targeting the 5-HT(1A), 5-HT(2A), and 5-HT(4) receptors and the serotonin reuptake transporter...... have been explored for their sensitivity to 5-HT fluctuations, but with mixed outcomes; tracers for these targets cannot reliably image endogenous 5-HT in humans. Shortcomings in our basic knowledge of the mechanisms underlying changes in binding potential are addressed, and suggestions are made...

  3. Co-factors necessary for PPAR mediated transactivation of endogenous target genes

    DEFF Research Database (Denmark)

    Grøntved, Lars; Nielsen, Ronni; Stunnenberg, Henk

    of endogenous target gene in different cell types are elusive. To mutually compare the ability of the PPAR subtypes to activate endogenous target genes in a given cell, PPARa, PPARb/d and PPARg2 were HA tagged and rapidly, equally and synchronously expressed using adenoviral delivery. Within a few hours after...... subtype specific activation of target genes. Accumulating evidence suggests that transcriptional co-factors can function as master regulators for nuclear receptors and impose promoter selectivity. To study co-factor necessity for PPAR mediated transactivation of endogenous target genes, specific co...

  4. Measuring endogenous 5-HT release by emission tomography: promises and pitfalls

    DEFF Research Database (Denmark)

    Paterson, Louise M; Tyacke, Robin J; Nutt, David J

    2010-01-01

    Molecular in vivo neuroimaging techniques can be used to measure regional changes in endogenous neurotransmitters, evoked by challenges that alter synaptic neurotransmitter concentration. This technique has most successfully been applied to the study of endogenous dopamine release using positron ...

  5. The issue of HPLC determination of endogenous lipoic acid in human plasma.

    Science.gov (United States)

    Sechovcová, Soňa; Královcová, Pavla; Kanďár, Roman; Ventura, Karel

    2018-05-01

    Lipoic acid (LA) is used extensively as a therapeutic agent for the treatment of various diseases. Many methods have been reported for the determination of LA plasma levels and its metabolites after its supplementation, but available information concerning endogenous plasma levels is still scarce. Studies which directly focused on determining the endogenous plasma levels provided highly controversial results, endogenous plasma levels of LA: 2.4 and 4.9 nmol/L respectively. However, the levels of free LA in the plasma of nonsupplemented voluntary blood donors were not detectable in all cases. The presented results of our study show that endogenous concentrations of LA are <1.85 nmol/L. Copyright © 2017 John Wiley & Sons, Ltd.

  6. Endogenous leukotriene formation during anaphylactic shock

    International Nuclear Information System (INIS)

    Keppler, A.; Oerning, L.; Bernstroem, K.; Hammarstroem, S.

    1987-01-01

    Leukotriene (LT)C 4 is a biologically active substance, presumed to play major roles as a mediator of allergic and anaphylactic reactions. It is formed e.g. by basophilic and eosinophilic leukocytes, monocytes, macrophages, and mast cells. In cells having IgE receptors, bridging of these by divalent anti-IgE-receptor antibodies or by interaction between receptor-bound IgE and anti-IgE will induce LTC 4 formation. Leukotriene formation has also been demonstrated in other in vitro models of immediate hypersensivity. The biological actions of LTC 4 , comprise induction of airway obstruction, constriction of coronary arteries, hypotension, and plasma extravasation. Leukotriene formation in vivo may mediate anaphylactic shock symptoms and cause the death of an animal. In order to prove the presumed mediator role of this substance in anaphylactic reactions, it is necessary to demonstrate its endogenous formation during shock. Studies on the metabolism of LTC 4 have revealed rapid catabolism by various transformations of the peptide substituent. Recently, three metabolites were demonstrated to be excreted as end-products in man (LTE 4 ,) and the rat (N-acetyl LTE 4 and N-acetyl 11-trans LTE 4 ). By monitoring biliary N-acetyl LTE 4 levels, endogenous leukotriene formation in the rat was demonstrated in vivo after tissue trauma and endotoxin shock. We now wish to report evidence for endogenous leukotriene C 4 production during anaphylactic shock in guinea pigs. 37 refs. (author)

  7. Mitochondrial DNA: An Endogenous Trigger for Immune Paralysis.

    Science.gov (United States)

    Schäfer, Simon T; Franken, Lars; Adamzik, Michael; Schumak, Beatrix; Scherag, André; Engler, Andrea; Schönborn, Niels; Walden, Jennifer; Koch, Susanne; Baba, Hideo A; Steinmann, Jörg; Westendorf, Astrid M; Fandrey, Joachim; Bieber, Thomas; Kurts, Christian; Frede, Stilla; Peters, Jürgen; Limmer, Andreas

    2016-04-01

    Critically ill patients are at high risk to suffer from sepsis, even in the absence of an initial infectious source, but the molecular mechanisms for their increased sepsis susceptibility, including a suppressed immune system, remain unclear. Although microbes and pathogen-associated molecular pattern are accepted inducers of sepsis and septic immunosuppression, the role of endogenous Toll-like receptor (TLR) ligands, such as mitochondrial DNA (mtDNA), in altering the immune response is unknown. Mitochondrial DNA serum concentrations of the mitochondrial genes D-Loop and adenosine triphosphatase 6 were determined (quantitative polymerase chain reaction) in 165 septic patients and 50 healthy volunteers. Furthermore, cytotoxic T-cell activity was analyzed in wild-type and TLR9 knockout mice, with/without previous mtDNA administration, followed by injection of an ovalbumin-expressing adenoviral vector. Mitochondrial DNA serum concentrations were increased in septic patients (adenosine triphosphatase 6, 123-fold; D-Loop, 76-fold, P < 0.0001) compared with volunteers. Furthermore, a single mtDNA injection caused profound, TLR9-dependent immunosuppression of adaptive T-cell cytotoxicity in wild-type but not in TLR9 knockout mice and evoked various immunosuppressive mechanisms including the destruction of the splenic microstructure, deletion of cross-presenting dendritic cells, and up-regulation of programmed cell death ligand 1 and indoleamine 2,3-dioxygenase. Several of these findings in mice were mirrored in septic patients, and mtDNA concentrations were associated with an increased 30-day mortality. The findings of this study imply that mtDNA, an endogenous danger associated molecular pattern, is a hitherto unknown inducer of septic immunoparalysis and one possible link between initial inflammation and subsequent immunosuppression in critically ill patients.

  8. Inhibitor specificity of recombinant and endogenous caspase-9.

    Science.gov (United States)

    Ryan, Ciara A; Stennicke, Henning R; Nava, Victor E; Burch, Jennifer B; Hardwick, J Marie; Salvesen, Guy S

    2002-01-01

    Apoptosis triggered through the intrinsic pathway by radiation and anti-neoplastic drugs is initiated by the activation of caspase-9. To elucidate control mechanisms in this pathway we used a range of synthetic and natural reagents. The inhibitory potency of acetyl-Asp-Glu-Val-Asp-aldehyde ('Ac-DEVD-CHO'), benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone ('Z-VAD-FMK') and the endogenous caspase inhibitor X-chromosome-linked inhibitor of apoptosis protein ('XIAP') against recombinant caspase-9 were predictive of the efficacy of these compounds in a cell-free system. However, the viral proteins CrmA and p35, although potent inhibitors of recombinant caspase-9, had almost no ability to block caspase-9 in this system. These findings were also mirrored in cell expression studies. We hypothesize that the viral inhibitors CrmA and p35 are excluded from reacting productively with the natural form of active caspase-9 in vivo, making the potency of inhibitors highly context-dependent. This is supported by survival data from a mouse model of apoptosis driven by Sindbis virus expressing either p35 or a catalytic mutant of caspase-9. These results consolidate previous findings that CrmA is a potent inhibitor of caspase-9 in vitro, yet fails to block caspase-9-mediated cell death. PMID:12067274

  9. Pharmacology of functional endogenous IP prostanoid receptors in NCB-20 cells: comparison with binding data from human platelets.

    Science.gov (United States)

    Crider, J Y; Xu, S X; Sharif, N A

    2001-01-01

    The objective of these studies was to characterize the effects of a broad range of prostanoid agonists upon the stimulation of cAMP production in National Cancer Bank (NCB-20; mouse neuroblastoma/hamster brain hybridoma) cells. The pharmacology of these functional responses in NCB-20 cells was compared with that of the classic endogenous IP receptor present on human platelets using [3H]-iloprost binding techniques. In both assay systems, agonists from the IP prostanoid class exhibited the highest affinities and functional potencies. Specific prostanoids exhibited the following rank order of potency (EC50 +/- SEM) in stimulating cAMP production in the NCB-20 cells: carbaprostacyclin (4.3 +/- 0.9 nM) = PGI2 (6.6 +/-1.5 nM) > iloprost (75+/-13 nM) > 11-deoxy PGE, (378+/-138 nM) > misoprostol (1,243+/-48) > PGE2 (3020+/-700 nM) > ZK-118182 (7265+/-455 nM). Iloprost wasthe most potent compound in the human platelet binding assay while prostanoidsfromthe DPand EP receptor classes showed modest affinity. These studies provide functional and binding information for a broad range of both natural and synthetic prostanoid receptor ligands at the endogenous IP receptor in two different cell types.

  10. Treatment of skeletal impairment in patients with endogenous hypercortisolism: when and how?

    Science.gov (United States)

    Scillitani, A; Mazziotti, G; Di Somma, C; Moretti, S; Stigliano, A; Pivonello, R; Giustina, A; Colao, A

    2014-02-01

    Guidelines for the management of osteoporosis induced by endogenous hypercortisolism are not available. Both the American College of Rheumatology and the International Osteoporosis Foundation recommend to modulate the treatment of exogenous glucocorticoid-induced osteoporosis (GIO) based on the individual fracture risk profile (calculated by FRAX) and dose of glucocorticoid used, but it is difficult to translate corticosteroid dosages to different degrees of endogenous hypercortisolism, and there are no data on validation of FRAX stratification method in patients with endogenous hypercortisolism. Consequently, it is unclear whether such recommendations may be adapted to patients with endogenous hypercortisolism. Moreover, patients with exogenous GIO take glucocorticoids since suffering a disease that commonly affects bone. On the other hand, the correction of coexistent risk factors, which may contribute to increase the fracture risk in patients exposed to glucocorticoid excess, and the removal of the cause of endogenous hypercortisolism, may lead to the recovery of bone health. Although the correction of hypercortisolism and of possible coexistent risk factors is necessary to favor the normalization of bone turnover with recovery of bone mass; in some patients, the fracture risk could not be normalized and specific anti-osteoporotic drugs should be given. Who, when, and how the patient with endogenous hypercortisolism should be treated with bone-active therapy is discussed.

  11. [Endogenous Endophthalmitis: Epidemiology, Clinic, Therapy and Visual Outcome].

    Science.gov (United States)

    Mayer, Christian; Loos, Daria; Feucht, Nikolaus; Zapp, Daniel; Prahs, Philipp Maximilian; Tandogan, Tamer; Khoramnia, Ramin

    2018-04-11

    Endogenous endophthalmitis is a rare and severe inflammation of the eye in the context of a systemic infectious disease, which can lead to the loss of the affected eye in the worst case. In a 5-year period, 20 eyes were treated for endogenous endophthalmitis and evaluated retrospectively. Evaluation parameters were epidemiological data, causes, concomitant diseases, assessment of the pathogen spectrum, therapy and visual acuity. 13.2% (n = 20/152; 20 eyes of 17 patients) of all endophthalmitis cases were of endogenous origin. In 15% (n = 3/20) of the cases, bilateral endogenous endophthalmitis was present. The cause for the endophthalmitis was generalised sepsis in 9 of 17 cases, an infection of the urogenital tract in 2 of 17 cases and endocarditis and liver abscess in 1 of 17 cases, respectively. In 4 of 17 cases, no primary foci were detected. Eight of 17 patients suffered from diabetes mellitus, 6 of 17 from renal insufficiency and 2 of 17 from malignancies, pneumonia or rheumatism. Two of 17 patients had had an organ transplantation, 15 of 17 suffered from cardiovascular diseases, 3 of 17 were immunosuppressed and 2 of 17 reported drug abuse. Four of 17 infections were caused by streptococci, 3 of 17 by Candida, 2 of 17 by herpes viruses and 1 of 17 by Staphylococcus aureus and Bacillus cereus. No pathogen could be found in 5 cases. The time interval between the onset of symptoms and diagnosis and the beginning of the therapy was 4 days (min.: 1 day; max.: 39 days). This was significantly longer in comparison with other causes of endophthalmitis (p Endogenous endophthalmitis is often misdiagnosed due to a severe underlying non-ophthalmological disease. Delayed presentation with consequent late initiation of therapy is an unresolved problem, because colleagues from other fields are often unexperienced in diagnosing the ocular infection. This is also a cause of the already poor visual prognosis. Ophthalmologists can usually only influence the choice

  12. Inhibition of endogenous lactate turnover with lactate infusion in humans

    International Nuclear Information System (INIS)

    Searle, G.L.; Feingold, K.R.; Hsu, F.S.; Clark, O.H.; Gertz, E.W.; Stanley, W.C.

    1989-01-01

    The extent to which lactate infusion may inhibit endogenous lactate production, though previously considered, has never been critically assessed. To examine this proposition, single injection tracer methodology (U- 14 C Lactate) has been used for the estimation of lactate kinetics in 12 human subjects under basal conditions and with the infusion of sodium lactate. The basal rate of lactate turnover was measured on a day before the study with lactate infusion, and averaged 63.7 + 5.5 mg/kg/h. Six of these individuals received a stable lactate infusion at an approximate rate of 160 mg/kg/h, while the remaining six individuals were infused at the approximate rate of 100 mg/kg/h. It has been found that stable lactate infused at rates approximating 160 mg/kg/h consistently produced a complete inhibition of endogenous lactate production. Infusion of lactate at 100 mg/kg/h caused a lesser and more variable inhibition of endogenous lactate production (12% to 64%). In conclusion, lactate infusion significantly inhibits endogenous lactate production

  13. Quantitative live imaging of endogenous DNA replication in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Andrew Burgess

    Full Text Available Historically, the analysis of DNA replication in mammalian tissue culture cells has been limited to static time points, and the use of nucleoside analogues to pulse-label replicating DNA. Here we characterize for the first time a novel Chromobody cell line that specifically labels endogenous PCNA. By combining this with high-resolution confocal time-lapse microscopy, and with a simplified analysis workflow, we were able to produce highly detailed, reproducible, quantitative 4D data on endogenous DNA replication. The increased resolution allowed accurate classification and segregation of S phase into early-, mid-, and late-stages based on the unique subcellular localization of endogenous PCNA. Surprisingly, this localization was slightly but significantly different from previous studies, which utilized over-expressed GFP tagged forms of PCNA. Finally, low dose exposure to Hydroxyurea caused the loss of mid- and late-S phase localization patterns of endogenous PCNA, despite cells eventually completing S phase. Taken together, these results indicate that this simplified method can be used to accurately identify and quantify DNA replication under multiple and various experimental conditions.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  16. Endogenous hydrogen peroxide production in the epithelium of the developing embryonic lens.

    Science.gov (United States)

    Basu, Subhasree; Rajakaruna, Suren; Dickinson, Bryan C; Chang, Christopher J; Menko, A Sue

    2014-01-01

    Hydrogen peroxide (H2O2) is an endogenously produced reactive oxygen species (ROS) present in a variety of mammalian systems. This particular ROS can play dichotomous roles, being beneficial in some cases and deleterious in others, which reflects the level and location of H2O2 production. While much is known about the redox regulation of ROS by antioxidant and repair systems in the lens, little is known about the endogenous production of H2O2 in embryonic lens tissue or the physiologic relevance of endogenous H2O2 to lens development. This gap in knowledge exists primarily from a lack of reagents that can specifically detect endogenous H2O2 in the intact lens. Here, using a recently developed chemoselective fluorescent boronate probe, peroxyfluor-6 acetoxymethyl ester (PF6-AM), which selectively detects H2O2 over related ROS, we examined the endogenous H2O2 signals in the embryonic lens. Embryonic day 10 chick whole lenses in ex vivo organ culture and lens epithelial cells in primary culture were loaded with the H2O2 probe PF6-AM. To determine the relationship between localization of mitochondria with active membrane potential and the region of H2O2 production in the lens, cells were exposed to the mitochondrial probe MitoTracker Red CMXRos together with PF6-AM. Diphenyleneiodonium (DPI), a flavin inhibitor that blocks generation of intracellular ROS production, was used to confirm that the signal from PF6-AM was due to endogenous ROS production. All imaging was performed by live confocal microscopy. PF6-AM detected endogenous H2O2 in lens epithelial cells in whole lenses in ex vivo culture and in lens epithelial cells grown in primary culture. No endogenous H2O2 signal could be detected in differentiating lens fiber cells with this probe. Treatment with DPI markedly attenuated the fluorescence signal from the peroxide-specific probe PF6-AM in the lens epithelium, suggesting that basal generation of ROS occurs in this region. The lens epithelial cells producing an

  17. Compound K, a Ginsenoside Metabolite, Inhibits Colon Cancer Growth via Multiple Pathways Including p53-p21 Interactions

    Directory of Open Access Journals (Sweden)

    Eugene B. Chang

    2013-01-01

    Full Text Available Compound K (20-O-beta-D-glucopyranosyl-20(S-protopanaxadiol, CK, an intestinal bacterial metabolite of ginseng protopanaxadiol saponins, has been shown to inhibit cell growth in a variety of cancers. However, the mechanisms are not completely understood, especially in colorectal cancer (CRC. A xenograft tumor model was used first to examine the anti-CRC effect of CK in vivo. Then, multiple in vitro assays were applied to investigate the anticancer effects of CK including antiproliferation, apoptosis and cell cycle distribution. In addition, a qPCR array and western blot analysis were executed to screen and validate the molecules and pathways involved. We observed that CK significantly inhibited the growth of HCT-116 tumors in an athymic nude mouse xenograft model. CK significantly inhibited the proliferation of human CRC cell lines HCT-116, SW-480, and HT-29 in a dose- and time-dependent manner. We also observed that CK induced cell apoptosis and arrested the cell cycle in the G1 phase in HCT-116 cells. The processes were related to the upregulation of p53/p21, FoxO3a-p27/p15 and Smad3, and downregulation of cdc25A, CDK4/6 and cyclin D1/3. The major regulated targets of CK were cyclin dependent inhibitors, including p21, p27, and p15. These results indicate that CK inhibits transcriptional activation of multiple tumor-promoting pathways in CRC, suggesting that CK could be an active compound in the prevention or treatment of CRC.

  18. DMPD: Regulation of endogenous apolipoprotein E secretion by macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18388328 Regulation of endogenous apolipoprotein E secretion by macrophages. Kockx ...svg) (.html) (.csml) Show Regulation of endogenous apolipoprotein E secretion by macrophages. PubmedID 18388...328 Title Regulation of endogenous apolipoprotein E secretion by macrophages. Aut

  19. Endogenous Natural Complement Inhibitor Regulates Cardiac Development

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  20. A Reformulation of Normative Economics for Models with Endogenous

    OpenAIRE

    Bhatt, Vipul; Ogaki, Masao; Yaguchi, Yuichi

    2015-01-01

    This paper proposes a framework to balance considerations of welfarism and virtue ethics in the normative analysis of economic models with endogenous preferences. We introduce the moral evaluation function (MEF), which ranks alternatives based purely on virtue ethics, and define the social objective function (SOF), which combines the Social Welfare Function (SWF) and the MEF. In a model of intergenerational altruism with endogenous time preference, using numerical simulations we show that max...

  1. Glacial cycles:exogenous orbital changes vs. endogenous climate dynamics

    OpenAIRE

    Kaufmann, R. K.; Juselius, Katarina

    2010-01-01

    We use a statistical model, the cointegrated vector autoregressive model, to assess the degree to which variations in Earth's orbit and endogenous climate dynamics can be used to simulate glacial cycles during the late Quaternary (390 kyr-present). To do so, we estimate models of varying complexity and compare the accuracy of their in-sample simulations. Results indicate that strong statistical associations between endogenous climate variables are not enough for statistical models to reproduc...

  2. Evidence for arginine as the endogenous precursor of necines in heliotropium.

    Science.gov (United States)

    Birecka, H; Birecki, M; Frohlich, M W

    1987-05-01

    In pyrrolizidine alkaloid-bearing Heliotropium angiospermum and H. indicum shoots exposed, in the light, to (14)C-labeled CO(2) for 44 hours, the incorporation of (14)C into 1,2-epoxy-1-hydroxymethylpyrrolizidine and retronecine amounted to 0.23 and 0.15%, respectively, of the total carbon assimilated. Treatment of the shoots with alpha-dl-difluoromethylornithine, the specific ornithine decarboxylase inhibitor, at 1 to 2 millimolar had no effect on (14)C incorporation into the necines. In contrast, alpha-dl-difluoromethylarginine, the specific arginine decarboxylase inhibitor, prevented the incorporation of (14)C into the necines of both species; the inhibitor did not affect the absolute incorporation of (14)C from exogenous [1,4-(14)C] putrescine in either species. Thus, arginine is the only apparent endogenous precursor of the putrescine channeled into pyrrolizidines, at least in these two Heliotropium species that exhibited a relatively much higher in vitro activity of arginine decarboxylase than of ornithine decarboxylase. However, within 28 hours after administration, not only exogenous l-[5-(14)C]arginine, but also exogenous l-[5-(14)C]ornithine exhibited significant incorporation of their label into the necines, incorporation that could be partially prevented by both inhibitors. Neither inhibitor affected the rates of (14)C-labeled CO(2) assimilation, transformation of labeled assimilates into ethanol-insoluble compounds, or the very high degree of conversion of the introduced amino acids into other compounds. Methodology related to alkaloid biosynthetic studies is discussed.

  3. Investigation of endogenous biomass efficiency in the treatment of unhairing effluents from the tanning industry.

    Science.gov (United States)

    Mlaik, Najwa; Bouzid, Jalel; Gharsallah, Neji; Belbahri, Lassad; Woodward, Steve; Mechichi, Tahar

    2009-08-01

    The tanning industry is of great economic importance worldwide; however, the potential environmental impact of tanning is significant. An important component in tanning is the removal of hair from the hide (unhairing), a process which generates considerable amounts of toxic effluent characterized by a high concentration of sulphur, rich mineral compounds, a high alkalinity and a high organic load. The purpose of the work described here was to evaluate the biodegradability of the unhairing wastewater by endogenous biomass in batch culture and continuous systems. The detoxification of the effluent was assessed by seed germination tests. The batch culture experiments showed that variations in COD, temperature and pH significantly affected the endogenous biomass growth and activity. The optimal treatment condition corresponded to an initial COD of 6 g/L, pH of 7 and 30 degrees C. Under continuous culture conditions, the reactor was fed for 48 days with the unhairing effluent. The optimal COD removal efficiency was 85.5%. During treatment, a transformation of sulphides into thiosulphates and then sulphates was also observed. The effect of untreated and treated unhairing wastewater on seed germination of different plant species was studied. The data suggested that treatment decreased the wastewater toxicity. Indeed, germination was inhibited when the effluent dilution was lower than 20% and 10% for treated and untreated wastewater, respectively.

  4. Neural correlates of endogenous attention, exogenous attention and inhibition of return in touch.

    Science.gov (United States)

    Jones, Alexander; Forster, Bettina

    2014-07-01

    Selective attention helps process the myriad of information constantly touching our body. Both endogenous and exogenous mechanisms are relied upon to effectively process this information; however, it is unclear how they relate in the sense of touch. In three tasks we contrasted endogenous and exogenous event-related potential (ERP) and behavioural effects. Unilateral tactile cues were followed by a tactile target at the same or opposite hand. Clear behavioural effects showed facilitation of expected targets both when the cue predicted targets at the same (endogenous predictive task) and opposite hand (endogenous counter-predictive task), and these effects also correlated with ERP effects of endogenous attention. In an exogenous task, where the cue was non-informative, inhibition of return (IOR) was observed. The electrophysiological results demonstrated early effects of exogenous attention followed by later endogenous attention modulations. These effects were independent in both the endogenous predictive and exogenous tasks. However, voluntarily directing attention away from a cued body part influenced the early exogenous marker (N80). This suggests that the two mechanisms are interdependent, at least when the task requires more demanding shifts of attention. The early marker of exogenous tactile attention, the N80, was not directly related to IOR, which may suggest that exogenous attention and IOR are not necessarily two sides of the same coin. This study adds valuable new insight into how we process and select information presented to our body, showing both independent and interdependent effects of endogenous and exogenous attention in touch. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  5. Endogenous sex steroids and cardio- and cerebro-vascular disease in the postmenopausal period.

    Science.gov (United States)

    Pappa, Theodora; Alevizaki, Maria

    2012-08-01

    Cardio- and cerebro-vascular diseases are two leading causes of death and long-term disability in postmenopausal women. The acute fall of estrogen in menopause is associated with increased cardiovascular risk. The relative contribution of androgen to this risk is also being recognized. The use of more sensitive assays for estradiol measurement and the study of receptor and carrier protein gene polymorphisms have provided some new information on the clinical relevance of endogenous sex steroids. We provide an update on the role of endogenous sex steroids on cardio- and cerebro-vascular disease in the postmenopausal period. We performed a PubMed search using the terms 'endogenous estrogen', 'androgen', 'cardiovascular disease', 'cerebro-vascular disease', 'stroke', 'carotid artery disease', and 'subclinical atherosclerosis'. The majority of studies show a beneficial effect of endogenous estrogen on the vasculature; however, there are a few studies reporting the contrary. A significant body of literature has reported associations of endogenous estrogen and androgen with early markers of atherosclerosis and metabolic parameters. Data on the relevance of endogenous sex steroids in heart disease and stroke are inconclusive. Most studies support a beneficial role of endogenous estrogens and, probably, an adverse effect of androgens in the vasculature in postmenopausal women. However, the described associations may not always be considered as causal. It is possible that circulating estrogen might represent a marker of general health status or alternatively reflect the sum of endogenous androgens aromatized in the periphery. Elucidating the role of sex steroids in cardio- and cerebro-vascular disease remains an interesting field of future research.

  6. Gene expression analysis in prostate cancer: the importance of the endogenous control.

    LENUS (Irish Health Repository)

    Vajda, Alice

    2013-03-01

    Aberrant gene expression is a hallmark of cancer. Quantitative reverse-transcription PCR (qRT-PCR) is the gold-standard for quantifying gene expression, and commonly employs a house-keeping gene (HKG) as an endogenous control to normalize results; the choice of which is critical for accurate data interpretation. Many factors, including sample type, pathological state, and oxygen levels influence gene expression including putative HKGs. The aim of this study was to determine the suitability of commonly used HKGs for qRT-PCR in prostate cancer.

  7. Activation of endogenous opioid gene expression in human keratinocytes and fibroblasts by pulsed radiofrequency energy fields

    Directory of Open Access Journals (Sweden)

    Moffett J

    2012-09-01

    Full Text Available John Moffett,1 Linley M Fray,1 Nicole J Kubat21Life Science Department, 2Independent Consultant, Regenesis Biomedical Inc, Scottsdale, AZ, USABackground: Pulsed radiofrequency energy (PRFE fields are being used increasingly for the treatment of pain arising from dermal trauma. However, despite their increased use, little is known about the biological and molecular mechanism(s responsible for PRFE-mediated analgesia. In general, current therapeutics used for analgesia target either endogenous factors involved in inflammation, or act on endogenous opioid pathways.Methods and Results: Using cultured human dermal fibroblasts (HDF and human epidermal keratinocytes (HEK, we investigated the effect of PRFE treatment on factors, which are involved in modulating peripheral analgesia in vivo. We found that PRFE treatment did not inhibit cyclooxygenase enzyme activity, but instead had a positive effect on levels of endogenous opioid precursor mRNA (proenkephalin, pro-opiomelanocortin, prodynorphin and corresponding opioid peptide. In HEK cells, increases in opioid mRNA were dependent, at least in part, on endothelin-1. In HDF cells, additional pathways also appear to be involved. PRFE treatment was also followed by changes in endogenous expression of several cytokines, including increased levels of interleukin-10 mRNA and decreased levels of interleukin-1β mRNA in both cell types.Conclusion: These findings provide a new insight into the molecular mechanism underlying PRFE-mediated analgesia reported in the clinical setting.Keywords: peripheral analgesia, endogenous opioids, endothelin-1, endothelin receptor A, endothelin receptor B, pulsed radiofrequency energy field, cyclooxygenase

  8. Organic solute carrier 22 (SLC22 family: Potential for interactions with food, herbal/dietary supplements, endogenous compounds, and drugs

    Directory of Open Access Journals (Sweden)

    Raymond E. Lai

    2018-04-01

    Full Text Available Many drugs, hormones, components of herbal medicines, environmental pesticides and toxins are Solute Carrier family 22 (SLC22 substrates. The last twenty years has seen great progress in determining SLC22 tissue expression profiles, membrane localization, energetics, substrate profiles and biopharmaceutical significance. However, much still remains to be answered in terms of SLC22 family member's roles in ‘normal’ physiology as compared to pathophysiological states, as well as in drug interactions that impact pharmacokinetics, efficacy and toxicity. This review begins with a brief synopsis of SLC22 family discovery, function and tissue expression. Subsequent sections provide examples establishing a role for SLC22 transporters in food-drug, herbal supplement-drug, endogenous substrate-drug and drug–drug interactions. Keywords: Hepatic transport, Nephrotoxicity, Organic anion transporter, Organic cation transporter, Renal transport

  9. Price Endogeneity and Marginal Cost Effects on Incentive Compatible Stormwater Management Policies

    OpenAIRE

    Huber, Matthew C.; Willis, David B.; Hayes, John C.; Privette, Charles V., III

    2010-01-01

    Incentive based stormwater management policies offer the prospect of reducing urban stormwater runoff while increasing developer profits. An incentive compatible Stormwater Banking Program (SBP) is presented that allows developers to build at higher residential densities in exchange for including low impact stormwater Best Management Practices (BMPs) in the development’s stormwater management infrastructure. Price endogeneity presents itself when the smaller residential lots created by buildi...

  10. Erbium-doped yttrium aluminium garnet ablative laser treatment for endogenous ochronosis.

    Science.gov (United States)

    Chaptini, Cassandra; Huilgol, Shyamala C

    2015-08-01

    Ochronosis is a rare disease characterised clinically by bluish-grey skin discolouration and histologically by yellow-brown pigment deposits in the dermis. It occurs in endogenous and exogenous forms. Endogenous ochronosis, also known as alkaptonuria, is an autosomal recessive disease of tyrosine metabolism, resulting in the accumulation and deposition of homogentisic acid in connective tissue. We report a case of facial endogenous ochronosis and coexistent photodamage, which was successfully treated with erbium-doped yttrium aluminium garnet laser resurfacing and deep focal point treatment to remove areas of residual deep pigment. © 2014 The Australasian College of Dermatologists.

  11. The Influence of Endogenous and Exogenous Spatial Attention on Decision Confidence.

    Science.gov (United States)

    Kurtz, Phillipp; Shapcott, Katharine A; Kaiser, Jochen; Schmiedt, Joscha T; Schmid, Michael C

    2017-07-25

    Spatial attention allows us to make more accurate decisions about events in our environment. Decision confidence is thought to be intimately linked to the decision making process as confidence ratings are tightly coupled to decision accuracy. While both spatial attention and decision confidence have been subjected to extensive research, surprisingly little is known about the interaction between these two processes. Since attention increases performance it might be expected that confidence would also increase. However, two studies investigating the effects of endogenous attention on decision confidence found contradictory results. Here we investigated the effects of two distinct forms of spatial attention on decision confidence; endogenous attention and exogenous attention. We used an orientation-matching task, comparing the two attention conditions (endogenous and exogenous) to a control condition without directed attention. Participants performed better under both attention conditions than in the control condition. Higher confidence ratings than the control condition were found under endogenous attention but not under exogenous attention. This finding suggests that while attention can increase confidence ratings, it must be voluntarily deployed for this increase to take place. We discuss possible implications of this relative overconfidence found only during endogenous attention with respect to the theoretical background of decision confidence.

  12. Measuring endogenous 5-HT release by emission tomography: promises and pitfalls

    Science.gov (United States)

    Paterson, Louise M; Tyacke, Robin J; Nutt, David J; Knudsen, Gitte M

    2010-01-01

    Molecular in vivo neuroimaging techniques can be used to measure regional changes in endogenous neurotransmitters, evoked by challenges that alter synaptic neurotransmitter concentration. This technique has most successfully been applied to the study of endogenous dopamine release using positron emission tomography, but has not yet been adequately extended to other neurotransmitter systems. This review focuses on how the technique has been applied to the study of the 5-hydroxytryptamine (5-HT) system. The principles behind visualising fluctuations in neurotransmitters are introduced, with reference to the dopaminergic system. Studies that aim to image acute, endogenous 5-HT release or depletion at 5-HT receptor targets are summarised, with particular attention to studies in humans. Radiotracers targeting the 5-HT1A, 5-HT2A, and 5-HT4 receptors and the serotonin reuptake transporter have been explored for their sensitivity to 5-HT fluctuations, but with mixed outcomes; tracers for these targets cannot reliably image endogenous 5-HT in humans. Shortcomings in our basic knowledge of the mechanisms underlying changes in binding potential are addressed, and suggestions are made as to how the selection of targets, radiotracers, challenge paradigms, and experimental design might be optimised to improve our chances of successfully imaging endogenous neurotransmitters in the future. PMID:20664611

  13. Use of isotope ratio mass spectrometry to differentiate between endogenous steroids and synthetic homologues in cattle: A review

    Energy Technology Data Exchange (ETDEWEB)

    Janssens, Geert, E-mail: Geert.janssens@favv.be [Federal Agency for the Safety of the Food Chain, Directorate General Laboratories, Kruidtuinlaan 55, 1000 Brussels (Belgium); Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent (Belgium); Courtheyn, Dirk [Federal Agency for the Safety of the Food Chain, Directorate General Laboratories, Kruidtuinlaan 55, 1000 Brussels (Belgium); Mangelinckx, Sven [Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent (Belgium); Prévost, Stéphanie; Bichon, Emmanuelle; Monteau, Fabrice [LUNAM Université, Oniris, Laboratoire d’Etude des Résidus et Contaminants dans les Aliments (LABERCA), F-44307 Nantes (France); De Poorter, Geert [Federal Agency for the Safety of the Food Chain, Directorate General Laboratories, Kruidtuinlaan 55, 1000 Brussels (Belgium); De Kimpe, Norbert [Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent (Belgium); Le Bizec, Bruno [LUNAM Université, Oniris, Laboratoire d’Etude des Résidus et Contaminants dans les Aliments (LABERCA), F-44307 Nantes (France)

    2013-04-15

    Graphical abstract: Scheme: Representation of the observed isotope ratios and the relation to exogenous and endogenous natural steroids. AS stands for “amount of steroid”. Highlights: ► The difference between endogenous and exogenous steroids is thoroughly laid out. ► Factors influencing the carbon ratio and the use of Δ{sup 13}C-values are explained. ► Implementation of GC/C/IRMS to detect steroid abuse in cattle is reviewed. ► Alternative methods and upcoming techniques are discussed. ► The differences and similarities with sports doping control are highlighted. -- Abstract: Although substantial technical advances have been achieved during the past decades to extend and facilitate the analysis of growth promoters in cattle, the detection of abuse of synthetic analogs of naturally occurring hormones has remained a challenging issue. When it became clear that the exogenous origin of steroid hormones could be traced based on the {sup 13}C/{sup 12}C isotope ratio of the substances, GC/C/IRMS has been successfully implemented to this aim since the end of the past century. However, due to the costly character of the instrumental setup, the susceptibility of the equipment to errors and the complex and time consuming sample preparation, this method is up until now only applied by a limited number of laboratories. In this review, the general principles as well as the practical application of GC/C/IRMS to differentiate between endogenous steroids and exogenously synthesized homologous compounds in cattle will be discussed in detail, and will be placed next to other existing and to be developed methods based on isotope ratio mass spectrometry. Finally, the link will be made with the field of sports doping, where GC/C/IRMS has been established within the World Anti-Doping Agency (WADA) approved methods as the official technique to differentiate between exogenous and endogenous steroids over the past few years.

  14. Microbial endogenous response to acute inhibitory impact of antibiotics.

    Science.gov (United States)

    Pala-Ozkok, I; Kor-Bicakci, G; Çokgör, E U; Jonas, D; Orhon, D

    2017-06-13

    Enhanced endogenous respiration was observed as the significant/main response of the aerobic microbial culture under pulse exposure to antibiotics: sulfamethoxazole, tetracycline and erythromycin. Peptone mixture and acetate were selected as organic substrates to compare the effect of complex and simple substrates. Experiments were conducted with microbial cultures acclimated to different sludge ages of 10 and 2 days, to visualize the effect of culture history. Evaluation relied on modeling of oxygen uptake rate profiles, reflecting the effect of all biochemical reactions associated with substrate utilization. Model calibration exhibited significant increase in values of endogenous respiration rate coefficient with all antibiotic doses. Enhancement of endogenous respiration was different with antibiotic type and initial dose. Results showed that both peptone mixture and acetate cultures harbored resistance genes against the tested antibiotics, which suggests that biomass spends cellular maintenance energy for activating the required antibiotic resistance mechanisms to survive, supporting higher endogenous decay rates. [Formula: see text]: maximum growth rate for X H (day -1 ); K S : half saturation constant for growth of X H (mg COD/L); b H : endogenous decay rate for X H (day -1 ); k h : maximum hydrolysis rate for S H1 (day -1 ); K X : hydrolysis half saturation constant for S H1 (mg COD/L); k hx : maximum hydrolysis rate for X S1 (day -1 ); K XX : hydrolysis half saturation constant for X S1 (mg COD/L); k STO : maximum storage rate of PHA by X H (day -1 ); [Formula: see text]: maximum growth rate on PHA for X H (day -1 ); K STO : half saturation constant for storage of PHA by X H (mg COD/L); X H1 : initial active biomass (mg COD/L).

  15. Positive versus negative modulation of different endogenous chemokines for CC-chemokine receptor 1 by small molecule agonists through allosteric versus orthosteric binding

    DEFF Research Database (Denmark)

    Jensen, Pia C; Thiele, Stefanie; Ulven, Trond

    2008-01-01

    7 transmembrane-spanning (7TM) chemokine receptors having multiple endogenous ligands offer special opportunities to understand the molecular basis for allosteric mechanisms. Thus, CC-chemokine receptor 1 (CCR1) binds CC-chemokine 3 and 5 (CCL3 and CCL5) with K(d) values of 7.3 and 0.16 nm......5 and not CCL3 activation is affected by substitutions in the main ligand binding pocket including the conserved GluVII:06 anchor point. A series of metal ion chelator complexes were found to act as full agonists on CCR1 and to be critically affected by the same substitutions in the main ligand...... binding pocket as CCL5 but not by mutations in the extracellular domain. In agreement with the overlapping binding sites, the small non-peptide agonists displaced radiolabeled CCL5 with high affinity. Interestingly, the same compounds acted as allosteric enhancers of the binding of CCL3, with which...

  16. Multi-spectral endogenous fluorescence imaging for bacterial differentiation

    Science.gov (United States)

    Chernomyrdin, Nikita V.; Babayants, Margarita V.; Korotkov, Oleg V.; Kudrin, Konstantin G.; Rimskaya, Elena N.; Shikunova, Irina A.; Kurlov, Vladimir N.; Cherkasova, Olga P.; Komandin, Gennady A.; Reshetov, Igor V.; Zaytsev, Kirill I.

    2017-07-01

    In this paper, the multi-spectral endogenous fluorescence imaging was implemented for bacterial differentiation. The fluorescence imaging was performed using a digital camera equipped with a set of visual bandpass filters. Narrowband 365 nm ultraviolet radiation passed through a beam homogenizer was used to excite the sample fluorescence. In order to increase a signal-to-noise ratio and suppress a non-fluorescence background in images, the intensity of the UV excitation was modulated using a mechanical chopper. The principal components were introduced for differentiating the samples of bacteria based on the multi-spectral endogenous fluorescence images.

  17. Exogenous vs. Endogenous Separation

    OpenAIRE

    Ramey, Garey

    2008-01-01

    This paper assesses how various approaches to modelling the separation margin a¤ect the ability of the Mortensen-Pissarides job matching model to explain key facts about the aggregate labor market. Allowing for realistic time variation in the separation rate, whether exogenous or endogenous, greatly in- creases the unemployment variability generated by the model. Speci…cations with exogenous separation rates, whether constant or time-varying, fail to pro- duce realistic volatility and prod...

  18. Endogenous reverse transcriptase (RT) activity and Chromatin remodeling in normal and transformed cells and early embryos

    International Nuclear Information System (INIS)

    Spadafora, C.; Sciamanna, I.; Misteli, T.

    2009-01-01

    Endogenous Reverse Transcriptase (RT) is an enzyme encoded by two classes of genomic retro-elements: retro-transposons and endogenous retroviruses. Basal levels of RT are expressed in all non pathological, differentiated tissues while high RT expression levels characterize tumorigenic cells, germ cells and embryonic tissues. Preliminary studies carried out in our laboratory have shown that RT inhibition using pharmacological inhibitors (nevirapine and efavirenz, two drugs currently used in AIDS therapy) drastically reduces cell proliferation, promotes differentiation of tumorigenic cells in vitro, induces a reprogrammed gene expression and antagonizes tumor progression in nude mice inoculated with tumorigenic human cell lines, including melanoma, prostate and colon carcinoma and microcitoma

  19. Endogenous retinal neural stem cell reprogramming for neuronal regeneration

    Directory of Open Access Journals (Sweden)

    Romain Madelaine

    2017-01-01

    Full Text Available In humans, optic nerve injuries and associated neurodegenerative diseases are often followed by permanent vision loss. Consequently, an important challenge is to develop safe and effective methods to replace retinal neurons and thereby restore neuronal functions and vision. Identifying cellular and molecular mechanisms allowing to replace damaged neurons is a major goal for basic and translational research in regenerative medicine. Contrary to mammals, the zebrafish has the capacity to fully regenerate entire parts of the nervous system, including retina. This regenerative process depends on endogenous retinal neural stem cells, the Müller glial cells. Following injury, zebrafish Müller cells go back into cell cycle to proliferate and generate new neurons, while mammalian Müller cells undergo reactive gliosis. Recently, transcription factors and microRNAs have been identified to control the formation of new neurons derived from zebrafish and mammalian Müller cells, indicating that cellular reprogramming can be an efficient strategy to regenerate human retinal neurons. Here we discuss recent insights into the use of endogenous neural stem cell reprogramming for neuronal regeneration, differences between zebrafish and mammalian Müller cells, and the need to pursue the identification and characterization of new molecular factors with an instructive and potent function in order to develop theurapeutic strategies for eye diseases.

  20. ON THE EMPIRICAL FINDING OF A HIGHER RISK OF POVERTY IN RURAL AREAS: IS RURAL RESIDENCE ENDOGENOUS TO POVERTY?

    OpenAIRE

    Fisher, Monica G.

    2004-01-01

    Includes: On the Empirical Finding of a Higher Risk of Poverty in Rural Areas: Is Rural Residence Endogenous to Poverty?:COMMENT, by Thomas A. Hirschl; On the Empirical Finding of a Higher Risk of Poverty in Rural Areas: Is Rural Residence Endogenous to Poverty?: REPLY, by Monica Fisher. Research shows people are more likely to be poor in rural versus urban America. Does this phenomenon partly reflect that people who choose rural residence have unmeasured attributes related to human impoveris...

  1. Reduced endogenous Ca2+ buffering speeds active zone Ca2+ signaling.

    Science.gov (United States)

    Delvendahl, Igor; Jablonski, Lukasz; Baade, Carolin; Matveev, Victor; Neher, Erwin; Hallermann, Stefan

    2015-06-09

    Fast synchronous neurotransmitter release at the presynaptic active zone is triggered by local Ca(2+) signals, which are confined in their spatiotemporal extent by endogenous Ca(2+) buffers. However, it remains elusive how rapid and reliable Ca(2+) signaling can be sustained during repetitive release. Here, we established quantitative two-photon Ca(2+) imaging in cerebellar mossy fiber boutons, which fire at exceptionally high rates. We show that endogenous fixed buffers have a surprisingly low Ca(2+)-binding ratio (∼ 15) and low affinity, whereas mobile buffers have high affinity. Experimentally constrained modeling revealed that the low endogenous buffering promotes fast clearance of Ca(2+) from the active zone during repetitive firing. Measuring Ca(2+) signals at different distances from active zones with ultra-high-resolution confirmed our model predictions. Our results lead to the concept that reduced Ca(2+) buffering enables fast active zone Ca(2+) signaling, suggesting that the strength of endogenous Ca(2+) buffering limits the rate of synchronous synaptic transmission.

  2. Endogenous α-crystallin inhibits expression of caspase-3 induced by hypoxia in retinal neurons.

    Science.gov (United States)

    Ying, Xi; Peng, Yanli; Zhang, Jiaping; Wang, Xingli; Wu, Nan; Zeng, Yuxiao; Wang, Yi

    2014-08-28

    To investigate the expression of endogenous, hypoxic stress-induced α-crystallin and caspase-3 in rat retinal neurons in vitro. Retinal neurons were cultured from Long-Evans rats. The expression of endogenous α-crystallin was analyzed by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). Furthermore, hypoxic exposure was performed in cultured cells, and the expression of endogenous α-crystallin and caspase-3 was assayed by Western blotting. Positive α-crystallin staining was observed in cultured retinal neurons, and expression of endogenous α-crystallin mRNA peaked 3-5d after inoculation (Pendogenous, hypoxic stress-induced α-crystallin expression increased gradually, peaking 6h after hypoxia. The expression was more abundant compared to the control (Pendogenous α-crystallin in retinal neurons, especially over-expression induced by hypoxic stress, results in the down regulation of caspase-3. The data suggest that endogenous α-crystallin may act as an endogenous neuroprotective factor in retinal neurons. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Cinnamaldehyde promotes root branching by regulating endogenous hydrogen sulfide.

    Science.gov (United States)

    Xue, Yan-Feng; Zhang, Meng; Qi, Zhong-Qiang; Li, You-Qin; Shi, Zhiqi; Chen, Jian

    2016-02-01

    Cinnamaldehyde (CA) has been widely applied in medicine and food preservation. However, whether and how CA regulates plant physiology is largely unknown. To address these gaps, the present study investigated the beneficial effect of CA on root branching and its possible biochemical mechanism. The lateral root (LR) formation of pepper seedlings could be markedly induced by CA at specific concentrations without any inhibitory effect on primary root (PR) growth. CA could induce the generation of endogenous hydrogen sulfide (H2S) by increasing the activity of L-cysteine desulfhydrase in roots. By fluorescently tracking endogenous H2S in situ, it could be clearly observed that H2S accumulated in the outer layer cells of the PR where LRs emerge. Sodium hydrosulfide (H2S donor) treatment induced LR formation, while hypotaurine (H2S scavenger) showed an adverse effect. The addition of hypotaurine mitigated the CA-induced increase in endogenous H2S level, which in turn counteracted the inducible effect of CA on LR formation. CA showed great potential in promoting LR formation, which was mediated by endogenous H2S. These results not only shed new light on the application of CA in agriculture but also extend the knowledge of H2S signaling in the regulation of root branching. © 2015 Society of Chemical Industry.

  4. Glucocorticoid-related bone changes from endogenous or exogenous glucocorticoids.

    Science.gov (United States)

    Warriner, Amy H; Saag, Kenneth G

    2013-12-01

    Glucocorticoids have a negative impact on bone through direct effects on bone cells and indirect effects on calcium absorption. Here, recent findings regarding glucocorticoid-induced osteoporosis, bone changes in patients with endogenous glucocorticoid derangements, and treatment of steroid-induced bone disease are reviewed. Although the majority of our understanding arises from the outcomes of patients treated with exogenous steroids, endogenous overproduction appears to be similarly destructive to bone, but these effects are reversible with cure of the underlying disease process. Additionally, there are bone changes that occur in diseases that interrupt adrenal glucocorticoid production, both in response to our inability to perfectly match glucocorticoid replacement and also related to the underlying disease process. More investigation is required to understand which patients with endogenous overproduction or underproduction of glucocorticoid would benefit from osteoporosis treatment. Better understood is the benefit that can be achieved with currently approved treatments for glucocorticoid-induced osteoporosis from exogenous steroids. With growing concern of long-term use of bisphosphonates, however, further investigation into the duration of use and use in certain populations, such as children and premenopausal women, is essential. Glucocorticoid-induced osteoporosis is a complex disease that is becoming better understood through advances in the study of exogenous and endogenous glucocorticoid exposure. Further advancement of proper treatment and prevention is on the horizon.

  5. Cetuximab modified collagen scaffold directs neurogenesis of injury-activated endogenous neural stem cells for acute spinal cord injury repair.

    Science.gov (United States)

    Li, Xing; Zhao, Yannan; Cheng, Shixiang; Han, Sufang; Shu, Muya; Chen, Bing; Chen, Xuyi; Tang, Fengwu; Wang, Nuo; Tu, Yue; Wang, Bin; Xiao, Zhifeng; Zhang, Sai; Dai, Jianwu

    2017-08-01

    Studies have shown that endogenous neural stem cells (NSCs) activated by spinal cord injury (SCI) primarily generate astrocytes to form glial scar. The NSCs do not differentiate into neurons because of the adverse microenvironment. In this study, we defined the activation timeline of endogenous NSCs in rats with severe SCI. These injury-activated NSCs then migrated into the lesion site. Cetuximab, an EGFR signaling antagonist, significantly increased neurogenesis in the lesion site. Meanwhile, implanting cetuximab modified linear ordered collagen scaffolds (LOCS) into SCI lesion sites in dogs resulted in neuronal regeneration, including neuronal differentiation, maturation, myelination, and synapse formation. The neuronal regeneration eventually led to a significant locomotion recovery. Furthermore, LOCS implantation could also greatly decrease chondroitin sulfate proteoglycan (CSPG) deposition at the lesion site. These findings suggest that endogenous neurogenesis following acute complete SCI is achievable in species ranging from rodents to large animals via functional scaffold implantation. LOCS-based Cetuximab delivery system has a promising therapeutic effect on activating endogenous neurogenesis, reducing CSPGs deposition and improving motor function recovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Endogenous Quality Effects of Trade Policy

    NARCIS (Netherlands)

    J.L. Moraga-Gonzalez (José Luis); J.M.A. Viaene (Jean-Marie)

    1999-01-01

    textabstractWe study the optimal trade policy against a foreign oligopoly with endogenous quality. We show that, under the Most Favoured Nation (MFN) clause, a uniform tariff policy is always welfare improving over the free trade equilibrium. However, a nonuniform tariff policy is always desirable

  7. Conditions for Effective Application of Analysis of Symmetrically-Predicted Endogenous Subgroups

    Science.gov (United States)

    Peck, Laura R.

    2015-01-01

    Several analytic strategies exist for opening up the "black box" to reveal more about what drives policy and program impacts. This article focuses on one of these strategies: the Analysis of Symmetrically-Predicted Endogenous Subgroups (ASPES). ASPES uses exogenous baseline data to identify endogenously-defined subgroups, keeping the…

  8. Endogenous PTH deficiency impairs fracture healing and impedes the fracture-healing efficacy of exogenous PTH(1-34.

    Directory of Open Access Journals (Sweden)

    Yongxin Ren

    Full Text Available Although the capacity of exogenous PTH1-34 to enhance the rate of bone repair is well established in animal models, our understanding of the mechanism(s whereby PTH induces an anabolic response during skeletal repair remains limited. Furthermore it is unknown whether endogenous PTH is required for fracture healing and how the absence of endogenous PTH would influence the fracture-healing capacity of exogenous PTH.Closed mid-diaphyseal femur fractures were created and stabilized with an intramedullary pin in 8-week-old wild-type and Pth null (Pth(-/- mice. Mice received daily injections of vehicle or of PTH1-34 (80 µg/kg for 1-4 weeks post-fracture, and callus tissue properties were analyzed at 1, 2 and 4 weeks post-fracture. Cartilaginous callus areas were reduced at 1 week post-fracture, but were increased at 2 weeks post-fracture in vehicle-treated and PTH-treated Pth(-/- mice compared to vehicle-treated and PTH-treated wild-type mice respectively. The mineralized callus areas, bony callus areas, osteoblast number and activity, osteoclast number and surface in callus tissues were all reduced in vehicle-treated and PTH-treated Pth(-/- mice compared to vehicle-treated and PTH-treated wild-type mice, but were increased in PTH-treated wild-type and Pth(-/- mice compared to vehicle-treated wild-type and Pth(-/- mice.Absence of endogenous PTH1-84 impedes bone fracture healing. Exogenous PTH1-34 can act in the absence of endogenous PTH but callus formation, including accelerated endochondral bone formation and callus remodeling as well as mechanical strength of the bone are greater when endogenous PTH is present. Results of this study suggest a complementary role for endogenous PTH1-84 and exogenous PTH1-34 in accelerating fracture healing.

  9. Endogenous PTH deficiency impairs fracture healing and impedes the fracture-healing efficacy of exogenous PTH(1-34).

    Science.gov (United States)

    Ren, Yongxin; Liu, Bo; Feng, Yuxu; Shu, Lei; Cao, Xiaojian; Karaplis, Andrew; Goltzman, David; Miao, Dengshun

    2011-01-01

    Although the capacity of exogenous PTH1-34 to enhance the rate of bone repair is well established in animal models, our understanding of the mechanism(s) whereby PTH induces an anabolic response during skeletal repair remains limited. Furthermore it is unknown whether endogenous PTH is required for fracture healing and how the absence of endogenous PTH would influence the fracture-healing capacity of exogenous PTH. Closed mid-diaphyseal femur fractures were created and stabilized with an intramedullary pin in 8-week-old wild-type and Pth null (Pth(-/-)) mice. Mice received daily injections of vehicle or of PTH1-34 (80 µg/kg) for 1-4 weeks post-fracture, and callus tissue properties were analyzed at 1, 2 and 4 weeks post-fracture. Cartilaginous callus areas were reduced at 1 week post-fracture, but were increased at 2 weeks post-fracture in vehicle-treated and PTH-treated Pth(-/-) mice compared to vehicle-treated and PTH-treated wild-type mice respectively. The mineralized callus areas, bony callus areas, osteoblast number and activity, osteoclast number and surface in callus tissues were all reduced in vehicle-treated and PTH-treated Pth(-/-) mice compared to vehicle-treated and PTH-treated wild-type mice, but were increased in PTH-treated wild-type and Pth(-/-) mice compared to vehicle-treated wild-type and Pth(-/-) mice. Absence of endogenous PTH1-84 impedes bone fracture healing. Exogenous PTH1-34 can act in the absence of endogenous PTH but callus formation, including accelerated endochondral bone formation and callus remodeling as well as mechanical strength of the bone are greater when endogenous PTH is present. Results of this study suggest a complementary role for endogenous PTH1-84 and exogenous PTH1-34 in accelerating fracture healing.

  10. Human-Specific Endogenous Retroviruses

    Directory of Open Access Journals (Sweden)

    Anton Buzdin

    2007-01-01

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

  11. Endogenous and exogenous testosterone and prostate cancer: decreased-, increased- or null-risk?

    Science.gov (United States)

    Lopez, David S; Advani, Shailesh; Tsilidis, Konstantinos K; Wang, Run; Canfield, Steven

    2017-06-01

    For more than 70 years, the contention that high levels of testosterone or that the use of testosterone therapy (TTh) increases the development and progression of prostate cancer (PCa) has been widely accepted and practiced. Yet, the increasing and emerging evidence on testosterone research seems to challenge that contention. To review literature on the associations of endogenous and exogenous testosterone with decreased-, increased-, or null-risk of PCa, and to further evaluate only those studies that reported magnitude of associations from multivariable modeling as it minimizes confounding effects. We conducted a literature search to identify studies that investigated the association of endogenous total testosterone [continuous (per 1 unit increment and 5 nmol/L increment) and categorical (high vs. low)] and use of TTh with PCa events [1990-2016]. Emphasis was given to studies/analyses that reported magnitude of associations [odds ratio (OR), relative risk (RR) and hazard ratios (HRs)] from multivariable analyses to determine risk of PCa and their statistical significance. Most identified studies/analyses included observational and randomized placebo-controlled trials. This review was organized in three parts: (I) association of endogenous total testosterone (per 1 unit increment and 5 nmol/L increment) with PCa; (II) relationship of endogenous total testosterone (categorical high vs. low) with PCa; and (III) association of use of TTh with PCa in meta-analyses of randomized placebo-controlled trials. The first part included 31 observational studies [20 prospective (per 5 nmol/L increment) and 11 prospective and retrospective cohort studies (per 1 unit increment)]. None of the 20 prospective studies found a significant association between total testosterone (5 nmol/L increment) and increased- or decreased-risk of PCa. Two out of the 11 studies/analyses showed a significant decreased-risk of PCa for total testosterone per 1 unit increment, but also two other

  12. The role of endogenous lipids in the emulsifying properties of cocoa

    Science.gov (United States)

    Gould, Joanne; Furse, Samuel; Wolf, Bettina

    2016-03-01

    This paper describes a study in which the emulsifying properties of cocoa material with and without its lipid fraction were explored. This study was motivated by the commercial interest in naturally-occurring particulate emulsifiers as opposed to the chemically modified emulsifying particles presently available for commercial use. The hypothesis was that endogenous lipids from cocoa were responsible for driving the formation of stable oil-in-water (o/w) emulsions. The data presented includes relative quantification of phospholipids from different commercially available cocoa material using 31P NMR spectroscopy and analyses of the emulsifying power of delipidified cocoa material. The commercially available cocoa material comprised several phospholipids, with phosphatidylcholine being the most abundant in all samples. Dispersions of delipidified cocoa material were found to drive the formation of o/w emulsions despite the absence of lipids. We therefore concluded that the emulsifying behaviour of cocoa material is not entirely reliant upon the endogenous lipids. This suggests that cocoa material may have a new and potentially widespread use in industrial food preparation and may inform manufacturing strategies for novel food grade emulsifiers.

  13. Diffuse fluorescence tomography of exo- and endogenously labeled tumors

    Science.gov (United States)

    Balalaeva, Irina V.; Turchin, Ilya V.; Orlova, Anna G.; Plekhanov, Vladimir I.; Shirmanova, Marina V.; Kleshnin, Michail S.; Fiks, Ilya I.; Zagainova, Elena V.; Kamensky, Vladislav A.

    2007-06-01

    Strong light scattering and absorption limit observation of the internal structure of biological tissue. Only special tools for turbid media imaging, such as optical diffuse tomography, enable noninvasive investigation of the internal biological tissues, including visualization and intravital monitoring of deep tumors. In this work the preliminary results of diffuse fluorescence tomography (DFT) of small animals are presented. Usage of exogenous fluorophores, targeted specifically at tumor cells, and fluorescent proteins expressed endogenously can significantly increase the contrast of obtained images. Fluorescent compounds of different nature, such as sulphonated aluminium phthalocyanine (Photosens), red fluorescing proteins and CdTe/CdSe-core/shell nanocrystals (quantum dots) were applied. We tested diffuse fluorescence tomography method at model media, in post mortem and in vivo experiments. The animal was scanned in transilluminative configuration by low-frequency modulated light (1 kHz) from Nd:YAG laser with second harmonic generation at wavelength of 532 nm or semiconductor laser at wavelength of 655 nm. Quantum dots or protein DsRed2 in glass capsules (inner diameter 2-3 mm) were placed post mortem inside the esophagus of 7-day-old hairless rats to simulate marked tumors. Photosens was injected intravenously to linear mice with metastazing Lewis lung carcinoma. The reconstruction algorithm, based on Algebraic Reconstruction Technique, was created and tested numerically in model experiments. High contrast images of tumor simulating capsules with DsRed2 concentrations about 10 -6 M and quantum dots about 5x10 -11 M have been obtained. Organ distribution of Photosens and its accumulation in tumors and surrounding tissues of animals has been examined. We have conducted the monitoring of tumors, exogenously labeled by photosensitizer. This work demonstrates potential capabilities of DFT method for intravital detection and monitoring of deep fluorescent

  14. Endogenous Money, Output and Prices in India

    OpenAIRE

    Das, Rituparna

    2009-01-01

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

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

    DEFF Research Database (Denmark)

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

    1986-01-01

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

  16. Endogenous subclinical hyperthyroidism and cardiovascular system: time to reconsider?

    Science.gov (United States)

    Patanè, Salvatore; Marte, Filippo; Sturiale, Mauro

    2011-05-19

    Subclinical hyperthyroidism is an increasingly recognized entity that is defined as a normal serum free thyroxine and free triiodothyronine levels with a thyroid-stimulating hormone level suppressed below the normal range and usually undetectable. Exogenous sublinical hyperthyroidism is a thyroid metabolic state caused by L-thyroxine administration. Endogenous subclinical hyperthyroidism is a thyroid metabolic state in patients with autonomously functioning thyroid nodule or multinodular goiter, various forms of thyroiditis, in areas with endemic goiter and particularly in elderly subjects. Endogenous subclinical hyperthyroidism is currently the subject of numerous studies and it yet remains controversial particularly as it relates to its treatment and to cardiovascular impact nevertheless established effects have been demonstrated. Recently, acute myocardial infarction without significant coronary stenoses and recurrent acute pulmonary embolism have been reported associated with subclinical hyperthyroidism without L-thyroxine administration. So, it is very important to recognize and to treat promptly also endogenous subclinical hyperthyroidism. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

  17. The Deacetylase HDAC6 Mediates Endogenous Neuritic Tau Pathology

    Directory of Open Access Journals (Sweden)

    Jui-Heng Tseng

    2017-08-01

    Full Text Available The initiating events that promote tau mislocalization and pathology in Alzheimer’s disease (AD are not well defined, partly because of the lack of endogenous models that recapitulate tau dysfunction. We exposed wild-type neurons to a neuroinflammatory trigger and examined the effect on endogenous tau. We found that tau re-localized and accumulated within pathological neuritic foci, or beads, comprised of mostly hypo-phosphorylated, acetylated, and oligomeric tau. These structures were detected in aged wild-type mice and were enhanced in response to neuroinflammation in vivo, highlighting a previously undescribed endogenous age-related tau pathology. Strikingly, deletion or inhibition of the cytoplasmic shuttling factor HDAC6 suppressed neuritic tau bead formation in neurons and mice. Using mass spectrometry-based profiling, we identified a single neuroinflammatory factor, the metalloproteinase MMP-9, as a mediator of neuritic tau beading. Thus, our study uncovers a link between neuroinflammation and neuritic tau beading as a potential early-stage pathogenic mechanism in AD.

  18. Hume and Endogenous Money

    OpenAIRE

    Maria Pia Paganelli

    2006-01-01

    David Hume’s monetary theory has three standard yet inconsistent readings. As a forefather of the quantity theory of money, Hume sees money as neutral. As an inflationist, Hume sees an active positive role for monetary policy. As a monetarist, Hume sees an active positive role for monetary policy only in the short run. This paper reads Hume consistently instead by showing that for Hume money is endogenous and demand-driven. Hume would read the money equation in terms of reverse causation and ...

  19. [Protective effects of endogenous carbon monoxide against myocardial ischemia-reperfusion injury in rats].

    Science.gov (United States)

    Zhou, Zhen; Ma, Shuang; Liu, Jie; Ji, Qiao-Rong; Cao, Cheng-Zhu; Li, Xiao-Na; Tang, Feng; Zhang, Wei

    2018-04-25

    The present study is aimed to explore the effects of endogenous carbon monoxide on the ischemia-reperfusion in rats. Wistar rats were intraperitoneally injected with protoporphyrin cobalt chloride (CoPP, an endogenous carbon monoxide agonist, 5 mg/kg), zinc protoporphyrin (ZnPP, an endogenous carbon monoxide inhibitor, 5 mg/kg) or saline. Twenty-four hours after injection, the myocardial ischemia-reperfusion model was made by Langendorff isolated cardiac perfusion system, and cardiac function parameters were collected. Myocardial cGMP content was measured by ELISA, and the endogenous carbon monoxide in plasma and myocardial enzymes in perfusate at 10 min after reperfusion were measured by colorimetry. The results showed that before ischemia the cardiac functions of CoPP, ZnPP and control groups were stable, and there were no significant differences. After reperfusion, cardiac functions had significant differences among the three groups (P endogenous carbon monoxide can maintain cardiac function, shorten the time of cardiac function recovery, and play a protective role in cardiac ischemia-reperfusion.

  20. Endogenous Jaagsiekte Sheep Retrovirus RNA is expressed by different cell types in ovine foetus and placenta

    Directory of Open Access Journals (Sweden)

    E Sanna

    2010-01-01

    Full Text Available The endogenous retroviruses are inherited elements transmitted trough the germline of most animal species and their biological role is still controversial. Ovine Pulmonary Carcinoma (OPC represents a good model for studying the interactions of endogenous retroviruses with their exogenous counterparts. The type D exogenous retrovirus known as Jaagsiekte Sheep Retro-Virus (JSRV is necessary and sufficient to cause OPC in domestic and wild sheep, but both affected and unaffected animals host in their genome 15 to 20 copies of related endogenous retroviruses named endogenous JSRV (enJSRV. In this study we evaluated the expression of enJSRV gag sequences in ovine foetal and placental tissues. RNA in situ hybridisation was performed on tissue sections of thymi, lymph nodes and lungs from ovine foetuses and related placentas, taken at a late stage of development. Reverse transcriptase- in situ polymerase chain reactions were also carried out on placental samples to better define the involved cells. In foetal tissues, specific signals were observed in the thymus medulla, lymph nodes and, at a lesser extent, in foetal bronchiolar cells. In the placental tissues, positive areas were detected in various cell types in the sincythium-and cyto-trophoblast. These data demonstrate that en JSRV RNA is largely expressed in a broad spectrum of cells including tissues which are critical for the development of the immune system.

  1. Pathophysiological Features of Endogenous Intoxication in Pregnant Women with Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    N. V. Kabanova

    2008-01-01

    Full Text Available Objective: to determine the nature and specific features of development of endogenous intoxication in pregnant women with arterial hypertension. Subjects and materials. Humoral extracellular fluid volume regulation, partial renal functions, placental hormonal function, membranous lipid peroxidation activity, antiradical defense, the parameters of central hemodynamics, endogenous intoxication, and a biochemical coagulogram were studied and differential blood count with the leukocytic ratio indices was estimated in 172 pregnant females with arterial hypertension and 54 healthy pregnant ones in the third trimester. The statistical package «Stadia» was applied. Results. Arterial hypertension caused by pregnancy was ascertained to involve pathogenetically different types: low-, normal-, and high-renin ones. In pregnant women with arterial hypertension, the general pathogenetic homeostatic changes were placental hormonal imbalance, activated membranous lipid peroxidation, impaired lymph outflow, sodium and water retention, hepatic and renal failure, and endogenous intoxication. Conclusion. Placental ischemia appearing as placental hormonal imbalance (extrarenal pressor system was accompanied by a compensatory humoral response: arterial hypertension and metabolic disturbances. Changes in medium-weight molecule 280, leukocytic intoxication index, erythrocytic sorption capacity, and Paramecium test, by confirming the presence of endogenous intoxication in pregnant females with arterial hypertension, were caused by a type of arterial hypertension (by the hemodynamic profile and the type of impaired partial renal functions. Key words: pregnancy, arterial hypertension, endogenous intoxication.

  2. Differences in clinical ocular outcomes between exogenous and endogenous endophthalmitis caused by Sporothrix: a systematic review of published literature.

    Science.gov (United States)

    Ramírez Soto, Max Carlos

    2017-09-28

    Sporotrichosis is an implantation mycosis caused by Sporothrix species prevalent worldwide, which occasionally can also result in intraocular infection presenting as an exogenous or endogenous infection (disseminated sporotrichosis). Knowledge in its clinical recognition and management is limited. To systematically review and analyse data from published literature with a view to comparing clinical outcomes between exogenous and endogenous endophthalmitis caused by Sporothrix . Case reports of intraocular sporotrichosis, published from 1960 to 2016, were retrieved from MEDLINE, Embase, Cochrane, LILACS and SciELO databases. The entire data set was divided into two patient groups: (1) exogenous endophthalmitis and (2) endogenous endophthalmitis. Primary outcomes were differences in ocular findings and clinical ocular outcomes between the two groups. From 16 publications retrieved, a total of 8 eyes of 8 patients with exogenous endophthalmitis and 13 eyes of 10 patients with endogenous endophthalmitis were identified. Compared with exogenous endophthalmitis, endogenous endophthalmitis was more common in patients infected with HIV (p=0.001) and those from hyperendemic areas (p=0.036). Anterior uveitis (p=0.015) and posterior uveitis (p=0.04) were more common in the exogenous and endogenous endophthalmitis groups, respectively. The majority of patients with endogenous endophthalmitis had partial or full clinical resolution of ocular lesions with systemic amphotericin B alone or in combination with an oral antifungal, whereas patients with exogenous endophthalmitis had poor outcomes with irreversible vision loss, enucleation and evisceration. Anterior uveitis is more common in exogenous endophthalmitis with worse overall outcomes and complications, compared with endogenous endophthalmitis where posterior uveitis is the most common clinical manifestation, especially in patients infected with HIV and those from hyperendemic areas. Sporothrix infection should be included in

  3. Characterization of the fusion core in zebrafish endogenous retroviral envelope protein

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Jian [State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072 (China); State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071 (China); Zhang, Huaidong [CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071 (China); Gong, Rui, E-mail: gongr@wh.iov.cn [CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071 (China); Xiao, Gengfu, E-mail: xiaogf@wh.iov.cn [State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072 (China); State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071 (China)

    2015-05-08

    Zebrafish endogenous retrovirus (ZFERV) is the unique endogenous retrovirus in zebrafish, as yet, containing intact open reading frames of its envelope protein gene in zebrafish genome. Similarly, several envelope proteins of endogenous retroviruses in human and other mammalian animal genomes (such as syncytin-1 and 2 in human, syncytin-A and B in mouse) were identified and shown to be functional in induction of cell–cell fusion involved in placental development. ZFERV envelope protein (Env) gene appears to be also functional in vivo because it is expressible. After sequence alignment, we found ZFERV Env shares similar structural profiles with syncytin and other type I viral envelopes, especially in the regions of N- and C-terminal heptad repeats (NHR and CHR) which were crucial for membrane fusion. We expressed the regions of N + C protein in the ZFERV Env (residues 459–567, including predicted NHR and CHR) to characterize the fusion core structure. We found N + C protein could form a stable coiled-coil trimer that consists of three helical NHR regions forming a central trimeric core, and three helical CHR regions packing into the grooves on the surface of the central core. The structural characterization of the fusion core revealed the possible mechanism of fusion mediated by ZFERV Env. These results gave comprehensive explanation of how the ancient virus infects the zebrafish and integrates into the genome million years ago, and showed a rational clue for discovery of physiological significance (e.g., medicate cell–cell fusion). - Highlights: • ZFERV Env shares similar structural profiles with syncytin and other type I viral envelopes. • The fusion core of ZFERV Env forms stable coiled-coil trimer including three NHRs and three CHRs. • The structural mechanism of viral entry mediated by ZFERV Env is disclosed. • The results are helpful for further discovery of physiological function of ZFERV Env in zebrafish.

  4. Changes of endogenous hormones in irradiated potato tubers

    International Nuclear Information System (INIS)

    Farag, S.E.A.; El-Saeid, H.M.; Abou-Hadid, A.F.

    1992-01-01

    Potato tubers Solatum tuberosum L. cv. Alpha were irradiated with 0.12 kgy and stored at room temperature. The endogenous hormones were extracted and determined using bioassay at dormant, budding and sprouting stages. The studied promoters were IAA, IAN, GA3 and Gibberellin like substances besides the inhibitors which included ABA and B-inhibitors. The results indicated that IAA was more sensitive to irradiation than IAN, GA3 but ABA was more stable than B-inhibitors during the dormancy. Irradiation decreased IAA and Gibberellin like substances and B-inhibitors but no change was observed in ABA content at dormant period. Irradiation caused a balance between promoters inhibitors at the end of tuber storage and after tubers sprouting

  5. Modelling the vicious circle between obesity and physical activity in children and adolescents using a bivariate probit model with endogenous regressors.

    Science.gov (United States)

    Yeh, C-Y; Chen, L-J; Ku, P-W; Chen, C-M

    2015-01-01

    The increasing prevalence of obesity in children and adolescents has become one of the most important public health issues around the world. Lack of physical activity is a risk factor for obesity, while being obese could reduce the likelihood of participating in physical activity. Failing to account for the endogeneity between obesity and physical activity would result in biased estimation. This study investigates the relationship between overweight and physical activity by taking endogeneity into consideration. It develops an endogenous bivariate probit model estimated by the maximum likelihood method. The data included 4008 boys and 4197 girls in the 5th-9th grades in Taiwan in 2007-2008. The relationship between overweight and physical activity is significantly negative in the endogenous model, but insignificant in the comparative exogenous model. This endogenous relationship presents a vicious circle in which lower levels of physical activity lead to overweight, while those who are already overweight engage in less physical activity. The results not only reveal the importance of endogenous treatment, but also demonstrate the robust negative relationship between these two factors. An emphasis should be put on overweight and obese children and adolescents in order to break the vicious circle. Promotion of physical activity by appropriate counselling programmes and peer support could be effective in reducing the prevalence of obesity in children and adolescents.

  6. INVESTMENT EFFECTS OF ENDOGENOUS AND EXOGENOUS DEPRECIATION: IMPROVED PASTURES IN URUGUAY

    OpenAIRE

    Ekboir, Javier M.; Jarvis, Lovell S.; Rey, Carlos

    1998-01-01

    The depreciation rate for capital assets may have endogenous and exogenous components. Change in the exogenous component depends on technological change and/or environmental factors, shifts the production function, and independently affects profitability and investment. Change in the endogenous component does not. These hypotheses are tested using data on Uruguayan grass-legume pastures.

  7. The effect of in vitro mycorrhization on growth characteristics, changes in endogenous hormones and performance of microplants in potato (Solanum tuberosum L.

    Directory of Open Access Journals (Sweden)

    Khosro PARVIZI

    2015-12-01

    Full Text Available Potato (Solanum tuberosum L. plantlets were inoculated in vitro with an arbuscular mycorrhizal fungus (Glomus intraradices and their growth response, performance and endogenous hormonal status evaluated. A factorial experiment based on a completely randomized design consisting of two potato cultivars (Agria and Sante and four culture media was conducted with four replications. The culture media included non-inoculated Murashige and Skoog (MS medium (control, inoculated MS medium, inoculated half-strength MS medium and inoculated MS medium without vitamins and sugar. To do inoculation, germinated spores of fungus were transferred to the root zone of plantlets. Colonization percentage, total chlorophyll content, internodes and stolon length, shoot diameter, shoot and root fresh and dry weight, leaf area and the level of three endogenous hormones (total auxins, gibberellins and cytokinins were determined. In addition, mini-tuber production was assayed quantitatively and qualitatively. Results demonstrated that the effect of two factors on all characteristics including mini-tuber production was different significantly. Interaction between cultivar and inoculation systems was significantly associated with endogen auxins as well as all range of mini-tuber production. The inoculated MS medium showed the better results, but it did not have significant difference to half-strength MS in terms of plantlet performance and growing parameters. Responses of both cultivars to inoculation were very conspicuous in the production of endogen hormones. Higher endogen hormone levels were associated with elevated growth parameters, greater biomass production and better plantlet performance.

  8. Exogenous and endogenous landforms in the Mediterranean

    Science.gov (United States)

    Acar, Julia

    2017-04-01

    11th graders have already learned about endogenous forces and now we are having a closer look at the exogenous forces which act on the Earth's surface. The Po River-system, for example, is responsible for the formation of the alpine region. Students are asked to find out how this works with the help of the rock-cycle scheme, several suitable maps and information on weathering and the texture of rocks, erosion, etc. We will form groups that will look at different types of rock formations (including an example in the Mediterranean region each). Depending on the number of lessons available we will add the exogenous effect of flowing water and ice (glacial over forming) to the topic. At the end every group will present their findings explaining the scientific context by using topographic examples.

  9. THE ROLE OF ENTEROSORBENTS IN TREATMENT OF ENDOGENOUS INTOXICATION SYNDROME

    OpenAIRE

    N. I. Ursova

    2012-01-01

    Usage of enterosorbents in treatment of almost all types of acute and chronic disorders accompanied with endogenous intoxication syndrome takes on special significance. The critical point of endogenous intoxication pathogenesis is dysfunction of microbiocenosis and intestinal barrier. The necessity of enterosorbents usage is very high due to their efficacy, safety and wide availability. Smectite dioctaedric (diosmectite), which has been successfully used in clinical practice for a long period...

  10. Influence of endogenous pyrogen on the cerebral prostaglandin-synthetase system.

    Science.gov (United States)

    Ziel, R; Krupp, P

    1976-11-15

    The biotransformation of arachidonic acid to prostaglandins in vitro is specifically augmented by endogenous pyrogen to a degree depending on the concentration applied, providing that the microsomal fraction of the cerebral cortex is used as prostaglandin-synthetase system. This effect is inhibited by non-steroidal anti-inflammatory agents. These findings are compatible with the hypothesis that prostaglandins might act as mediators of the febrile reaction induced by endogenous pyrogen.

  11. Endogenous Magnetic Reconnection in Solar Coronal Loops

    Science.gov (United States)

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

    2017-12-01

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

  12. Early social environment affects the endogenous oxytocin system: a review and future directions

    Directory of Open Access Journals (Sweden)

    Emily eAlves

    2015-03-01

    Full Text Available Endogenous oxytocin plays an important role in a wide range of human functions including birth, milk ejection during lactation and facilitation of social interaction. There is increasing evidence that both variations in the oxytocin receptor (OXTR and concentrations of oxytocin are associated with differences in these functions. The causes for the differences that have been observed in tonic and stimulated oxytocin release remain unclear. Previous reviews have suggested that across the life course, these differences may be due to individual factors, e.g. genetic variation (of the OXTR, age or sex, or be the result of early environmental influences such as social experiences, stress or trauma partly by inducing epigenetic changes. This review has three aims. First, we briefly discuss the endogenous oxytocin system, including physiology, development, individual differences and function. Secondly, current models describing the relationship between the early life environment and the development of the oxytocin system in humans and animals are discussed. Finally, we describe research designs that can be used to investigate the effects of the early environment on the oxytocin system, identifying specific areas of research that need further attention.

  13. Comparison of endogenous and radiolabeled bile acid excretion in patients with idiopathic chronic diarrhea

    International Nuclear Information System (INIS)

    Schiller, L.R.; Bilhartz, L.E.; Santa Ana, C.A.

    1990-01-01

    Fecal recovery of radioactivity after ingestion of a bolus of radiolabeled bile acid is abnormally high in most patients with idiopathic chronic diarrhea. To evaluate the significance of this malabsorption, concurrent fecal excretion of both exogenous radiolabeled bile acid and endogenous (unlabeled) bile acid were measured in patients with idiopathic chronic diarrhea. Subjects received a 2.5-microCi oral dose of taurocholic acid labeled with 14C in the 24th position of the steroid moiety. Endogenous bile acid excretion was measured by a hydroxysteroid dehydrogenase assay on a concurrent 72-h stool collection. Both radiolabeled and endogenous bile acid excretion were abnormally high in most patients with chronic diarrhea compared with normal subjects, even when equivoluminous diarrhea was induced in normal subjects by ingestion of osmotically active solutions. The correlation between radiolabeled and endogenous bile acid excretion was good. However, neither radiolabeled nor endogenous bile acid excretion was as abnormal as is typically seen in patients with ileal resection, and none of these diarrhea patients responded to treatment with cholestyramine with stool weights less than 200 g. These results suggest (a) that this radiolabeled bile acid excretion test accurately reflects excess endogenous bile acid excretion; (b) that excess endogenous bile acid excretion is not caused by diarrhea per se; (c) that spontaneously occurring idiopathic chronic diarrhea is often associated with increased endogenous bile acid excretion; and (d) that bile acid malabsorption is not likely to be the primary cause of diarrhea in most of these patients

  14. Fungal mycelia show lag time before re-growth on endogenous carbon.

    Science.gov (United States)

    Pollack, Judith K; Li, Zheng Jian; Marten, Mark R

    2008-06-15

    Nutrient starvation is a common occurrence for filamentous fungi. To better understand the effects of starvation, we used a parallel plate flow chamber to study individual fungal mycelia when subjected to a step change in glucose concentration. We report the presence of a finite "lag time" in starved mycelia during which they ceased to grow/extend while switching from growth on exogenous carbon to re-growth on endogenous carbon. This lag time precedes other morphological or physiological changes such as change in growth rate (50-70% reduction), vacuolation (up to 16%), and decreased hyphal diameter (almost 50% reduction). Data suggests that during lag time, vacuolar degradation produces sufficient endogenous carbon to support survival and restart hyphal extension. Lag time is inversely related to the size of the mycelium at the time of starvation, which suggests a critical flow of endogenous carbon to the apical tip. We present a mathematical model consistent with our experimental observations that relate lag time, area, and flow of endogenous carbon. (c) 2008 Wiley Periodicals, Inc.

  15. Evidence for endogenous opioid release in the amygdala during positive emotion.

    Science.gov (United States)

    Koepp, M J; Hammers, A; Lawrence, A D; Asselin, M C; Grasby, P M; Bench, C J

    2009-01-01

    Endogenous opioid release has been linked to relief from aversive emotional memories, thereby promoting a euphoric state and subsequent interactions towards social stimuli resulting in the formation of social preferences. However, this theory remains controversial. Using positron emission tomography and [(11)C]diprenorphine (DPN) in healthy volunteers, we found significantly reduced DPN binding to opioid receptor in the hippocampus during positive mood induction compared to neutral mood. Furthermore, the magnitude of positive mood change correlated negatively with DPN binding in the amygdala bilaterally. Our finding of reduced DPN binding is consistent with increased release of endogenous opioids, providing direct evidence that localised release of endogenous opioids is involved in the regulation of positive emotion in humans.

  16. Evidence for Arginine as the Endogenous Precursor of Necines in Heliotropium1

    Science.gov (United States)

    Birecka, Helena; Birecki, Mieczyslaw; Frohlich, M. W.

    1987-01-01

    In pyrrolizidine alkaloid-bearing Heliotropium angiospermum and H. indicum shoots exposed, in the light, to 14C-labeled CO2 for 44 hours, the incorporation of 14C into 1,2-epoxy-1-hydroxymethylpyrrolizidine and retronecine amounted to 0.23 and 0.15%, respectively, of the total carbon assimilated. Treatment of the shoots with α-dl-difluoromethylornithine, the specific ornithine decarboxylase inhibitor, at 1 to 2 millimolar had no effect on 14C incorporation into the necines. In contrast, α-dl-difluoromethylarginine, the specific arginine decarboxylase inhibitor, prevented the incorporation of 14C into the necines of both species; the inhibitor did not affect the absolute incorporation of 14C from exogenous [1,4-14C] putrescine in either species. Thus, arginine is the only apparent endogenous precursor of the putrescine channeled into pyrrolizidines, at least in these two Heliotropium species that exhibited a relatively much higher in vitro activity of arginine decarboxylase than of ornithine decarboxylase. However, within 28 hours after administration, not only exogenous l-[5-14C]arginine, but also exogenous l-[5-14C]ornithine exhibited significant incorporation of their label into the necines, incorporation that could be partially prevented by both inhibitors. Neither inhibitor affected the rates of 14C-labeled CO2 assimilation, transformation of labeled assimilates into ethanol-insoluble compounds, or the very high degree of conversion of the introduced amino acids into other compounds. Methodology related to alkaloid biosynthetic studies is discussed. PMID:16665402

  17. [Exploration of the Essence of "Endogenous Turbidity" in Chinese Medicine].

    Science.gov (United States)

    Fan, Xin-rong; Tang, Nong; Ji, Yun-xi; Zhang, Yao-zhong; Jiang, Li; Huang, Gui-hua; Xie, Sheng; Li, Liu-mei; Song, Chun-hui; Ling, Jiang-hong

    2015-08-01

    The essence of endogenous turbidity in Chinese medicine (CM) is different from cream, fat, phlegm, retention, damp, toxicity, and stasis. Along with the development of modern scientific technologies and biology, researches on the essence of endogenous turbidity should keep pace with the time. Its material bases should be defined and new connotation endowed at the microscopic level. The essence of turbidity lies in abnormal functions of zang-fu organs. Sugar, fat, protein, and other nutrient substances cannot be properly decomposed, but into semi-finished products or intermediate metabolites. They are inactive and cannot participate in normal material syntheses and decomposition. They cannot be transformed to energy metabolism, but also cannot be synthesized as executive functioning of active proteins. If they cannot be degraded by autophagy-lysosome or ubiquitin-prosome into glucose, fatty acids, amino acids, and other basic nutrients to be used again, they will accumulate inside the human body and become endogenous turbidity. Therefore, endogenous turbidity is different from final metabolites such as urea, carbon dioxide, etc., which can transform vital qi. How to improve the function of zang-fu organs, enhance its degradation by autophagy-lysosome or ubiquitin-prosome is of great significance in normal operating of zang-fu organs and preventing the emergence and progress of related diseases.

  18. Immigration, Endogenous Technology Adoption and Wages

    NARCIS (Netherlands)

    Ray Chaudhuri, A.; Pandey, Manish

    2015-01-01

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

  19. MODELS OF AN-TYPE INNOVATIVE ENDOGENOUS GROWTH AND THEIR SUBSTANTIATION

    Directory of Open Access Journals (Sweden)

    Askar A. Akaev

    2015-01-01

    Full Text Available The article presents an analysis of some classical models of economic growth of exogenous and endogenous type, based on the calculation of the motion of physical capital. It is shown that the simplest AN-type model, based on the calculation of population dynamics and endogenous technological progress, is more adequate for the description of the current economic development and provides a more accurate long-term forecast of economic dynamics.

  20. A Reformulation of Normative Economics for Models with Endogenous Preferences

    OpenAIRE

    Vipul Bhatt; Masao Ogaki; Yuichi Yaguchi

    2014-01-01

    This paper proposes a framework to balance considerations of welfarism and virtue ethics in the normative analysis of economic models with endogenous preferences. We introduce the moral evaluation function (MEF), which ranks alternatives based purely on virtue ethics, and define the social objective function (SOF), which combines the Social Welfare Function (SWF) and the MEF. In a model of intergenerational altruism with endogenous time preference, using numerical simulations we show that max...

  1. How Active Are Porcine Endogenous Retroviruses (PERVs?

    Directory of Open Access Journals (Sweden)

    Joachim Denner

    2016-08-01

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

  2. Determination of Particular Endogenous Fires Hazard Zones in Goaf with Caving of Longwall

    Science.gov (United States)

    Tutak, Magdalena; Brodny, Jaroslaw

    2017-12-01

    Hazard of endogenous fires is one of the basic and common presented occupational safety hazards in coal mine in Poland and in the world. This hazard means possibility of coal self-ignition as the result of its self-heating process in mining heading or its surrounding. In underground coal-mining during ventilating of operating longwalls takes place migration of parts of airflow to goaf with caving. In a case when in these goaf a coal susceptible to selfignition occurs, then the airflow through these goaf may influence on formation of favourable conditions for coal oxidation and subsequently to its self-heating and self-ignition. Endogenous fire formed in such conditions can pose a serious hazard for the crew and for continuity of operation of mining plant. From the practical point of view, a very significant meaning has determination of the zone in the goaf with caving, in which necessary conditions for occurrence of endogenous fire are fulfilled. In the real conditions determination of such a zone is practically impossible. Therefore, authors of paper developed a methodology of determination of this zone basing on the results of modelling tests. This methodology includes a development of model of tested area, determination of boundary conditions and carrying out the simulation calculations. Based on the obtained results particular hazardous zone of endogenous fire is determined. A base for development of model of investigated region and selection of boundary conditions are the results of real tests. In the paper fundamental assumption of developed methodology, particularly in a range of assumed hazard criterion and sealing coefficient of goaf with caving were discussed. Also a mathematical model of gas flow through the porous media was characterized. Example of determination of a zone particularly endangered by endogenous fire for real system of mining heading in one of the hard coal mine was presented. Longwall ventilated in the „Y” system was subjected to the

  3. Endogenously and exogenously driven selective sustained attention: Contributions to learning in kindergarten children.

    Science.gov (United States)

    Erickson, Lucy C; Thiessen, Erik D; Godwin, Karrie E; Dickerson, John P; Fisher, Anna V

    2015-10-01

    Selective sustained attention is vital for higher order cognition. Although endogenous and exogenous factors influence selective sustained attention, assessment of the degree to which these factors influence performance and learning is often challenging. We report findings from the Track-It task, a paradigm that aims to assess the contribution of endogenous and exogenous factors to selective sustained attention within the same task. Behavioral accuracy and eye-tracking data on the Track-It task were correlated with performance on an explicit learning task. Behavioral accuracy and fixations to distractors during the Track-It task did not predict learning when exogenous factors supported selective sustained attention. In contrast, when endogenous factors supported selective sustained attention, fixations to distractors were negatively correlated with learning. Similarly, when endogenous factors supported selective sustained attention, higher behavioral accuracy was correlated with greater learning. These findings suggest that endogenously and exogenously driven selective sustained attention, as measured through different conditions of the Track-It task, may support different kinds of learning. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. DMPD: Endogenous anti-inflammatory substances, inter-alpha-inhibitor and bikunin. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17132099 Endogenous anti-inflammatory substances, inter-alpha-inhibitor and bikunin.... Kobayashi H. Biol Chem. 2006 Dec;387(12):1545-9. (.png) (.svg) (.html) (.csml) Show Endogenous anti-inflam...matory substances, inter-alpha-inhibitor and bikunin. PubmedID 17132099 Title Endogenous anti-inflammatory s

  5. Exogenous and Endogenous Learning Resources in the Actiotope Model of Giftedness and Its Significance for Gifted Education

    Science.gov (United States)

    Ziegler, Albert; Chandler, Kimberley L.; Vialle, Wilma; Stoeger, Heidrun

    2017-01-01

    Based on the Actiotope Model of Giftedness, this article introduces a learning-resource-oriented approach for gifted education. It provides a comprehensive categorization of learning resources, including five exogenous learning resources termed "educational capital" and five endogenous learning resources termed "learning…

  6. Structural classification of endogenous regulatory oligopeptides.

    Science.gov (United States)

    Zamyatnin, A A

    1991-07-01

    Based on the criteria of 50% identity in the amino acid sequence, a new method for grouping endogenous regulatory oligopeptides into structural families is presented. Data from the EROP-Moscow data bank on 579 oligopeptides fitting a preset spectrum of functional activities revealed 73 structural oligopeptide groups, 36 of which were called families.

  7. Endogenous neurogenesis in the human brain following cerebral infarction.

    Science.gov (United States)

    Minger, Stephen L; Ekonomou, Antigoni; Carta, Eloisa M; Chinoy, Amish; Perry, Robert H; Ballard, Clive G

    2007-01-01

    Increased endogenous neurogenesis has a significant regenerative role in many experimental models of cerebrovascular diseases, but there have been very few studies in humans. We therefore examined whether there was evidence of altered endogenous neurogenesis in an 84-year-old patient who suffered a cerebrovascular accident 1 week prior to death. Using antibodies that specifically label neural stem/neural progenitor cells, we examined the presence of immunopositive cells around and distant from the infarcted area, and compared this with a control, age-matched individual. Interestingly, a large number of neural stem cells, vascular endothelial growth factor-immunopositive cells and new blood vessels were observed only around the region of infarction, and none in the corresponding brain areas of the healthy control. In addition, an increased number of neural stem cells was observed in the neurogenic region of the lateral ventricle wall. Our results suggest increased endogenous neurogenesis associated with neovascularization and migration of newly-formed cells towards a region of cerebrovascular damage in the adult human brain and highlight possible mechanisms underlying this process.

  8. Endogenous technological and demographic change under increasing water scarcity

    Science.gov (United States)

    Pande, Saket; Ertsen, Maurits; Sivapalan, Murugesu

    2014-05-01

    The ancient civilization in the Indus Valley civilization dispersed under extreme dry conditions; there are indications that the same holds for many other ancient societies. Even contemporary societies, such as the one in Murrumbidgee river basin in Australia, have started to witness a decline in overall population under increasing water scarcity. Hydroclimatic change may not be the sole predictor of the fate of contemporary societies in water scarce regions and many critics of such (perceived) hydroclimatic determinism have suggested that technological change may ameliorate the effects of increasing water scarcity and as such counter the effects of hydroclimatic changes. To study the role of technological change on the dynamics of coupled human-water systems, we develop a simple overlapping-generations model of endogenous technological and demographic change. We model technological change as an endogenous process that depends on factors such as the investments that are (endogenously) made in a society, the (endogenous) diversification of a society into skilled and unskilled workers, a society's patience in terms of its present consumption vs. future consumption, production technology and the (endogenous) interaction of all of these factors. In the model the population growth rate is programmed to decline once consumption per capita crosses a "survival" threshold. This means we do not treat technology as an exogenous random sequence of events, but instead assume that it results (endogenously) from societal actions. The model demonstrates that technological change may indeed ameliorate the effects of increasing water scarcity but typically it does so only to a certain extent. It is possible that technological change may allow a society to escape the effect of increasing water scarcity, leading to a (super)-exponential rise in technology and population. However, such cases require the rate of success of investment in technological advancement to be high. In other

  9. Endogenous technological and population change under increasing water scarcity

    Science.gov (United States)

    Pande, S.; Ertsen, M.; Sivapalan, M.

    2013-11-01

    The ancient civilization in the Indus Valley civilization dispersed under extreme dry conditions; there are indications that the same holds for many other ancient societies. Even contemporary societies, such as the one in Murrumbidgee river basin in Australia, have started to witness a decline in overall population under increasing water scarcity. Hydroclimatic change may not be the sole predictor of the fate of contemporary societies in water scarce regions and many critics of such (perceived) hydroclimatic determinism have suggested that technological change may ameliorate the effects of increasing water scarcity and as such counter the effects of hydroclimatic changes. To study the role of technological change on the dynamics of coupled human-water systems, we develop a simple overlapping-generations model of endogenous technological and demographic change. We model technological change as an endogenous process that depends on factors such as the investments that are (endogenously) made in a society, the (endogenous) diversification of a society into skilled and unskilled workers, a society's patience in terms of its present consumption vs. future consumption, production technology and the (endogenous) interaction of all of these factors. In the model the population growth rate is programmed to decline once consumption per capita crosses a "survival" threshold. This means we do not treat technology as an exogenous random sequence of events, but instead assume that it results (endogenously) from societal actions. The model demonstrates that technological change may indeed ameliorate the effects of increasing water scarcity but typically it does so only to a certain extent. It is possible that technological change may allow a society to escape the effect of increasing water scarcity, leading to a (super)-exponential rise in technology and population. However, such cases require the rate of success of investment in technological advancement to be high. In other

  10. Identification of Phosphorylation Consensus Sequences and Endogenous Neuronal Substrates of the Psychiatric Risk Kinase TNIK.

    Science.gov (United States)

    Wang, Qi; Amato, Stephen P; Rubitski, David M; Hayward, Matthew M; Kormos, Bethany L; Verhoest, Patrick R; Xu, Lan; Brandon, Nicholas J; Ehlers, Michael D

    2016-02-01

    Traf2- and Nck-interacting kinase (TNIK) is a serine/threonine kinase highly expressed in the brain and enriched in the postsynaptic density of glutamatergic synapses in the mammalian brain. Accumulating genetic evidence and functional data have implicated TNIK as a risk factor for psychiatric disorders. However, the endogenous substrates of TNIK in neurons are unknown. Here, we describe a novel selective small molecule inhibitor of the TNIK kinase family. Using this inhibitor, we report the identification of endogenous neuronal TNIK substrates by immunoprecipitation with a phosphomotif antibody followed by mass spectrometry. Phosphorylation consensus sequences were defined by phosphopeptide sequence analysis. Among the identified substrates were members of the delta-catenin family including p120-catenin, δ-catenin, and armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF), each of which is linked to psychiatric or neurologic disorders. Using p120-catenin as a representative substrate, we show TNIK-induced p120-catenin phosphorylation in cells requires intact kinase activity and phosphorylation of TNIK at T181 and T187 in the activation loop. Addition of the small molecule TNIK inhibitor or knocking down TNIK by two shRNAs reduced endogenous p120-catenin phosphorylation in cells. Together, using a TNIK inhibitor and phosphomotif antibody, we identify endogenous substrates of TNIK in neurons, define consensus sequences for TNIK, and suggest signaling pathways by which TNIK influences synaptic development and function linked to psychiatric and neurologic disorders. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  11. Endogenous metabolites that are substrates of organic anion transporter's (OATs) predict methotrexate clearance.

    Science.gov (United States)

    Muhrez, Kienana; Benz-de Bretagne, Isabelle; Nadal-Desbarats, Lydie; Blasco, Hélène; Gyan, Emmanuel; Choquet, Sylvain; Montigny, Frédéric; Emond, Patrick; Barin-Le Guellec, Chantal

    2017-04-01

    Variable pharmacokinetics of high-dose-methotrexate (MTX) is responsible for severe toxicities. Unpredictable overexposure still occurs during some courses despite having controlled the main factors known to play a role in its elimination. The aim of our study was to evaluate whether the urine metabolomic profile measured at the time of MTX administration is predictive of the drug's clearance and/or of treatment-related toxicity. We analyzed the urine content of endogenous metabolites before MTX administration in a cohort of adult patients treated for lymphoid malignancies. Individual MTX clearance (MTX CL ) was estimated from population pharmacokinetic analyses of therapeutic drug monitoring data. We determined the urine metabolite content by gas chromatography-mass spectrometry (GC-MS) and applied Partial Least Square (PLS) analysis to assess the relationship between the urine metabolome and MTX CL . External validation was applied to evaluate the performances of the PLS model. We used orthogonal partial least squares discriminant analysis (OPLS-DA) to distinguish patients with normal or delayed elimination, and patients with or without toxicity. Sixty-two patients were studied. We obtained a very good prediction of individual MTX clearance using a set of 28 metabolites present in patient urine at baseline. The mean prediction error and precision were -0.36% and 21.4%, respectively, for patients not included in the model. The model included a set of endogenous organic anions, of which the tubular secretion depends on organic anion transporter (OAT) function. Our analyses did not allow us to discriminate between patients with or without delayed elimination or those who did or did not experience toxicity. Urinary metabolomics can be informative about an individual's ability to clear MTX. More broadly, it paves the way for the development of a biomarker of tubular secretion, easily measurable from endogenous substances. Copyright © 2016 Elsevier Ltd. All rights

  12. Endogenous WNT Signals Mediate BMP-Induced and Spontaneous Differentiation of Epiblast Stem Cells and Human Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    Dorota Kurek

    2015-01-01

    Full Text Available Therapeutic application of human embryonic stem cells (hESCs requires precise control over their differentiation. However, spontaneous differentiation is prevalent, and growth factors induce multiple cell types; e.g., the mesoderm inducer BMP4 generates both mesoderm and trophoblast. Here we identify endogenous WNT signals as BMP targets that are required and sufficient for mesoderm induction, while trophoblast induction is WNT independent, enabling the exclusive differentiation toward either lineage. Furthermore, endogenous WNT signals induce loss of pluripotency in hESCs and their murine counterparts, epiblast stem cells (EpiSCs. WNT inhibition obviates the need to manually remove differentiated cells to maintain cultures and improves the efficiency of directed differentiation. In EpiSCs, WNT inhibition stabilizes a pregastrula epiblast state with novel characteristics, including the ability to contribute to blastocyst chimeras. Our findings show that endogenous WNT signals function as hidden mediators of growth factor-induced differentiation and play critical roles in the self-renewal of hESCs and EpiSCs.

  13. Role of endogenous serotonin in the mechanism of action of radioprotective substances

    International Nuclear Information System (INIS)

    Konstantinova, M.M.; Nekrasova, I.V.; Gusareva, Eh.V.; Dontsova, G.V.

    1978-01-01

    A study is made of a correlation between radiomodifying activity of noradrenaline (NA), N-ethylmaleimide (NEM) and a combination of these agents and their effect on the content of endogenous serotonin in cells of Ehrlich's ascites tumor and E. coli B. There is no uniformity in the response of different cells and uniform direction of the changes in their radioresistance and endogenous serotonin content both under the effect of the substances (NA and NEM) given separately and under a combined effect of the protector and the agent, which removes the protective effect or prevents realization of the latter (NEM). This enables us to arrive at a conclusion that endogenous serotonin is not the only factor responsible for the radioprotective effect of the protective substances. At the same time, it is not excluded that endogenous serotonin is involved in the chain of reactions which are necessary for the radioprotective effect to come into play

  14. Endogenous and recombinant type I interferons and disease activity in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, Finn; Krakauer, Martin; Limborg, Signe

    2012-01-01

    the percentage of CD4+ T cells expressing CD71 and HLA-DR (activated T cells), and this was associated with an increased risk of clinical disease activity. In contrast, induction of CD71 and HLA-DR was not observed in untreated MS patients with evidence of endogenous type IFN I activity. In conclusion......Although treatment of multiple sclerosis (MS) with the type I interferon (IFN) IFN-ß lowers disease activity, the role of endogenous type I IFN in MS remains controversial. We studied CD4+ T cells and CD4+ T cell subsets, monocytes and dendritic cells by flow cytometry and analysed the relationship...... with endogenous type I IFN-like activity, the effect of IFN-ß therapy, and clinical and magnetic resonance imaging (MRI) disease activity in MS patients. Endogenous type I IFN activity was associated with decreased expression of the integrin subunit CD49d (VLA-4) on CD4+CD26(high) T cells (Th1 helper cells...

  15. Endogenous and exogenous testosterone and prostate cancer: decreased-, increased- or null-risk?

    Science.gov (United States)

    Advani, Shailesh; Tsilidis, Konstantinos K.; Wang, Run; Canfield, Steven

    2017-01-01

    For more than 70 years, the contention that high levels of testosterone or that the use of testosterone therapy (TTh) increases the development and progression of prostate cancer (PCa) has been widely accepted and practiced. Yet, the increasing and emerging evidence on testosterone research seems to challenge that contention. To review literature on the associations of endogenous and exogenous testosterone with decreased-, increased-, or null-risk of PCa, and to further evaluate only those studies that reported magnitude of associations from multivariable modeling as it minimizes confounding effects. We conducted a literature search to identify studies that investigated the association of endogenous total testosterone [continuous (per 1 unit increment and 5 nmol/L increment) and categorical (high vs. low)] and use of TTh with PCa events [1990–2016]. Emphasis was given to studies/analyses that reported magnitude of associations [odds ratio (OR), relative risk (RR) and hazard ratios (HRs)] from multivariable analyses to determine risk of PCa and their statistical significance. Most identified studies/analyses included observational and randomized placebo-controlled trials. This review was organized in three parts: (I) association of endogenous total testosterone (per 1 unit increment and 5 nmol/L increment) with PCa; (II) relationship of endogenous total testosterone (categorical high vs. low) with PCa; and (III) association of use of TTh with PCa in meta-analyses of randomized placebo-controlled trials. The first part included 31 observational studies [20 prospective (per 5 nmol/L increment) and 11 prospective and retrospective cohort studies (per 1 unit increment)]. None of the 20 prospective studies found a significant association between total testosterone (5 nmol/L increment) and increased- or decreased-risk of PCa. Two out of the 11 studies/analyses showed a significant decreased-risk of PCa for total testosterone per 1 unit increment, but also two other

  16. State or nature? Endogenous formal versus informal sanctions in the voluntary provision of public goods

    DEFF Research Database (Denmark)

    Kamei, Kenju; Putterman, Louis; Tyran, Jean-Robert Karl

    2015-01-01

    We investigate the endogenous formation of sanctioning institutions supposed to improve efficiency in the voluntary provision of public goods. Our paper parallels Markussen et al. (Rev Econ Stud 81:301–324, 2014) in that our experimental subjects vote over formal versus informal sanctions......, but it goes beyond that paper by endogenizing the formal sanction scheme. We find that self-determined formal sanctions schemes are popular and efficient when they carry no up-front cost, but as in Markussen et al. informal sanctions are more popular and efficient than formal sanctions when adopting...... the latter entails such a cost. Practice improves the performance of sanction schemes: they become more targeted and deterrent with learning. Voters’ characteristics, including their tendency to engage in perverse informal sanctioning, help to predict individual voting....

  17. Endogenous Receptor Agonists: Resolving Inflammation

    Directory of Open Access Journals (Sweden)

    Gerhard Bannenberg

    2007-01-01

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

  18. Breastfeeding and the risk of childhood asthma: A two-stage instrumental variable analysis to address endogeneity.

    Science.gov (United States)

    Sharma, Nivita D

    2017-09-01

    Several explanations for the inconsistent results on the effects of breastfeeding on childhood asthma have been suggested. The purpose of this study was to investigate one unexplored explanation, which is the presence of a potential endogenous relationship between breastfeeding and childhood asthma. Endogeneity exists when an explanatory variable is correlated with the error term for reasons such as selection bias, reverse causality, and unmeasured confounders. Unadjusted endogeneity will bias the effect of breastfeeding on childhood asthma. To investigate potential endogeneity, a cross-sectional study of breastfeeding practices and incidence of childhood asthma in 87 pediatric patients in Georgia, the USA, was conducted using generalized linear modeling and a two-stage instrumental variable analysis. First, the relationship between breastfeeding and childhood asthma was analyzed without considering endogeneity. Second, tests for presence of endogeneity were performed and having detected endogeneity between breastfeeding and childhood asthma, a two-stage instrumental variable analysis was performed. The first stage of this analysis estimated the duration of breastfeeding and the second-stage estimated the risk of childhood asthma. When endogeneity was not taken into account, duration of breastfeeding was found to significantly increase the risk of childhood asthma (relative risk ratio [RR]=2.020, 95% confidence interval [CI]: [1.143-3.570]). After adjusting for endogeneity, duration of breastfeeding significantly reduced the risk of childhood asthma (RR=0.003, 95% CI: [0.000-0.240]). The findings suggest that researchers should consider evaluating how the presence of endogeneity could affect the relationship between duration of breastfeeding and the risk of childhood asthma. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  19. Endogenous pyrogen production by Hodgkin's disease and human histiocytic lymphoma cell lines in vitro.

    Science.gov (United States)

    Bodel, P; Ralph, P; Wenc, K; Long, J C

    1980-02-01

    Fever not explained by infection may occur in patients with malignant lymphoma presumably caused by a release of endogenous pyrogen. Although pyrogen has been found in some tumors with a mixed cell population, production of endogenous pyrogen by the neoplastic cells has not been demonstrated. This report documents the apparently spontaneous synthesis and release of such pyrogen by two human tumor cell lines derived from patients with Hodgkin's disease and histiocytic lymphoma. The endogenous pyrogen from the two cell lines was similar and closely resembled that produced by normal human monocytes in antigenic properties as well as heat and pronase sensitivity. The Hodgkin's disease and histiocytic lymphoma cell lines do not require specific stimulation for the production of endogenous pyrogen suggesting that the mechanism of pyrogen release by neoplastic macrophage-related cells differs from that of normal phagocytic cells. The tumor-associated fever in some patients with malignant lymphoma may be caused by a release of endogenous pyrogen by proliferating neoplastic cells.

  20. γ-Secretase modulators reduce endogenous amyloid β42 levels in human neural progenitor cells without altering neuronal differentiation

    Science.gov (United States)

    D’Avanzo, Carla; Sliwinski, Christopher; Wagner, Steven L.; Tanzi, Rudolph E.; Kim, Doo Yeon; Kovacs, Dora M.

    2015-01-01

    Soluble γ-secretase modulators (SGSMs) selectively decrease toxic amyloid β (Aβ) peptides (Aβ42). However, their effect on the physiologic functions of γ-secretase has not been tested in human model systems. γ-Secretase regulates fate determination of neural progenitor cells. Thus, we studied the impact of SGSMs on the neuronal differentiation of ReNcell VM (ReN) human neural progenitor cells (hNPCs). Quantitative PCR analysis showed that treatment of neurosphere-like ReN cell aggregate cultures with γ-secretase inhibitors (GSIs), but not SGSMs, induced a 2- to 4-fold increase in the expression of the neuronal markers Tuj1 and doublecortin. GSI treatment also induced neuronal marker protein expression, as shown by Western blot analysis. In the same conditions, SGSM treatment selectively reduced endogenous Aβ42 levels by ∼80%. Mechanistically, we found that Notch target gene expressions were selectively inhibited by a GSI, not by SGSM treatment. We can assert, for the first time, that SGSMs do not affect the neuronal differentiation of hNPCs while selectively decreasing endogenous Aβ42 levels in the same conditions. Our results suggest that our hNPC differentiation system can serve as a useful model to test the impact of GSIs and SGSMs on both endogenous Aβ levels and γ-secretase physiologic functions including endogenous Notch signaling.—D’Avanzo, C., Sliwinski, C., Wagner, S. L., Tanzi, R. E., Kim, D. Y., Kovacs, D. M. γ-Secretase modulators reduce endogenous amyloid β42 levels in human neural progenitor cells without altering neuronal differentiation. PMID:25903103

  1. Endogenous reward mechanisms and their importance in stress reduction, exercise and the brain

    OpenAIRE

    Esch, Tobias; Stefano, George B.

    2010-01-01

    Stress can facilitate disease processes and causes strain on the health care budgets. It is responsible or involved in many human ailments of our time, such as cardiovascular illnesses, particularly related to the psychosocial stressors of daily life, including work. Besides pharmacological or clinical medical treatment options, behavioral stress reduction is much-needed. These latter approaches rely on an endogenous healing potential via life-style modification. Hence, research has suggested...

  2. Endogenous Opioid Function and Responses to Morphine: The Moderating Effects of Anger Expressiveness.

    Science.gov (United States)

    Burns, John W; Bruehl, Stephen; France, Christopher R; Schuster, Erik; Orlowska, Daria; Chont, Melissa; Gupta, Rajnish K; Buvanendran, Asokumar

    2017-08-01

    Long-term use of opioid analgesics may be ineffective or associated with significant negative side effects for some people. At present, there is no sound method of identifying optimal opioid candidates. Individuals with chronic low back pain (n = 89) and healthy control individuals (n = 102) underwent ischemic pain induction with placebo, opioid blockade (naloxone), and morphine in counterbalanced order. They completed the Spielberger Anger-Out subscale. Endogenous opioid function × Anger-out × Pain status (chronic pain, healthy control) interactions were tested for morphine responses to ischemic threshold, tolerance, and pain intensity (McGill Sensory and Affective subscales) and side effects. For individuals with chronic pain and healthy control participants, those with low endogenous opioid function and low anger-out scores exhibited the largest morphine analgesic responses, whereas those with high anger-out and low endogenous opioid function showed relatively weaker morphine analgesic responses. Further, individuals with chronic pain with low endogenous opioid function and low anger-out scores also reported the fewest negative effects to morphine, whereas those with low endogenous opioid function and high anger-out reported the most. Findings point toward individuals with chronic pain who may strike a favorable balance of good analgesia with few side effects, as well as those who have an unfavorable balance of poor analgesia and many side effects. We sought to identify optimal candidates for opioid pain management. Low back pain patients who express anger and also have deficient endogenous opioid function may be poor candidates for opioid therapy. In contrast, low back patients who tend not to express anger and who also have deficient endogenous opioid function may make optimal candidates for opioid therapy. Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

  3. Devices for collecting chemical compounds

    Science.gov (United States)

    Scott, Jill R; Groenewold, Gary S

    2013-12-24

    A device for sampling chemical compounds from fixed surfaces and related methods are disclosed. The device may include a vacuum source, a chamber and a sorbent material. The device may utilize vacuum extraction to volatilize the chemical compounds from a fixed surface so that they may be sorbed by the sorbent material. The sorbent material may then be analyzed using conventional thermal desorption/gas chromatography/mass spectrometry (TD/GC/MS) instrumentation to determine presence of the chemical compounds. The methods may include detecting release and presence of one or more chemical compounds and determining the efficacy of decontamination. The device may be useful in collection and analysis of a variety of chemical compounds, such as residual chemical warfare agents, chemical attribution signatures and toxic industrial chemicals.

  4. Endogenous field feedback promotes the detectability for exogenous electric signal in the hybrid coupled population

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Xile; Zhang, Danhong; Wang, Jiang; Yu, Haitao, E-mail: htyu@tju.edu.cn [Tianjin Key Laboratory of Process Measurement and Control, School of Electrical Engineering and Automation, Tianjin University, Tianjin 300072 (China); Lu, Meili [School of Informational Technology and Engineering, Tianjin University of Technology and Education, Tianjin 300222 (China); Che, Yanqiu [School of Automation and Electrical Engineering, Tianjin University of Technology and Education, Tianjin 300222 (China)

    2015-01-15

    This paper presents the endogenous electric field in chemical or electrical synaptic coupled networks, aiming to study the role of endogenous field feedback in the signal propagation in neural systems. It shows that the feedback of endogenous fields to network activities can reduce the required energy of the noise and enhance the transmission of input signals in hybrid coupled populations. As a common and important nonsynaptic interactive method among neurons, particularly, the endogenous filed feedback can not only promote the detectability of exogenous weak signal in hybrid coupled neural population but also enhance the robustness of the detectability against noise. Furthermore, with the increasing of field coupling strengths, the endogenous field feedback is conductive to the stochastic resonance by facilitating the transition of cluster activities from the no spiking to spiking regions. Distinct from synaptic coupling, the endogenous field feedback can play a role as internal driving force to boost the population activities, which is similar to the noise. Thus, it can help to transmit exogenous weak signals within the network in the absence of noise drive via the stochastic-like resonance.

  5. Discrepancy of neural response between exogenous and endogenous task switching: an event-related potentials study.

    Science.gov (United States)

    Miyajima, Maki; Toyomaki, Atsuhito; Hashimoto, Naoki; Kusumi, Ichiro; Murohashi, Harumitsu; Koyama, Tsukasa

    2012-08-01

    Task switching is a well-known cognitive paradigm to explore task-set reconfiguration processes such as rule shifting. In particular, endogenous task switching is thought to differ qualitatively from stimulus-triggered exogenous task switching. However, no previous study has examined the neural substrate of endogenous task switching. The purpose of the present study is to explore the differences between event-related potential responses to exogenous and endogenous rule switching at cue stimulus. We modified two patterns of cued switching tasks: exogenous (bottom-up) rule switching and endogenous (top-down) rule switching. In each task cue stimulus was configured to induce switching or maintaining rule. In exogenous switching tasks, late positive deflection was larger in the switch rule condition than in the maintain rule condition. However, in endogenous switching tasks late positive deflection was unexpectedly larger in the maintain-rule condition than in the switch-rule condition. These results indicate that exogenous rule switching is explicit stimulus-driven processes, whereas endogenous rule switching is implicitly parallel processes independent of external stimulus.

  6. Endogenous field feedback promotes the detectability for exogenous electric signal in the hybrid coupled population.

    Science.gov (United States)

    Wei, Xile; Zhang, Danhong; Lu, Meili; Wang, Jiang; Yu, Haitao; Che, Yanqiu

    2015-01-01

    This paper presents the endogenous electric field in chemical or electrical synaptic coupled networks, aiming to study the role of endogenous field feedback in the signal propagation in neural systems. It shows that the feedback of endogenous fields to network activities can reduce the required energy of the noise and enhance the transmission of input signals in hybrid coupled populations. As a common and important nonsynaptic interactive method among neurons, particularly, the endogenous filed feedback can not only promote the detectability of exogenous weak signal in hybrid coupled neural population but also enhance the robustness of the detectability against noise. Furthermore, with the increasing of field coupling strengths, the endogenous field feedback is conductive to the stochastic resonance by facilitating the transition of cluster activities from the no spiking to spiking regions. Distinct from synaptic coupling, the endogenous field feedback can play a role as internal driving force to boost the population activities, which is similar to the noise. Thus, it can help to transmit exogenous weak signals within the network in the absence of noise drive via the stochastic-like resonance.

  7. Endogenous field feedback promotes the detectability for exogenous electric signal in the hybrid coupled population

    International Nuclear Information System (INIS)

    Wei, Xile; Zhang, Danhong; Wang, Jiang; Yu, Haitao; Lu, Meili; Che, Yanqiu

    2015-01-01

    This paper presents the endogenous electric field in chemical or electrical synaptic coupled networks, aiming to study the role of endogenous field feedback in the signal propagation in neural systems. It shows that the feedback of endogenous fields to network activities can reduce the required energy of the noise and enhance the transmission of input signals in hybrid coupled populations. As a common and important nonsynaptic interactive method among neurons, particularly, the endogenous filed feedback can not only promote the detectability of exogenous weak signal in hybrid coupled neural population but also enhance the robustness of the detectability against noise. Furthermore, with the increasing of field coupling strengths, the endogenous field feedback is conductive to the stochastic resonance by facilitating the transition of cluster activities from the no spiking to spiking regions. Distinct from synaptic coupling, the endogenous field feedback can play a role as internal driving force to boost the population activities, which is similar to the noise. Thus, it can help to transmit exogenous weak signals within the network in the absence of noise drive via the stochastic-like resonance

  8. Lipid oxidation in baked products: impact of formula and process on the generation of volatile compounds.

    Science.gov (United States)

    Maire, Murielle; Rega, Barbara; Cuvelier, Marie-Elisabeth; Soto, Paola; Giampaoli, Pierre

    2013-12-15

    This paper investigates the effect of ingredients on the reactions occurring during the making of sponge cake and leading to the generation of volatile compounds related to flavour quality. To obtain systems sensitive to lipid oxidation (LO), a formulation design was applied varying the composition of fatty matter and eggs. Oxidation of polyunsaturated fatty acids (PUFA) and formation of related volatile compounds were followed at the different steps of cake-making. Optimised dynamic Solid Phase Micro Extraction was applied to selectively extract either volatile or semi-volatile compounds directly from the baking vapours. We show for the first time that in the case of alveolar baked products, lipid oxidation occurs very early during the step of dough preparation and to a minor extent during the baking process. The generation of lipid oxidation compounds depends on PUFA content and on the presence of endogenous antioxidants in the raw matter. Egg yolk seemed to play a double role on reactivity: protecting unsaturated lipids from oxidation and being necessary to generate a broad class of compounds of the Maillard reaction during baking and linked to the typical flavour of sponge cake. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Endogenous thrombin potential in polycystic ovary syndrome

    DEFF Research Database (Denmark)

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

    2015-01-01

    OBJECTIVES: The objective of this study is to investigate plasma endogenous thrombin generation in four different phenotypes of polycystic ovary syndrome (PCOS) defined by Body Mass Index (BMI) and insulin resistance (IR). PCOS is diagnosed according to the Rotterdam criteria. DESIGN: Multicenter...

  10. Endogenous Oxytocin, Vasopressin, and Aggression in Domestic Dogs

    Directory of Open Access Journals (Sweden)

    Evan L. MacLean

    2017-09-01

    Full Text Available Aggressive behavior in dogs poses public health and animal welfare concerns, however the biological mechanisms regulating dog aggression are not well understood. We investigated the relationships between endogenous plasma oxytocin (OT and vasopressin (AVP—neuropeptides that have been linked to affiliative and aggressive behavior in other mammalian species—and aggression in domestic dogs. We first validated enzyme-linked immunosorbent assays (ELISAs for the measurement of free (unbound and total (free + bound OT and AVP in dog plasma. In Experiment 1 we evaluated behavioral and neuroendocrine differences between a population of pet dogs with a history of chronic aggression toward conspecifics and a matched control group. Dogs with a history of aggression exhibited more aggressive behavior during simulated encounters with conspecifics, and had lower free, but higher total plasma AVP than matched controls, but there were no group differences for OT. In Experiment 2 we compared OT and AVP concentrations between pet dogs and a population of assistance dogs that have been bred for affiliative and non-aggressive temperaments, and investigated neuroendocrine predictors of individual differences in social behavior within the assistance dog population. Compared to pet dogs, assistance dogs had higher free and total OT, but there were no differences in either measure for AVP. Within the assistance dog population, dogs who behaved more aggressively toward a threatening stranger had higher total AVP than dogs who did not. Collectively these data suggest that endogenous OT and AVP may play critical roles in shaping dog social behavior, including aspects of both affiliation and aggression.

  11. Endophytic Bacterium Pseudomonas fluorescens RG11 May Transform Tryptophan to Melatonin and Promote Endogenous Melatonin Levels in the Roots of Four Grape Cultivars.

    Science.gov (United States)

    Ma, Yaner; Jiao, Jian; Fan, Xiucai; Sun, Haisheng; Zhang, Ying; Jiang, Jianfu; Liu, Chonghuai

    2016-01-01

    Endophytes have been verified to synthesize melatonin in vitro and promote abiotic stress-induced production of endogenous melatonin in grape ( Vitis vinifera L.) roots. This study aimed to further characterize the biotransformation of tryptophan to melatonin in the endophytic bacterium Pseudomonas fluorescens RG11 and to investigate its capacity for enhancing endogenous melatonin levels in the roots of different grape cultivars. Using ultra performance liquid chromatography-tandem mass spectrometry combined with 15N double-labeled L -tryptophan as the precursor for melatonin, we detected isotope-labeled 5-hydroxytryptophan, serotonin, N -acetylserotonin, and melatonin, but tryptamine was not detected during the in vitro incubation of P. fluorescens RG11. Furthermore, the production capacity of these four compounds peaked during the exponential growth phase. RG11 colonization increased the endogenous levels of 5-hydroxytryptophan, N -acetylserotonin, and melatonin, but reduced those of tryptamine and serotonin, in the roots of the Red Globe grape cultivar under salt stress conditions. Quantitative real-time PCR revealed that RG11 reduced the transcription of grapevine tryptophan decarboxylase and serotonin N -acetyltransferase genes when compared to the un-inoculated control. These results correlated with decreased reactive oxygen species bursts and cell damage, which were alleviated by RG11 colonization under salt stress conditions. Additionally, RG11 promoted plant growth and enhanced the levels of endogenous melatonin in different grape cultivars. Intraspecific variation in the levels of melatonin precursors was found among four grape cultivars, and the associated root crude extracts appeared to significantly induce RG11 melatonin biosynthesis in vitro . Overall, this study provides useful information that enhances the existing knowledge of a potential melatonin synthesis pathway in rhizobacteria, and it reveals plant-rhizobacterium interactions that affect

  12. Endogenous Retrovirus 3 – History, Physiology, and Pathology

    Science.gov (United States)

    Bustamante Rivera, Yomara Y.; Brütting, Christine; Schmidt, Caroline; Volkmer, Ines; Staege, Martin S.

    2018-01-01

    Endogenous viral elements (EVE) seem to be present in all eukaryotic genomes. The composition of EVE varies between different species. The endogenous retrovirus 3 (ERV3) is one of these elements that is present only in humans and other Catarrhini. Conservation of ERV3 in most of the investigated Catarrhini and the expression pattern in normal tissues suggest a putative physiological role of ERV3. On the other hand, ERV3 has been implicated in the pathogenesis of auto-immunity and cancer. In the present review we summarize knowledge about this interesting EVE. We propose the model that expression of ERV3 (and probably other EVE loci) under pathological conditions might be part of a metazoan SOS response. PMID:29379485

  13. Endogenous Retrovirus 3 – History, Physiology, and Pathology

    Directory of Open Access Journals (Sweden)

    Yomara Y. Bustamante Rivera

    2018-01-01

    Full Text Available Endogenous viral elements (EVE seem to be present in all eukaryotic genomes. The composition of EVE varies between different species. The endogenous retrovirus 3 (ERV3 is one of these elements that is present only in humans and other Catarrhini. Conservation of ERV3 in most of the investigated Catarrhini and the expression pattern in normal tissues suggest a putative physiological role of ERV3. On the other hand, ERV3 has been implicated in the pathogenesis of auto-immunity and cancer. In the present review we summarize knowledge about this interesting EVE. We propose the model that expression of ERV3 (and probably other EVE loci under pathological conditions might be part of a metazoan SOS response.

  14. Rapid identification of herbal compounds derived metabolites using zebrafish larvae as the biotransformation system.

    Science.gov (United States)

    Wang, Chen; Yin, Ying-Hao; Wei, Ying-Jie; Shi, Zi-Qi; Liu, Jian-Qun; Liu, Li-Fang; Xin, Gui-Zhong

    2017-09-15

    Metabolites derived from herbal compounds are becoming promising sources for discovering new drugs. However, the rapid identification of metabolites from biological matrixes is limited by massive endogenous interference and low abundance of metabolites. Thus, by using zebrafish larvae as the biotransformation system, we herein proposed and validated an integrated strategy for rapid identification of metabolites derived from herbal compounds. Two pivotal steps involved in this strategy are to differentiate metabolites from herbal compounds and match metabolites with their parent compounds. The differentiation step was achieved by cross orthogonal partial least-squares discriminant analysis. Automatic matching analysis was performed on R Project based on a self-developed program, of which the number of matched ionic clusters and its corresponding percentage between metabolite and parent compound were taken into account to assess their similarity. Using this strategy, 46 metabolites screened from incubation water samples of zebrafish treated with total Epimedium flavonoids (EFs) could be matched with their corresponding parent compounds, 37 of them were identified and validated by the known metabolic pathways and fragmentation patterns. Finally, 75% of the identified EFs metabolites were successfully detected in urine samples of rats treated with EFs. These experimental results indicate that the proposed strategy using zebrafish larvae as the biotransformation system will facilitate the rapid identification of metabolites derived from herbal compounds, which shows promising perspectives in providing additional resources for pharmaceutical developments from natural products. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. The interactions of multisensory integration with endogenous and exogenous attention

    Science.gov (United States)

    Tang, Xiaoyu; Wu, Jinglong; Shen, Yong

    2016-01-01

    Stimuli from multiple sensory organs can be integrated into a coherent representation through multiple phases of multisensory processing; this phenomenon is called multisensory integration. Multisensory integration can interact with attention. Here, we propose a framework in which attention modulates multisensory processing in both endogenous (goal-driven) and exogenous (stimulus-driven) ways. Moreover, multisensory integration exerts not only bottom-up but also top-down control over attention. Specifically, we propose the following: (1) endogenous attentional selectivity acts on multiple levels of multisensory processing to determine the extent to which simultaneous stimuli from different modalities can be integrated; (2) integrated multisensory events exert top-down control on attentional capture via multisensory search templates that are stored in the brain; (3) integrated multisensory events can capture attention efficiently, even in quite complex circumstances, due to their increased salience compared to unimodal events and can thus improve search accuracy; and (4) within a multisensory object, endogenous attention can spread from one modality to another in an exogenous manner. PMID:26546734

  16. Fungal Laccases Degradation of Endocrine Disrupting Compounds

    Directory of Open Access Journals (Sweden)

    Gemma Macellaro

    2014-01-01

    Full Text Available Over the past decades, water pollution by trace organic compounds (ng/L has become one of the key environmental issues in developed countries. This is the case of the emerging contaminants called endocrine disrupting compounds (EDCs. EDCs are a new class of environmental pollutants able to mimic or antagonize the effects of endogenous hormones, and are recently drawing scientific and public attention. Their widespread presence in the environment solicits the need of their removal from the contaminated sites. One promising approach to face this challenge consists in the use of enzymatic systems able to react with these molecules. Among the possible enzymes, oxidative enzymes are attracting increasing attention because of their versatility, the possibility to produce them on large scale, and to modify their properties. In this study five different EDCs were treated with four different fungal laccases, also in the presence of both synthetic and natural mediators. Mediators significantly increased the efficiency of the enzymatic treatment, promoting the degradation of substrates recalcitrant to laccase oxidation. The laccase showing the best performances was chosen to further investigate its oxidative capabilities against micropollutant mixtures. Improvement of enzyme performances in nonylphenol degradation rate was achieved through immobilization on glass beads.

  17. Catching the cheats: advances in the detection of endogenous steroid abuse in sport. Chemistry, pharmacology and biology have a pivotal role in doping control

    International Nuclear Information System (INIS)

    Kazlawskas, R.; Trout, G.J.; George, A.V.; Cawley, A.T.; Silk, A.J.; Marshall-Gradisnik, S.; Weatherby, R.P.

    2006-01-01

    Professional athletes: sport is their occupation; amateur athletes: sport is their vocation and many millions of spectators watch it for recreation. Sport is big business and for an athlete, the difference between a gold and silver medal can mean several million sponsorship dollars. This financial reward, fame and ambition drive some to use performance-enhancing substances to give them an edge. The science of doping control is a fast growing area. Responsibility for doping control is held by the World Anti-Doping Agency (WADA), which administers the list of prohibited substances, amongst other things. Endogenous steroids were included in this list in 1982 and WADA continues to prohibit the use of administered synthetic copies of steroids that are naturally produced by the body because of their performance-enhancing and possible adverse health effects. The detection of steroids originating from synthetic precursors in relation to their chemically identical natural analogues is a significant challenge for doping control laboratories accredited by WADA. In medicine, these substances are used for hormone replacement therapy, but they are open to abuse also. Androstenedione (Adione) is an endogenous steroid said to be a 'pro hormone' because it may be converted to testosterone in the body. Oral preparations of Adione are used to increase systemic levels of testosterone during training. Benchtop gas chromatography-mass spectrometry (GC-MS) is now the backbone of doping control laboratories, using purified steroid extract from urine with minimal preparation necessary. Increased excretion of both androsterone (A) and etiocholanolone (Et) are detected in volunteers taking Adione. These inactive C-5 isometric steroids are the terminal products of the androgen biosynthetic pathway. It is difficult to distinguish abuse from 'normal' metabolic states, however, but in our experiments we were able to observe that there is a slight but measurable difference in concentrations

  18. Endogenous pyrogen production by Hodgkin's disease and human histiocytic lymphoma cell lines in vitro.

    OpenAIRE

    Bodel, P; Ralph, P; Wenc, K; Long, J C

    1980-01-01

    Fever not explained by infection may occur in patients with malignant lymphoma presumably caused by a release of endogenous pyrogen. Although pyrogen has been found in some tumors with a mixed cell population, production of endogenous pyrogen by the neoplastic cells has not been demonstrated. This report documents the apparently spontaneous synthesis and release of such pyrogen by two human tumor cell lines derived from patients with Hodgkin's disease and histiocytic lymphoma. The endogenous ...

  19. Targeted detection of in vivo endogenous DNA base damage reveals preferential base excision repair in the transcribed strand.

    Science.gov (United States)

    Reis, António M C; Mills, Wilbur K; Ramachandran, Ilangovan; Friedberg, Errol C; Thompson, David; Queimado, Lurdes

    2012-01-01

    Endogenous DNA damage is removed mainly via base excision repair (BER), however, whether there is preferential strand repair of endogenous DNA damage is still under intense debate. We developed a highly sensitive primer-anchored DNA damage detection assay (PADDA) to map and quantify in vivo endogenous DNA damage. Using PADDA, we documented significantly higher levels of endogenous damage in Saccharomyces cerevisiae cells in stationary phase than in exponential phase. We also documented that yeast BER-defective cells have significantly higher levels of endogenous DNA damage than isogenic wild-type cells at any phase of growth. PADDA provided detailed fingerprint analysis at the single-nucleotide level, documenting for the first time that persistent endogenous nucleotide damage in CAN1 co-localizes with previously reported spontaneous CAN1 mutations. To quickly and reliably quantify endogenous strand-specific DNA damage in the constitutively expressed CAN1 gene, we used PADDA on a real-time PCR setting. We demonstrate that wild-type cells repair endogenous damage preferentially on the CAN1 transcribed strand. In contrast, yeast BER-defective cells accumulate endogenous damage preferentially on the CAN1 transcribed strand. These data provide the first direct evidence for preferential strand repair of endogenous DNA damage and documents the major role of BER in this process.

  20. Investigations into the differential reactivity of endogenous and exogenous mercury species in coastal sediments.

    Science.gov (United States)

    Bouchet, S; Rodriguez-Gonzalez, P; Bridou, R; Monperrus, M; Tessier, E; Anschutz, P; Guyoneaud, R; Amouroux, D

    2013-03-01

    Stable isotopic tracer methodologies now allow the evaluation of the reactivity of the endogenous (ambient) and exogenous (added) Hg to further predict the potential effect of Hg inputs in ecosystems. The differential reactivity of endogenous and exogenous Hg was compared in superficial sediments collected in a coastal lagoon (Arcachon Bay) and in an estuary (Adour River) from the Bay of Biscay (SW France). All Hg species (gaseous, aqueous, and solid fraction) and ancillary data were measured during time course slurry experiments under variable redox conditions. The average endogenous methylation yield was higher in the estuarine (1.2 %) than in the lagoonal sediment (0.5 %), although both methylation and demethylation rates were higher in the lagoonal sediment in relation with a higher sulfate-reducing activity. Demethylation was overall more consistent than methylation in both sediments. The endogenous and exogenous Hg behaviors were always correlated but the exogenous inorganic Hg (IHg) partitioning into water was 2.0-4.3 times higher than the endogenous one. Its methylation was just slightly higher (1.4) in the estuarine sediment while the difference in the lagoonal sediment was much larger (3.6). The relative endogenous and exogenous methylation yields were not correlated to IHg partitioning, demonstrating that the bioavailable species distributions were different for the two IHg pools. In both sediments, the exogenous IHg partitioning equaled the endogenous one within a week, while its higher methylation lasted for months. Such results provide an original assessment approach to compare coastal sediment response to Hg inputs.

  1. Alkyl caffeates as antioxidants in O/W emulsions: Impact of emulsifier type and endogenous tocopherols

    DEFF Research Database (Denmark)

    Sørensen, Ann-Dorit Moltke; Villeneuve, Pierre; Jacobsen, Charlotte

    2017-01-01

    , the aim was to evaluate the impact of emulsifiers (Citrem and Tween80) and presence of endogenous tocopherols on the efficacies of caffeic acid and caffeates (C1–C20) as antioxidants in emulsions. Lipid oxidation was evaluated during storage and partitioning of caffeic acid and caffeates was estimated...... by measuring their concentrations in the aqueous phase. Partitioning of caffeic acid and caffeates was influenced by emulsifier type and the presence of endogenous tocopherols. Caffeic acid was the most efficient antioxidant in Citrem and Tween stabilized emulsions in the presence of endogenous tocopherol....... In contrast, for Tween stabilized emulsions, caffeic acid acted as a prooxidant and the evaluated caffeates acted as strong antioxidants in the absence of endogenous tocopherol. Thus, when endogenous tocopherol was present lipophilization of caffeic acid did not increase its efficacy as an antioxidant...

  2. Optimal income taxation with endogenous human capital

    NARCIS (Netherlands)

    Jacobs, B.

    2005-01-01

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

  3. Managing spillovers: an endogenous sunk cost approach

    Czech Academy of Sciences Publication Activity Database

    Senyuta, Olena; Žigić, Krešimir

    2016-01-01

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

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

    African Journals Online (AJOL)

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

  5. Money, banks and endogenous volatility

    OpenAIRE

    Pere Gomis-Porqueras

    2000-01-01

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

  6. Exogenous or endogenous Toll-like receptor ligands: which is the MVP in tumorigenesis?

    Science.gov (United States)

    Yu, Li; Wang, Liantang; Chen, Shangwu

    2012-03-01

    Toll-like receptors (TLRs) are a class of pattern recognition receptors sensing microbial components and triggering an immune response against pathogens. In addition to their role in anti-infection immunity, increasing evidence indicates that engagement of TLRs can promote cancer cell survival and proliferation, induce tumor immune evasion, and enhance tumor metastasis and chemoresistance. Recent studies have demonstrated that endogenous molecules or damage-associated molecular patterns released from damaged/necrotic tissues are capable of activating TLRs and that the endogenous ligands-mediated TLR signaling is implicated in the tumor development and affects the therapeutic efficacy of tumors. Since both exogenous and endogenous TLR ligands can initiate TLR signaling, which is the most valuable player in tumor development becomes an interesting question. Here, we summarize the effect of TLR signaling on the development and progression of tumors, and discuss the role of exogenous and endogenous TLR ligands in the tumorigenesis.

  7. Quantitative regularities of development of endogenous infection in irradiated organism. (Survey of literature)

    Energy Technology Data Exchange (ETDEWEB)

    Mal' tsev, V N [Institut Biofiziki, Moscow (USSR)

    1979-01-01

    A statistical analysis of data from the literature and the author's own experimental results are reviewed to show the functional relationships between the radiation dose and the development of endogenous infection in irradiated organisms. A direct linear dependence was found between the dose of radiation and the severity of endogenous infection at doses causing death from the ''bone marrow'' syndrome in acute radiation sickness. In case of death from the ''intestinal'' syndrome, an inverse linear dependence can be observed between the radiation dose and the culture yield of microbes from internal organs. In this case, the pathological effect on the organism is due to bacterial endotoxins formed during the disintegration of microbial cells in the organism. Endogenous infection and endotoxinaemia essentially aggravate the progress of acute radiation disease. The importance of endogenous infection for the death of the organism is minimized in irradiation at doses causing death ''under the ray''.

  8. Differential effects of exogenous and endogenous attention on second-order texture contrast sensitivity

    Science.gov (United States)

    Barbot, Antoine; Landy, Michael S.; Carrasco, Marisa

    2012-01-01

    The visual system can use a rich variety of contours to segment visual scenes into distinct perceptually coherent regions. However, successfully segmenting an image is a computationally expensive process. Previously we have shown that exogenous attention—the more automatic, stimulus-driven component of spatial attention—helps extract contours by enhancing contrast sensitivity for second-order, texture-defined patterns at the attended location, while reducing sensitivity at unattended locations, relative to a neutral condition. Interestingly, the effects of exogenous attention depended on the second-order spatial frequency of the stimulus. At parafoveal locations, attention enhanced second-order contrast sensitivity to relatively high, but not to low second-order spatial frequencies. In the present study we investigated whether endogenous attention—the more voluntary, conceptually-driven component of spatial attention—affects second-order contrast sensitivity, and if so, whether its effects are similar to those of exogenous attention. To that end, we compared the effects of exogenous and endogenous attention on the sensitivity to second-order, orientation-defined, texture patterns of either high or low second-order spatial frequencies. The results show that, like exogenous attention, endogenous attention enhances second-order contrast sensitivity at the attended location and reduces it at unattended locations. However, whereas the effects of exogenous attention are a function of the second-order spatial frequency content, endogenous attention affected second-order contrast sensitivity independent of the second-order spatial frequency content. This finding supports the notion that both exogenous and endogenous attention can affect second-order contrast sensitivity, but that endogenous attention is more flexible, benefitting performance under different conditions. PMID:22895879

  9. Differential effects of exogenous and endogenous attention on second-order texture contrast sensitivity.

    Science.gov (United States)

    Barbot, Antoine; Landy, Michael S; Carrasco, Marisa

    2012-08-15

    The visual system can use a rich variety of contours to segment visual scenes into distinct perceptually coherent regions. However, successfully segmenting an image is a computationally expensive process. Previously we have shown that exogenous attention--the more automatic, stimulus-driven component of spatial attention--helps extract contours by enhancing contrast sensitivity for second-order, texture-defined patterns at the attended location, while reducing sensitivity at unattended locations, relative to a neutral condition. Interestingly, the effects of exogenous attention depended on the second-order spatial frequency of the stimulus. At parafoveal locations, attention enhanced second-order contrast sensitivity to relatively high, but not to low second-order spatial frequencies. In the present study we investigated whether endogenous attention-the more voluntary, conceptually-driven component of spatial attention--affects second-order contrast sensitivity, and if so, whether its effects are similar to those of exogenous attention. To that end, we compared the effects of exogenous and endogenous attention on the sensitivity to second-order, orientation-defined, texture patterns of either high or low second-order spatial frequencies. The results show that, like exogenous attention, endogenous attention enhances second-order contrast sensitivity at the attended location and reduces it at unattended locations. However, whereas the effects of exogenous attention are a function of the second-order spatial frequency content, endogenous attention affected second-order contrast sensitivity independent of the second-order spatial frequency content. This finding supports the notion that both exogenous and endogenous attention can affect second-order contrast sensitivity, but that endogenous attention is more flexible, benefitting performance under different conditions.

  10. Comparison of febrile responsiveness of rats and rabbits to endogenous pyrogen.

    Science.gov (United States)

    Stitt, J T; Shimada, S G; Bernheim, H A

    1985-12-01

    The fever responses of rats and rabbits were compared in detail using a single common source of semipurified endogenous pyrogen prepared from human monocytes. The characteristics and dynamics of the fever-response curves for each species were examined and their dose-response curves were determined and compared. The fevers displayed by rats were qualitatively similar to those of rabbits, but, typically, they developed and terminated more rapidly than those of rabbits. Rabbits were much more sensitive to the endogenous pyrogen than rats. The threshold dose of pyrogen required to elicit a fever was 5 times lower in the rabbit, and the slope of the rabbit's dose-response curve was 1.5 times steeper than that of the rat. The maximum fevers attainable in rabbits were approximately twice those attainable in rats. It was also shown that the more rapid febrile responses of the rat were not due to the 10-fold smaller mass of the rat; instead, we proposed that this difference was more likely due to a closer diffusional proximity of the pyrogen receptor sites to the circulation in rats. The lower sensitivity of the rat to endogenous pyrogen was attributed to a relative insensitivity of the pyrogen receptor sites in rats in the translation of the endogenous pyrogen stimulus into fever.

  11. Impact of androgenic/antiandrogenic compounds (AAC) on human sex steroid metabolizing key enzymes

    International Nuclear Information System (INIS)

    Allera, A.; Lo, S.; King, I.; Steglich, F.; Klingmueller, D.

    2004-01-01

    Various pesticides, industrial pollutants and synthetic compounds, to which human populations are exposed, are known or suspected to interfere with endogenous sex hormone functions. Such interference potentially affect the development and expression of the male and female reproductive system or both. Chemicals in this class are thus referred to as endocrine disruptors (ED). This emphazises on the relevance of screening ED for a wide range of sex hormone-mimicking effects. These compounds are believed to exert influence on hormonal actions predominantly by (i) interfering with endogenous steroids in that they functionally interact with plasma membrane-located receptors as well as with nuclear receptors both for estrogens and androgens or (ii) affecting the levels of sex hormones as a result of their impact on steroid metabolizing key enzymes. Essential sex hormone-related enzymes within the endocrine system of humans are aromatase, 5α-reductase 2 as well as specific sulfotransferases and sulfatases (so-called phase I and phase II enzymes, respectively). Using suitable human tissues and human cancer cell lines (placenta, prostate, liver and JEG-3, lymph node carcinoma of prostate (LnCaP) cells) we investigated the impact of 10 widely used chemicals suspected of acting as ED with androgenic or antiandrogenic activity (so-called AAC) on the activity of these sex hormone metabolizing key enzymes in humans. In addition, the respective effects of six substances were also studied as positive controls due to their well-known specific hormonal agonistic/antagonistic activities. The aim of this report and subsequent investigations is to improve human health risk assessment for AAC and other ED

  12. HERVd: the Human Endogenous Retrovirus Database: update

    Czech Academy of Sciences Publication Activity Database

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

    2004-01-01

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

  13. Endogenous technological change with leisure-dependent utility.

    NARCIS (Netherlands)

    Hek, de P.A.

    1999-01-01

    This paper investigates the effect of introducing leisure-dependent utility into two models of endogenous technological change. Due to the flexibility in the labour supply the dynamics of the models change significantly. It is shown that if agents attach enough value to leisure in comparison to

  14. Place branding, embeddedness and endogenous rural development

    NARCIS (Netherlands)

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

    2017-01-01

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

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

    African Journals Online (AJOL)

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

  16. The Limit of Public Policy : Endogenous Preferences

    NARCIS (Netherlands)

    Bar-Gill, O.; Fershtman, C.

    2000-01-01

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

  17. Molecular modeling of inorganic compounds

    National Research Council Canada - National Science Library

    Comba, Peter; Hambley, Trevor W; Martin, Bodo

    2009-01-01

    ... mechanics to inorganic and coordination compounds. Initially, simple metal complexes were modeled, but recently the field has been extended to include organometallic compounds, catalysis and the interaction of metal ions with biological macromolecules. The application of molecular mechanics to coordination compounds is complicated by the numbe...

  18. Endogenous egg immune defenses in the yellow mealworm beetle (Tenebrio molitor).

    Science.gov (United States)

    Jacobs, Chris G C; Gallagher, Joe D; Evison, Sophie E F; Heckel, David G; Vilcinskas, Andreas; Vogel, Heiko

    2017-05-01

    In order to survive microbe encounters, insects rely on both physical barriers as well as local and systemic immune responses. Most research focusses on adult or larval defenses however, whereas insect eggs are also in need of protection. Lately, the defense of eggs against microbes has received an increasing amount of attention, be it through endogenous egg defenses, trans-generational immune priming (TGIP) or parental investment. Here we studied the endogenous immune response in eggs and adults of Tenebrio molitor. We show that many immune genes are induced in both adults and eggs. Furthermore, we show that eggs reach comparable levels of immune gene expression as adults. These findings show that the eggs of Tenebrio are capable of an impressive endogenous immune response, and indicate that such inducible egg defenses are likely common in insects. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Photoactive devices including porphyrinoids with coordinating additives

    Science.gov (United States)

    Forrest, Stephen R; Zimmerman, Jeramy; Yu, Eric K; Thompson, Mark E; Trinh, Cong; Whited, Matthew; Diev, Vlacheslav

    2015-05-12

    Coordinating additives are included in porphyrinoid-based materials to promote intermolecular organization and improve one or more photoelectric characteristics of the materials. The coordinating additives are selected from fullerene compounds and organic compounds having free electron pairs. Combinations of different coordinating additives can be used to tailor the characteristic properties of such porphyrinoid-based materials, including porphyrin oligomers. Bidentate ligands are one type of coordinating additive that can form coordination bonds with a central metal ion of two different porphyrinoid compounds to promote porphyrinoid alignment and/or pi-stacking. The coordinating additives can shift the absorption spectrum of a photoactive material toward higher wavelengths, increase the external quantum efficiency of the material, or both.

  20. Endogenous opioid antagonism in physiological experimental pain models

    DEFF Research Database (Denmark)

    Werner, Mads U; Pereira, Manuel P; Andersen, Lars Peter H

    2015-01-01

    hyperalgesia models (6 studies), 'pain' models (25 studies), summation models (2 studies), nociceptive reflex models (3 studies) and miscellaneous models (2 studies). A consistent reversal of analgesia by a MOR-antagonist was demonstrated in 10 of the 25 ITP-studies, including stress-induced analgesia and r...... ratings, threshold assessments and somatosensory evoked potentials (SSEP), did not appear consistent in 28 out of 32 'pain' model studies. In conclusion, only in 2 experimental human pain models, i.e., stress-induced analgesia and rTMS, administration of MOR-antagonist demonstrated a consistent effect......Opioid antagonists are pharmacological tools applied as an indirect measure to detect activation of the endogenous opioid system (EOS) in experimental pain models. The objective of this systematic review was to examine the effect of mu-opioid-receptor (MOR) antagonists in placebo-controlled, double...

  1. Endogenous time-varying risk aversion and asset returns.

    Science.gov (United States)

    Berardi, Michele

    2016-01-01

    Stylized facts about statistical properties for short horizon returns in financial markets have been identified in the literature, but a satisfactory understanding for their manifestation is yet to be achieved. In this work, we show that a simple asset pricing model with representative agent is able to generate time series of returns that replicate such stylized facts if the risk aversion coefficient is allowed to change endogenously over time in response to unexpected excess returns under evolutionary forces. The same model, under constant risk aversion, would instead generate returns that are essentially Gaussian. We conclude that an endogenous time-varying risk aversion represents a very parsimonious way to make the model match real data on key statistical properties, and therefore deserves careful consideration from economists and practitioners alike.

  2. Endogenous-cue prospective memory involving incremental updating of working memory: an fMRI study.

    Science.gov (United States)

    Halahalli, Harsha N; John, John P; Lukose, Ammu; Jain, Sanjeev; Kutty, Bindu M

    2015-11-01

    Prospective memory paradigms are conventionally classified on the basis of event-, time-, or activity-based intention retrieval. In the vast majority of such paradigms, intention retrieval is provoked by some kind of external event. However, prospective memory retrieval cues that prompt intention retrieval in everyday life are commonly endogenous, i.e., linked to a specific imagined retrieval context. We describe herein a novel prospective memory paradigm wherein the endogenous cue is generated by incremental updating of working memory, and investigated the hemodynamic correlates of this task. Eighteen healthy adult volunteers underwent functional magnetic resonance imaging while they performed a prospective memory task where the delayed intention was triggered by an endogenous cue generated by incremental updating of working memory. Working memory and ongoing task control conditions were also administered. The 'endogenous-cue prospective memory condition' with incremental working memory updating was associated with maximum activations in the right rostral prefrontal cortex, and additional activations in the brain regions that constitute the bilateral fronto-parietal network, central and dorsal salience networks as well as cerebellum. In the working memory control condition, maximal activations were noted in the left dorsal anterior insula. Activation of the bilateral dorsal anterior insula, a component of the central salience network, was found to be unique to this 'endogenous-cue prospective memory task' in comparison to previously reported exogenous- and endogenous-cue prospective memory tasks without incremental working memory updating. Thus, the findings of the present study highlight the important role played by the dorsal anterior insula in incremental working memory updating that is integral to our endogenous-cue prospective memory task.

  3. Use of isotope ratio mass spectrometry to differentiate between endogenous steroids and synthetic homologues in cattle: a review.

    Science.gov (United States)

    Janssens, Geert; Courtheyn, Dirk; Mangelinckx, Sven; Prévost, Stéphanie; Bichon, Emmanuelle; Monteau, Fabrice; De Poorter, Geert; De Kimpe, Norbert; Le Bizec, Bruno

    2013-04-15

    Although substantial technical advances have been achieved during the past decades to extend and facilitate the analysis of growth promoters in cattle, the detection of abuse of synthetic analogs of naturally occurring hormones has remained a challenging issue. When it became clear that the exogenous origin of steroid hormones could be traced based on the (13)C/(12)C isotope ratio of the substances, GC/C/IRMS has been successfully implemented to this aim since the end of the past century. However, due to the costly character of the instrumental setup, the susceptibility of the equipment to errors and the complex and time consuming sample preparation, this method is up until now only applied by a limited number of laboratories. In this review, the general principles as well as the practical application of GC/C/IRMS to differentiate between endogenous steroids and exogenously synthesized homologous compounds in cattle will be discussed in detail, and will be placed next to other existing and to be developed methods based on isotope ratio mass spectrometry. Finally, the link will be made with the field of sports doping, where GC/C/IRMS has been established within the World Anti-Doping Agency (WADA) approved methods as the official technique to differentiate between exogenous and endogenous steroids over the past few years. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Stable isotopes labelled compounds

    International Nuclear Information System (INIS)

    1982-09-01

    The catalogue on stable isotopes labelled compounds offers deuterium, nitrogen-15, and multiply labelled compounds. It includes: (1) conditions of sale and delivery, (2) the application of stable isotopes, (3) technical information, (4) product specifications, and (5) the complete delivery programme

  5. Endogenous Technology Adoption and Medical Costs.

    Science.gov (United States)

    Lamiraud, Karine; Lhuillery, Stephane

    2016-09-01

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

  6. Endogenous money, circuits and financialization

    OpenAIRE

    Malcolm Sawyer

    2013-01-01

    This paper locates the endogenous money approach in a circuitist framework. It argues for the significance of the credit creation process for the evolution of the economy and the absence of any notion of ‘neutrality of money’. Clearing banks are distinguished from other financial institutions as the providers of initial finance in a circuit whereas other financial institutions operate in a final finance circuit. Financialization is here viewed in terms of the growth of financial assets an...

  7. Polishing compound for plastic surfaces

    Science.gov (United States)

    Stowell, M.S.

    1991-01-01

    This invention is comprised of a polishing compound for plastic materials. The compound includes approximately by approximately by weight 25 to 80 parts at least one petroleum distillate lubricant, 1 to 12 parts mineral spirits, 50 to 155 parts abrasive paste, and 15 to 60 parts water. Preferably, the compound includes approximately 37 to 42 parts at least one petroleum distillate lubricant, up to 8 parts mineral spirits, 95 to 110 parts abrasive paste, and 50 to 55 parts water. The proportions of the ingredients are varied in accordance with the particular application. The compound is used on PLEXIGLAS{trademark}, LEXAN{trademark}, LUCITE{trademark}, polyvinyl chloride (PVC), and similar plastic materials whenever a smooth, clear polished surface is desired.

  8. Bullet trains and steam engines: exogenous attention zips but endogenous attention chugs along.

    Science.gov (United States)

    Chakravarthi, Ramakrishna; VanRullen, Rufin

    2011-04-20

    Analyzing a scene requires shifting attention from object to object. Although several studies have attempted to determine the speed of these attentional shifts, there are large discrepancies in their estimates. Here, we adapt a method pioneered by T. A. Carlson, H. Hogendoorn, and F. A. J. Verstraten (2006) that directly measures pure attentional shift times. We also test if attentional shifts can be handled in parallel by the independent resources available in the two cortical hemispheres. We present 10 "clocks," with single revolving hands, in a ring around fixation. Observers are asked to report the hand position on one of the clocks at the onset of a transient cue. The delay between the reported time and the veridical time at cue onset can be used to infer processing and attentional shift times. With this setup, we use a novel subtraction method that utilizes different combinations of exogenous and endogenous cues to determine shift times for both types of attention. In one experiment, subjects shift attention to an exogenously cued clock (baseline condition) in one block, and in other blocks, subjects perform one further endogenous shift to a nearby clock (test condition). In another experiment, attention is endogenously cued to one clock (baseline condition), and on other trials, an exogenous cue further shifts attention to a nearby clock (test condition). Subtracting report delays in the baseline condition from those obtained in the test condition allows us to isolate genuine attentional shift times. In agreement with previous studies, our results reveal that endogenous attention is much slower than exogenous attention (endogenous: 250 ms; exogenous: 100 ms). Surprisingly, the dependence of shift time on distance is minimal for exogenous attention, whereas it is steep for endogenous attention. In the final experiment, we find that endogenous shifts are faster across hemifields than within a hemifield suggesting that the two hemispheres can simultaneously

  9. A novel endogenous betaretrovirus group characterized from polar bears (Ursus maritimus) and giant pandas (Ailuropoda melanoleuca)

    DEFF Research Database (Denmark)

    Mayer, Jens; Tsangaras, Kyriakos; Heeger, Felix

    2013-01-01

    . Molecular dating indicates the group originated before the divergence of bears from a common ancestor but is not present in all carnivores. Closely related sequences were identified in the giant panda (Ailuropoda melanoleuca) and characterized from its genome. We have designated the polar bear and giant...... panda sequences U. maritimus endogenous retrovirus (UmaERV) and A. melanoleuca endogenous retrovirus (AmeERV), respectively. Phylogenetic analysis demonstrated that the bear virus group is nested within the HERV-K supergroup among bovine and bat endogenous retroviruses suggesting a complex evolutionary......Transcriptome analysis of polar bears (Ursus maritimus) yielded sequences with highest similarity to the human endogenous retrovirus group HERV-K(HML-2). Further analysis of the polar bear draft genome identified an endogenous betaretrovirus group comprising 26 proviral copies and 231 solo LTRs...

  10. Abnormal nociception and opiate sensitivity of STOP null mice exhibiting elevated levels of the endogenous alkaloid morphine

    Directory of Open Access Journals (Sweden)

    Aunis Dominique

    2010-12-01

    Full Text Available Abstract Background- Mice deficient for the stable tubule only peptide (STOP display altered dopaminergic neurotransmission associated with severe behavioural defects including disorganized locomotor activity. Endogenous morphine, which is present in nervous tissues and synthesized from dopamine, may contribute to these behavioral alterations since it is thought to play a role in normal and pathological neurotransmission. Results- In this study, we showed that STOP null brain structures, including cortex, hippocampus, cerebellum and spinal cord, contain high endogenous morphine amounts. The presence of elevated levels of morphine was associated with the presence of a higher density of mu opioid receptor with a higher affinity for morphine in STOP null brains. Interestingly, STOP null mice exhibited significantly lower nociceptive thresholds to thermal and mechanical stimulations. They also had abnormal behavioural responses to the administration of exogenous morphine and naloxone. Low dose of morphine (1 mg/kg, i.p. produced a significant mechanical antinociception in STOP null mice whereas it has no effect on wild-type mice. High concentration of naloxone (1 mg/kg was pronociceptive for both mice strain, a lower concentration (0.1 mg/kg was found to increase the mean mechanical nociceptive threshold only in the case of STOP null mice. Conclusions- Together, our data show that STOP null mice displayed elevated levels of endogenous morphine, as well as an increase of morphine receptor affinity and density in brain. This was correlated with hypernociception and impaired pharmacological sensitivity to mu opioid receptor ligands.

  11. Purple Corn (Zea mays L.) Phenolic Compounds Profile and Its Assessment as an Agent Against Oxidative Stress in Isolated Mouse Organs

    Science.gov (United States)

    Ramos-Escudero, Fernando; Muñoz, Ana María; Alvarado-Ortíz, Carlos; Alvarado, Ángel

    2012-01-01

    Abstract This study was designed to determine the contents of total polyphenols, flavonoids, flavonols, flavanols, and anthocyanins of purple corn (Zea mays L.) extracts obtained with different methanol:water concentrations, acidified with 1% HCl (1 N). Another objective was to determine the antioxidant activity by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and deoxyribose assay, individual phenolic compounds by high-performance liquid chromatography (HPLC), and endogenous antioxidant enzyme (superoxide dismutase [SOD], catalase [CAT], and total peroxidase [TPX]) activity and lipid peroxidation activity (thiobarbituric acid–reactive substances [TBARS] assay) in isolated mouse organs. Overall, the highest total content of polyphenols, anthocyanins, flavonoids, flavonols, and flavanols was obtained with the 80:20 methanol:water extract, acidified with 1% HCl (1 N). The 50% inhibitory concentration values obtained by the DPPH and ABTS assays with this extract were 66.3 μg/mL and 250 μg/mL, respectively. The antioxidant activity by the FRAP assay was 26.1 μM Trolox equivalents/g, whereas the deoxyribose assay presented 93.6% inhibition. Because of these results, the 80:20 methanol:water extract, acidified with 1% HCl (1 N), was used for the remaining tests. Eight phenolic compounds were identified by HPLC: chlorogenic acid, caffeic acid, rutin, ferulic acid, morin, quercetin, naringenin, and kaempferol. Furthermore, it was observed that the purple corn extract was capable of significantly reducing lipid peroxidation (lower malondialdehyde [MDA] concentrations by the TBARS assay) and at the same time increasing endogenous antioxidant enzyme (CAT, TPX, and SOD) activities in isolated mouse kidney, liver, and brain. On the basis of the results, it was concluded that the purple corn extract contained various bioactive phenolic compounds that exhibited

  12. Purple corn (Zea mays L.) phenolic compounds profile and its assessment as an agent against oxidative stress in isolated mouse organs.

    Science.gov (United States)

    Ramos-Escudero, Fernando; Muñoz, Ana María; Alvarado-Ortíz, Carlos; Alvarado, Ángel; Yáñez, Jaime A

    2012-02-01

    This study was designed to determine the contents of total polyphenols, flavonoids, flavonols, flavanols, and anthocyanins of purple corn (Zea mays L.) extracts obtained with different methanol:water concentrations, acidified with 1% HCl (1 N). Another objective was to determine the antioxidant activity by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and deoxyribose assay, individual phenolic compounds by high-performance liquid chromatography (HPLC), and endogenous antioxidant enzyme (superoxide dismutase [SOD], catalase [CAT], and total peroxidase [TPX]) activity and lipid peroxidation activity (thiobarbituric acid-reactive substances [TBARS] assay) in isolated mouse organs. Overall, the highest total content of polyphenols, anthocyanins, flavonoids, flavonols, and flavanols was obtained with the 80:20 methanol:water extract, acidified with 1% HCl (1 N). The 50% inhibitory concentration values obtained by the DPPH and ABTS assays with this extract were 66.3 μg/mL and 250 μg/mL, respectively. The antioxidant activity by the FRAP assay was 26.1 μM Trolox equivalents/g, whereas the deoxyribose assay presented 93.6% inhibition. Because of these results, the 80:20 methanol:water extract, acidified with 1% HCl (1 N), was used for the remaining tests. Eight phenolic compounds were identified by HPLC: chlorogenic acid, caffeic acid, rutin, ferulic acid, morin, quercetin, naringenin, and kaempferol. Furthermore, it was observed that the purple corn extract was capable of significantly reducing lipid peroxidation (lower malondialdehyde [MDA] concentrations by the TBARS assay) and at the same time increasing endogenous antioxidant enzyme (CAT, TPX, and SOD) activities in isolated mouse kidney, liver, and brain. On the basis of the results, it was concluded that the purple corn extract contained various bioactive phenolic compounds that exhibited considerable in vitro

  13. The interactions of multisensory integration with endogenous and exogenous attention.

    Science.gov (United States)

    Tang, Xiaoyu; Wu, Jinglong; Shen, Yong

    2016-02-01

    Stimuli from multiple sensory organs can be integrated into a coherent representation through multiple phases of multisensory processing; this phenomenon is called multisensory integration. Multisensory integration can interact with attention. Here, we propose a framework in which attention modulates multisensory processing in both endogenous (goal-driven) and exogenous (stimulus-driven) ways. Moreover, multisensory integration exerts not only bottom-up but also top-down control over attention. Specifically, we propose the following: (1) endogenous attentional selectivity acts on multiple levels of multisensory processing to determine the extent to which simultaneous stimuli from different modalities can be integrated; (2) integrated multisensory events exert top-down control on attentional capture via multisensory search templates that are stored in the brain; (3) integrated multisensory events can capture attention efficiently, even in quite complex circumstances, due to their increased salience compared to unimodal events and can thus improve search accuracy; and (4) within a multisensory object, endogenous attention can spread from one modality to another in an exogenous manner. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. II-VI semiconductor compounds

    CERN Document Server

    1993-01-01

    For condensed matter physicists and electronic engineers, this volume deals with aspects of II-VI semiconductor compounds. Areas covered include devices and applications of II-VI compounds; Co-based II-IV semi-magnetic semiconductors; and electronic structure of strained II-VI superlattices.

  15. Packaging of human endogenous retrovirus sequences is undetectable in porcine endogenous retrovirus particles produced from human cells

    International Nuclear Information System (INIS)

    Suling, Kristen; Quinn, Gary; Wood, James; Patience, Clive

    2003-01-01

    The chronic shortage of human donor organs and tissues for allotransplantation could be relieved if clinical xenotransplantation were to become a viable clinical therapy. Balanced against the benefits of xenotransplantation are the possible consequences of zoonotic infections, and in particular, infection by porcine endogenous retrovirus (PERV). An often-proclaimed risk of PERV infection is the possible recombination of PERV with human endogenous retroviruses (HERV) . To address this issue, we examined the potential for HERV sequences to be cross-packaged into PERV particles produced from infected human 293 cells. Although HERV-K, W, E, R, and ERV-9 RNA transcripts are expressed in 293 cells, we did not detect cross-packaging of any of these HERV groups. Quantitative analysis indicated that less than approximately 1 in 10 4 -10 7 PERV particles might contain HERV sequences. In comparison, we found that murine leukemia virus (MLV)-based vector transcripts were cross-packaged at a rate of approximately one copy in 10 4 PERV particles. Our results indicate that the potential for recombination of PERV and HERV sequences is low and that novel viruses generated by this mechanism are unlikely to represent a significant risk for xenotransplantation

  16. Levels of potential bioactive compounds including carotenoids, vitamin C and phenolic compounds, and expression of their cognate biosynthetic genes vary significantly in different varieties of potato (Solanum tuberosum L.) grown under uniform cultural conditions.

    Science.gov (United States)

    Valcarcel, Jesus; Reilly, Kim; Gaffney, Michael; O'Brien, Nora M

    2016-02-01

    In addition to their high carbohydrate content, potatoes are also an important dietary source of vitamin C and bioactive secondary metabolites, including phenolic compounds and carotenoids, which have been suggested to play a role in human health. The expression of genes encoding key enzymes involved in the synthesis of these compounds was assessed by reverse transcription-quantitative polymerase chain reaction and compared to the accumulation of the corresponding product in seven potato varieties showing contrasting levels of metabolite accumulation. Strong positive correlations were found between phenolic content in the flesh of tubers and transcript levels of phenylalanine ammonia lyase (PAL) and chalcone synthase (CHS) genes. The expression of PAL and CHS was also related to that of AN1, a transcription factor involved in the synthesis of anthocyanins, suggesting that these genes are regulated in a coordinated manner. No clear relationship was found between transcript levels of phytoene synthase (PSY) or L-galactono-1,4-lactone dehydrogenase (GLDH) genes and total carotenoid or vitamin C accumulation, respectively. Data indicate that levels of total phenolic and flavonoid compounds in potato are controlled primarily by PAL and CHS gene expression. Transcript levels of PSY and GLDH did not control accumulation of carotenoids or vitamin C. © 2015 Society of Chemical Industry.

  17. Two cognitive and neural systems for endogenous and exogenous spatial attention.

    Science.gov (United States)

    Chica, Ana B; Bartolomeo, Paolo; Lupiáñez, Juan

    2013-01-15

    Orienting of spatial attention is a family of phylogenetically old mechanisms developed to select information for further processing. Information can be selected via top-down or endogenous mechanisms, depending on the goals of the observers or on the task at hand. Moreover, salient and potentially dangerous events also attract spatial attention via bottom-up or exogenous mechanisms, allowing a rapid and efficient reaction to unexpected but important events. Fronto-parietal brain networks have been demonstrated to play an important role in supporting spatial attentional orienting, although there is no consensus on whether there is a single attentional system supporting both endogenous and exogenous attention, or two anatomical and functionally different attentional systems. In the present paper we review behavioral evidence emphasizing the differential characteristics of both systems, as well as their possible interactions for the control of the final orienting response. Behavioral studies reporting qualitative differences between the effects of both systems as well as double dissociations of the effects of endogenous and exogenous attention on information processing, suggest that they constitute two independent attentional systems, rather than a single one. Recent models of attentional orienting in humans have put forward the hypothesis of a dorsal fronto-parietal network for orienting spatial attention, and a more ventral fronto-parietal network for detecting unexpected but behaviorally relevant events. Non-invasive neurostimulation techniques, as well as neuropsychological data, suggest that endogenous and exogenous attention are implemented in overlapping, although partially segregated, brain circuits. Although more research is needed in order to refine our anatomical and functional knowledge of the brain circuits underlying spatial attention, we conclude that endogenous and exogenous spatial orienting constitute two independent attentional systems, with

  18. Glacial cycles: exogenous orbital changes vs. endogenous climate dynamics

    Science.gov (United States)

    Kaufmann, R. K.; Juselius, K.

    2010-04-01

    We use a statistical model, the cointegrated vector autoregressive model, to assess the degree to which variations in Earth's orbit and endogenous climate dynamics can be used to simulate glacial cycles during the late Quaternary (390 kyr-present). To do so, we estimate models of varying complexity and compare the accuracy of their in-sample simulations. Results indicate that strong statistical associations between endogenous climate variables are not enough for statistical models to reproduce glacial cycles. Rather, changes in solar insolation associated with changes in Earth's orbit are needed to simulate glacial cycles accurately. Also, results suggest that non-linear dynamics, threshold effects, and/or free oscillations may not play an overriding role in glacial cycles.

  19. Essays on Policy Evaluation with Endogenous Adoption

    Science.gov (United States)

    Gentile, Elisabetta

    2011-01-01

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

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

    African Journals Online (AJOL)

    In humans, one ERV family, human endogenous retrovirus- K (HERV-K) is abundantly expressed, and is associated with germ cell tumours, while ERV3 env is expressed in normal human testis. Conclusion: The expression of ERVs in male reproductive tissues suggests a possible role in normal and disease conditions ...

  1. Shotgun glycomics of pig lung identifies natural endogenous receptors for influenza viruses.

    Science.gov (United States)

    Byrd-Leotis, Lauren; Liu, Renpeng; Bradley, Konrad C; Lasanajak, Yi; Cummings, Sandra F; Song, Xuezheng; Heimburg-Molinaro, Jamie; Galloway, Summer E; Culhane, Marie R; Smith, David F; Steinhauer, David A; Cummings, Richard D

    2014-06-03

    Influenza viruses bind to host cell surface glycans containing terminal sialic acids, but as studies on influenza binding become more sophisticated, it is becoming evident that although sialic acid may be necessary, it is not sufficient for productive binding. To better define endogenous glycans that serve as viral receptors, we have explored glycan recognition in the pig lung, because influenza is broadly disseminated in swine, and swine have been postulated as an intermediary host for the emergence of pandemic strains. For these studies, we used the technology of "shotgun glycomics" to identify natural receptor glycans. The total released N- and O-glycans from pig lung glycoproteins and glycolipid-derived glycans were fluorescently tagged and separated by multidimensional HPLC, and individual glycans were covalently printed to generate pig lung shotgun glycan microarrays. All viruses tested interacted with one or more sialylated N-glycans but not O-glycans or glycolipid-derived glycans, and each virus demonstrated novel and unexpected differences in endogenous N-glycan recognition. The results illustrate the repertoire of specific, endogenous N-glycans of pig lung glycoproteins for virus recognition and offer a new direction for studying endogenous glycan functions in viral pathogenesis.

  2. Post-stimulus endogenous and exogenous oscillations are differentially modulated by task difficulty.

    Science.gov (United States)

    Li, Yun; Lou, Bin; Gao, Xiaorong; Sajda, Paul

    2013-01-01

    We investigate the modulation of post-stimulus endogenous and exogenous oscillations when a visual discrimination is made more difficult. We use exogenous frequency tagging to induce steady-state visually evoked potentials (SSVEP) while subjects perform a face-car discrimination task, the difficulty of which varies on a trial-to-trial basis by varying the noise (phase coherence) in the image. We simultaneously analyze amplitude modulations of the SSVEP and endogenous alpha activity as a function of task difficulty. SSVEP modulation can be viewed as a neural marker of attention toward/away from the primary task, while modulation of post-stimulus alpha is closely related to cortical information processing. We find that as the task becomes more difficult, the amplitude of SSVEP decreases significantly, approximately 250-450 ms post-stimulus. Significant changes in endogenous alpha amplitude follow SSVEP modulation, occurring at approximately 400-700 ms post-stimulus and, unlike the SSVEP, the alpha amplitude is increasingly suppressed as the task becomes less difficult. Our results demonstrate simultaneous measurement of endogenous and exogenous oscillations that are modulated by task difficulty, and that the specific timing of these modulations likely reflects underlying information processing flow during perceptual decision-making.

  3. Endogenous rhythm and pattern-generating circuit interactions in cockroach motor centres

    Directory of Open Access Journals (Sweden)

    Izhak David

    2016-09-01

    Full Text Available Cockroaches are rapid and stable runners whose gaits emerge from the intricate, and not fully resolved, interplay between endogenous oscillatory pattern-generating networks and sensory feedback that shapes their rhythmic output. Here we studied the endogenous motor output of a brainless, deafferented preparation. We monitored the pilocarpine-induced rhythmic activity of levator and depressor motor neurons in the mesothoracic and metathoracic segments in order to reveal the oscillatory networks’ architecture and interactions. Data analyses included phase relations, latencies between and overlaps of rhythmic bursts, spike frequencies, and the dependence of these parameters on cycle frequency. We found that, overall, ipsilateral connections are stronger than contralateral ones. Our findings revealed asymmetries in connectivity among the different ganglia, in which meta-to-mesothoracic ascending coupling is stronger than meso-to-metathoracic descending coupling. Within-ganglion coupling between the metathoracic hemiganglia is stronger than that in the mesothoracic ganglion. We also report differences in the role and mode of operation of homologue network units (manifested by levator and depressor nerve activity. Many observed characteristics are similar to those exhibited by intact animals, suggesting a dominant role for feedforward control in cockroach locomotion. Based on these data we posit a connectivity scheme among components of the locomotion pattern generating system.

  4. A Novel, In-solution Separation of Endogenous Cardiac Sarcomeric Proteins and Identification of Distinct Charged Variants of Regulatory Light Chain*

    Science.gov (United States)

    Scruggs, Sarah B.; Reisdorph, Rick; Armstrong, Mike L.; Warren, Chad M.; Reisdorph, Nichole; Solaro, R. John; Buttrick, Peter M.

    2010-01-01

    The molecular conformation of the cardiac myosin motor is modulated by intermolecular interactions among the heavy chain, the light chains, myosin binding protein-C, and titin and is governed by post-translational modifications (PTMs). In-gel digestion followed by LC/MS/MS has classically been applied to identify cardiac sarcomeric PTMs; however, this approach is limited by protein size, pI, and difficulties in peptide extraction. We report a solution-based work flow for global separation of endogenous cardiac sarcomeric proteins with a focus on the regulatory light chain (RLC) in which specific sites of phosphorylation have been unclear. Subcellular fractionation followed by OFFGEL electrophoresis resulted in isolation of endogenous charge variants of sarcomeric proteins, including regulatory and essential light chains, myosin heavy chain, and myosin-binding protein-C of the thick filament. Further purification of RLC using reverse-phase HPLC separation and UV detection enriched for RLC PTMs at the intact protein level and provided a stoichiometric and quantitative assessment of endogenous RLC charge variants. Digestion and subsequent LC/MS/MS unequivocally identified that the endogenous charge variants of cardiac RLC focused in unique OFFGEL electrophoresis fractions were unphosphorylated (78.8%), singly phosphorylated (18.1%), and doubly phosphorylated (3.1%) RLC. The novel aspects of this study are that 1) milligram amounts of endogenous cardiac sarcomeric subproteome were focused with resolution comparable with two-dimensional electrophoresis, 2) separation and quantification of post-translationally modified variants were achieved at the intact protein level, 3) separation of intact high molecular weight thick filament proteins was achieved in solution, and 4) endogenous charge variants of RLC were separated; a novel doubly phosphorylated form was identified in mouse, and singly phosphorylated, singly deamidated, and deamidated/phosphorylated forms were

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

    Science.gov (United States)

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

    2018-01-01

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

  6. Managing the endogeneity problem of the market structure: a study on banking competition

    Directory of Open Access Journals (Sweden)

    Tri Mulyaningsih

    2015-10-01

    Full Text Available Recent literature suggests that the market structure is an endogenous variable that is determined by a firm’s behaviour and the competitive environment of the industry. This study examines the relation between the market structure and the banks’ behaviour in Indonesian banking by considering the endogeneity problem of them as variables. The estimations using the Vector-Error-Correction approach suggest that the structural approach provides a valid prediction of the relationship between market structure and bank behaviour by recognizing the endogeneity issue between those two variables. The banking industry would be more competitive if the market was less concentrated.

  7. Immunoadjuvants enhance the febrile responses of rats to endogenous pyrogen.

    Science.gov (United States)

    Stitt, J T; Shimada, S G

    1989-11-01

    The febrile responses of male Sprague-Dawley rats to a semipurified endogenous pyrogen produced from human monocytes were characterized by establishing fever dose-response curves. The animals were then injected intravenously with a number of substances that possessed the common properties of stimulating the phagocytic activity of the cells of the reticuloendothelial system and of acting as immunoadjuvants. The substances used were zymosan, lipopolysaccharide endotoxin, and muramyl dipeptide. Three days after any of these immunoadjuvants were injected, the fever sensitivity of the rats was remeasured. In each case, the slope of the fever dose-response curve tripled, and in some instances the response threshold for fever response was reduced by factors of three to eight. Furthermore, the maximum increase in body temperature produced by the endogenous pyrogen was more than doubled after immunoadjuvant treatment. By contrast latex beads, which are also phagocytized by the cells of the reticuloendothelial system but do not subsequently increase their phagocytic index nor do they enhance immune responses, had no effect on the fever sensitivity of rats in response to endogenous pyrogen. In the light of these findings, it is suggested that the febrile responses of rats to endogenous pyrogen are mediated in some manner by cells that possess some of the properties of reticuloendothelial cells. The location of these putative cells must be close to the circulation, because the immunoadjuvants used in this study were, for the most part, large molecular weight molecules that could not cross the blood-brain barrier easily.

  8. Differentiation of endogenous and exogenous steroids by gas chromatography-combustion-mass spectrometry isotope ratio

    International Nuclear Information System (INIS)

    Montes de Oca Porto, Rodny; Rosado Perez, Aristides; Correa Vidal, Margarita Teresa

    2007-01-01

    Urinary steroids profiles are used to control the misuse of endogenous steroids such as testosterone and dihydrotestosterone. The testosterone/epistestosterone ratio, measured by Gas Chromatography-Mass Spectrometry, is used to control testosterone administration. When T/E ratio is higher than 4, consumption of testosterone or its precursors is suspected. Recent researches have demonstrated the effectiveness of Carbon Isotope Ratio Mass Spectrometry to detect and confirm endogenous steroids administration. The ratio of the two stable carbon isotopes 1 3 C and 1 2 C allows the differentiation of natural and synthetic steroids because synthetic steroids have lower 1 3 C abundance. In fact, the carbon isotope ratios can be used to determine endogenous steroids administration even when testosterone/epistestosterone ratio is at its normal value. In the current work, some of the most important aspects related to differentiation of endogenous and exogenous steroids by means of Gas Chromatography-Combustion-Isotope Ratio Mass Spectrometry are discussed. Also, this article provides a review about the purification and sample preparation previous to the analysis, and diet effects on carbon isotope ratio of endogenous anabolics steroids is presented too

  9. Biology and evolution of the endogenous koala retrovirus.

    Science.gov (United States)

    Tarlinton, R; Meers, J; Young, P

    2008-11-01

    Although endogenous retroviruses are ubiquitous features of all mammalian genomes, the process of initial germ line invasion and subsequent inactivation from a pathogenic element has not yet been observed in a wild species. Koala retrovirus (KoRV) provides a unique opportunity to study this process of endogenisation in action as it still appears to be spreading through the koala population. Ongoing expression of the endogenous sequence and consequent high levels of viraemia have been linked to neoplasia and immunosuppression in koalas. This apparently recent invader of the koala genome shares a remarkably close sequence relationship with the pathogenic exogenous Gibbon ape leukaemia virus (GALV), and comparative analyses of KoRV and GALVare helping to shed light on how retroviruses in general adapt to a relatively benign or at least less pathogenic existence within a new host genome. (Part of a multi-author review).

  10. Endogenous MMTV proviruses induce susceptibility to both viral and bacterial pathogens.

    Directory of Open Access Journals (Sweden)

    Sanchita Bhadra

    2006-12-01

    Full Text Available Most inbred mice carry germline proviruses of the retrovirus, mouse mammary tumor virus (MMTV (called Mtvs, which have multiple replication defects. A BALB/c congenic mouse strain lacking all endogenous Mtvs (Mtv-null was resistant to MMTV oral and intraperitoneal infection and tumorigenesis compared to wild-type BALB/c mice. Infection of Mtv-null mice with an MMTV-related retrovirus, type B leukemogenic virus, also resulted in severely reduced viral loads and failure to induce T-cell lymphomas, indicating that resistance is not dependent on expression of a superantigen (Sag encoded by exogenous MMTV. Resistance to MMTV in Mtv-null animals was not due to neutralizing antibodies. Further, Mtv-null mice were resistant to rapid mortality induced by intragastric inoculation of the Gram-negative bacterium, Vibrio cholerae, but susceptibility to Salmonella typhimurium was not significantly different from BALB/c mice. Susceptibility to both MMTV and V. cholerae was reconstituted by the presence of any one of three endogenous Mtvs located on different chromosomes and was associated with increased pathogen load. One of these endogenous proviruses is known to encode only Sag. Therefore, Mtv-encoded Sag appears to provide a unique genetic susceptibility to specific viruses and bacteria. Since human endogenous retroviruses also encode Sags, these studies have broad implications for pathogen-induced responses in mice and humans.

  11. Studies on the pathogenesis of fever. IX. Characteristics of endogenous serum pyrogen and mechanisms governing its release.

    Science.gov (United States)

    PETERSDORF, R G; KEENE, W R; BENNETT, I L

    1957-12-01

    The "endogenous serum pyrogen" that appears in the circulating blood after a single intravenous injection of endotoxin does not produce leukopenia in normal animals, fails to provoke the local Shwartzman reaction, and elicits no "tolerance" when injected daily. Suppression of the febrile response to endotoxin by prednisone does not prevent the appearance of pyrogen in the blood. Animals given large amounts of endotoxin daily continue to respond with high fevers despite failure of endogenous serum pyrogen to appear in detectable amounts after the first two or three injections. Analysis of the response to daily injections shows clearly that the fever during the first 2 hours after administration of endotoxin is unrelated to levels of endogenous serum pyrogen; in contrast, the magnitude of the fever after the 2nd hour correlates well with endogenous pyrogen in some instances. The leukopenic response to endotoxin could not be correlated with the appearance of endogenous serum pyrogen. The differences between endotoxin and endogenous pyrogen and the similarities between leukocyte extracts (sterile exudates) and endogenous pyrogen are summarized and discussed. Dissociation of the febrile response to bacterial endotoxin and levels of endogenous serum pyrogen are discussed and it is concluded that a mechanism involving both direct and indirect action of endotoxins offers the best explanation for the pyrogenic action of these bacterial products.

  12. Endogenous lycopene improves ethanol production under acetic acid stress in Saccharomyces cerevisiae.

    Science.gov (United States)

    Pan, Shuo; Jia, Bin; Liu, Hong; Wang, Zhen; Chai, Meng-Zhe; Ding, Ming-Zhu; Zhou, Xiao; Li, Xia; Li, Chun; Li, Bing-Zhi; Yuan, Ying-Jin

    2018-01-01

    Acetic acid, generated from the pretreatment of lignocellulosic biomass, is a significant obstacle for lignocellulosic ethanol production. Reactive oxidative species (ROS)-mediated cell damage is one of important issues caused by acetic acid. It has been reported that decreasing ROS level can improve the acetic acid tolerance of Saccharomyces cerevisiae . Lycopene is known as an antioxidant. In the study, we investigated effects of endogenous lycopene on cell growth and ethanol production of S. cerevisiae in acetic acid media. By accumulating endogenous lycopene during the aerobic fermentation of the seed stage, the intracellular ROS level of strain decreased to 1.4% of that of the control strain during ethanol fermentation. In the ethanol fermentation system containing 100 g/L glucose and 5.5 g/L acetic acid, the lag phase of strain was 24 h shorter than that of control strain. Glucose consumption rate and ethanol titer of yPS002 got to 2.08 g/L/h and 44.25 g/L, respectively, which were 2.6- and 1.3-fold of the control strain. Transcriptional changes of INO1 gene and CTT1 gene confirmed that endogenous lycopene can decrease oxidative stress and improve intracellular environment. Biosynthesis of endogenous lycopene is first associated with enhancing tolerance to acetic acid in S. cerevisiae . We demonstrate that endogenous lycopene can decrease intracellular ROS level caused by acetic acid, thus increasing cell growth and ethanol production. This work innovatively   puts forward a new strategy for second generation bioethanol production during lignocellulosic fermentation.

  13. MALDI Mass Spectrometry Imaging for Visualizing In Situ Metabolism of Endogenous Metabolites and Dietary Phytochemicals

    Science.gov (United States)

    Fujimura, Yoshinori; Miura, Daisuke

    2014-01-01

    Understanding the spatial distribution of bioactive small molecules is indispensable for elucidating their biological or pharmaceutical roles. Mass spectrometry imaging (MSI) enables determination of the distribution of ionizable molecules present in tissue sections of whole-body or single heterogeneous organ samples by direct ionization and detection. This emerging technique is now widely used for in situ label-free molecular imaging of endogenous or exogenous small molecules. MSI allows the simultaneous visualization of many types of molecules including a parent molecule and its metabolites. Thus, MSI has received much attention as a potential tool for pathological analysis, understanding pharmaceutical mechanisms, and biomarker discovery. On the other hand, several issues regarding the technical limitations of MSI are as of yet still unresolved. In this review, we describe the capabilities of the latest matrix-assisted laser desorption/ionization (MALDI)-MSI technology for visualizing in situ metabolism of endogenous metabolites or dietary phytochemicals (food factors), and also discuss the technical problems and new challenges, including MALDI matrix selection and metabolite identification, that need to be addressed for effective and widespread application of MSI in the diverse fields of biological, biomedical, and nutraceutical (food functionality) research. PMID:24957029

  14. Persistent Inflammation Alters the Function of the Endogenous Brain Stem Cell Compartment

    OpenAIRE

    Pluchino, Stefano; Muzio, Luca; Alfaro-Cervello, Clara; Salani, Giuliana; Porcheri, Cristina; Brambilla, Elena; Cavasinni, Francesca; Bergamaschi, Andrea; Garcia-Verdugo, Jose Manuel; Comi, Giancarlo; Martino, Gianvito; Imitola, Jaime; Deleidi, Michela; Khoury, Samia Joseph

    2008-01-01

    Endogenous neural stem/precursor cells (NPCs) are considered a functional reservoir for promoting tissue homeostasis and repair after injury, therefore regenerative strategies that mobilize these cells have recently been proposed. Despite evidence of increased neurogenesis upon acute inflammatory insults (e.g. ischaemic stroke), the plasticity of the endogenous brain stem cell compartment in chronic CNS inflammatory disorders remains poorly characterized. Here we show that persistent brain in...

  15. Endogenous oxytocin levels are associated with the perception of emotion in dynamic body expressions in schizophrenia.

    Science.gov (United States)

    Strauss, Gregory P; Keller, William R; Koenig, James I; Sullivan, Sara K; Gold, James M; Buchanan, Robert W

    2015-03-01

    Lower endogenous oxytocin levels have been associated with impaired social cognition in schizophrenia, particularly facial affect identification. Little is known about the relationship between oxytocin and other forms of emotion perception. In the current study, 41 individuals with schizophrenia (SZ) and 22 demographically matched healthy controls (CN) completed a forced-choice affective body expression classification task. Stimuli included dynamic videos of male and female actors portraying 4 discrete emotions: happiness, sadness, anger, and neutral. Plasma oxytocin levels were determined via radioimmunoassay. Results indicated that SZ had significantly higher plasma oxytocin concentrations than CN. SZ were also less accurate at identifying expressions of happiness and sadness; however, there were no group differences for anger or neutral stimuli. A group×sex interaction was also present, such that female CN were more accurate than male CN, whereas male SZ were more accurate than female SZ. Higher endogenous oxytocin levels were associated with better total recognition in both SZ and CN; this association was specific to females in SZ. Findings indicate that sex plays an important role in identifying emotional expressions in body gestures in SZ, and that individual differences in endogenous oxytocin predict emotion perception accuracy. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Radioactive decay and labeled compounds

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    This chapter on radioactive decay and labeled compounds has numerous intext equations and worked, sample problems. Topics covered include the following: terms and mathematics of radioactive decay; examples of calculations; graphs of decay equations; radioactivity or activity; activity measurements; activity decay; half-life determinations; labeled compounds. A 20 problem set is also included. 1 ref., 4 figs., 1 tab

  17. An active role for endogenous beta-1,3-glucanase genes in transgene-mediated co-suppression in tobacco.

    Science.gov (United States)

    Sanders, Matthew; Maddelein, Wendy; Depicker, Anna; Van Montagu, Marc; Cornelissen, Marc; Jacobs, John

    2002-11-01

    Post-transcriptional gene silencing (PTGS) is characterized by the accumulation of short interfering RNAs that are proposed to mediate sequence-specific degradation of cognate and secondary target mRNAs. In plants, it is unclear to what extent endogenous genes contribute to this process. Here, we address the role of the endogenous target genes in transgene-mediated PTGS of beta-1,3-glucanases in tobacco. We found that mRNA sequences of the endogenous glucanase glb gene with varying degrees of homology to the Nicotiana plumbaginifolia gn1 transgene are targeted by the silencing machinery, although less efficiently than corresponding transgene regions. Importantly, we show that endogene-specific nucleotides in the glb sequence provide specificity to the silencing process. Consistent with this finding, small sense and antisense 21- to 23-nucleotide RNAs homologous to the endogenous glb gene were detected. Combined, these data demonstrate that a co-suppressed endogenous glucan ase gene is involved in signal amplification and selection of homologous targets, and show that endogenous genes can actively participate in PTGS in plants. The findings are introduced as a further sophistication of the post-transciptional silencing model.

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

    African Journals Online (AJOL)

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

  19. Indicators for the total duration of premenopausal endogenous estrogen exposure in relation to BMD

    NARCIS (Netherlands)

    Hagemans, M.L.C.; Schouw, van der Y.T.; Kleijn, de M.J.J.; Staveren, van W.A.; Pop, V.J.M.; Leusink, G.L.; Grobbee, D.E.

    2004-01-01

    BACKGROUND: Previous studies have shown that age at menopause is an important indicator of duration of endogenous estrogen exposure. The present study investigates whether combining more information on reproductive factors is useful in estimating individual total duration of exposure to endogenous

  20. Endogenous electromagnetic forces emissions during cell respiration as additional factor in cancer origin.

    Science.gov (United States)

    Embi, Abraham A

    2016-01-01

    Seven decades ago, a seminal paper by Dr. Denham Harman in (J Gerontol 11(3):298-300, 1956), introduced a theory stating that there are good reasons for assuming that endogenous irradiation in the living cells could lead to cancer via an obscure mechanism. The main purpose of this manuscript is to shed some light in said mechanism by proposing a five-step eukaryotic cell cancer triggering cycle. In other words, a new factor is introduced, namely the recently found emissions of electromagnetic forces (EMFs) as a possible causing agent in diseases, including cancer. Introduced is an eukaryotic cell cancer inducing cycle. It includes five sequential steps of endogenous biological process that are backed by published scientific reports. It is a known fact that in order to achieve homeostasis, toxic reactive oxygen species (ROS) i.e. H2O2 molecules are broken down by the protein enzyme catalase. During this reaction EMFs are generated (Embi in AIS Physics 2(3):226-230, 2016). The EMFs recording breakthrough was possible due to the introduction of a novel table top microscopy technique to detect EMFs by using Prussian Blue Stain and nano-sized iron particles. There are different roots in molecular and clinical biology through which DNA damage could be programmed, EMFs emitted (during cell respiration) are herein proposed as an additional cause.

  1. Isolating Exogenous and Endogenous Modes of Temporal Attention

    Science.gov (United States)

    Lawrence, Michael A.; Klein, Raymond M.

    2013-01-01

    The differential allocation of information processing resources over time, here termed "temporal attention," may be achieved by relatively automatic "exogenous" or controlled "endogenous" mechanisms. Over 100 years of research has confounded these theoretically distinct dimensions of temporal attention. The current…

  2. Endogenous heparin levels in the controlled asthmatic patient ...

    African Journals Online (AJOL)

    Background. Since heparin possesses anti-inflammatory properties, it is hypothesised that asthmatic patients have decreased levels of circulating heparin compared with healthy individuals. Design. We compared endogenous heparin levels in controlled asthmatic patients (53 adults) from the Asthma Clinic at ...

  3. [Significance of endogenous sulfur dioxide in the regulation of cardiovascular system].

    Science.gov (United States)

    Jin, Hong Fang; DU, Shu Xu; Zhao, Xia; Zhang, Su Qing; Tian, Yue; Bu, Ding Fang; Tang, Chao Shu; DU, Jun Bao

    2007-08-18

    Since the 1980's nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H(2)S), the endogenous gas molecules produced from metabolic pathway, have been realized as signal molecules to be involved in the regulation of body homeostasis and to play important roles under physiological and pathophysiological conditions. The researches on these endogenous gas signal molecules opened a new avenue in life science. To explore the new member of gasotransmitter family, other endogenous gas molecules which have been regarded as metabolic waste up to date, and their biological regulatory effects have been paid close attention to in the current fields of life science and medicine. Sulfur dioxide (SO(2)) can be produced endogenously from normal metabolism of sulfur-containing amino acids. L-cysteine is oxidized via cysteine dioxygenase to L-cysteinesulfinate, and the latter can proceed through transamination by glutamate oxaloacetate transaminase (GOT) to beta-sulfinyl pyruvate which decomposes spontaneously to pyruvate and SO(2). In mammals, activated neutrophils by oxidative stress can convert H(2)S to sulfite through a reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase-dependent process. The authors detected endogenous production of SO(2) in all cardiovascular tissues, including in heart, aorta, pulmonary artery, mesenteric artery, renal artery, tail artery and the plasma SO(2) content. As the key enzyme producing SO(2), GOT mRNA in cardiovascular system was detected and found to be located enriched in endothelial cells and vascular smooth muscle cells near the endothelial layer. When the normal rats were treated with hydroxamate(HDX), a GOT inhibitor, at a dose of 3.7 mg/kg body weight, the blood pressure (BP) went high markedly, the ratio of wall thickness to lumen radius was increased by 18.34%, and smooth muscle cell proliferation was enhanced. The plasma SO(2) level in the rats injected with 125 micromol/kg body weight SO(2) donor was

  4. Impact of estrogenic compounds on DNA integrity in human spermatozoa: Evidence for cross-linking and redox cycling activities

    International Nuclear Information System (INIS)

    Bennetts, L.E.; De Iuliis, G.N.; Nixon, B.; Kime, M.; Zelski, K.; McVicar, C.M.; Lewis, S.E.; Aitken, R.J.

    2008-01-01

    A great deal of circumstantial evidence has linked DNA damage in human spermatozoa with adverse reproductive outcomes including reduced fertility and high rates of miscarriage. Although oxidative stress is thought to make a significant contribution to DNA damage in the male germ line, the factors responsible for creating this stress have not been elucidated. One group of compounds that are thought to be active in this context are the estrogens, either generated as a result of the endogenous metabolism of androgens within the male reproductive tract or gaining access to the latter as a consequence of environmental exposure. In this study, a wide variety of estrogenic compounds were assessed for their direct effects on human spermatozoa in vitro. DNA integrity was assessed using the Comet and TUNEL assays, lesion frequencies were quantified by QPCR using targets within the mitochondrial and nuclear (β-globin) genomes, DNA adducts were characterized by mass spectrometry and redox activity was monitored using dihydroethidium (DHE) as the probe. Of the estrogenic and estrogen analogue compounds evaluated, catechol estrogens, quercetin, diethylstilbestrol and pyrocatechol stimulated intense redox activity while genistein was only active at the highest doses tested. Other estrogens and estrogen analogues, such as 17β-estradiol, nonylphenol, bisphenol A and 2,3-dihydroxynaphthalene were inactive. Estrogen-induced redox activity was associated with a dramatic loss of motility and, in the case of 2-hydroxyestradiol, the induction of significant DNA fragmentation. Mass spectrometry also indicated that catechol estrogens were capable of forming dimers that can cross-link the densely packed DNA strands in sperm chromatin, impairing nuclear decondensation. These results highlight the potential importance of estrogenic compounds in creating oxidative stress and DNA damage in the male germ line and suggest that further exploration of these compounds in the aetiology of male

  5. Impact of estrogenic compounds on DNA integrity in human spermatozoa: Evidence for cross-linking and redox cycling activities

    Energy Technology Data Exchange (ETDEWEB)

    Bennetts, L.E.; De Iuliis, G.N.; Nixon, B.; Kime, M.; Zelski, K. [ARC Centre of Excellence in Biotechnology and Development and Discipline of Biological Sciences, University of Newcastle, NSW (Australia); McVicar, C.M.; Lewis, S.E. [Obstetrics and Gynaecology, Queen' s University, Belfast (United Kingdom); Aitken, R.J. [ARC Centre of Excellence in Biotechnology and Development and Discipline of Biological Sciences, University of Newcastle, NSW (Australia)], E-mail: jaitken@mail.newcastle.edu.au

    2008-05-10

    A great deal of circumstantial evidence has linked DNA damage in human spermatozoa with adverse reproductive outcomes including reduced fertility and high rates of miscarriage. Although oxidative stress is thought to make a significant contribution to DNA damage in the male germ line, the factors responsible for creating this stress have not been elucidated. One group of compounds that are thought to be active in this context are the estrogens, either generated as a result of the endogenous metabolism of androgens within the male reproductive tract or gaining access to the latter as a consequence of environmental exposure. In this study, a wide variety of estrogenic compounds were assessed for their direct effects on human spermatozoa in vitro. DNA integrity was assessed using the Comet and TUNEL assays, lesion frequencies were quantified by QPCR using targets within the mitochondrial and nuclear ({beta}-globin) genomes, DNA adducts were characterized by mass spectrometry and redox activity was monitored using dihydroethidium (DHE) as the probe. Of the estrogenic and estrogen analogue compounds evaluated, catechol estrogens, quercetin, diethylstilbestrol and pyrocatechol stimulated intense redox activity while genistein was only active at the highest doses tested. Other estrogens and estrogen analogues, such as 17{beta}-estradiol, nonylphenol, bisphenol A and 2,3-dihydroxynaphthalene were inactive. Estrogen-induced redox activity was associated with a dramatic loss of motility and, in the case of 2-hydroxyestradiol, the induction of significant DNA fragmentation. Mass spectrometry also indicated that catechol estrogens were capable of forming dimers that can cross-link the densely packed DNA strands in sperm chromatin, impairing nuclear decondensation. These results highlight the potential importance of estrogenic compounds in creating oxidative stress and DNA damage in the male germ line and suggest that further exploration of these compounds in the aetiology of

  6. Ageing, human capital and demographic dividends with endogenous growth, labour supply and foreign capital

    NARCIS (Netherlands)

    Edle von Gaessler, Anne; Ziesemer, Thomas

    2017-01-01

    We modify a Lucas-type endogenous growth model to contain endogenous labour supply, imperfect international capital movements, and estimated interest and education time functions. Solutions based on realistic calibrations show that (i) the rate of human capital depreciation through ageing has a much

  7. Endogenous Endophthalmitis in Patients with MRSA Septicemia: A Case Series and Review of Literature.

    Science.gov (United States)

    Shenoy, Shailaja Bhat; Thotakura, Meena; Kamath, Yogish; Bekur, Ragini

    2016-10-01

    To report the presentation, predisposing factors, clinical features and outcome in 6 eyes of 3 patients with endogenous endophthalmitis secondary to methicillin resistant staphylococcus aureus (MRSA) septicaemia. Retrospective review of case records of 3 patients who were treated for endogenous endophthalmitis secondary to MRSA septicaemia in a tertiary referral institution. All three patients had systemic predisposition to endogenous endophthalmitis (diabetes, urosepsis). Two patients presented within 1 week of onset of visual symptoms and the third after 3 months. Blood culture was positive for MRSA in all patients. Visual and anatomical improvement was noted in two patients who presented early. The third patient's visual outcome despite early treatment with intravitreal antibiotics and vitrectomy was not satisfactory. Endogenous endophthalmitis by MRSA is a rare but serious condition. Early and specific therapy based on reliable detection of the underlying microorganism is needed for good anatomical and functional outcome.

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

    Directory of Open Access Journals (Sweden)

    John eHamlyn

    2014-12-01

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

  9. Endogenous and exogenous control of ecosystem function: N cycling in headwater streams

    OpenAIRE

    Valett, H. M.; Thomas, S. A.; Mulholland, P. J.; Webster, J. R.; Dahm, C. N.; Fellows, C. S.; Crenshaw, C. L.; Peterson, C. G.

    2008-01-01

    Allochthonous inputs act as resource subsidies to many ecosystems, where they exert strong influences on metabolism and material cycling. At the same time, metabolic theory proposes endogenous thermal control independent of resource supply. To address the relative importance of exogenous and endogenous influences, we quantified spatial and temporal variation in ecosystem metabolism and nitrogen (N) uptake using seasonal releases of (15)N as nitrate in six streams differing in riparian-stream ...

  10. Endogenous scheduling preferences and congestion

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; Small, Kenneth

    2010-01-01

    and leisure, but agglomeration economies at home and at work lead to scheduling preferences forming endogenously. Using bottleneck congestion technology, we obtain an equilibrium queuing pattern consistent with a general version of the Vickrey bottleneck model. However, the policy implications are different....... Compared to the predictions of an analyst observing untolled equilibrium and taking scheduling preferences as exogenous, we find that both the optimal capacity and the marginal external cost of congestion have changed. The benefits of tolling are greater, and the optimal time varying toll is different....

  11. Estimation of endogenous faecal calcium in buffalo (BOS bubalis) by isotope dilution technique

    International Nuclear Information System (INIS)

    Singh, S.; Sareen, V.K.; Marwaha, S.R.; Sekhon, B.; Bhatia, I.S.

    1973-01-01

    Detailed investigations on the isotope-dilution technique for the estimation of endogenous faecal calcium were conducted with buffalo calves fed on growing ration. The ration consisted of wheat straw, green lucerne and concentrate mix. The endogenous faecal calcium was 3.71 g/day, which is 17.8 percent of the total faecal calcium. The apparent and true digestibilities of Ca were calculated as 51 and 60 percent respectively. The endogenous faecal calcium can be estimated in buffalo calves by giving single subcutaneous injection of Ca 45 and collecting blood samples on 12th and 21st days only, and representative sample from the faeces collected from 13th through 22nd day after the injection. (author)

  12. Lethal doses of ionizing radiation versus endogenous level of superoxide dismutase

    Energy Technology Data Exchange (ETDEWEB)

    Lipecka, K; Domanski, T; Dniaszewska, K; Grabowska, B; Pietrowicz, D; Lindner, P; Cisowska, B; Gorski, H [Military Medical Academy, Lodz (Poland). Inst. of Occupational Medicine

    1982-06-22

    The stability of superoxide dismutase (SOD) as well as its activity distribution in a human population were investigated. The SOD activity level of the erythrocytes proved to be an index for the endogenous SOD activity in the whole body. In a rat population, having similar SOD frequency distribution as a human population, the mortality due to acute irradiation depended on the SOD level; after a single acute dose approximating the lethal dose (LD/sub 50/30/) the survival depended distinctly on the endogenous SOD activity level.

  13. Endogenous opioid systems: physiological role in the self-limitation of seizures.

    Science.gov (United States)

    Tortella, F C; Long, J B; Holaday, J W

    1985-04-15

    Immediately following a seizure, the severity of subsequent seizures is significantly reduced. The involvement of endogenous opioid systems as a physiological regulator of this postseizure inhibition was studied in rats using repeated maximal electroshock (MES) seizures. Both the opiate antagonist (-)-naloxone and morphine tolerance abolished the progressive seizure protection associated with repeated MES. We propose that endogenous opioids, activated by a prior seizure, provide a central homeostatic inhibitory mechanism which may be responsible for the initiation of a postictal refractory state in the epileptic.

  14. Detailed NMR, Including 1,1-ADEQUATE, and Anticancer Studies of Compounds from the Echinoderm Colobometra perspinosa

    Directory of Open Access Journals (Sweden)

    Catherine H. Liptrot

    2009-11-01

    Full Text Available From the dichloromethane/methanol extract of the crinoid Colobometra perspinosa, collected south east of Richards Island (Bedara, Family Islands, Central Great Barrier Reef, Australia, 3-(1'-hydroxypropyl-1,6,8-trihydroxy-9,10-anthraquinone [one of the two stereoisomers of rhodoptilometrin, (1], 3-propyl-1,6,8-trihydroxy-9,10-anthraquinone (3, 2-[(phenylacetylamino]ethanesulfonic acid (4, and 4-hydroxybutanoic acid (5 were isolated. Comparison of 1H- and 13C-NMR data for rhodoptilometrin (1 with those reported in the literature showed significant differences for some resonances associated with rings A and C. In an attempt to provide accurately assigned 1H- and 13C-NMR data, as well as to confirm the structure of 1, a thorough NMR investigation of this compound was undertaken. Measurements included: concentration dependent 13C, 1D selective NOE, HSQC, HMBC and 1,1-ADEQUATE. The NMR data for 4 and 5 are reported here for the first time, as is their occurrence from the marine environment. The in vitro anticancer activity of the original extract was found to be associated with 1, 3 and 5.

  15. Inflation Targeting and Liquidity Traps under Endogenous Credibility

    NARCIS (Netherlands)

    Hommes, C.; Lustenhouwer, J.

    2015-01-01

    We derive policy implications for an inflation targeting central bank, who's credibility is endogenous and depends on its past ability to achieve its targets. We do this in a New Keynesian framework with heterogeneous agents and boundely rational expectations. Our assumptions about expectation

  16. Endogenous and Exogenous Attention Shifts are Mediated by the Same Large-Scale Neural Network.

    NARCIS (Netherlands)

    Peelen, M.V.; Heslenfeld, D.J.; Theeuwes, J.

    2004-01-01

    Event-related fMRI was used to examine the neural basis of endogenous (top-down) and exogenous (bottom-up) spatial orienting. Shifts of attention were induced by central (endogenous) or peripheral (exogenous) cues. Reaction times on subsequently presented targets showed the expected pattern of

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

    Science.gov (United States)

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

    2018-01-01

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

  18. Catalytic properties of niobium compounds

    International Nuclear Information System (INIS)

    Tanabe, K.; Iizuka, T.

    1983-04-01

    The catalytic activity and selectivity of niobium compounds including oxides, salts, organometallic compounds and others are outlined. The application of these compounds as catalysts to diversified reactions is reported. The nature and action of niobium catalysts are characteristic and sometimes anomalous, suggesting the necessity of basic research and the potential use as catalysts for important processes in the chemical industry. (Author) [pt

  19. Endogenous bile acid disposition in rat and human sandwich-cultured hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Marion, Tracy L., E-mail: tracylmarion@qualyst.com [Curriculum in Toxicology, UNC School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7270 (United States); Perry, Cassandra H., E-mail: cassandraperry@qualyst.com [Qualyst, Inc., Durham, NC 27713 (United States); St Claire, Robert L., E-mail: bobstclaire@qualyst.com [Qualyst, Inc., Durham, NC 27713 (United States); Brouwer, Kim L.R., E-mail: kbrouwer@unc.edu [Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, CB 7569 Kerr Hall, Chapel Hill, NC 27599-7569 (United States)

    2012-05-15

    Sandwich-cultured hepatocytes (SCH) are used commonly to investigate hepatic transport protein-mediated uptake and biliary excretion of substrates. However, little is known about the disposition of endogenous bile acids (BAs) in SCH. In this study, four endogenous conjugated BAs common to rats and humans [taurocholic acid (TCA), glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), and glycochenodeoxycholic acid (GCDCA)], as well as two BA species specific to rodents (α- and β-tauromuricholic acid; α/β TMCA), were profiled in primary rat and human SCH. Using B-CLEAR{sup ®} technology, BAs were measured in cells + bile canaliculi, cells, and medium of SCH by LC-MS/MS. Results indicated that, just as in vivo, taurine-conjugated BA species were predominant in rat SCH, while glycine-conjugated BAs were predominant in human SCH. Total intracellular BAs remained relatively constant over days in culture in rat SCH. Total BAs in control (CTL) cells + bile, cells, and medium were approximately 3.4, 2.9, and 8.3-fold greater in human than in rat. The estimated intracellular concentrations of the measured total BAs were 64.3 ± 5.9 μM in CTL rat and 183 ± 56 μM in CTL human SCH, while medium concentrations of the total BAs measured were 1.16 ± 0.21 μM in CTL rat SCH and 9.61 ± 6.36 μM in CTL human SCH. Treatment of cells for 24 h with 10 μM troglitazone (TRO), an inhibitor of the bile salt export pump (BSEP) and the Na{sup +}-taurocholate cotransporting polypeptide (NTCP), had no significant effect on endogenous BAs measured at the end of the 24-h culture period, potentially due to compensatory mechanisms that maintain BA homeostasis. These data demonstrate that BAs in SCH are similar to in vivo, and that SCH may be a useful in vitro model to study alterations in BA disposition if species differences are taken into account. -- Highlights: ► Bile acids (BAs) were measured in rat and human sandwich-cultured hepatocytes (SCH). ► Cell and medium BA

  20. Endogenous bile acid disposition in rat and human sandwich-cultured hepatocytes

    International Nuclear Information System (INIS)

    Marion, Tracy L.; Perry, Cassandra H.; St Claire, Robert L.; Brouwer, Kim L.R.

    2012-01-01

    Sandwich-cultured hepatocytes (SCH) are used commonly to investigate hepatic transport protein-mediated uptake and biliary excretion of substrates. However, little is known about the disposition of endogenous bile acids (BAs) in SCH. In this study, four endogenous conjugated BAs common to rats and humans [taurocholic acid (TCA), glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), and glycochenodeoxycholic acid (GCDCA)], as well as two BA species specific to rodents (α- and β-tauromuricholic acid; α/β TMCA), were profiled in primary rat and human SCH. Using B-CLEAR ® technology, BAs were measured in cells + bile canaliculi, cells, and medium of SCH by LC-MS/MS. Results indicated that, just as in vivo, taurine-conjugated BA species were predominant in rat SCH, while glycine-conjugated BAs were predominant in human SCH. Total intracellular BAs remained relatively constant over days in culture in rat SCH. Total BAs in control (CTL) cells + bile, cells, and medium were approximately 3.4, 2.9, and 8.3-fold greater in human than in rat. The estimated intracellular concentrations of the measured total BAs were 64.3 ± 5.9 μM in CTL rat and 183 ± 56 μM in CTL human SCH, while medium concentrations of the total BAs measured were 1.16 ± 0.21 μM in CTL rat SCH and 9.61 ± 6.36 μM in CTL human SCH. Treatment of cells for 24 h with 10 μM troglitazone (TRO), an inhibitor of the bile salt export pump (BSEP) and the Na + -taurocholate cotransporting polypeptide (NTCP), had no significant effect on endogenous BAs measured at the end of the 24-h culture period, potentially due to compensatory mechanisms that maintain BA homeostasis. These data demonstrate that BAs in SCH are similar to in vivo, and that SCH may be a useful in vitro model to study alterations in BA disposition if species differences are taken into account. -- Highlights: ► Bile acids (BAs) were measured in rat and human sandwich-cultured hepatocytes (SCH). ► Cell and medium BA concentrations