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Sample records for endogenous ouabain-like compounds

  1. Are endogenous cardenolides controlled by atrial natriuretic peptide.

    PubMed

    Brar, Kanwarjeet S; Gao, Yonglin; El-Mallakh, Rif S

    2016-07-01

    Endogenous cardenolides are digoxin-like substances and ouabain-like substances that have been implicated in the pathogenesis of hypertension and mood disorders in clinical and pre-clinical studies. Regulatory signals for endogenous cardenolides are still unknown. These endogenous compounds are believed to be produced by the adrenal gland in the periphery and the hypothalamus in the central nervous system, and constitute part of an hormonal axis that may regulate the catalytic activity of the α subunit of Na(+)/K(+)-ATPase. A review of literature suggests that there is great overlap in physiological environments that are associated with either elevations or reductions in the levels of atrial natriuretic peptide (ANP) and endogenous cardenolides. This suggests that these two factors may share a common regulatory signal or perhaps that ANP may be involved in the regulation of endogenous cardenolides. PMID:27241248

  2. Endogenous morphine-like compound immunoreactivity increases in parkinsonism.

    PubMed

    Charron, Giselle; Doudnikoff, Evelyne; Laux, Alexis; Berthet, Amandine; Porras, Gregory; Canron, Marie-Hélène; Barroso-Chinea, Pedro; Li, Qin; Qin, Chuan; Nosten-Bertrand, Marika; Giros, Bruno; Delalande, François; Van Dorsselaer, Alain; Vital, Anne; Goumon, Yannick; Bezard, Erwan

    2011-08-01

    Morphine is endogenously synthesized in the central nervous system and endogenous dopamine is thought to be necessary for endogenous morphine formation. As Parkinson's disease results from the loss of dopamine and is associated with central pain, we considered how endogenous morphine is regulated in the untreated and l-DOPA-treated parkinsonian brain. However, as the cellular origin and overall distribution of endogenous morphine remains obscure in the pathological adult brain, we first characterized the distribution of endogenous morphine-like compound immunoreactive cells in the rat striatum. We then studied changes in the endogenous morphine-like compound immunoreactivity of medium spiny neurons in normal, Parkinson's disease-like and l-DOPA-treated Parkinson's disease-like conditions in experimental (rat and monkey) and human Parkinson's disease. Our results reveal an unexpected dramatic upregulation of neuronal endogenous morphine-like compound immunoreactivity and levels in experimental and human Parkinson's disease, only partially normalized by l-DOPA treatment. Our data suggest that endogenous morphine formation is more complex than originally proposed and that the parkinsonian brain experiences a dramatic upregulation of endogenous morphine immunoreactivity. The functional consequences of such endogenous morphine upregulation are as yet unknown, but based upon the current knowledge of morphine signalling, we hypothesize that it is involved in fatigue, depression and pain symptoms experienced by patients with Parkinson's disease.

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

    EPA Science Inventory

    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 ...

  4. Influence of plasma volume expansion with saline on the plasma levels of an ouabain-like factor

    SciTech Connect

    Rauch, A.L.; Morris, M.; Buckalew, V.M. Jr.

    1986-03-05

    Plasma volume expansion with saline activates the cardiopulmonary baroreflex and causes the release of natriuretic factors(s). One putative natriuretic factor has ouabain-like activity (OLA). To examine the relationship between this factor and plasma volume expansion, the OLA of plasma was examined in rats that were volume expanded with 0.9% saline at a rate of 150..mu..l/min/100 g of rat for 15, 30, 60 and 120 minutes. Plasma OLA was quantitated with a radioreceptor assay utilizing /sup 3/H-ouabain and erythrocytes ghosts. The OLA and hematocrit of control rats were 18.2 +/- 2.93 pmoles of OLA/ml of plasma and 43.7 +/- 0.65. After plasma volume expansion for 15 and 30 minutes, plasma OLA was not significantly altered (27.1 +/- 6.64 and 15.3 +/- 2.80, respectively). However, the hematocrit was reduced 13.9% (37.6 +/- 1.34, p < 0.05) and 33.6% (29.0 +/- 1.92, p < 0.01) for 15 and 30 minutes of volume expansion, respectively. After 60 minutes of volume expansion the hematocrit began to recover (33.7 +/- 2.16) although it was still significantly depressed (p < 0.01). At this time point the OLA was increased 248% to 63.4 +/- 22.7 pmoles of OLA/ml of plasma (p < 0.01). At 120 minutes of volume expansion the hematocrit was 38.3 +/- 1.24 and the OLA returned to control values (13.4 +/- 5.17). This data indicates that volume expansion causes an increase in plasma OLA and this increase in activity may contribute to the recovery of hematocrit that is seen with continued volume expansion.

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

    PubMed

    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 < 0.05). The KNC meat lost significant amounts of all bioactive compounds during cooking (P < 0.05). Leg meat had high retention percentages of carnosine and anserine after 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. PMID:24812230

  6. [UDP-glucuronyltransferases in detoxification and activation metabolism of endogenous compounds and xenobiotics].

    PubMed

    Fedejko, Barbara; Mazerska, Zofia

    2011-01-01

    Glucuronidation is a crucial pathway of metabolism and excretion of endogenous compounds and xenobiotics. UDP-glucuronyltransferases, UGT, catalyse transformations of bilirubine, steroids and thyroid hormones, bile acids as well as exogenous compounds, including drugs, carcinogens, environmental pollutants and nutrient components. From therapeutic point of view, the participation of UGTs in drug metabolism is of particular significance. Polymorphism of UGT1A and UGT2B genes resulted in various susceptibility of substrates to conjugation with glucuronic acid. Deactivation of xenobiotics and the following excretion of hydrophilic conjugates is a common task of glucuronidation, which should lead to detoxification. However, a lot of glucuronides were known, which expressed the comparable or even higher reactivity than that of the native compound. There are, among others, acyl glucuronides of carboxylic acids, morphine 6-O-glucuronide or retinoid glucuronides. They are able to bind cellular macromolecules with low or high strength and, as a consequence, their toxicity is saved or even increased, respectively.

  7. An endogenous digitalis-like compound extracted from human urine: biochemical and chemical studies.

    PubMed

    Cloix, J F; Crabos, M; Grichois, M L; Meyer, P

    1987-08-01

    Plasma and urine levels of an endogenous digitalis-like compound (EDLC) are increased in low renin Na+-dependent experimental hypertension, in some normotensive offspring of hypertensive patients and in some essential hypertensive patients. Urine-drived EDLC was purified from 550 L of urine from essential hypertensive patients (n = 8) and from normotensive subjects with a family history of hypertension (n = 27), using flash chromatography on C18 reversed-phase, anion exchange chromatography and various reversed-phase high performance liquid chromatographies. The mechanism of Na+-K+ ATPase inhibition and the related effects of semipurified urine-derived EDLC were studied and compared with those of ouabain. Its action was similar to that of ouabain in 8 out of 10 of the tests applied. The main effects of such a compound were the depression of Na+-K+ pump activity of human erythrocytes, the inhibition of 5-hydroxytryptamine reuptake by human platelets, and the induction of natriuresis in urethanized rats. Therefore, EDLC may be considered as one of the natriuretic hormones whose mechanism of action closely resembles that of ouabain. PMID:2825938

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

    PubMed

    Weidemann, Heidrun

    2012-01-01

    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. PMID:22438768

  9. Direct laser desorption ionization of endogenous and exogenous compounds from insect cuticles: practical and methodologic aspects.

    PubMed

    Yew, Joanne Y; Soltwisch, Jens; Pirkl, Alexander; Dreisewerd, Klaus

    2011-07-01

    We recently demonstrated that ultraviolet laser desorption ionization orthogonal time-of-flight mass spectrometry (UV-LDI o-TOF MS) could be used for the matrix-free analysis of cuticular lipids (unsaturated aliphatic and oxygen-containing hydrocarbons and triacylglycerides) directly from individual Drosophila melanogaster fruit flies (Yew, J. Y.; Dreisewerd, K.; Luftmann, H.; Pohlentz, G.; Kravitz, E. A., Curr. Biol. 2009, 19, 1245-1254). In this report, we show that the cuticular hydrocarbon, fatty acid, and triglyceride profiles of other insects and spiders can also be directly analyzed from intact body parts. Mandibular pheromones from the jaw of a queen honey bee are provided as one example. In addition, we describe analytical features and examine mechanisms underlying the methodology. Molecular ions of lipids can be generated by direct UV-LDI when non-endogenous compounds are applied to insect wings or other body parts. Current sensitivity limits are in the 10 pmol range. We show also the dependence of ion signal intensity on collisional cooling gas pressure in the ion source, laser wavelength (varied between 280-380 nm and set to 2.94 μm for infrared LDI), and laser pulse energy.

  10. Direct Laser Desorption Ionization of Endogenous and Exogenous Compounds from Insect Cuticles: Practical and Methodologic Aspects

    NASA Astrophysics Data System (ADS)

    Yew, Joanne Y.; Soltwisch, Jens; Pirkl, Alexander; Dreisewerd, Klaus

    2011-07-01

    We recently demonstrated that ultraviolet laser desorption ionization orthogonal time-of-flight mass spectrometry (UV-LDI o-TOF MS) could be used for the matrix-free analysis of cuticular lipids (unsaturated aliphatic and oxygen-containing hydrocarbons and triacylglycerides) directly from individual Drosophila melanogaster fruit flies (Yew, J. Y.; Dreisewerd, K.; Luftmann, H.; Pohlentz, G.; Kravitz, E. A., Curr. Biol. 2009, 19, 1245-1254). In this report, we show that the cuticular hydrocarbon, fatty acid, and triglyceride profiles of other insects and spiders can also be directly analyzed from intact body parts. Mandibular pheromones from the jaw of a queen honey bee are provided as one example. In addition, we describe analytical features and examine mechanisms underlying the methodology. Molecular ions of lipids can be generated by direct UV-LDI when non-endogenous compounds are applied to insect wings or other body parts. Current sensitivity limits are in the 10 pmol range. We show also the dependence of ion signal intensity on collisional cooling gas pressure in the ion source, laser wavelength (varied between 280-380 nm and set to 2.94 μm for infrared LDI), and laser pulse energy.

  11. Effects of Toxic Compounds in Montipora capitata on Exogenous and Endogenous Zooxanthellae Performance and Fertilization Success

    PubMed Central

    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. PMID:25714606

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

    PubMed

    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. PMID:25714606

  13. ENHANCED CONCENTRATION AND ANALYSIS METHOD FOR MEASURING WATER SOLUABLE ENDOGENOUS COMPOUNDS IN HUMAN BREATH

    EPA Science Inventory

    Exhaled human breath analysis has become a standard technique for assessing exposure to exogenous volatile organic compounds (VOCs) such as trihalomethanes from water chlorination; aromatics, hydrocarbons, and oxygenates from fuels usage; and various chlorinated solvents from i...

  14. Antidigoxin antiserum prevents endogenous digitalis-like compound-mediated reperfusion injury via modulating sodium pump isoform gene expression.

    PubMed

    Wang, He-Gui; Chu, Yue-Feng; Zou, Jian-Gang; Ke, Yong-Sheng

    2010-01-01

    Endogenous digitalis-like compound (EDLC) is an endogenous ligand of the digitalis receptor and can remarkably inhibit Na+/K+-ATPase activity. Antidigoxin antiserum (ADA), a selective EDLC antagonist, may lessen myocardial reperfusion injury; however, the molecular mechanisms underlying the effect remain unclear. Therefore, this study investigated whether ADA may prevent myocardial reperfusion injury and modulate gene expression of sodium pump alpha isoforms. Cardiac function was examined in isolated rat hearts subjected to ischemia and reperfusion (I/R). The infarct size, EDLC level, Na+/K+-ATPase activity, and the levels of mRNA for sodium pump alpha isoforms were measured in vivo I/R rat hearts in the presence or absence of ADA. It was found that ADA significantly improved the recovery of cardiac function, decreased infarct size, decreased EDLC level, and recovered Na+/K+-ATPase activity in I/R hearts. Further studies showed that sodium pump alpha1, alpha2, and alpha3 isoform mRNA levels were significantly reduced in I/R hearts, and pretreatment with ADA induced a large increase in the mRNA levels. These results indicate that EDLC may participate in depressing Na+/K+-ATPase activity and sodium pump alpha isoform gene expression in I/R heart. It is suggested that treatment with ADA may prevent EDLC-mediated reperfusion injury via modulating sodium pump isoform gene expression. PMID:20130737

  15. Detection of endogenous ethanol and other compounds in the breath by gas chromatography with on-column concentration of sample.

    PubMed

    Phillips, M; Greenberg, J

    1987-05-15

    A new method is described for collecting and concentrating volatile compounds in the breath, in order to facilitate their assay by gas chromatography. Breath was collected into sealed Mylar bags containing an internal standard (isopropyl alcohol). The sample was pumped through a cooled gas chromatograph column, where the volatile compounds were concentrated by adsorption onto the resin packing (Porapak Q) at 35 degrees C. The column was then heated, and the volatilized sample was separated for assay by flame ionization detection. The assay was highly sensitive for ethanol (detecting at least 4.0 nmol) and linear up to 20 nmol (r2 = 0.98). Accuracy and precision were determined by assaying nine replicates of a sample containing 12.0 nmol ethanol; a mean value of 12.18 nmol ethanol was obtained with a coefficient of variation of 10.26%. In a group of normal volunteers, endogenous breath ethanol concentrations ranged from 2.23 to 6.51 nmol/liter. This assay provided a number of advantages over previously described methods: The use of breath collection bags enabled the collection of samples outside the laboratory. The use of an internal standard in the collection bag reduced errors that might have resulted from leakage of the specimen. An on-column concentration of the sample in the gas chromatograph eliminated the need for an additional preconcentration device, such as a cryogenic or adsorptive trapping apparatus.

  16. Moonlight detection by Drosophila's endogenous clock depends on multiple photopigments in the compound eyes.

    PubMed

    Schlichting, Matthias; Grebler, Rudi; Peschel, Nicolai; Yoshii, Taishi; Helfrich-Förster, Charlotte

    2014-04-01

    Many organisms change their activity on moonlit nights. Even the fruit fly Drosophila melanogaster responds to moonlight with a shift of activity into the night, at least under laboratory conditions. The compound eyes have been shown to be essential for the perception of moonlight, but it is unknown which of the 5 rhodopsins in the eyes are responsible for the observed moonlight effects. Here, we show that the outer (R1-R6) and inner (R7 and R8) photoreceptor cells in a fly's ommatidium interact in a complex manner to provoke the moonlight effects on locomotor activity. The shift of the evening activity peak into the night depends on several rhodopsins in the inner and outer photoreceptor cells. The increase in relative nocturnal activity in response to moonlight is mainly mediated by the rhodopsin 6-expressing inner photoreceptor cell R8 together with the rhodopsin 1-expressing outer receptor cells (R1-R6), whereas just rhodopsin 1 of R1 to R6 seems necessary for increasing nocturnal activity in response to increasing daylight intensity.

  17. “The Lower Threshold” phenomenon in tumor cells toward endogenous digitalis-like compounds: Responsible for tumorigenesis?

    PubMed Central

    Weidemann, Heidrun

    2012-01-01

    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. PMID:22438768

  18. Potent endogenous allelopathic compounds in Lepidium sativum seed exudate: effects on epidermal cell growth in Amaranthus caudatus seedlings.

    PubMed

    Iqbal, Amjad; Fry, Stephen C

    2012-04-01

    Many plants exude allelochemicals--compounds that affect the growth of neighbouring plants. This study reports further studies of the reported effect of cress (Lepidium sativum) seed(ling) exudates on seedling growth in Amaranthus caudatus and Lactuca sativa. In the presence of live cress seedlings, both species grew longer hypocotyls and shorter roots than cress-free controls. The effects of cress seedlings were allelopathic and not due to competition for resources. Amaranthus seedlings grown in the presence of cress allelochemical(s) had longer, thinner hypocotyls and shorter, thicker roots--effects previously attributed to lepidimoide. The active principle was more abundant in cress seed exudate than in seedling (root) exudates. It was present in non-imbibed seeds and releasable from heat-killed seeds. Release from live seeds was biphasic, starting rapidly but then continuing gradually for 24 h. The active principle was generated by aseptic cress tissue and was not a microbial digestion product or seed-treatment chemical. Crude seed exudate affected hypocotyl and root growth at ~25 and ~450 μg ml(-1) respectively. The exudate slightly (28%) increased epidermal cell number along the length of the Amaranthus hypocotyl but increased total hypocotyl elongation by 129%; it resulted in a 26% smaller hypocotyl circumference but a 55% greater epidermal cell number counted round the circumference. Therefore, the effect of the allelochemical(s) on organ morphology was imposed primarily by regulation of cell expansion, not cell division. It is concluded that cress seeds exude endogenous substances, probably including lepidimoide, that principally regulate cell expansion in receiver plants.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  20. Factors affecting the determination of drugs and endogenous low molecular mass compounds in human serum by micellar electrokinetic capillary chromatography with direct sample injection.

    PubMed

    Schmutz, A; Thormann, W

    1994-01-01

    Factors influencing the establishment of an analytical window in front of the solubilized proteins in micellar electrokinetic capillary chromatography (MECC) with direct serum injection (DSI) are discussed. Both drugs and endogenous low molecular mass compounds eluting within the analytical window are identified concurrently by multi-wavelength absorption detection. Variables such as the concentration of the micelle forming substance, ionic strength, applied voltage, initial sample zone length, capillary length, selected buffer additives, insufficient renewal of the buffer in the anodic buffer vial and sample matrix are shown to impact MECC of endogenous compounds and model drugs, such as antiepileptics. For two drugs eluting within the analytical window, phenobarbital and ethosuximide, serum levels determined by DSI with external calibration are shown to compare well with levels obtained after liquid-liquid extraction and internal calibration (use of an internal standard). In addition, reproducibility of both assays is excellent. The limit of employing DSI is demonstrated with the determination of the hydrophobic drug phenytoin. Using an automated, commercial instrument and naproxen as model drug, high-speed MECC separations of high reproducibility and with a throughput of 12-15 samples per h are presented.

  1. Nondestructive pollution exposure assessment in the European hedgehog (Erinaceus europaeus): III. Hair as an indicator of endogenous organochlorine compound concentrations.

    PubMed

    D'Havé, Helga; Scheirs, Jan; Covaci, Adrian; Schepens, Paul; Verhagen, Ron; De Coen, Wim

    2006-01-01

    Concentrations of organochlorine persistent pollutants were investigated in tissues of the European hedgehog (Erinaceus europaeus). Road kills and carcasses from wildlife rescue centers were used to characterize organochlorine compound tissue distribution and tissue profile dissimilarities (hair, liver, kidney, muscle, and adipose tissue). The most important contaminants were polychlorinated biphenyls (PCBs), chlordanes (CHLs), and DDTs, with median concentrations of 75, 5.1, and 1.4 ng/g liver wet weight, respectively. Median levels for the remaining compounds-hexachlorobenzene (HCB), hexachlorocyclohexanes (HCHs), and octachlorostyrene-were less than 0.5 ng/g liver wet weight. Compared to results with other mammalian wildlife, the present results indicate that hedgehogs may accumulate considerable concentrations of organochlorine compounds. Polychlorinated biphenyls and HCB preferably accumulated in liver and muscle tissue. Concentrations of DDTs and HCHs were highest in muscle tissue and hair, respectively. Octachlorostyrene and CHL levels were predominant in liver. The observed positive relationships between concentrations in hair and internal tissues for PCBs, DDTs, HCB, HCHs, and CHLs (0.49 < r < 0.91) and for several individual PCB, DDT, and CHL compounds (0.31 < r < 0.76) indicate the usefulness of hair as a biomonitoring tool of organochlorine compounds. Multivariate profile analyses revealed a higher dominance of less-persistent compounds (p,p'-DDT, alpha-HCH, and PCBs 95, 101, and 149) in hair compared to internal tissues. The present study demonstrates the suitability of hedgehog hair as a nondestructive biomonitoring tool regarding pollution with organochlorine compounds and the promising role of the hedgehog as a mammalian indicator species of pollution in terrestrial environments.

  2. The effect of haem in red and processed meat on the endogenous formation of N-nitroso compounds in the upper gastrointestinal tract.

    PubMed

    Lunn, J C; Kuhnle, G; Mai, V; Frankenfeld, C; Shuker, D E G; Glen, R C; Goodman, J M; Pollock, J R A; Bingham, S A

    2007-03-01

    Red and processed meat (PM) consumption increases the risk of large bowel cancer and it has been demonstrated that haem in red meat (RM) stimulates the endogenous production of N-nitroso compounds (NOCs) within the human intestine. To investigate whether N-nitrosation occurs in the upper gastrointestinal tract, 27 ileostomists were fed diets containing no meat, or 240 g RM or 240 g PM in a randomly assigned crossover intervention design carried out in a volunteer suite. Endogenous NOC were assessed as apparent total N-nitroso compounds (ATNC) in the ileostomy output. ATNC concentration in the diets was 22 microg ATNC/kg (RM) and 37 microg ATNC/kg (PM), and 9 microg ATNC/kg in the no meat diet. Levels significantly increased to 1175 microg ATNC/kg SEM = 226 microg ATNC/kg) following the RM (P=0.001) and 1832 microg ATNC/kg (SEM=294 microg ATNC/kg) following PM (P<0.001) compared to the no meat diet (283 microg ATNC/kg, SEM=74 microg ATNC/kg). ATNC concentrations in the ileal output were equivalent to those measured in faeces in similarly designed feeding studies. Supplementation with either 1 g ascorbic acid or 400 IU alpha-tocopherol had no effect on the concentration of ATNC detected in the ileal output. In in vitro experiments, N-nitrosomorpholine (NMor) was formed in the presence of nitrosated haemoglobin, at pH 6.8 but not in the absence of nitrosated haemoglobin. These findings demonstrate that haem may facilitate the formation of NOC in the absence of colonic flora in the upper human gastrointestinal tract.

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

    PubMed

    Jakszyn, Paula; Bingham, Sheila; Pera, Guillem; Agudo, Antonio; Luben, Robert; Welch, Ailsa; Boeing, Heiner; Del Giudice, Giuseppe; 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 R; Key, Timothy J; Allen, Naomi; Lund, Eiliv; Carneiro, Fátima; Linseisen, Jakob; Nagel, Gabriele; Overvad, Kim; Tjonneland, Anne; Olsen, Anja; Bueno-de-Mesquita, H Bas; Ocké, Marga O; Peeters, Petra Hm; Numans, Mattijs E; Clavel-Chapelon, Françoise; Trichopoulou, Antonia; Fenger, Claus; Stenling, Roger; Ferrari, Pietro; Jenab, Mazda; Norat, Teresa; Riboli, Elio; Gonzalez, Carlos A

    2006-07-01

    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 cases of GC that had occurred after 6.6 average years of follow-up. An index of endogenous NOC (ENOC) formation was estimated using data of the iron content from meat intake and faecal apparent total NOC formation according to previous published studies. Antibodies to Helicobacter pylori and vitamin C levels were measured in a sub-sample of cases and matched controls included in a nested case-control within the cohort. Exposure to NDMA was < 1 microg on average compared with 93 mug on average from ENOC. There was no association between NDMA intake and GC risk (HR, 1.00; 95% CI, 0.7-1.43). ENOC was significantly associated with non-cardia cancer risk (HR, 1.42; 95% CI, 1.14-1.78 for an increase of 40 microg/day) but not with cardia cancer (HR, 0.96; 95% CI, 0.69-1.33). Although the number of not infected cases is low, our data suggest a possible interaction between ENOC and H.pylori infection (P for interaction = 0.09). Moreover, we observed an interaction between plasma vitamin C and ENOC (P < 0.02). ENOC formation may account for our previously reported association between red and processed meat consumption and gastric cancer risk. PMID:16571648

  4. Endogenous benzodiazepine-like compounds and diazepam binding inhibitor in serum of patients with liver cirrhosis with and without overt encephalopathy

    PubMed Central

    Avallone, R; Zeneroli, M; Venturini, I; Corsi, L; Schreier, P; Kleinschnitz, M; Ferrarese, C; Farina, F; Baraldi, C; Pecora, N; Frigo, M; Baraldi, M

    1998-01-01

    Background/Aim—Despite some controversy, it has been suggested that endogenous benzodiazepine plays a role in the pathogenesis of hepatic encephalopathy. The aim of the present study was to evaluate the concentrations of endogenous benzodiazepines and the peptide, diazepam binding inhibitor, in the blood of patients with liver cirrhosis with and without overt encephalopathy, and to compare these levels with those of consumers of commercial benzodiazepines. 
Subjects—Normal subjects (90), benzodiazepine consumers (14), and cirrhotic patients (113) were studied. 
Methods—Endogenous benzodiazepines were measured by the radioligand binding technique after high performance liquid chromatography (HPLC) purification. The presence of diazepam and N-desmethyldiazepam was assayed by HPLC-electrospray tandem mass spectrometry. Diazepam binding inhibitor was studied in serum by radioimmunoassay. 
Results—Endogenous benzodiazepines were below the limit of detection in 7% of patients with encephalopathy. When detectable, their levels were at least comparable with those of benzodiazepine consumers and correlated with the liver dysfunction but not the stage of encephalopathy. Serum levels of diazepam binding inhibitor tended to decrease when endogenous benzodiazepines levels increased. 
Conclusions—Endogenous benzodiazepines may accumulate in patients with liver cirrhosis during the course of the disease, and the phenomenon appears to be independent of the presence or absence of encephalopathy. 

 Keywords: benzodiazepine consumers; diazepam binding inhibitor; endogenous benzodiazepines; liver cirrhosis; overt hepatic encephalopathy PMID:9691927

  5. Effects of endogenous small molecular compounds on the rheological properties, texture and microstructure of soymilk coagulum: Removal of phytate using ultrafiltration.

    PubMed

    Wang, Ruican; Guo, Shuntang

    2016-11-15

    This study aims to clarify the roles played by endogenous small molecular components in soymilk coagulation process and the properties of gels. Soymilk samples with decreasing levels of small molecules were prepared by ultrafiltration, to reduce the amount of phytate and salts. CaSO4-induced coagulation process was analyzed using rheological methods. Results showed that removal of free small molecules decreased the activation energy of protein coagulation, resulting in accelerated reaction and increased gel strength. However, too fast a reaction led to the drop in storage modulus (G'). Microscopic observation suggested that accelerated coagulation generated a coarse and non-uniform gel network with large pores. This network could not hold much water, leading to serious syneresis. Endogenous small molecules in soymilk were vital in the fine gel structure. Coagulation rate could be controlled by adjusting the amount of small molecules to obtain tofu products with the optimal texture. PMID:27283662

  6. Moderate consumption of wine, through both its phenolic compounds and alcohol content, promotes hydroxytyrosol endogenous generation in humans. A randomized controlled trial.

    PubMed

    Pérez-Mañá, Clara; Farré, Magí; Rodríguez-Morató, Jose; Papaseit, Esther; Pujadas, Mitona; Fitó, Montserrat; Robledo, Patricia; Covas, Maria-Isabel; Cheynier, Véronique; Meudec, Emmanuelle; Escudier, Jean-Louis; de la Torre, Rafael

    2015-06-01

    In humans, urinary hydroxytyrosol (OHTyr) concentrations have been associated to alcohol and wine consumption. To explore the role of wine components on promoting an endogenous OHTyr generation we performed a cross-over, double-blind, randomized controlled clinical trial (n = 28 healthy volunteers). Ethanol (wine and vodka), dealcoholized wine, and placebo were administered. Alcohol, dealcoholized wine, and particularly wine promoted a de novo OHTyr generation in vivo in humans. Potential OHTyr precursors (tyrosine, tyrosol, tyramine) were investigated in rats. Tyrosol was metabolized to OHTyr. Collating both studies, it is postulated that an increased Tyr bioavailability, a shift to a reductive pathway in dopamine and tyramine oxidative metabolism, and the biotransformation of Tyr to OHTyr were mechanisms involved in the OHTyr endogenous generation.

  7. Neurotoxic compound N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4) depletes endogenous norepinephrine and enhances release of (/sup 3/H)norepinephrine from rat cortical slices

    SciTech Connect

    Landa, M.E.; Rubio, M.C.; Jaim-Etcheverry, G.

    1984-10-01

    The alkylating compound N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4) injected to rodents blocks norepinephrine (NE) uptake and reduces endogenous NE levels in the central nervous system and in the periphery. To investigate the processes leading to these alterations, rat cortical slices were incubated in the presence of DSP4. Cortical NE was depleted by 40% after incubation of slices in 10(-5) M DSP4 for 60 min and this was blocked by desipramine. The spontaneous outflow of radioactivity from cortical slices labeled previously with (/sup 3/H)NE was enhanced markedly both during exposure to DSP4 and during the subsequent washings, suggesting that NE depletion could be due to this stimulation of NE release. The radioactivity released by DSP4 was accounted for mainly by NE and its deaminated metabolite 3,4-dihydroxyphenylglycol. The enhanced release, independent of external Ca++, apparently originated from the vesicular pool as it was absent after reserpine pretreatment. Activities of the enzymes related to NE synthesis were not altered by DSP4 in vitro and only monoamine oxidase activity was inhibited at high concentrations. Thus, the depletion of endogenous NE produced by DSP4 is probably due to a persistent enhancement of its release from the vesicular pool. Fixation of DSP4 to the NE transport system is necessary but not sufficient to produce the acute NE depletion and the characteristic long-term actions of the compound.

  8. Cold-induced activities of cytochromes P450 1A1 and 1A2 in rat liver: putative role of endogenous compounds in induction mechanism.

    PubMed

    Perepechaeva, M L; Grishanova, A Yu

    2013-03-01

    Adaptation to cold includes adaptive changes at the organism and molecular levels. One of the interesting facts is induction of cytochromes P450 subfamily 1A (CYP1A) in the liver of rats, inducible enzymes participating in biotransformation of procarcinogenic xenobiotics, under the effect of moderate cold exposure. Cold activation of CYP1A can be mediated by adaptive changes and the resultant redistribution or intensification of the synthesis of mediator compounds. This hypothesis is verified in the present study. The role of bilirubin, tocopherol, and corticosterone as mediators of cold induction of CYP1A in the rat liver was evaluated. The results indicate that these compounds can be involved in cold induction of CYP1A, but none of them is the only mediator in this process.

  9. Fluctuations of different endogenous phenolic compounds and cinnamic acid in the first days of the rooting process of cherry rootstock 'GiSelA 5' leafy cuttings.

    PubMed

    Trobec, Mateja; Stampar, Franci; Veberic, Robert; Osterc, Gregor

    2005-05-01

    The relationship between the phenol composition of rooting zones and rootability was studied in the first days after the establishment of cuttings. The trial included two different types of cuttings (basal and terminal). Additionally, the influence of exogenously applied auxin (IBA) was observed. The best rooting results (55.6%) were achieved with terminal IBA treated cuttings, while only 1.9% of basal cuttings formed roots. The auxin treatment increased the root formation in terminal, but not in basal cuttings. Low rooting rate of basal cuttings was probably due to higher lignification rate of the basal tissue which can represent a mechanical barrier for root emergence. When measuring phenolic compounds and cinnamic acid, terminal cuttings contained higher (rutin, vanillic acid, (-)-epicatechin, caffeic acid and sinapinic acid) or equal concentrations of detected phenols as basal cuttings, while applied auxin did not influence the level of any of discussed phenolics, neither of cinnamic acid. It is to assume that cuttings for starting of root induction phase should contain certain levels of several phenolic compounds, but higher influence on rooting success is to be ascribed to the impact of the auxin level. During the time of the experiment concentrations of monophenols sinapinic acid and vanillic acid rapidly decreased. This decrease was more pronounced in terminal cuttings, which might have a better mechanism of lowering those two compounds to which a negative influence on rooting is ascribed. Fluctuations and differences between treatments of other phenolics were not significant enough to influence the rooting process. PMID:15940876

  10. Fluctuations of different endogenous phenolic compounds and cinnamic acid in the first days of the rooting process of cherry rootstock 'GiSelA 5' leafy cuttings.

    PubMed

    Trobec, Mateja; Stampar, Franci; Veberic, Robert; Osterc, Gregor

    2005-05-01

    The relationship between the phenol composition of rooting zones and rootability was studied in the first days after the establishment of cuttings. The trial included two different types of cuttings (basal and terminal). Additionally, the influence of exogenously applied auxin (IBA) was observed. The best rooting results (55.6%) were achieved with terminal IBA treated cuttings, while only 1.9% of basal cuttings formed roots. The auxin treatment increased the root formation in terminal, but not in basal cuttings. Low rooting rate of basal cuttings was probably due to higher lignification rate of the basal tissue which can represent a mechanical barrier for root emergence. When measuring phenolic compounds and cinnamic acid, terminal cuttings contained higher (rutin, vanillic acid, (-)-epicatechin, caffeic acid and sinapinic acid) or equal concentrations of detected phenols as basal cuttings, while applied auxin did not influence the level of any of discussed phenolics, neither of cinnamic acid. It is to assume that cuttings for starting of root induction phase should contain certain levels of several phenolic compounds, but higher influence on rooting success is to be ascribed to the impact of the auxin level. During the time of the experiment concentrations of monophenols sinapinic acid and vanillic acid rapidly decreased. This decrease was more pronounced in terminal cuttings, which might have a better mechanism of lowering those two compounds to which a negative influence on rooting is ascribed. Fluctuations and differences between treatments of other phenolics were not significant enough to influence the rooting process.

  11. Bioactive compounds during storage of fresh-cut spinach: the role of endogenous ascorbic acid in the improvement of product quality.

    PubMed

    Bottino, Antonella; Degl'Innocenti, Elena; Guidi, Lucia; Graziani, Giulia; Fogliano, Vincenzo

    2009-04-01

    Spinach is rich in bioactive constituents such as vitamin C, flavonoids and phenolic acids. In this work, the biochemical modifications occurring during one week of storage at 4 degrees C were evaluated both in intact and in fresh-cut spinach. Results showed that vitamin C concentration is less affected by storage in fresh-cut spinach with respect to intact spinach. MS/MS analysis showed that the main flavonoids are not modified during storage in intact leaves, while some of them increased significantly during storage in the fresh-cut samples. Fresh-cut spinach did not show color alteration even if PPO activity increased significantly during storage. This finding was related to the high ascorbic acid content, which delays the subsequent polymerization events. This finding was confirmed by the unaltered concentration of phenolic compounds in fresh-cut spinach during storage. In conclusion, data about nutritional content and visual performance concurrently suggest that spinach is a suitable species for marketing as a fresh-cut product. PMID:19253961

  12. Quantitative structure-retention relationships models for prediction of high performance liquid chromatography retention time of small molecules: endogenous metabolites and banned compounds.

    PubMed

    Goryński, Krzysztof; Bojko, Barbara; Nowaczyk, Alicja; Buciński, Adam; Pawliszyn, Janusz; Kaliszan, Roman

    2013-10-01

    Quantitative structure-retention relationship (QSRR) is a technique capable of improving the identification of analytes by predicting their retention time on a liquid chromatography column (LC) and/or their properties. This approach is particularly useful when LC is coupled with a high-resolution mass spectrometry (HRMS) platform. The main aim of the present study was to develop and describe appropriate QSRR models that provide usable predictive capability, allowing false positive identification to be removed during the interpretation of metabolomics data, while additionally increasing confidence of experimental results in doping control area. For this purpose, a dataset consisting of 146 drugs, metabolites and banned compounds from World Anti-Doping Agency (WADA) lists, was used. A QSRR study was carried out separately on high quality retention data determined by reversed-phase (RP-LC-HRMS) and hydrophilic interaction chromatography (HILIC-LC-HRMS) systems, employing a single protocol for each system. Multiple linear regression (MLR) was applied to construct the linear QSRR models based on a variety of theoretical molecular descriptors. The regression equations included a set of three descriptors for each model: ALogP, BELe6, R2p and ALogP(2), FDI, BLTA96, were used in the analysis of reversed-phase and HILIC column models, respectively. Statistically significant QSRR models (squared correlation coefficient for model fitting, R(2)=0.95 for RP and R(2)=0.84 for HILIC) indicate a strong correlation between retention time and the molecular descriptors. An evaluation of the best correlation models, performed by validation of each model using three tests (leave-one-out, leave-many-out, external tests), demonstrated the reliability of the models. This paper provides a practical and effective method for analytical chemists working with LC/HRMS platforms to improve predictive confidence of studies that seek to identify small molecules.

  13. The Endogenous Exposome

    PubMed Central

    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

  14. Endogenous ethanol--its metabolic, behavioral and biomedical significance.

    PubMed

    Ostrovsky YuM

    1986-01-01

    Ethanol is constantly formed endogenously from acetaldehyde, and level of the former can be measured in both human beings and animals. Acetaldehyde can be generated in situ from the metabolism of pyruvate, threonine, deoxyribose-5-phosphate, phosphoethanolamine, alanine and presumably from other substrates. The levels of blood and tissue endogenous ethanol change as a function of various physiologic and experimental conditions such as starvation, aging, stress, cooling, adrenalectomy, etc. and are regulated by many exogenous compounds such as antimetabolites, derivatives of amino acids, lithium salts, disulfiram, cyanamide, etc. Under free choice alcohol selection situations, the levels of endogenous ethanol in rat blood and alcohol preference by the animals are negatively correlated. Similar negative correlations have been found between the levels of blood endogenous ethanol and the frequency of delirium in alcoholic patients undergoing alcohol withdrawal. Endogenous ethanol and acetaldehyde can therefore be regarded as compounds which fulfil substrate, regulatory and modulator functions.

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

    PubMed Central

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

    2010-01-01

    Glucagon-like peptide-1 (GLP-1) mediates antidiabetogenic effects through the GLP-1 receptor (GLP-1R), which is targeted for the treatment of type 2 diabetes. Small-molecule GLP-1R agonists have been sought due to difficulties with peptide therapeutics. Recently, 6,7-dichloro-2-methylsulfonyl-3-N-tert-butylaminoquinoxaline (compound 2) has been described as a GLP-1R allosteric modulator and agonist. Using human embryonic kidney-293 cells expressing human GLP-1Rs, we extended this work to consider the impact of compound 2 on G protein activation, Ca2+ signaling and receptor internalization and particularly to compare compound 2 and GLP-1 across a range of functional assays in intact cells. GLP-1 and compound 2 activated Gαs in cell membranes and increased cellular cAMP in intact cells, with compound 2 being a partial and almost full agonist, respectively. GLP-1 increased intracellular [Ca2+] by release from intracellular stores, which was mimicked by compound 2, with slower kinetics. In either intact cells or membranes, the orthosteric antagonist exendin-(9-39), inhibited GLP-1 cAMP generation but increased the efficacy of compound 2. GLP-1 internalized enhanced green fluorescent protein-tagged GLP-1Rs, but the speed and magnitude evoked by compound 2 were less. Exendin-(9-39) inhibited internalization by GLP-1 and also surprisingly that by compound 2. Compound 2 displays GLP-1R agonism consistent with action at an allosteric site, although an orthosteric antagonist increased its efficacy on cAMP and blocked compound 2-mediated receptor internalization. Full assessment of the properties of compound 2 was potentially hampered by damaging effects that were particularly manifest in either longer term assays with intact cells or in acute assays with membranes. PMID:20507928

  16. [Endogenous venous thrombolysis].

    PubMed

    Porembskaya, O Ya; Khmelniker, S M; Shaidakov, E V

    2015-01-01

    Widely incorporated into vascular surgery pharmacological thrombolysis in treatment for deep vain thrombosis is fraught with a series of unsolved problems requiring further consideration. In spite of aggressive nature of treatment in a series of cases pharmacological thrombolysis sometimes turns out ineffective. Along with it, the results of experimental studies suggest a possibility of accelerating resorption of thrombotic masses and inhibiting remodelling of the venous wall by means of influencing effector cells of endogenous thrombolysis. A detailed study of the mechanisms of thrombolysis would make it possible to formulate strict criteria for carrying out pharmacological thrombolysis and to increase its efficacy. PMID:26355926

  17. [Genetics of endogenous psychoses].

    PubMed

    Zerbin-Rüdin, E

    1979-01-01

    As the endogeneous psychoses do not show a Mendelian mode of inheritance, empirical risk figures have to be calculated. They are heterogeneous and nurture as well as nature have a share in the manifestation of illness. The genetic basis of the schizophrenias is demonstrated by twin and adoption studies. The concordance rate in monozygotic twins is four times the rate in dizygotic twins. Schizophrenia is to be found in the biological families of schizophrenic adoptees but not in the adoptive families. However, despite their genetic identity, monozygotic twins do not show 100% concordance but 60% only. Nongenetic factors must be considered. Obviously they are nonspecific and vary between individuals. The same principles apply to the affective psychoses. At present research is most interested in the problem of heterogeneity. Do pure depressive and manic-depressive disease form one genetic entity, or two different ones, or have they in common part of their genetic basis? Some remarks on genetic counselling are made.

  18. Pushing the endogenous envelope

    PubMed Central

    Henzy, Jamie E.; Johnson, Welkin E.

    2013-01-01

    The majority of retroviral envelope glycoproteins characterized to date are typical of type I viral fusion proteins, having a receptor binding subunit associated with a fusion subunit. The fusion subunits of lentiviruses and alpha-, beta-, delta- and gammaretroviruses have a very conserved domain organization and conserved features of secondary structure, making them suitable for phylogenetic analyses. Such analyses, along with sequence comparisons, reveal evidence of numerous recombination events in which retroviruses have acquired envelope glycoproteins from heterologous sequences. Thus, the envelope gene (env) can have a history separate from that of the polymerase gene (pol), which is the most commonly used gene in phylogenetic analyses of retroviruses. Focusing on the fusion subunits of the genera listed above, we describe three distinct types of retroviral envelope glycoproteins, which we refer to as gamma-type, avian gamma-type and beta-type. By tracing these types within the ‘fossil record’ provided by endogenous retroviruses, we show that they have surprisingly distinct evolutionary histories and dynamics, with important implications for cross-species transmissions and the generation of novel lineages. These findings validate the utility of env sequences in contributing phylogenetic signal that enlarges our understanding of retrovirus evolution. PMID:23938755

  19. English walnuts (Juglans regia L.) protect endogenous antioxidants in humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ellagic acid monomers, polymeric tannins and related phenolic compounds isolated from English walnuts (Juglans regia L.) have been reported to inhibit LDL oxidation ex vivo and decrease biomarkers of oxidative stress in animal models. To determine whether dietary and endogenous antioxidants are pres...

  20. Endogenous Antibodies for Tumor Detection

    PubMed Central

    Rich, Barrie S.; Honeyman, Joshua N.; Darcy, David G.; Smith, Peter T.; Williams, Andrew R.; Lim, Irene Isabel P.; Johnson, Linda K.; Gönen, Mithat; Simon, Joel S.; LaQuaglia, Michael P.; Simon, Sanford M.

    2014-01-01

    The study of cancer immunology has provided diagnostic and therapeutic instruments through serum autoantibody biomarkers and exogenous monoclonal antibodies. While some endogenous antibodies are found within or surrounding transformed tissue, the extent to which this exists has not been entirely characterized. We find that in transgenic and xenograft mouse models of cancer, endogenous gamma immunoglobulin (IgG) is present at higher concentration in malignantly transformed organs compared to non-transformed organs in the same mouse or organs of cognate wild-type mice. The enrichment of endogenous antibodies within the malignant tissue provides a potential means of identifying and tracking malignant cells in vivo as they mutate and diversify. Exploiting these antibodies for diagnostic and therapeutic purposes is possible through the use of agents that bind endogenous antibodies. PMID:24875800

  1. Endogenous Metabolism of Azotobacter agilis

    PubMed Central

    Sobek, J. M.; Charba, J. F.; Foust, W. N.

    1966-01-01

    Sobek, J. M. (University of Southwestern Louisiana, Lafayette), J. F. Charba, and W. N. Foust. Endogenous metabolism of Azotobacter agilis. J. Bacteriol. 92:687–695. 1966—Ribonucleic acid, deoxyribonucleic acid, cellular carbohydrate, and the cold trichloroacetic acid and acidic alcohol fractions of the cell do not appear to function as endogenous reserves for Azotobacter agilis. The immediate endogenous reserve of cells grown on glucose, acetate, or succinate was poly-β-hydroxybutyric acid (PHB). Viability of the cells during starvation was dependent upon the initial levels of PHB and the growth substrate. Cells with high initial PHB levels survived longer than cells with lower levels. Cells from succinate-grown cultures had lower PHB levels than cells from glucose-grown cultures, but were capable of maintaining their viability longer. Cellular protein may also serve as a secondary endogenous reserve substrate for this organism. PMID:5922542

  2. ENDOGENOUS RESPIRATION OF STAPHYLOCOCCUS AUREUS

    PubMed Central

    Ramsey, H. H.

    1962-01-01

    Ramsey, H. H. (Stanford University, Palo Alto, Calif.). Endogenous respiration of Staphylococcus aureus. J. Bacteriol. 83:507–514. 1962.—The endogenous respiration of Staphylococcus aureus is dependent upon the medium used to grow the cell suspension. Within wide ranges, the concentration of glucose in the medium has no effect upon subsequent endogenous respiration of the cells, but the concentration of amino acids in the medium, within certain limits, has a very marked effect. The total carbohydrate content of the cells does not decrease during endogenous respiration. As endogenous respiration proceeds, ammonia appears in the supernatant, and the concentration of glutamic acid in the free amino acid pool decreases. Organisms grown in the presence of labeled glutamic acid liberate labeled CO2 when allowed to respire without added substrate. The principal source of this CO2 is the free glutamate in the metabolic pool; its liberation is not suppressed by exogenous glucose or glutamate. With totally labeled cells, the free pool undergoes a rapid, but not total, depletion and remains at a low level for a long time. Activity of the protein fraction declines with time and shows the largest net decrease of all fractions. Exogenous glucose does not inhibit the release of labeled CO2 by totally labeled cells. Other amino acids in the free pool which can serve as endogenous substrates are aspartic acid and, to much lesser extents, glycine and alanine. The results indicate that both free amino acids and cellular protein may serve as endogenous substrates of S. aureus. PMID:14490204

  3. Endogenous rhythms influence interpersonal synchrony.

    PubMed

    Zamm, Anna; Wellman, Chelsea; Palmer, Caroline

    2016-05-01

    Interpersonal synchrony, the temporal coordination of actions between individuals, is fundamental to social behaviors from conversational speech to dance and music-making. Animal models indicate constraints on synchrony that arise from endogenous rhythms: Intrinsic periodic behaviors or processes that continue in the absence of change in external stimulus conditions. We report evidence for a direct causal link between endogenous rhythms and interpersonal synchrony in a music performance task, which places high demands on temporal coordination. We first establish that endogenous rhythms, measured by spontaneous rates of individual performance, are stable within individuals across stimulus materials, limb movements, and time points. We then test a causal link between endogenous rhythms and interpersonal synchrony by pairing each musician with a partner who is either matched or mismatched in spontaneous rate and by measuring their joint behavior up to 1 year later. Partners performed melodies together, using either the same or different hands. Partners who were matched for spontaneous rate showed greater interpersonal synchrony in joint performance than mismatched partners, regardless of hand used. Endogenous rhythms offer potential to predict optimal group membership in joint behaviors that require temporal coordination. PMID:26820249

  4. Endogenous formation of morphine in human cells.

    PubMed

    Poeaknapo, Chotima; Schmidt, Jürgen; Brandsch, Matthias; Dräger, Birgit; Zenk, Meinhart H

    2004-09-28

    Morphine is a plant (opium poppy)-derived alkaloid and one of the strongest known analgesic compounds. Studies from several laboratories have suggested that animal and human tissue or fluids contain trace amounts of morphine. Its origin in mammals has been believed to be of dietary origin. Here, we address the question of whether morphine is of endogenous origin or derived from exogenous sources. Benzylisoquinoline alkaloids present in human neuroblastoma cells (SH-SY5Y) and human pancreas carcinoma cells (DAN-G) were identified by GC/tandem MS (MS/MS) as norlaudanosoline (DAN-G), reticuline (DAN-G and SH-SY5Y), and morphine (10 nM, SH-SY5Y). The stereochemistry of reticuline was determined to be 1-(S). Growth of the SH-SY5Y cell line in the presence of (18)O(2) led to the [(18)O]-labeled morphine that had the molecular weight 4 mass units higher than if grown in (16)O(2), indicating the presence of two atoms of (18)O per molecule of morphine. Growth of DAN-G cells in an (18)O(2) atmosphere yielded norlaudanosoline and (S)-reticuline, both labeled at only two of the four oxygen atoms. This result clearly demonstrates that all three alkaloids are of biosynthetic origin and suggests that norlaudanosoline and (S)-reticuline are endogenous precursors of morphine. Feeding of [ring-(13)C(6)]-tyramine, [1-(13)C, N-(13)CH(3)]-(S)-reticuline and [N-CD(3)]-thebaine to the neuroblastoma cells led each to the position-specific labeling of morphine, as established by GC/MS/MS. Without doubt, human cells can produce the alkaloid morphine. The studies presented here serve as a platform for the exploration of the function of "endogenous morphine" in the neurosciences and immunosciences.

  5. The Search for Endogenous Activators of the Aryl Hydrocarbon Receptor

    PubMed Central

    Nguyen, Linh P.; Bradfield, Christopher A.

    2008-01-01

    In its simplest aspect, this review is an attempt to describe the major ligand classes of the aryl hydrocarbon receptor (AHR). A grander objective is to provide models that may help define the physiological activator or “endogenous ligand” of the AHR. We begin by presenting evidence that supports a developmental function for the AHR. This is followed by proposing mechanisms by which an endogenous ligand and consequent AHR activation might be important during normal physiology and development. With this background, we then present a survey of the known xenobiotic, endogenous, dietary and “un-conventional” activators of the AHR. When possible, this includes information about their induction potency, receptor binding affinity and potential for exposure. Because of the essential function of the AHR in embryonic development, we discuss the candidacy of each of these compounds as physiologically important activators. PMID:18076143

  6. Skeletal Fragility in Endogenous Hypercortisolism.

    PubMed

    Mazziotti, Gherardo; Delgado, Adriano; Maffezzoni, Filippo; Formenti, Annamaria; Giustina, Andrea

    2016-01-01

    Skeletal fragility is a frequent complication of endogenous hypercortisolism, and fragility fractures may be the first clinical manifestation of the disease. Fractures involve more frequently the vertebrae and may occur in 30-50% of the patients exposed to glucocorticoid excess, in close relationship with severity and duration of hypercortisolism. Although improvement of bone mineral density was reported after resolution of hypercortisolism, there are patients with persistently high fracture risk after the cure of hypercortisolism, and other patients in whom the resolution of hypercortisolism may take a long time, implying a multistep therapeutic approach. Since vertebral fractures tend to occur early during the natural history of disease, a skeletal-specific approach should be undertaken in these patients; however, the cost-effectiveness of this approach is still largely unknown since data on effectiveness and safety of bone-active drugs in endogenous hypercortisolism are scarce. PMID:27210111

  7. Endogenous opiates and behavior: 2013.

    PubMed

    Bodnar, Richard J

    2014-12-01

    This paper is the thirty-sixth consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2013 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, and the roles of these opioid peptides and receptors in pain and analgesia; stress and social status; tolerance and dependence; learning and memory; eating and drinking; alcohol and drugs of abuse; sexual activity and hormones, pregnancy, development and endocrinology; mental illness and mood; seizures and neurologic disorders; electrical-related activity and neurophysiology; general activity and locomotion; gastrointestinal, renal and hepatic functions; cardiovascular responses; respiration and thermoregulation; and immunological responses.

  8. Endogenous respiration of Polyporus sulphureus

    SciTech Connect

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

    1980-01-01

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

  9. Endogenous zinc in neurological diseases.

    PubMed

    Koh, Jae-Yong

    2005-10-01

    The use of zinc in medicinal skin cream was mentioned in Egyptian papyri from 2000 BC (for example, the Smith Papyrus), and zinc has apparently been used fairly steadily throughout Roman and modern times (for example, as the American lotion named for its zinc ore, 'Calamine'). It is, therefore, somewhat ironic that zinc is a relatively late addition to the pantheon of signal ions in biology and medicine. However, the number of biological functions, health implications and pharmacological targets that are emerging for zinc indicate that it might turn out to be 'the calcium of the twenty-first century'. Here neurobiological roles of endogenous zinc is summarized.

  10. Endogenous Zinc in Neurological Diseases

    PubMed Central

    2005-01-01

    The use of zinc in medicinal skin cream was mentioned in Egyptian papyri from 2000 BC (for example, the Smith Papyrus), and zinc has apparently been used fairly steadily throughout Roman and modern times (for example, as the American lotion named for its zinc ore, 'Calamine'). It is, therefore, somewhat ironic that zinc is a relatively late addition to the pantheon of signal ions in biology and medicine. However, the number of biological functions, health implications and pharmacological targets that are emerging for zinc indicate that it might turn out to be 'the calcium of the twenty-first century'. Here neurobiological roles of endogenous zinc is summarized. PMID:20396459

  11. ASSAYS FOR ENDOGENOUS COMPONENTS OF HUMAN MILK: COMPARISON OF FRESH AND FROZEN SAMPLES AND CORRESPONDING ANALYTES IN SERUM

    EPA Science Inventory

    Breast milk is a primary source of nutrition that contains many endogenous compounds that may affect infant development. The goals of this study were to develop reliable assays for selected endogenous breast milk components and to compare levels of those in milk and serum collect...

  12. Endogenous mitigation of H2S inside of the landfills.

    PubMed

    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.

  13. Floral Scent Diversity is Differently Expressed in Emitted and Endogenous Components in Petunia axillaris Lines

    PubMed Central

    KONDO, M.; OYAMA-OKUBO, N.; ANDO, T.; MARCHESI, E.; NAKAYAMA, M.

    2006-01-01

    • Background and Aims Among the subspecies of Petunia axillaris are various lines emitting sensorially different scents. Analysis of variations in floral scent among genetically close individuals is a powerful approach to understanding the mechanisms for generating scent diversity. • Methods Emitted and endogenous components were analysed independently to gain information about evaporation and endogenous production in 13 wild lines of P. axillaris. A dynamic headspace method was used to collect emitted components. Endogenous components were extracted with solvent. Both of these sample types were subjected to quantitative and qualitative analysis by gas chromatography (GC)–flame ionization detector (FID) and GC–mass spectrometry (MS). • Key Results and Conclusions Whereas the profiles of emitted compounds showed qualitative homogeneity, being mainly composed of methyl benzoate with quantitative variation, the profiles of endogenous compounds showed both qualitative and quantitative variation. A negative correlation was found between the evaporation ratio and boiling point of each compound examined. Lower boiling point compounds were strongly represented in the emitted component, resulting in the reduction of qualitative variation in floral scent. In conclusion, floral scent diversity results from variation in both the endogenous production and the evaporation rate of the individual volatile compounds. PMID:17060364

  14. Endogenous Opiates and Behavior: 2006

    PubMed Central

    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

  15. Endogenous Inhibitors of Kidney Inflammation

    PubMed Central

    Trostel, Jessica; Garcia, Gabriela E.

    2015-01-01

    Although inflammation is the physiological response to pathogen invasion and tissue damage, it can also be responsible for significant tissue damage. Therefore, the inflammatory response must be carefully regulated to prevent critical inflammatory damage to vital organs. Typically, local endogenous regulatory mechanisms adjust the magnitude of the response such that the injurious condition is resolved and homeostasis is mantained. Humoral mechanisms that restrain or inhibit inflammation include glucocorticoid hormones, anti-inflammatory cytokines such as IL-10 and transforming growth factor-β (TGF-β), and soluble cytokine receptors; other mediators facilitate tissue healing, like lipoxins and resolvins. There is growing evidence that inflammation plays a critical role in the development and progression of heart disease, cancer, stroke, diabetes, kidney diseases, sepsis, and several fibroproliferative disorders. Consequently, understanding the mechanisms that regulate inflammation may offer therapeutic targets for inhibiting the progression of several diseases. In this article, we review the significance of several novel endogenous anti-inflammatory mediators in the protection from kidney injury and the potential of these regulatory molecules as therapeutic targets for treatment of kidney inflammatory diseases. PMID:26779569

  16. Endogeneity in prison risk classification.

    PubMed

    Shermer, Lauren O'Neill; Bierie, David M; Stock, Amber

    2013-10-01

    Security designation tools are a key feature of all prisons in the United States, intended as objective measures of risk that funnel inmates into security levels-to prison environments varying in degree of intrusiveness, restriction, dangerousness, and cost. These tools are mostly (if not all) validated by measuring inmates on a set of characteristics, using scores from summations of that information to assign inmates to prisons of varying security level, and then observing whether inmates assumed more risky did in fact offend more. That approach leaves open the possibility of endogeneity--that the harsher prisons are themselves bringing about higher misconduct and thus biasing coefficients assessing individual risk. The current study assesses this potential bias by following an entry cohort of inmates to more than 100 facilities in the Federal Bureau of Prisons (BOP) and exploiting the substantial variation in classification scores within a given prison that derive from systematic overrides of security-level designations for reasons not associated with risk of misconduct. By estimating pooled models of misconduct along with prison-fixed effects specifications, the data show that a portion of the predictive accuracy thought associated with the risk-designation tool used in BOP was a function of facility-level contamination (endogeneity).

  17. Endogenous Auxin and Ethylene in Pellia (Bryophyta) 1

    PubMed Central

    Thomas, Robert J.; Harrison, Marcia A.; Taylor, Jane; Kaufman, Peter B.

    1983-01-01

    The occurrence of endogenous indole-3-acetic acid and ethylene in bryophyte tissue was tentatively demonstrated using gas chromatography, high performance liquid chromatography, and double-standard isotope dilution techniques. Rapidly elongating stalks (or setae) of Pellia epiphylla (L.) Corda sporophytes contain approximately 2.5 to 2.9 micrograms per gram fresh weight of putative free IAA. Ethylene released by setae increases during growth from 0.027 to 0.035 nanoliter per seta per hour. Application of 5 microliters per liter ethylene inhibits auxin-stimulated elongation growth of this tissue, a result which suggests that both endogenously produced compounds act in tandem as natural growth modulators. Images Fig. 1 PMID:16663227

  18. The discovery of endogenous retroviruses

    PubMed Central

    Weiss, Robin A

    2006-01-01

    When endogenous retroviruses (ERV) were discovered in the late 1960s, the Mendelian inheritance of retroviral genomes by their hosts was an entirely new concept. Indeed Howard M Temin's DNA provirus hypothesis enunciated in 1964 was not generally accepted, and reverse transcriptase was yet to be discovered. Nonetheless, the evidence that we accrued in the pre-molecular era has stood the test of time, and our hypothesis on ERV, which one reviewer described as 'impossible', proved to be correct. Here I recount some of the key observations in birds and mammals that led to the discovery of ERV, and comment on their evolution, cross-species dispersion, and what remains to be elucidated. PMID:17018135

  19. Endogenous Retroviruses and Human Evolution

    PubMed Central

    Lebedev, Yuri; Sverdlov, Eugene

    2002-01-01

    Humans share about 99% of their genomic DNA with chimpanzees and bonobos; thus, the differences between these species are unlikely to be in gene content but could be caused by inherited changes in regulatory systems. Endogenous retroviruses (ERVs) comprise ∼ 5% of the human genome. The LTRs of ERVs contain many regulatory sequences, such as promoters, enhancers, polyadenylation signals and factor-binding sites. Thus, they can influence the expression of nearby human genes. All known human-specific LTRs belong to the HERV-K (human ERV) family, the most active family in the human genome. It is likely that some of these ERVs could have integrated into regulatory regions of the human genome, and therefore could have had an impact on the expression of adjacent genes, which have consequently contributed to human evolution. This review discusses possible functional consequences of ERV integration in active coding regions. PMID:18629260

  20. Endogenous Peer Effects: Fact or Fiction?

    ERIC Educational Resources Information Center

    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…

  1. Endogenous timing factors in bird migration

    NASA Technical Reports Server (NTRS)

    Gwinner, E. G.

    1972-01-01

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

  2. Population aging and endogenous economic growth.

    PubMed

    Prettner, Klaus

    2013-04-01

    We investigate the consequences of population aging for long-run economic growth perspectives. Our framework incorporates endogenous growth models and semi-endogenous growth models as special cases. We show that (1) increases in longevity have a positive impact on per capita output growth, (2) decreases in fertility have a negative impact on per capita output growth, (3) the positive longevity effect dominates the negative fertility effect in case of the endogenous growth framework, and (4) population aging fosters long-run growth in the endogenous growth framework, while its effect depends on the relative change between fertility and mortality in the semi-endogenous growth framework.Electronic supplementary material The online version of this article (doi:10.1007/s00148-012-0441-9) contains supplementary material, which is available to authorized users.

  3. Excretion of low-molecular weight volatile substances in human breath: focus on endogenous ethanol.

    PubMed

    Jones, A W

    1985-01-01

    This paper describes a gas chromatographic method suitable for the analysis of low-molecular endogenous volatiles in human breath. The use of an on-column gas sampling device allowed serial determinations at 10-min intervals. With a flame ionization detector and Porapak Q as stationary phase, the four major endogenous breath volatiles were methanol, ethanol, acetone, and isoprene (2-methyl-1,3-butadiene). These same compounds were present in the breath of healthy individuals and abstinent alcoholics. In 10 healthy men, the breath concentration of endogenous ethanol, methanol, and acetone ranged from 0.07 to 0.39 microgram/L, 0.21 to 0.07 microgram/L, and 0.57 to 4.01 micrograms/L, respectively. When a man drank 5 g of exogenous ethanol, the blood concentration increased 200 times above the endogenous level. This small dose of ethanol was eliminated with a half-life of 16 min.

  4. Gravity effects on endogenous movements

    NASA Astrophysics Data System (ADS)

    Johnsson, Anders; Antonsen, Frank

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

  5. Age-related changes of the endogenous cardiolipin and plasmalogens of guinea pig kidney and their in vitro hydrolysis by endogenous phospholipases: a thin layer chromatographic analysis in conjunction with densitometric measurement.

    PubMed

    Helmy, Fatma M; Hack, Marvin H; Juracka, Amal

    2003-12-01

    The phosphoglycerides profile of guinea pig kidney, fetal, young adult, and aged, and their in vitro response to the endogenous lipolytic enzymes, mainly in the phospholipase group were determined by TLC technology in conjunction with densitometric measurement. Changes in phosphoglycerides profile subsequent to in vitro incubation of these tissues at pH 7.4, and 38 degrees C for 45 min and prior to phospholipid extraction has provided evidence relating to their respective lipolytic enzymes capabilities and age. These changes are mainly related to endogenous cardiolipin (CL), alkenyl phospholipids (phosphatidyl ethanolamine and phosphatidyl choline) and their endogenous deacylation to their respective lyso derivatives monolysocardiolipin (MLCL), lyso alkenyl phosphatidyl ethanolamine (LPE), and lyso alkenyl phosphatidyl choline (LPC) by endogenous phospholipases. The hydrolysis of the plasmalogen confirms the action of endogenous PLA(2) on sn-2 fatty acids of these compounds.

  6. BioArena studies: unique function of endogenous formaldehyde and ozone in the antibiotic effect--a review.

    PubMed

    Tyihák, Erno; Móricz, Agnes M; Ott, Péter G

    2012-01-01

    The investigations demonstrated clearly a unique function and role of endogenous formaldehyde (HCHO) and ozone (O3) in the antibiotic effect of diverse molecules having different chemical structure. Elimination of HCHO and/or O3 from the layer chromatographic spots resulted in a decrease in the antimicrobial activity. On the basis of detection and measure of endogenous HCHO and O3 BioArena enables to both direct isolation and biological evaluation of new bioactive compounds.

  7. Overview of endogenous and synthetic melanocortin peptides.

    PubMed

    Wilson, K R; Todorovic, A; Proneth, B; Haskell-Luevano, C

    2006-01-01

    The melanocortin system consists of five seven-transmembrane spanning G-protein coupled (GPCRs) receptors (MC1R-MC5R), the endogenous agonists a-, B- and melanocyte stimulating hormone (MSH), adrenocorticotropic hormone (ACTH), and the endogenous antagonists Agouti and Agouti-related protein (AGRP). Melanocortin agonists are involved in the regulation of feeding behavior and weight omeostasis in mammals. Structure-activity relationships (SAR) have been performed on the endogenous melanocortin receptor agonists and antagonists that have identified ligand amino acid residues implicated as important for receptor binding and stimulation. Knowledge of putative ligand-receptor interactions may help to design molecules as therapeutic agents for the treatment of physiological diseases. PMID:16914082

  8. Analysis of the Human Endogenous Coregulator Complexome

    PubMed Central

    Malovannaya, Anna; Lanz, Rainer B.; Jung, Sung Yun; Bulynko, Yaroslava; Le, Nguyen T.; Chan, Doug W.; Ding, Chen; Shi, Yi; Yucer, Nur; Krenciute, Giedre; Kim, Beom-Jun; Li, Chunshu; Chen, Rui; Li, Wei; Wang, Yi; O’Malley, Bert W.; Qin, Jun

    2011-01-01

    Summary Elucidation of endogenous cellular protein-protein interactions and their networks is most desirable for biological studies. Here we report our study of endogenous human coregulator protein complex networks obtained from integrative mass spectrometry-based analysis of 3,290 affinity purifications. By preserving weak protein interactions during complex isolation and utilizing high levels of reciprocity in the large dataset we identified many unreported protein associations, such as a transcriptional network formed by ZMYND8, ZNF687 and ZNF592. Furthermore, our work revealed a tiered interplay within networks that share common proteins, providing a conceptual organization of a cellular proteome composed of minimal endogenous modules (MEMOs), functional uniCOREs and regulatory complex-complex interaction networks (CCIs). This resource will effectively fill a void in linking correlative genomic studies with an understanding of transcriptional regulatory protein functions within the proteome for formulation and testing of new hypotheses. PMID:21620140

  9. Endogenous RNAi pathways in C. elegans.

    PubMed Central

    Billi, Allison C; Fischer, Sylvia E J; Kim, John K

    2014-01-01

    In addition to several hundred microRNAs, C. elegans produces thousands of other small RNAs targeting coding genes, pseudogenes, transposons, and other noncoding RNAs. Here we review what is currently known about these endogenous small interfering RNAs (siRNAs) and piwi-interacting RNAs (piRNAs), providing an overview of their biogenesis, their associated protein factors, and their effects on mRNA dynamics and chromatin structure. Additionally, we describe how the molecular actions of these classes of endogenous small RNAs connect to their physiological roles in the organism. PMID:24816713

  10. Animal spirits, competitive markets, and endogenous growth

    NASA Astrophysics Data System (ADS)

    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.

  11. Cellular responses to endogenous electrochemical gradients in morphological development

    NASA Technical Reports Server (NTRS)

    Desrosiers, M. F.

    1996-01-01

    Endogenous electric fields give vectorial direction to morphological development in Zea mays (sweet corn) in response to gravity. Endogenous electrical fields are important because of their ability to influence: (1) intercellular organization and development through their effects on the membrane potential, (2) direct effects such as electrophoresis of membrane components, and (3) both intracellular and extracellular transport of charged compounds. Their primary influence is in providing a vectorial dimension to the progression of one physiological state to another. Gravity perception and transduction in the mesocotyl of vascular plants is a complex interplay of electrical and chemical gradients which ultimately provide the driving force for the resulting growth curvature called gravitropism. Among the earliest events in gravitropism are changes in impedance, voltage, and conductance between the vascular stele and the growth tissues, the cortex, in the mesocotyl of corn shoots. In response to gravistimulation: (1) a potential develops which is vectorial and of sufficient magnitude to be a driving force for transport between the vascular stele and cortex, (2) the ionic conductance changes within seconds showing altered transport between the tissues, and (3) the impedance shows a transient biphasic response which indicates that the mobility of charges is altered following gravistimulation and is possibly the triggering event for the cascade of actions which leads to growth curvature.

  12. Endogenous cannabinoid system as a modulator of food intake.

    PubMed

    Cota, D; Marsicano, G; Lutz, B; Vicennati, V; Stalla, G K; Pasquali, R; Pagotto, U

    2003-03-01

    The ability of Cannabis sativa (marijuana) to increase hunger has been noticed for centuries, although intensive research on its molecular mode of action started only after the characterization of its main psychoactive component Delta(9)-tetrahydrocannabinol in the late 1960s. Despite the public concern related to the abuse of marijuana and its derivatives, scientific studies have pointed to the therapeutic potentials of cannabinoid compounds and have highlighted their ability to stimulate appetite, especially for sweet and palatable food. Later, the discovery of specific receptors and their endogenous ligands (endocannabinoids) suggested the existence of an endogenous cannabinoid system, providing a physiological basis for biological effects induced by marijuana and other cannabinoids. Epidemiological reports describing the appetite-stimulating properties of cannabinoids and the recent insights into the molecular mechanisms underlying cannabinoid action have proposed a central role of the cannabinoid system in obesity. The aim of this review is to provide an extensive overview on the role of this neuromodulatory system in feeding behavior by summarizing the most relevant data obtained from human and animal studies and by elucidating the interactions of the cannabinoid system with the most important neuronal networks and metabolic pathways involved in the control of food intake. Finally, a critical evaluation of future potential therapeutical applications of cannabinoid antagonists in the therapy of obesity and eating disorders will be discussed.

  13. Cellular responses to endogenous electrochemical gradients in morphological development.

    PubMed

    Desrosiers, M F

    1996-01-01

    Endogenous electric fields give vectorial direction to morphological development in Zea mays (sweet corn) in response to gravity. Endogenous electrical fields are important because of their ability to influence: 1) intercellular organization and development through their effects on the membrane potential, 2) direct effects such as electrophoresis of membrane components, and 3) both intracellular and extracellular transport of charged compounds. Their primary influence is in providing a vectorial dimension to the progression of one physiological state to another. Gravity perception and transduction in the mesocotyl of vascular plants is a complex interplay of electrical and chemical gradients which ultimately provide the driving force for the resulting growth curvature called gravitropism. Among the earliest events in gravitropism are changes in impedance, voltage, and conductance between the vascular stele and the growth tissues, the cortex, in the mesocotyl of corn shoots. In response to gravistimulation: 1) a potential develops which is vectorial and of sufficient magnitude to be a driving force for transport between the vascular stele and cortex, 2) the ionic conductance changes within seconds showing altered transport between the tissues, and 3) the impedance shows a transient biphasic response which indicates that the mobility of charges is altered following gravistimulation and is possibly the triggering event for the cascade of actions which leads to growth curvature. PMID:11538627

  14. Studies on endogenous circulating calcium entry blocker and stimulator

    SciTech Connect

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

    1986-03-01

    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 /sup 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.

  15. The role of endogenous H2S in cardiovascular physiology.

    PubMed

    Skovgaard, Nini; Gouliaev, Anja; Aalling, Mathilde; Simonsen, Ulf

    2011-09-01

    Recent research has shown that the endogenous gas hydrogen sulphide (H2S) is a signalling molecule of considerable biological potential and has been suggested to be involved in a vast number of physiological processes. In the vascular system, H2S is synthesized from cysteine by cystathionine-γ-lyase (CSE) in smooth muscle cells (SMC) and 3- mercaptopyruvate sulfuresterase (3MST) and CSE in the endothelial cells. In pulmonary and systemic arteries, H2S induces relaxation and/or contraction dependent on the concentration of H2S, type of vessel and species. H2S relaxes SMC through a direct effect on KATP-channels or Kv-channels causing hyperpolarization and closure of voltage-dependent Ca2+-channels followed by a reduction in intracellular calcium. H2S also relaxes SMC through the release of endothelium- derived hyperpolarizing factor (EDHF) and nitric oxide (NO) from the endothelium. H2S contracts SMC through a reduction in nitric oxide (NO) availability by reacting with NO forming a nitrosothiol compound and through an inhibitory effect on endothelial nitric oxide synthase (eNOS) as well as a reduction in SMC cyclic AMP concentration. Evidence supports a role for H2S in oxygen sensing. Furthermore, reduced endogenous H2S production may also play a role in ischemic heart diseases and hypertension, and treatment with H2S donors and cysteine analogues may be beneficial in treatment of cardiovascular disease.

  16. Cellular responses to endogenous electrochemical gradients in morphological development

    NASA Astrophysics Data System (ADS)

    Desrosiers, M. F.

    Endogenous electric fields give vectorial direction to morphological development in Zea mays (sweet corn) in response to gravity. Endogenous electrical fields are important because of their ability to influence: 1) intercellular organization and development through their effects on the membrane potential, 2) direct effects such as electrophoresis of membrane components, and 3) both intracellular and extracellular transport of charged compounds. Their primary influence is in providing a vectorial dimension to the progression of one physiological state to another. Gravity perception and transduction in the mesocotyl of vascular plants is a complex interplay of electrical and chemical gradients which ultimately provide the driving force for the resulting growth curvature called gravitropism. Among the earliest events in gravitropism are changes in impedance, voltage, and conductance between the vascular stele and the growth tissues, the cortex, in the mesocotyl of corn shoots. In response to gravistimulation: 1) a potential develops which is vectorial and of sufficient magnitude to be a driving force for transport between the vascular stele and cortex, 2) the ionic conductance changes within seconds showing altered transport between the tissues, and 3) the impedance shows a transient biphasic response which indicates that the mobility of charges is altered following gravistimulation and is possibly the triggering event for the cascade of actions which leads to growth curvature.

  17. Excretion of artifactual endogenous digitalis-like factors

    SciTech Connect

    Kelly, R.A.

    1986-07-01

    Radioimmunoassays have been used to detect digoxin-like immunoreactive factors (DLF) in the plasma and urine of hypertensive patients and rats with deoxycorticosterone acetate (DOCA)-salt hypertension. DLF, partially purified from DOCA-HS urine by antidigoxin antibody immunoaffinity chromatography, was found to have a molecular weight <2000. When DOCA-HS rats were switched to the low-sodium chow, DLF excretion dropped precipitously. No measurable DLF was detected in the plasma of rats eating either chow. However, >95% of the urinary DLF could be attributed to a contaminant in the standard laboratory chow. These data document the importance of excluding nonspecific compounds and exogenous sources of DLF when sensitive radioligand and biologic assays are used to detect endogenous inhibitors of the sodium pump.

  18. Nicotine effects and the endogenous opioid system.

    PubMed

    Kishioka, Shiroh; Kiguchi, Norikazu; Kobayashi, Yuka; Saika, Fumihiro

    2014-01-01

    Nicotine (NIC) is an exogenous ligand of the nicotinic acetylcholine receptor (nAChR), and it influences various functions in the central nervous system. Systemic administration of NIC elicits the release of endogenous opioids (endorphins, enkephalins, and dynorphins) in the supraspinal cord. Additionally, systemic NIC administration induces the release of methionine-enkephalin in the spinal dorsal horn. NIC has acute neurophysiological actions, including antinociceptive effects, and the ability to activate the hypothalamic-pituitary-adrenal (HPA) axis. The endogenous opioid system participates in NIC-induced antinociception, but not HPA axis activation. Moreover, NIC-induced antinociception is mediated by α4β2 and α7 nAChRs, while NIC-induced HPA axis activation is mediated by α4β2, not α7, suggesting that the effects of NIC on the endogenous opioid system are mediated by α7, not α4β2. NIC has substantial physical dependence liability. The opioid-receptor antagonist naloxone (NLX) elicits NIC withdrawal after repeated NIC administration, and NLX-induced NIC withdrawal is inhibited by concomitant administration of an opioid-receptor antagonist. NLX-induced NIC withdrawal is also inhibited by concomitant administration of an α7 antagonist, but not an α4β2 antagonist. Taken together, these findings suggest that NIC-induced antinociception and the development of physical dependence are mediated by the endogenous opioid system, via the α7 nAChR.

  19. Shedding "UV" light on endogenous opioid dependence.

    PubMed

    Tejeda, Hugo A; Bonci, Antonello

    2014-06-19

    Excessive sun tanning can result in addictive behavior. In this issue of Cell, Fell et al. utilize a combination of behavioral pharmacology and transgenic mice to demonstrate that chronic UV light exposure recruits p53 signaling in keratinocytes, subsequently increasing β-endorphin signaling at opioid receptors, and produces an endogenous opioid-dependent state.

  20. Biochemical and physiological aspects of endogenous androgens.

    PubMed

    Kicman, Andrew T

    2010-01-01

    This review attempts to give a synopsis of the major aspects concerning the biochemistry of endogenous androgens, supplemented with several facets of physiology, particularly with respect to testosterone. Testosterone continues to be the most common adverse finding declared by World Anti-Doping Agency accredited laboratories, such samples having an augmented testosterone to epitestosterone ratio. Knowledge regarding the precursors and metabolism of endogenous testosterone is therefore fundamental to understanding many of the issues concerning doping with testosterone and its prohormones, including the detection of their administration. Further, adverse findings for nandrolone are frequent, but this steroid and 19-norandrostenedione are also produced endogenously, an appealing hypothesis being that they are minor by-products of the aromatization of androgens. At sports tribunals pertaining to adverse analytical findings of natural androgen administration, experts often raise issues that concern some aspect of steroid biochemistry and physiology. Salient topics included within this review are the origins and interconversion of endogenous androgens, the biosynthesis of testosterone and epitestosterone, the mechanism of aromatization, the molecular biology of the androgen receptor, the hypothalamic-pituitary-testicular axis, disturbances to this axis by anabolic steroid administration, the transport (binding) of androgens in blood, and briefly the metabolism and excretion of androgens.

  1. Shedding "UV" light on endogenous opioid dependence.

    PubMed

    Tejeda, Hugo A; Bonci, Antonello

    2014-06-19

    Excessive sun tanning can result in addictive behavior. In this issue of Cell, Fell et al. utilize a combination of behavioral pharmacology and transgenic mice to demonstrate that chronic UV light exposure recruits p53 signaling in keratinocytes, subsequently increasing β-endorphin signaling at opioid receptors, and produces an endogenous opioid-dependent state. PMID:24949960

  2. Nicotine effects and the endogenous opioid system.

    PubMed

    Kishioka, Shiroh; Kiguchi, Norikazu; Kobayashi, Yuka; Saika, Fumihiro

    2014-01-01

    Nicotine (NIC) is an exogenous ligand of the nicotinic acetylcholine receptor (nAChR), and it influences various functions in the central nervous system. Systemic administration of NIC elicits the release of endogenous opioids (endorphins, enkephalins, and dynorphins) in the supraspinal cord. Additionally, systemic NIC administration induces the release of methionine-enkephalin in the spinal dorsal horn. NIC has acute neurophysiological actions, including antinociceptive effects, and the ability to activate the hypothalamic-pituitary-adrenal (HPA) axis. The endogenous opioid system participates in NIC-induced antinociception, but not HPA axis activation. Moreover, NIC-induced antinociception is mediated by α4β2 and α7 nAChRs, while NIC-induced HPA axis activation is mediated by α4β2, not α7, suggesting that the effects of NIC on the endogenous opioid system are mediated by α7, not α4β2. NIC has substantial physical dependence liability. The opioid-receptor antagonist naloxone (NLX) elicits NIC withdrawal after repeated NIC administration, and NLX-induced NIC withdrawal is inhibited by concomitant administration of an opioid-receptor antagonist. NLX-induced NIC withdrawal is also inhibited by concomitant administration of an α7 antagonist, but not an α4β2 antagonist. Taken together, these findings suggest that NIC-induced antinociception and the development of physical dependence are mediated by the endogenous opioid system, via the α7 nAChR. PMID:24882143

  3. Characterization of Endogenous Ethanol in the Mammal.

    PubMed

    McManus, I R; Contag, A O; Olson, R E

    1960-01-01

    Ethanol has been isolated from the tissues of several animal species in amounts ranging from 23 to 145 micromole/100 gm of tissue. Intestinal bacterial flora appear to be excluded as a source of this ethanol. Radioactivity from pyruvate-2-C(14) appeared in ethanol after incubation with liver slices; this finding indicates an endogenous synthesis.

  4. Essays on Policy Evaluation with Endogenous Adoption

    ERIC Educational Resources Information Center

    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…

  5. Hypobromous acid, a powerful endogenous electrophile: Experimental and theoretical studies.

    PubMed

    Ximenes, Valdecir Farias; Morgon, Nelson Henrique; de Souza, Aguinaldo Robinson

    2015-05-01

    Hypobromous acid (HOBr) is an inorganic acid produced by the oxidation of the bromide anion (Br(-)). The blood plasma level of Br(-) is more than 1,000-fold lower than that of chloride anion (Cl(-)). Consequently, the endogenous production of HOBr is also lower compared to hypochlorous acid (HOCl). Nevertheless, there is much evidence of the deleterious effects of HOBr. From these data, we hypothesized that the reactivity of HOBr could be better associated with its electrophilic strength. Our hypothesis was confirmed, since HOBr was significantly more reactive than HOCl when the oxidability of the studied compounds was not relevant. For instance: anisole (HOBr, k2=2.3×10(2)M(-1)s(-1), HOCl non-reactive); dansylglycine (HOBr, k2=7.3×10(6)M(-1)s(-1), HOCl, 5.2×10(2)M(-1)s(-1)); salicylic acid (HOBr, k2=4.0×10(4)M(-1)s(-1), non-reactive); 3-hydroxybenzoic acid (HOBr, k2=5.9×10(4)M(-1)s(-1), HOCl, k2=1.1×10(1)M(-1)s(-1)); uridine (HOBr, k2=1.3×10(3)M(-1)s(-1), HOCl non-reactive). The compounds 4-bromoanisole and 5-bromouridine were identified as the products of the reactions between HOBr and anisole or uridine, respectively, i.e. typical products of electrophilic substitutions. Together, these results show that, rather than an oxidant, HOBr is a powerful electrophilic reactant. This chemical property was theoretically confirmed by measuring the positive Mulliken and ChelpG charges upon bromine and chlorine. In conclusion, the high electrophilicity of HOBr could be behind its well-established deleterious effects. We propose that HOBr is the most powerful endogenous electrophile. PMID:25771434

  6. ENDOGENOUS ANALGESIA, DEPENDENCE, AND LATENT PAIN SENSITIZATION

    PubMed Central

    Taylor, Bradley K; Corder, Gregory

    2015-01-01

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

  7. [Effect of female sex steroids on levels of endogenous ethanol].

    PubMed

    Garber, M R; Kovalenko, A E

    1988-01-01

    The authors presented the results of a study of the effect of female sex steroids on the level of endogenous ethanol. The time course of endogenous ethanol during the menstrual cycle was investigated. The concentration of endogenous ethanol was compared in the groups of women receiving and not receiving hormonal contraceptives. An increase in sex steroids during the menstrual cycle was accompanied by a decrease in the level of endogenous ethanol. The use of hormonal contraceptives caused an increase in the background concentration of endogenous ethanol. A possible effect of endogenous and exogenous female sex steroids on different levels of regulation of ethanol metabolism was assumed.

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

    PubMed

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

    2009-02-13

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

  9. [Concentration of endogenous ethanol and alcoholic motivation].

    PubMed

    Burov, Iu V; Treskov, V G; Kampov-Polevoĭ, A B; Kovalenko, A E; Rodionov, A P

    1983-11-01

    Trials with patients suffering from stage II chronic alcoholism and normal test subjects as well as experiments made on male C57BL mice (with genetically determined alcoholic motivation) and CBA mice (with genetically determined alcoholic aversion) and random-bred male rats with different levels of initial alcoholic motivation have shown the presence of reverse proportional dependence between blood plasma endogenous ethanol and alcoholic motivation.

  10. HERVd: database of human endogenous retroviruses.

    PubMed

    Paces, Jan; Pavlícek, Adam; Paces, Václav

    2002-01-01

    The human endogenous retroviruses database (HERVd) is maintained at the Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, and is accessible via the World Wide Web at http://herv.img.cas.cz. The HERVd provides complex information on and analysis of retroviral elements found in the human genome. It can be used for searches of individual HERV families, identification of HERV parts, graphical output of HERV structures, comparison of HERVs and identification of retrovirus integration sites.

  11. Endogenous Retroviruses in the Genomics Era.

    PubMed

    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. PMID:26958910

  12. Endogenous growth of persistently active volcanoes

    NASA Astrophysics Data System (ADS)

    Francis, Peter; Oppenheimer, Clive; Stevenson, David

    1993-12-01

    LAVA lakes and active strombolian vents have persisted at some volcanoes for periods exceeding the historic record. They liberate prodigious amounts of volatiles and thermal energy but erupt little lava, a paradox that raises questions about how volcanoes grow. Although long-lasting surface manifestations can be sustained by convective exchange of magma with deeper reservoirs, residence times of magmas beneath several basaltic volcanoes are & sim10-100 years1,2, indicating that where surface activity continues for more than 100-1,000 years, the reservoirs are replenished by new magma. Endogenous growth of Kilauea volcano (Hawaii) through dyke intrusion and cumulate formation is a well-understood consequence of the steady supply of mantle-derived magma3,4. As we show here, inferred heat losses from the Halemaumau lava lake indicate a period of dominantly endogenous growth of Kilauea volcano during the nineteenth century. Moreover, heat losses and degassing rates for several other volcanoes, including Stromboli, also indicate cryptic influxes of magma that far exceed visible effluxes of lavas. We propose that persistent activity at Stromboli, and at other volcanoes in different tectonic settings, is evidence of endogenous growth, involving processes similar to those at Kilauea.

  13. Induced pluripotency with endogenous and inducible genes

    SciTech Connect

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

    2008-10-15

    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{sup 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.

  14. Endogenous Viral Elements in Animal Genomes

    PubMed Central

    Katzourakis, Aris; Gifford, Robert J.

    2010-01-01

    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. PMID:21124940

  15. Endogenous opioid peptides and the control of gonadotrophin secretion.

    PubMed

    Brooks, A N; Lamming, G E; Haynes, N B

    1986-11-01

    The endogenous opioid peptides are a group of recently discovered compounds which occur in the brain of a wide variety of species. Originally named because of their opiate-like activity, they have since been demonstrated to have multifaceted actions, one of which appears to be the modulation of luteinising hormone (LH) secretion. Because of the prime position of LH in the ovulatory process, this role for the opioids has attracted considerable interest. Their mode of action is essentially one of suppression and they work by inhibiting the release of hypothalamic gonadotrophin releasing hormone. Through this mechanism they have been implicated in the suppression of LH secretion during the prepubertal period and the modulation of LH during the oestrous cycle. It is well established that gonadal steroids suppress LH secretion by negative feedback upon the hypothalamic-pituitary axis, and this action may be brought about, in part, through intermediary opioidergic neurones. Much of the research to date has been carried out upon laboratory rodents and primates, but there is evidence now accruing that the opioids have similar actions in domestic animals. Knowledge of the role of these compounds may therefore aid in the understanding of an area of commercial importance, namely the control of ovulation in farm livestock.

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

    PubMed Central

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

    2015-01-01

    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. PMID:25819161

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

    PubMed

    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.

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

    EPA Science Inventory

    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 ...

  19. Endogenous Synthesis of Coenzyme Q in Eukaryotes

    PubMed Central

    Tran, UyenPhuong C.; Clarke, Catherine F.

    2007-01-01

    Coenzyme Q (Q) functions in the mitochondrial respiratory chain and serves as a lipophilic antioxidant. There is increasing interest in the use of Q as a nutritional supplement. Although the physiological significance of Q is extensively investigated in eukaryotes, ranging from yeast to human, the eukaryotic Q biosynthesis pathway is best characterized in the budding yeast Saccharomyces cerevisiae. At least ten genes (COQ1-COQ10) have been shown to be required for Q biosynthesis and function in respiration. This review highlights recent knowledge about the endogenous synthesis of Q in eukaryotes, with emphasis on S. cerevisiae as a model system. PMID:17482885

  20. Human endogenous retroviruses: friend or foe?

    PubMed

    Weiss, Robin A

    2016-01-01

    The integration of proviral DNA into host chromosomal DNA as an obligatory step in the replication cycle of retroviruses is a natural event of genetic recombination between virus and host. When integration occurs in cells of the germ line, it results in mendelian inheritance of viral sequences that we call endogenous retroviruses (ERV) and HERV for humans. HERVs and host often establish a symbiotic relationship, especially in the placenta and in pluripotent embryonic stem cells, but HERVs occasionally have deleterious consequences for the host. This special issue of APMIS features the fascinating relationships between HERV and humans in health and disease. PMID:26818257

  1. Endogenous cannabinoid signaling at inhibitory interneurons

    PubMed Central

    Younts, Thomas J.; Castillo, Pablo E.

    2014-01-01

    Significant progress has been made in our understanding of how endogenous cannabinoids (eCBs) signal at excitatory and inhibitory synapses in the central nervous system (CNS). This review discusses how eCBs regulate inhibitory interneurons, their synapses, and the networks in which they are embedded. eCB signaling plays a pivotal role in brain physiology by means of their synaptic signal transduction, spatiotemporal signaling profile, routing of information through inhibitory microcircuits, and experience-dependent plasticity. Understanding the normal processes underlying eCB signaling is beginning to shed light on how their dysregulation contributes to disease. PMID:24650503

  2. Human endogenous retroviruses in neurologic disease.

    PubMed

    Christensen, Tove

    2016-01-01

    Endogenous retroviruses are pathogenic - in other species than the human. Disease associations for Human Endogenous RetroViruses (HERVs) are emerging, but so far an unequivocal pathogenetic cause-effect relationship has not been established. A role for HERVs has been proposed in neurological and neuropsychiatric diseases as diverse as multiple sclerosis (MS) and schizophrenia (SCZ). Particularly for MS, many aspects of the activation and involvement of specific HERV families (HERV-H/F and HERV-W/MSRV) have been reported, both for cells in the circulation and in the central nervous system. Notably envelope genes and their gene products (Envs) appear strongly associated with the disease. For SCZ, for ALS, and for HIV-associated dementia (HAD), indications are accumulating for involvement of the HERV-K family, and also HERV-H/F and/or HERV-W. Activation is reasonably a prerequisite for causality as most HERV sequences remain quiescent in non-pathological conditions, so the importance of regulatory pathways and epigenetics involved in regulating HERV activation, derepression, and also involvement of retroviral restriction factors, is emerging. HERV-directed antiretrovirals have potential as novel therapeutic paradigms in neurologic disease, particularly in MS. The possible protective or ameliorative effects of antiretroviral therapy in MS are substantiated by reports that treatment of HIV infection may be associated with a significantly decreased risk of MS. Further studies of HERVs, their role in neurologic diseases, and their potential as therapeutic targets are essential. PMID:26818266

  3. Endogenous Technology Adoption and Medical Costs.

    PubMed

    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. PMID:27492052

  4. Endogenous Technology Adoption and Medical Costs.

    PubMed

    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.

  5. Biological redundancy of endogenous GPCR ligands in the gut and the potential for endogenous functional selectivity

    PubMed Central

    Thompson, Georgina L.; Canals, Meritxell; Poole, Daniel P.

    2014-01-01

    This review focuses on the existence and function of multiple endogenous agonists of the somatostatin and opioid receptors with an emphasis on their expression in the gastrointestinal tract. These agonists generally arise from the proteolytic cleavage of prepropeptides during peptide maturation or from degradation of peptides by extracellular or intracellular endopeptidases. In other examples, endogenous peptide agonists for the same G protein-coupled receptors can be products of distinct genes but contain high sequence homology. This apparent biological redundancy has recently been challenged by the realization that different ligands may engender distinct receptor conformations linked to different intracellular signaling profiles and, as such the existence of distinct ligands may underlie mechanisms to finely tune physiological responses. We propose that further characterization of signaling pathways activated by these endogenous ligands will provide invaluable insight into the mechanisms governing biased agonism. Moreover, these ligands may prove useful in the design of novel therapeutic tools to target distinct signaling pathways, thereby favoring desirable effects and limiting detrimental on-target effects. Finally we will discuss the limitations of this area of research and we will highlight the difficulties that need to be addressed when examining endogenous bias in tissues and in animals. PMID:25506328

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

    PubMed

    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. PMID:26681326

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

    PubMed

    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.

  8. Endogenizing geopolitical boundaries with agent-based modeling

    PubMed Central

    Cederman, Lars-Erik

    2002-01-01

    Agent-based modeling promises to overcome the reification of actors. Whereas this common, but limiting, assumption makes a lot of sense during periods characterized by stable actor boundaries, other historical junctures, such as the end of the Cold War, exhibit far-reaching and swift transformations of actors' spatial and organizational existence. Moreover, because actors cannot be assumed to remain constant in the long run, analysis of macrohistorical processes virtually always requires “sociational” endogenization. This paper presents a series of computational models, implemented with the software package REPAST, which trace complex macrohistorical transformations of actors be they hierarchically organized as relational networks or as collections of symbolic categories. With respect to the former, dynamic networks featuring emergent compound actors with agent compartments represented in a spatial grid capture organizational domination of the territorial state. In addition, models of “tagged” social processes allows the analyst to show how democratic states predicate their behavior on categorical traits. Finally, categorical schemata that select out politically relevant cultural traits in ethnic landscapes formalize a constructivist notion of national identity in conformance with the qualitative literature on nationalism. This “finite-agent method”, representing both states and nations as higher-level structures superimposed on a lower-level grid of primitive agents or cultural traits, avoids reification of agency. Furthermore, it opens the door to explicit analysis of entity processes, such as the integration and disintegration of actors as well as boundary transformations. PMID:12011409

  9. Endogenous Group Formation via Unproductive Costs.

    PubMed

    Aimone, Jason A; Iannaccone, Laurence R; Makowsky, Michael D; Rubin, Jared

    2013-10-01

    Sacrifice is widely believed to enhance cooperation in churches, communes, gangs, clans, military units, and many other groups. We find that sacrifice can also work in the lab, apart from special ideologies, identities, or interactions. Our subjects play a modified VCM game-one in which they can voluntarily join groups that provide reduced rates of return on private investment. This leads to both endogenous sorting (because free-riders tend to reject the reduced-rate option) and substitution (because reduced private productivity favours increased club involvement). Seemingly unproductive costs thus serve to screen out free-riders, attract conditional cooperators, boost club production, and increase member welfare. The sacrifice mechanism is simple and particularly useful where monitoring difficulties impede punishment, exclusion, fees, and other more standard solutions. PMID:24808623

  10. Endogenous Group Formation via Unproductive Costs

    PubMed Central

    Aimone, Jason A.; Iannaccone, Laurence R.; Makowsky, Michael D.; Rubin, Jared

    2013-01-01

    Sacrifice is widely believed to enhance cooperation in churches, communes, gangs, clans, military units, and many other groups. We find that sacrifice can also work in the lab, apart from special ideologies, identities, or interactions. Our subjects play a modified VCM game—one in which they can voluntarily join groups that provide reduced rates of return on private investment. This leads to both endogenous sorting (because free-riders tend to reject the reduced-rate option) and substitution (because reduced private productivity favours increased club involvement). Seemingly unproductive costs thus serve to screen out free-riders, attract conditional cooperators, boost club production, and increase member welfare. The sacrifice mechanism is simple and particularly useful where monitoring difficulties impede punishment, exclusion, fees, and other more standard solutions. PMID:24808623

  11. [Endogenous retroviruses are associated with autoimmune diseases].

    PubMed

    Nexø, Bjørn A; Jensen, Sara B; Hansen, Bettina; Laska, Magdalena J

    2016-06-13

    Retroviruses can be transmitted in two fundamentally different ways: 1) They can be horizontally transmitted as infectious virus, or 2) they can integrate in the germ line and be transmitted to offspring and the offsprings' offspring as DNA. The latter is called endogenous viruses. The mode of transmission is called vertical. Viral variants of importance for development of disease must be more frequent among diseased persons than among healthy individuals. Multiple sclerosis, diabetes and rheumatoid arthritis are all associated with sets of endogenouos retroviruses but not the same sets. If a virus grows and this contributes to disease, one should be able to alleviate disease with antiretroviral drugs. We call for clinical trials to elucidate this issue. PMID:27292833

  12. Chitin is endogenously produced in vertebrates

    PubMed Central

    Sohn, Joel J.; Amemiya, Chris T.

    2015-01-01

    Chitin, a biopolymer of N-acetylglucosamine, is abundant in invertebrates and fungi, and is an important structural molecule. There has been a longstanding belief that vertebrates do not produce chitin, however, we have obtained compelling evidence to the contrary. Chitin synthase genes are present in numerous fishes and amphibians, and chitin is localized in situ to the lumen of the developing zebrafish gut, in epithelial cells of fish scales, and in at least three different cell types in larval salamander appendages. Chitin synthase gene knockdowns and various histochemical experiments in zebrafish further authenticated our results. Finally, a polysaccharide was extracted from scales of salmon that exhibited all the chemical hallmarks of chitin. Our data and analyses demonstrate the existence of endogenous chitin in vertebrates and suggest that it serves multiple roles in vertebrate biology. PMID:25772447

  13. Parental representations of neurotic and endogenous depressives.

    PubMed

    Parker, G; Kiloh, L; Hayward, L

    1987-01-01

    Low parental care and parental overprotection have been incriminated as risk factors to depression in adult life. The relevance of these parental characteristics to broad depressive 'types' with their varying imputed aetiologies was assessed by having 26 patients with endogenous depression (ED) and 40 with neurotic depression (ND) complete the Parental Bonding Instrument (PBI) self-report measure. In comparison to their controls, the EDs did not differ on the parental care and overprotection scales. The NDs, by contrast, were more likely than their controls to report their parents as uncaring and overprotective. A PBI care scale score of less than 10 was particularly discriminating, being reported by 3.8% of the EDs and 37.5% of the NDs. While findings support the binary view of depression in terms of broad imputed aetiological factors, several response biases which might influence the findings are considered. PMID:2959703

  14. How Active Are Porcine Endogenous Retroviruses (PERVs)?

    PubMed Central

    Denner, Joachim

    2016-01-01

    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. PMID:27527207

  15. Endogenous cardiotonic steroids in chronic renal failure

    PubMed Central

    Kolmakova, Elena V.; Haller, Steven T.; Kennedy, David J.; Isachkina, Alina N.; Budny, George V.; Frolova, Elena V.; Piecha, Grzegorz; Nikitina, Elena R.; Malhotra, Deepak; Fedorova, Olga V.; Shapiro, Joseph I.

    2011-01-01

    Background. Previous reports demonstrated that digitalis-like cardiotonic steroids (CTS) contribute to the pathogenesis of end-stage renal disease. The goal of the present study was to define the nature of CTS in patients with chronic kidney disease (CKD) and in partially nephrectomized (PNx) rats. Methods. In patients with CKD and in healthy controls, we determined plasma levels of marinobufagenin (MBG) and endogenous ouabain (EO) and erythrocyte Na/K-ATPase activity in the absence and in the presence of 3E9 anti-MBG monoclonal antibody (mAb) and Digibind. Levels of MBG and EO were also determined in sham-operated Sprague–Dawley rats and in rats following 4 weeks of PNx. Results. In 25 patients with CKD plasma, MBG but not EO was increased (0.86 ± 0.07 versus 0.28 ± 0.02 nmol/L, P < 0.01) and erythrocyte Na/K-ATPase was inhibited (1.24 ± 0.10 versus 2.80 ± 0.09 μmol Pi/mL/h, P < 0.01) as compared to that in 19 healthy subjects. Ex vivo, 3E9 mAb restored Na/K-ATPase in erythrocytes from patients with CKD but did not affect Na/K-ATPase from control subjects. Following chromatographic fractionation of uremic versus normal plasma, a competitive immunoassay based on anti-MBG mAb detected a 3-fold increase in the level of endogenous material having retention time similar to that seen with MBG. A similar pattern of CTS changes was observed in uremic rats. As compared to sham-operated animals, PNx rats exhibited 3-fold elevated levels of MBG but not that of EO. Conclusions. In chronic renal failure, elevated levels of a bufadienolide CTS, MBG, contribute to Na/K-ATPase inhibition and may represent a potential target for therapy. PMID:21292813

  16. Identification of some volatile endogenous constituents in rat brain tissue and the effects of lithium carbonate and chloral hydrate.

    PubMed

    Politzer, I R; McDonald, L K; Laseter, J L

    1976-11-01

    Nine endogenous volatile compounds were found in rat brain tissue, and were identified by mass spectrometry as chloroform, a 5-C-aldehyde, dimethyl disulphide, 2,5-dimethyl tetrahydrofuran, a 8-C-alkane, xylene, 2-heptanone, heptaldehyde and 2-n-pentylfuran. Using gas chromatographic and gas chromatographic mass spectrometric techniques, it was established that lithium carbonate did not induce the production of detectable amounts of any new volatile compounds in brain tissue. However, after administration of chloral hydrate, trichloroethanol, a compound not normally present in rat brain tissue, was found to be present. PMID:996360

  17. Polybenzimidazole compounds

    DOEpatents

    Klaehn, John R.; Peterson, Eric S.; Wertsching, Alan K.; Orme, Christopher J.; Luther, Thomas A.; Jones, Michael G.

    2010-08-10

    A PBI compound that includes imidazole nitrogens, at least a portion of which are substituted with an organic-inorganic hybrid moiety. At least 85% of the imidazole nitrogens may be substituted. The organic-inorganic hybrid moiety may be an organosilane moiety, for example, (R)Me.sub.2SiCH.sub.2--, where R is selected from among methyl, phenyl, vinyl, and allyl. The PBI compound may exhibit similar thermal properties in comparison to the unsubstituted PBI. The PBI compound may exhibit a solubility in an organic solvent greater than the solubility of the unsubstituted PBI. The PBI compound may be included in separatory media. A substituted PBI synthesis method may include providing a parent PBI in a less than 5 wt % solvent solution. Substituting may occur at about room temperature and/or at about atmospheric pressure. Substituting may use at least five equivalents in relation to the imidazole nitrogens to be substituted or, preferably, about fifteen equivalents.

  18. Polybenzimidazole compounds

    DOEpatents

    Klaehn, John R.; Peterson, Eric S.; Orme, Christopher J.; Jones, Michael G.; Wertsching, Alan K.; Luther, Thomas A.; Trowbridge, Tammy L.

    2011-11-22

    A PBI compound includes imidazole nitrogens at least a portion of which are substituted with a moiety containing a carbonyl group, the substituted imidazole nitrogens being bonded to carbon of the carbonyl group. At least 85% of the nitrogens may be substituted. The carbonyl-containing moiety may include RCO--, where R is alkoxy or haloalkyl. The PBI compound may exhibit a first temperature marking an onset of weight loss corresponding to reversion of the substituted PBI that is less than a second temperature marking an onset of decomposition of an otherwise identical PBI compound without the substituted moiety. The PBI compound may be included in separatory media. A substituted PBI synthesis method may include providing a parent PBI in a less than 5 wt % solvent solution. Substituting may use more than 5 equivalents in relation to the imidazole nitrogens to be substituted.

  19. Cyanobacterium sp. host cell and vector for production of chemical compounds in Cyanobacterial cultures

    DOEpatents

    Piven, Irina; Friedrich, Alexandra; Duhring, Ulf; Uliczka, Frank; Baier, Kerstin; Inaba, Masami; Shi, Tuo; Wang, Kui; Enke, Heike; Kramer, Dan

    2016-04-19

    A cyanobacterial host cell, Cyanobacterium sp., that harbors at least one recombinant gene for the production of a chemical compounds is provided, as well as vectors derived from an endogenous plasmid isolated from the cell.

  20. Cyanobacterium sp. host cell and vector for production of chemical compounds in cyanobacterial cultures

    SciTech Connect

    Piven, Irina; Friedrich, Alexandra; Duhring, Ulf; Uliczka, Frank; Baier, Kerstin; Inaba, Masami; Shi, Tuo; Wang, Kui; Enke, Heike; Kramer, Dan

    2014-09-30

    A cyanobacterial host cell, Cyanobacterium sp., that harbors at least one recombinant gene for the production of a chemical compounds is provided, as well as vectors derived from an endogenous plasmid isolated from the cell.

  1. Strategies for endogenous spinal cord repair: HPMA hydrogel to recruit migrating endogenous stem cells.

    PubMed

    Espinosa-Jeffrey, Araceli; Oregel, Karlos; Wiggins, Laurent; Valera, Remelyn; Bosnoyan, Kathrin; Agbo, Chioma; Awosika, Oluwole; Zhao, Paul M; de Vellis, Jean; Woerly, Stéphane

    2012-01-01

    Injury to the spinal cord disrupts ascending and descending axonal pathways and causes tissue damage with a subsequent limited cellular regeneration. Successful treatment would encompass the restoration of the cytoarchitecture, homeostasis and function all in dear need. Transplantation-based treatments using exogenous cells are the most favoured approach. Yet, with the advent of the stem cell concept and continuous progress in the field it became clear that the endogenous potential for repair is greater than previously thought. As an alternative to neural grafting, we and other researchers have aimed at understanding what are the elements needed for a successful repair with self progenitors that would give rise to the cell types needed to restore function of the central nervous system. Some studies involve both scaffolds and cell grafts. Here we describe studies on spinal cord repair using what we call "endogenous tissue engineering for regenerative medicine". The approach involves a hydrogel that mimics the natural milieu where endogenous pre-existing and newly formed cells populate the gel progressively allowing for the integration of CNS self populations leading to a successful recovery of function. Highlight aspects learned from this type of studies are that: Endogenous reconstruction of the injured spinal cord is possible by using the adequate support. The contribution of nestin-expressing progenitors to spinal cord regeneration is continuous and substantial both, in the reconstructed segment as well as, along the distal and caudal segments of the reconstructed spinal cord. Most of these cells appear to have been in a quiescent state until the injury occurred and only a small fraction of these neural progenitors was produced via cell proliferation. The hydrogel combined with exercise was necessary and sufficient to restore locomotor function in cats that underwent spinal transaction followed by reconstructive surgery. This recovery of function was first seen

  2. INTESTINAL EXCRETION OF ENDOGENOUS ZINC IN GUATEMALAN SCHOOL CHILDREN

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The intestine is the major route of excretion of endogenous zinc and has a key role in maintaining zinc homeostasis. Phytate has been reported to increase these losses. Objective: To determine the rate of excretion of endogenous zinc in school-aged children in a poor rural community for ...

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

  5. Social Interactions with Endogenous Associations. NBER Working Paper No. 13038

    ERIC Educational Resources Information Center

    Weinberg, Bruce A.

    2007-01-01

    This paper develops a model of social interactions with endogenous association. People are assumed to invest in relationships to maximize their utility. Even in a linear-in-means model, when associations are endogenous, the effect of macro-group composition on behavior is non-linear and varies across individuals. We also show that larger groups…

  6. Identification of Putative Natriuretic Hormones Isolated from Human Urine.

    PubMed

    Kramer, Herbert J

    2015-01-01

    This brief review describes some representative methodological approaches to the isolation of putative endogenous inhibitors of epithelial sodium transport - i.e., as ouabain-like factors (OLF) that inhibit the sodium transport enzyme Na-K-ATPase or inhibit the epithelial sodium channel (ENaC). Gel chromatography and reverse-phase (RP)-high performance liquid chromatography (HPLC) of lyophilized and reconstituted 24 h-urine from salt-loaded healthy humans led to two active fractions, a hydrophilic OLF-1 and a lipophilic OLF-2, whose mass (Ms)-spectroscopic data indicate a Mr of 391 (1, 2). Further identification was attempted by Ms-, infrared (IR)-, ultraviolet (UV)-, and (1)H-NMR-spectroscopy. OLF-1 and OLF-2 may be closely related if not identical to (di)ascorbic acid or its salts such as vanadium (V)-V(v)-diascorbate with Mr 403 (3) and V(IV)-diascorbate. OLF-1 and V(v)-diascorbate are about 10-fold stronger inhibitors of Na-K-ATPase than OLF-2 and V(IV)-diascorbate, respectively. In conscious rats, i.v. infusion of OLF-1 and OLF-2 resulted in a strong natriuresis. In a similar study, Cain et al. (4) isolated a sodium transport inhibitor from the urine of uremic patients by gel chromatography and RP-HPLC. In uremic rats, a natriuretic response to the injection of the active material was found. Xanthurenic acid 8-O-β-d-glucoside (Mr 368) and xanthurenic acid 8-O-sulfate (Mr 284) were identified as endogenous inhibitors of sodium transport acting, e.g., by ENaC blockade. No definite relation to blood pressure, body fluid volume, or sodium balance has been reported for any of these above factors, and further studies to identify the natriuretic and/or ouabain-like compound(s) or hormone(s) will be needed. PMID:26052310

  7. Endogenous Synthesis of Prebiotic Organic Molecules

    NASA Technical Reports Server (NTRS)

    Miller, Stanley L.

    1996-01-01

    The necessary condition for the synthesis of organic compounds on the primitive earth is the presence of reducing conditions. This means an atmosphere of CH4, CO, or CO2 + H2. The atmospheric nitrogen can be N2 with a trace of NH3, but NH4(+) is needed in the ocean at least for amino acid synthesis. Many attempts have been made to use CO2 + H2O atmospheres for prebiotic synthesis, but these give at best extremely low yields of organic compounds, except in the presence of H2. Even strong reducing agents such as FeS + H2S or the mineral assemblages of the submarine vents fail to give significant yields of organic compounds with CO2. There appears to be a high kinetic barrier to the non-biological reduction of CO2 at low temperatures using geological reducing agents. The most abundant source of energy for prebiotic synthesis is ultraviolet light followed by electric discharges, with electric discharges being more efficient, although it is not clear which was the important energy source. Photochemical process would also make significant contributions. In an atmosphere Of CO2, N2, and H2O with no H2, the production rates of HCN and H2CO would be very low, 0.001 or less than that of a relatively reducing atmosphere. The concentration of organic compounds under these non-reducing conditions would be so low that there is doubt whether the concentration mechanism would be adequate for further steps toward the origin of life. A number of workers have calculated the influx of comets and meteorites on the primitive earth as a source of organic compounds. We conclude that while some organic material was added to the earth from comets and meteorites the amount available from these sources at a given time was at best only a few percent of that from earth bases syntheses under reducing conditions.

  8. Multipurpose Compound

    NASA Technical Reports Server (NTRS)

    1983-01-01

    Specially formulated derivatives of an unusual basic compound known as Alcide may be the answer to effective treatment and prevention of the disease bovine mastitis, a bacterial inflammation of a cow's mammary gland that results in loss of milk production and in extreme cases, death. Manufactured by Alcide Corporation the Alcide compound has killed all tested bacteria, virus and fungi, shortly after contact, with minimal toxic effects on humans or animals. Alcide Corporation credits the existence of the mastitis treatment/prevention products to assistance provided the company by NERAC, Inc.

  9. Retinal photodamage by endogenous and xenobiotic agents.

    PubMed

    Wielgus, Albert R; Roberts, Joan E

    2012-01-01

    The human eye is constantly exposed to sunlight and artificial lighting. Light transmission through the eye is fundamental to its unique biological functions of directing vision and circadian rhythm and therefore light absorbed by the eye must be benign. However, exposure to the very intense ambient radiation can pose a hazard particularly if the recipient is over 40 years of age. There are age-related changes in the endogenous (natural) chromophores (lipofuscin, A2E and all-trans-retinal derivatives) in the human retina that makes it more susceptible to visible light damage. Intense visible light sources that do not filter short blue visible light (400-440 nm) used for phototherapy of circadian imbalance (i.e. seasonal affective disorder) increase the risk for age-related light damage to the retina. Moreover, many drugs, dietary supplements, nanoparticles and diagnostic dyes (xenobiotics) absorb ocular light and have the potential to induce photodamage to the retina, leading to transient or permanent blinding disorders. This article will review the underlying reasons why visible light in general and short blue visible light in particular dramatically raises the risk of photodamage to the human retina.

  10. Endogenous hepadnaviruses, bornaviruses and circoviruses in snakes

    PubMed Central

    Gilbert, C.; Meik, J. M.; Dashevsky, D.; Card, D. C.; Castoe, T. A.; Schaack, S.

    2014-01-01

    We report the discovery of endogenous viral elements (EVEs) from Hepadnaviridae, Bornaviridae and Circoviridae in the speckled rattlesnake, Crotalus mitchellii, the first viperid snake for which a draft whole genome sequence assembly is available. Analysis of the draft assembly reveals genome fragments from the three virus families were inserted into the genome of this snake over the past 50 Myr. Cross-species PCR screening of orthologous loci and computational scanning of the python and king cobra genomes reveals that circoviruses integrated most recently (within the last approx. 10 Myr), whereas bornaviruses and hepadnaviruses integrated at least approximately 13 and approximately 50 Ma, respectively. This is, to our knowledge, the first report of circo-, borna- and hepadnaviruses in snakes and the first characterization of non-retroviral EVEs in non-avian reptiles. Our study provides a window into the historical dynamics of viruses in these host lineages and shows that their evolution involved multiple host-switches between mammals and reptiles. PMID:25080342

  11. Endogenous hepadnaviruses, bornaviruses and circoviruses in snakes.

    PubMed

    Gilbert, C; Meik, J M; Dashevsky, D; Card, D C; Castoe, T A; Schaack, S

    2014-09-22

    We report the discovery of endogenous viral elements (EVEs) from Hepadnaviridae, Bornaviridae and Circoviridae in the speckled rattlesnake, Crotalus mitchellii, the first viperid snake for which a draft whole genome sequence assembly is available. Analysis of the draft assembly reveals genome fragments from the three virus families were inserted into the genome of this snake over the past 50 Myr. Cross-species PCR screening of orthologous loci and computational scanning of the python and king cobra genomes reveals that circoviruses integrated most recently (within the last approx. 10 Myr), whereas bornaviruses and hepadnaviruses integrated at least approximately 13 and approximately 50 Ma, respectively. This is, to our knowledge, the first report of circo-, borna- and hepadnaviruses in snakes and the first characterization of non-retroviral EVEs in non-avian reptiles. Our study provides a window into the historical dynamics of viruses in these host lineages and shows that their evolution involved multiple host-switches between mammals and reptiles. PMID:25080342

  12. Endogenous polyamine function—the RNA perspective

    PubMed Central

    Lightfoot, Helen L.; Hall, Jonathan

    2014-01-01

    Recent progress with techniques for monitoring RNA structure in cells such as ‘DMS-Seq’ and ‘Structure-Seq’ suggests that a new era of RNA structure-function exploration is on the horizon. This will also include systematic investigation of the factors required for the structural integrity of RNA. In this context, much evidence accumulated over 50 years suggests that polyamines play important roles as modulators of RNA structure. Here, we summarize and discuss recent literature relating to the roles of these small endogenous molecules in RNA function. We have included studies directed at understanding the binding interactions of polyamines with polynucleotides, tRNA, rRNA, mRNA and ribozymes using chemical, biochemical and spectroscopic tools. In brief, polyamines bind RNA in a sequence-selective fashion and induce changes in RNA structure in context-dependent manners. In some cases the functional consequences of these interactions have been observed in cells. Most notably, polyamine-mediated effects on RNA are frequently distinct from those of divalent cations (i.e. Mg2+) confirming their roles as independent molecular entities which help drive RNA-mediated processes. PMID:25232095

  13. Endogenous neural noise and stochastic resonance

    NASA Astrophysics Data System (ADS)

    Emberson, Lauren; Kitajo, Keiichi; Ward, Lawrence M.

    2007-06-01

    We discuss the relationship of endogenous neural noise (ENN) to performance of behavioral tasks and to information processing in the brain. Spontaneous neural activity is closely linked to development and perception, and is correlated with behavior. Some of this activity is probably related to internal processing of task- and goal-relevant information, but some is simply noise. Two previous studies have reported correlations between performance on behavioral tasks and measures of neural noise and have characterized these relationships as intrinsic stochastic resonance (SR). We argue that neither of these studies demonstrated intrinsic SR, and discuss several alternative ways of measuring ENN in humans from EEG or MEG records. Using one of these, random-phase power in the 30-50 Hz range 1 sec before the onset of the signal, we demonstrate a kind of intrinsic SR that optimizes detection of weak visual signals. Minimum response time was obtained when this EEG measure of ENN was in a middle decile. No other measure of ENN was related either to response time or to an unbiased measure of detection accuracy (e.g., d'). A discussion of the implications of these findings for the study of intrinsic SR concludes the paper.

  14. Spontaneous endogenous hypermelatoninemia: a new disease?

    PubMed

    Duman, Ozgur; Durmaz, Erdem; Akcurin, Sema; Serteser, Mustafa; Haspolat, Senay

    2010-01-01

    Melatonin, a major photoperiod-dependent hormone, regulates circadian rhythms and biological rhythms and acts as a prominent sleep promoter. Symptoms related to hypermelatoninemia have been reported in individuals supplemented with melatonin. However, spontaneous endogenous hypermelatoninemia has not been reported previously. A 6-year-old girl previously diagnosed with Shapiro's syndrome was admitted to our hospital on several occasions during a 1-year period with complaints of altered consciousness, syncope, hypothermia and episodes of sweating. The episodes occurred daily and during sleep and lasted for 1-6 h. During these episodes, she sweated profusely and felt faint and her skin was pale and cool. Other complaints included recurrent abdominal pain, urge incontinence and myopia. She was shown to have hypermelatoninemia (>1,000 pg/ml, normal range 0-150 pg/ml) during these episodes. The duration of her attacks decreased with phototherapy and she was successfully treated with propranolol. To our knowledge, this is the first case of hypermelatoninemia without any detectable organic pathology. We did not determine the exact mechanism of hypermelatoninemia in this patient; however, it might have been related to irregular control of pinealocytes by the suprachiasmatic nucleus or related pathways. Hypermelatoninemia should be considered in patients with spontaneous periodic hypothermia and hyperhidrosis, and also in patients with Shapiro's syndrome. PMID:21041995

  15. Absolute Quantification of Endogenous Ras Isoform Abundance

    PubMed Central

    Mageean, Craig J.; Griffiths, John R.; Smith, Duncan L.; Clague, Michael J.; Prior, Ian A.

    2015-01-01

    Ras proteins are important signalling hubs situated near the top of networks controlling cell proliferation, differentiation and survival. Three almost identical isoforms, HRAS, KRAS and NRAS, are ubiquitously expressed yet have differing biological and oncogenic properties. In order to help understand the relative biological contributions of each isoform we have optimised a quantitative proteomics method for accurately measuring Ras isoform protein copy number per cell. The use of isotopic protein standards together with selected reaction monitoring for diagnostic peptides is sensitive, robust and suitable for application to sub-milligram quantities of lysates. We find that in a panel of isogenic SW48 colorectal cancer cells, endogenous Ras proteins are highly abundant with ≥260,000 total Ras protein copies per cell and the rank order of isoform abundance is KRAS>NRAS≥HRAS. A subset of oncogenic KRAS mutants exhibit increased total cellular Ras abundance and altered the ratio of mutant versus wild type KRAS protein. These data and methodology are significant because Ras protein copy number is required to parameterise models of signalling networks and informs interpretation of isoform-specific Ras functional data. PMID:26560143

  16. Endogenous Candida endophthalmitis after induced abortion.

    PubMed

    Chen, S J; Chung, Y M; Liu, J H

    1998-06-01

    Reported, in this article, are the cases of two young women who developed endogenous Candida endophthalmitis after induced abortion. Both women experienced transient fever, chills, and abdominal pain after the abortion and were given antibiotics. The diagnosis of endophthalmitis was established on the basis of typical fundus appearance, positive vaginal culture, and (in one case) positive vitreous culture. In the first woman, who received vitrectomy and intravitreal amphotericin B injection, the affected eye had a best corrected visual acuity of 20/200. In the second woman, who was given systemic corticosteroid treatment before the correct diagnosis was reached, recurrent retinal detachment developed and the best corrected visual acuity was counting fingers. It appears that Candida organisms harbored in the genital tract are directly inoculated into the venous system during induced abortion. Once in the blood, if sufficient fungal load is present, Candida albicans tends to localize in the choroid and to spread toward the retina and vitreous cavity. The immunosuppressive effect of corticosteroids further increases the risk of endophthalmitis. PMID:9645729

  17. Perfluorinated Compounds

    EPA Science Inventory

    Perfluorinated compounds such as the perfluoroalkyl acids (PFAAs) and their derivatives are important man-made chemicals that have wide consumer and industrial applications. They are relatively contemporary chemicals, being in use only since the 1950s, and until recently, have be...

  18. Magnesium compounds

    USGS Publications Warehouse

    Kramer, D.A.

    2001-01-01

    Seawater and natural brines accounted for about 63% of US magnesium compounds production during 2000. Premier Services in Florida, Dow Chemical in Michigan, Martin Marietta Magnesia Specialties, and Rohm & Haas recovered dead-burned and caustic-calcined magnesias from seawater. And Premier Services' recoveries, in Nevada, were from magnasite.

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

    SciTech Connect

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

    1989-12-01

    To interpret the metabolism of radiolabeled gibberellins A{sub 12}-aldehyde and A{sub 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 ({sup 14}C)GA{sub 12} and ({sup 14}C)GA{sub 12}-aldehyde were synthesized using a pumpkin endosperm enzyme preparation, and purified by high performance liquid chromatography (HPLC). ({sup 14}C)GA{sub 12} was supplied to upper shoots of pea, line G2, to produce radiolabeled metabolites on the 13-OH pathway. Endogenous compounds copurifying with the ({sup 14}C)GAs on HPLC were analyzed by gas chromatography-mass spectrometry. The endogenous presence of GA{sub 53}, GA{sub 44}, GA{sub 19} and GA{sub 20} was demonstrated and their HPLC peak identity ascertained. The {sup 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{sub 53} to 4% in GA{sub 20}. Calculated levels of GA{sub 20}, GA{sub 19}, GA{sub 44}, and GA{sub 53} were 42, 8, 10, and 0.5 nanograms/gram, respectively.

  20. Peroxynitrite: an endogenous oxidizing and nitrating agent.

    PubMed

    Ducrocq, C; Blanchard, B; Pignatelli, B; Ohshima, H

    1999-07-01

    Peroxynitrite, the reaction product between nitric oxide (.NO) and superoxide, has been presumed to be a mediator of cellular and tissue injury in various pathological situations. It is formed at the convergence of two independent radical-generating metabolic pathways. Its biological effects are due to its reactivity towards a large range of molecules including amino acids such as cysteine, methionine, tyrosine and tryptophan, nucleic bases and antioxidants (e.g. phenolics, selenium- and metal-containing compounds, ascorbate and urate). Peroxynitrite reactions involve oxidation and nitration. The chemical properties depend on the presence of CO2 and metallic compounds as well as the concentrations of reagents and kinetic laws. This complex chemistry can be explained by the formation of several structural forms and active intermediates released from peroxynitrite. PMID:10442088

  1. Receptors on lymphocytes for endogenous splenic glycosaminoglycans.

    PubMed Central

    Bradbury, M G; Parish, C R

    1989-01-01

    Previous studies have shown that lymphocytes carry cell surface receptors for sulphated polysaccharides (SPS), and SPS recognition may play a role in lymphocyte migration and positioning in vivo. This paper describes attempts to isolate and characterize the endogenous glycosaminoglycans (GAGs) of murine spleen and determine whether splenic lymphocytes carry cell surface receptors for these GAGs. A procedure was devised for isolating GAGs from murine spleen in good yield and high purity and the GAG preparation was then radiolabelled for subsequent binding studies. It was found that the splenic GAGs bound to murine splenocytes in a saturable, rapid and reversible manner with only a small subpopulation of the splenic GAG preparation being involved in binding. This reactive species was chondroitinase ABC-resistant and nitrous acid-sensitive, indicative of a heparan sulphate/heparin-like molecule. Furthermore, using immunofluorescent flow cytometry studies it was demonstrated that the majority of spleen cells have receptors for these GAGs. Subsequent ion-exchange fractionation and SDS-PAGE analysis of chondroitinase ABC-resistant GAGs confirmed that the splenic GAG recognized by splenocytes was a heparan sulphate/heparin molecule of approximately 20,000 MW with a binding affinity to splenocytes of approximately 5 X 10(-8) M. Additional binding inhibition studies indicated two possible binding sites for splenic GAGs on the splenocyte surface, one being fully inhibited by a range of SPS such as heparin (both coagulant and anticoagulant forms), pentosan sulphate, fucoidan, dextran sulphate, lambda- and iota-carrageenan, and the second being partially inhibited by kappa-carrageenan. The possible relevance of these heparan sulphate/heparin receptors on splenocytes to lymphocyte positioning in vivo is discussed. Images Figure 6 PMID:2541072

  2. Minority Aging and Endogenous Pain Facilitatory Processes

    PubMed Central

    Bulls, Hailey W.; Goodin, Burel R.; McNew, Myriah; Gossett, Ethan W.; Bradley, Laurence A.

    2016-01-01

    Objective The aim of the current study was to examine the relationships among age, ethnicity, and endogenous pain facilitation using temporal summation (TS) responses to mechanical and heat stimuli. Design The present study assessed hyperalgesia and pain facilitation to thermal and mechanical stimuli at the knee and distal sites in 98 pain-free men and women. Participants were drawn from two ethnic (African-Americans, AA; and non-Hispanic whites, NHW) and age groups (19-35 and 45-85). Results Significant main effects of ethnicity were demonstrated for both mechanical and heat modalities (all p’s≤0.05), suggesting that AA participants, relative to NHW counterparts, demonstrated enhanced hyperalgesia. Age differences (older > younger) in hyperalgesia were found in mechanical pain ratings only. Results indicated that mechanical pain ratings significantly increased from first to maximal pain as a function of both age group and ethnicity (all p’s≤0.05), and a significant ethnicity by age interaction for TS of mechanical pain was found at the forearm (p<0.05) and trended towards significance at the knee (p=0.071). Post-hoc tests suggested that results were primarily driven by the older AA participants, who demonstrated the greatest mechanical TS. Additionally, evidence of differences in heat TS due to both ethnicity alone (all p’s≤0.05) and minority aging was also found. Conclusions This study provides evidence suggesting that older AAs demonstrate enhanced pain facilitatory processes, which is important because this group may be at increased risk for development of chronic pain. These results underscore the necessity of testing pain modulatory mechanisms when addressing questions related to pain perception and minority aging. PMID:26814250

  3. Endogenous opioids: The downside of opposing stress

    PubMed Central

    Valentino, Rita J.; Van Bockstaele, Elisabeth

    2014-01-01

    Our dynamic environment regularly exposes us to potentially life-threatening challenges or stressors. To answer these challenges and maintain homeostasis, the stress response, an innate coordinated engagement of central and peripheral neural systems is initiated. Although essential for survival, the inappropriate initiation of the stress response or its continuation after the stressor is terminated has pathological consequences that have been linked to diverse neuropsychiatric and medical diseases. Substantial individual variability exists in the pathological consequences of stressors. A theme of this Special Issue is that elucidating the basis of individual differences in resilience or its flipside, vulnerability, will greatly advance our ability to prevent and treat stress-related diseases. This can be approached by studying individual differences in “pro-stress” mediators such as corticosteroids or the hypothalamic orchestrator of the stress response, corticotropin-releasing factor. More recently, the recognition of endogenous neuromodulators with “anti-stress” activity that have opposing actions or that restrain stress-response systems suggests additional bases for individual differences in stress pathology. These “anti-stress” neuromodulators offer alternative strategies for manipulating the stress response and its pathological consequences. This review uses the major brain norepinephrine system as a model stress-response system to demonstrate how co-regulation by opposing pro-stress (corticotropin-releasing factor) and anti-stress (enkephalin) neuromodulators must be fine-tuned to produce an adaptive response to stress. The clinical consequences of tipping this fine-tuned balance in the direction of either the pro- or anti-stress systems are emphasized. Finally, that each system provides multiple points at which individual differences could confer stress vulnerability or resilience is discussed. PMID:25506603

  4. Mitochondrial respiratory function induces endogenous hypoxia.

    PubMed

    Prior, Sara; Kim, Ara; Yoshihara, Toshitada; Tobita, Seiji; Takeuchi, Toshiyuki; Higuchi, Masahiro

    2014-01-01

    Hypoxia influences many key biological functions. In cancer, it is generally believed that hypoxic condition is generated deep inside the tumor because of the lack of oxygen supply. However, consumption of oxygen by cancer should be one of the key means of regulating oxygen concentration to induce hypoxia but has not been well studied. Here, we provide direct evidence of the mitochondrial role in the induction of intracellular hypoxia. We used Acetylacetonatobis [2-(2'-benzothienyl) pyridinato-kN, kC3'] iridium (III) (BTP), a novel oxygen sensor, to detect intracellular hypoxia in living cells via microscopy. The well-differentiated cancer cell lines, LNCaP and MCF-7, showed intracellular hypoxia without exogenous hypoxia in an open environment. This may be caused by high oxygen consumption, low oxygen diffusion in water, and low oxygen incorporation to the cells. In contrast, the poorly-differentiated cancer cell lines: PC-3 and MDAMB231 exhibited intracellular normoxia by low oxygen consumption. The specific complex I inhibitor, rotenone, and the reduction of mitochondrial DNA (mtDNA) content reduced intracellular hypoxia, indicating that intracellular oxygen concentration is regulated by the consumption of oxygen by mitochondria. HIF-1α was activated in endogenously hypoxic LNCaP and the activation was dependent on mitochondrial respiratory function. Intracellular hypoxic status is regulated by glucose by parabolic dose response. The low concentration of glucose (0.045 mg/ml) induced strongest intracellular hypoxia possibly because of the Crabtree effect. Addition of FCS to the media induced intracellular hypoxia in LNCaP, and this effect was partially mimicked by an androgen analog, R1881, and inhibited by the anti-androgen, flutamide. These results indicate that mitochondrial respiratory function determines intracellular hypoxic status and may regulate oxygen-dependent biological functions. PMID:24586439

  5. Functional epialleles at an endogenous human centromere.

    PubMed

    Maloney, Kristin A; Sullivan, Lori L; Matheny, Justyne E; Strome, Erin D; Merrett, Stephanie L; Ferris, Alyssa; Sullivan, Beth A

    2012-08-21

    Human centromeres are defined by megabases of homogenous alpha-satellite DNA arrays that are packaged into specialized chromatin marked by the centromeric histone variant, centromeric protein A (CENP-A). Although most human chromosomes have a single higher-order repeat (HOR) array of alpha satellites, several chromosomes have more than one HOR array. Homo sapiens chromosome 17 (HSA17) has two juxtaposed HOR arrays, D17Z1 and D17Z1-B. Only D17Z1 has been linked to CENP-A chromatin assembly. Here, we use human artificial chromosome assembly assays to show that both D17Z1 and D17Z1-B can support de novo centromere assembly independently. We extend these in vitro studies and demonstrate, using immunostaining and chromatin analyses, that in human cells the centromere can be assembled at D17Z1 or D17Z1-B. Intriguingly, some humans are functional heterozygotes, meaning that CENP-A is located at a different HOR array on the two HSA17 homologs. The site of CENP-A assembly on HSA17 is stable and is transmitted through meiosis, as evidenced by inheritance of CENP-A location through multigenerational families. Differences in histone modifications are not linked clearly with active and inactive D17Z1 and D17Z1-B arrays; however, we detect a correlation between the presence of variant repeat units of D17Z1 and CENP-A assembly at the opposite array, D17Z1-B. Our studies reveal the presence of centromeric epialleles on an endogenous human chromosome and suggest genomic complexities underlying the mechanisms that determine centromere identity in humans.

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

    NASA Astrophysics Data System (ADS)

    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

  7. Demonstration of endogenous imipramine like material in rat brain

    SciTech Connect

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

    1985-02-18

    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 (/sup 3/H) imipramine specific binding and mimics the inhibitory effect of imipramine on (/sup 3/H) serotonin uptake in both brain and platelet preparations. The effects of the endogenous material are dose-dependent and it inhibits (/sup 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.

  8. Endogenous allergen upregulation: transgenic vs. traditionally bred crops.

    PubMed

    Herman, Rod A; Ladics, Gregory S

    2011-10-01

    The safety assessment for transgenic food crops currently includes an evaluation of the endogenous allergy potential (via serum IgE screening) when the non-transgenic counterpart is a commonly allergenic food. The value of this analysis in the safety assessment of transgenic crops, especially with reference to recent requests to quantify individual allergen concentrations in raw commodities, is examined. We conclude that the likelihood of upregulating an endogenous allergen due to transgenesis is no greater than from traditional breeding which has a history of safety and is largely unregulated. The potential consequences of upregulating an endogenous allergen are also unclear.

  9. Magnesium compounds

    USGS Publications Warehouse

    Kramer, D.A.

    2006-01-01

    In 2005, seawater and natural brines accounted for 51% of US magnesium compounds production. World magnesia production was estimated to be 14.5 Mt. Most of the production came from China, North Korea, Russia and Turkey. Although no specific production figures are available, Japan and the United States are estimated to account for almost one-half of the world's capacity from seawater and brines.

  10. Organic Compounds

    NASA Astrophysics Data System (ADS)

    Shankland, Kenneth

    For many years, powder X-ray diffraction was used primarily as a fingerprinting method for phase identification in the context of molecular organic materials. In the early 1990s, with only a few notable exceptions, structures of even moderate complexity were not solvable from PXRD data alone. Global optimisation methods and highly-modified direct methods have transformed this situation by specifically exploiting some well-known properties of molecular compounds. This chapter will consider some of these properties.

  11. Magnesium compounds

    USGS Publications Warehouse

    Kramer, D.A.

    2003-01-01

    Seawater and natural brines accounted for about 60 percent of U.S. magnesium compounds production during 2002. Dead-burned and caustic-calcined magnesias were recovered from seawater by Premier Chemicals in Florida. They were also recovered from well brines in Michigan by Dow Chemical, Martin Marietta Magnesia Specialties and Rohm & Haas. And they were recovered from magnesite in Nevada by Premier Chemicals.

  12. Modulation of sweet taste sensitivities by endogenous leptin and endocannabinoids in mice

    PubMed Central

    Niki, Mayu; Jyotaki, Masafumi; Yoshida, Ryusuke; Yasumatsu, Keiko; Shigemura, Noriatsu; DiPatrizio, Nicholas V; Piomelli, Daniele; Ninomiya, Yuzo

    2015-01-01

    Leptin is an anorexigenic mediator that reduces food intake by acting on hypothalamic receptor Ob-Rb. In contrast, endocannabinoids are orexigenic mediators that act via cannabinoid CB1 receptors in hypothalamus, limbic forebrain, and brainstem. In the peripheral taste system, leptin administration selectively inhibits behavioural, taste nerve and taste cell responses to sweet compounds. Opposing the action of leptin, endocannabinoids enhance sweet taste responses. However, potential roles of endogenous leptin and endocannabinoids in sweet taste remain unclear. Here, we used pharmacological antagonists (Ob-Rb: L39A/D40A/F41A (LA), CB1: AM251) and examined the effects of their blocking activation of endogenous leptin and endocannabinoid signalling on taste responses in lean control, leptin receptor deficient db/db, and diet-induced obese (DIO) mice. Lean mice exhibited significant increases in chorda tympani (CT) nerve responses to sweet compounds after LA administration, while they showed no significant changes in CT responses after AM251. In contrast, db/db mice showed clear suppression of CT responses to sweet compounds after AM251, increased endocannabinoid (2-arachidonoyl-sn-glycerol (2-AG)) levels in the taste organ, and enhanced expression of a biosynthesizing enzyme (diacylglycerol lipase α (DAGLα)) of 2-AG in taste cells. In DIO mice, the LA effect was gradually decreased and the AM251 effect was increased during the course of obesity. Taken together, our results suggest that circulating leptin, but not local endocannabinoids, may be a dominant modulator for sweet taste in lean mice; however, endocannabinoids may become more effective modulators of sweet taste under conditions of deficient leptin signalling, possibly due to increased production of endocannabinoids in taste tissue. Key points Potential roles of endogenous leptin and endocannabinoids in sweet taste were examined by using pharmacological antagonists and mouse models including leptin receptor

  13. Endogenous Protease Activation of ENaC

    PubMed Central

    Adebamiro, Adedotun; Cheng, Yi; Johnson, John P.; Bridges, Robert J.

    2005-01-01

    Endogenous serine proteases have been reported to control the reabsorption of Na+ by kidney- and lung-derived epithelial cells via stimulation of electrogenic Na+ transport mediated by the epithelial Na+ channel (ENaC). In this study we investigated the effects of aprotinin on ENaC single channel properties using transepithelial fluctuation analysis in the amphibian kidney epithelium, A6. Aprotinin caused a time- and concentration-dependent inhibition (84 ± 10.5%) in the amiloride-sensitive sodium transport (INa) with a time constant of 18 min and half maximal inhibition constant of 1 μM. Analysis of amiloride analogue blocker–induced fluctuations in INa showed linear rate–concentration plots with identical blocker on and off rates in control and aprotinin-inhibited conditions. Verification of open-block kinetics allowed for the use of a pulse protocol method (Helman, S.I., X. Liu, K. Baldwin, B.L. Blazer-Yost, and W.J. Els. 1998. Am. J. Physiol. 274:C947–C957) to study the same cells under different conditions as well as the reversibility of the aprotinin effect on single channel properties. Aprotinin caused reversible changes in all three single channel properties but only the change in the number of open channels was consistent with the inhibition of INa. A 50% decrease in INa was accompanied by 50% increases in the single channel current and open probability but an 80% decrease in the number of open channels. Washout of aprotinin led to a time-dependent restoration of INa as well as the single channel properties to the control, pre-aprotinin, values. We conclude that protease regulation of INa is mediated by changes in the number of open channels in the apical membrane. The increase in the single channel current caused by protease inhibition can be explained by a hyperpolarization of the apical membrane potential as active Na+ channels are retrieved. The paradoxical increase in channel open probability caused by protease inhibition will require further

  14. Endogenous pacemaker activity of rat tumour somatotrophs

    PubMed Central

    Kwiecien, Renata; Robert, Christophe; Cannon, Robert; Vigues, Stephan; Arnoux, Annie; Kordon, Claude; Hammond, Constance

    1998-01-01

    Cells derived from a rat pituitary tumour (GC cell line) that continuously release growth hormone behave as endogenous pacemakers. In simultaneous patch clamp recordings and cytosolic Ca2+ concentration ([Ca2+]i) imaging, they displayed rhythmic action potentials (44.7 ± 2.7 mV, 178 ± 40 ms, 0.30 ± 0.04 Hz) and concomitant [Ca2+]i transients (374 ± 57 nM, 1.0 ± 0.2 s, 0.27 ± 0.03 Hz). Action potentials and [Ca2+]i transients were reversibly blocked by removal of external Ca2+, addition of nifedipine (1 μM) or Ni2+ (40 μM), but were insensitive to TTX (1 μM). An L-type Ca2+ current activated at -33.6 ± 0.4 mV (holding potential (Vh), −40 mV), peaked at -1.8 ± 1.3 mV, was reduced by nifedipine and enhanced by S-(+)-SDZ 202 791. A T/R-type Ca2+ current activated at -41.7 ± 2.7 mV (Vh, -80 or -60 mV), peaked at -9.2 ± 3.0 mV, was reduced by low concentrations of Ni2+ (40 μM) or Cd2+ (10 μM) and was toxin resistant. Parallel experiments revealed the expression of the class E calcium channel α1-subunit mRNA. The K+ channel blockers TEA (25 mM) and charybdotoxin (10–100 nM) enhanced spike amplitude and/or duration. Apamin (100 nM) also strongly reduced the after-spike hyperpolarization. The outward K+ tail current evoked by a depolarizing step that mimicked an action potential reversed at −69.8 ± 0.3 mV, presented two components, lasted 2–3 s and was totally blocked by Cd2+ (400 μM). The slow pacemaker depolarization (3.5 ± 0.4 s) that separated consecutive spikes corresponded to a 2- to 3-fold increase in membrane resistance, was strongly Na+ sensitive but TTX insensitive. Computer simulations showed that pacemaker activity can be reproduced by a minimum of six currents: an L-type Ca2+ current underlies the rising phase of action potentials that are repolarized by a delayed rectifier and Ca2+-activated K+ currents. In between spikes, the decay of Ca2+-activated K+ currents and a persistent inward cationic current depolarize the membrane

  15. Formation and Stabilization of Raphasatin and Sulforaphene from Radish Roots by Endogenous Enzymolysis

    PubMed Central

    Kim, Jae-Won; Kim, Mi-Bo; Lim, Sang-Bin

    2015-01-01

    The biologically active compounds raphasatin and sulforaphene are formed during the hydrolysis of radishes by an endogenous myrosinase. Raphasatin is very unstable, and it is generated and simultaneously degraded to less active compounds during hydrolysis in aqueous media. This study determined the hydrolysis conditions to maximize the formation of raphasatin and sulforaphene by an endogenous myrosinase and minimize their degradation during the hydrolysis of radish roots. The reaction parameters, such as the reaction medium, reaction time, type of mixing, and reaction temperature were optimized. A stability test for raphasatin and sulforaphene was also performed during storage of the hydrolyzed products at 25°C for 10 days. The formation and breakdown of raphasatin and sulforaphene in radish roots by endogenous enzymolysis was strongly influenced by the reaction medium, reaction time, and type of mixing. The production and stabilization of raphasatin in radishes was efficient in water and dichloromethane with shaking for 15 min at 25°C. For sulforaphene, the favorable condition was water as the reaction medium without shaking for 10 min at 25°C. The maximum yields of raphasatin and sulforaphene were achieved in a concurrent hydrolysis reaction without shaking in water for 10 min and then with shaking in dichloromethane for 15 min at 25°C. Under these conditions, the yields of raphasatin and sulforaphene were maximized at 12.89 and 1.93 μmol/g of dry radish, respectively. The stabilities of raphasatin and sulforaphene in the hydrolyzed products were 56.4% and 86.5% after 10 days of storage in water and dichloromethane at 25°C. PMID:26175999

  16. The role of endogenous molecules in modulating pain through transient receptor potential vanilloid 1 (TRPV1)

    PubMed Central

    Morales-Lázaro, Sara L; Simon, Sidney A; Rosenbaum, Tamara

    2013-01-01

    Pain is a physiological response to a noxious stimulus that decreases the quality of life of those sufferring from it. Research aimed at finding new therapeutic targets for the treatment of several maladies, including pain, has led to the discovery of numerous molecular regulators of ion channels in primary afferent nociceptive neurons. Among these receptors is TRPV1 (transient receptor potential vanilloid 1), a member of the TRP family of ion channels. TRPV1 is a calcium-permeable channel, which is activated or modulated by diverse exogenous noxious stimuli such as high temperatures, changes in pH, and irritant and pungent compounds, and by selected molecules released during tissue damage and inflammatory processes. During the last decade the number of endogenous regulators of TRPV1's activity has increased to include lipids that can negatively regulate TRPV1, as is the case for cholesterol and PIP2 (phosphatidylinositol 4,5-biphosphate) while, in contrast, other lipids produced in response to tissue injury and ischaemic processes are known to positively regulate TRPV1. Among the latter, lysophosphatidic acid activates TRPV1 while amines such as N-acyl-ethanolamines and N-acyl-dopamines can sensitize or directly activate TRPV1. It has also been found that nucleotides such as ATP act as mediators of chemically induced nociception and pain and gases, such as hydrogen sulphide and nitric oxide, lead to TRPV1 activation. Finally, the products of lipoxygenases and omega-3 fatty acids among other molecules, such as divalent cations, have also been shown to endogenously regulate TRPV1 activity. Here we provide a comprehensive review of endogenous small molecules that regulate the function of TRPV1. Acting through mechanisms that lead to sensitization and desensitization of TRPV1, these molecules regulate pathways involved in pain and nociception. Understanding how these compounds modify TRPV1 activity will allow us to comprehend how some pathologies are associated with

  17. The role of endogenous molecules in modulating pain through transient receptor potential vanilloid 1 (TRPV1).

    PubMed

    Morales-Lázaro, Sara L; Simon, Sidney A; Rosenbaum, Tamara

    2013-07-01

    Pain is a physiological response to a noxious stimulus that decreases the quality of life of those sufferring from it. Research aimed at finding new therapeutic targets for the treatment of several maladies, including pain, has led to the discovery of numerous molecular regulators of ion channels in primary afferent nociceptive neurons. Among these receptors is TRPV1 (transient receptor potential vanilloid 1), a member of the TRP family of ion channels. TRPV1 is a calcium-permeable channel, which is activated or modulated by diverse exogenous noxious stimuli such as high temperatures, changes in pH, and irritant and pungent compounds, and by selected molecules released during tissue damage and inflammatory processes. During the last decade the number of endogenous regulators of TRPV1's activity has increased to include lipids that can negatively regulate TRPV1, as is the case for cholesterol and PIP2 (phosphatidylinositol 4,5-biphosphate) while, in contrast, other lipids produced in response to tissue injury and ischaemic processes are known to positively regulate TRPV1. Among the latter, lysophosphatidic acid activates TRPV1 while amines such as N-acyl-ethanolamines and N-acyl-dopamines can sensitize or directly activate TRPV1. It has also been found that nucleotides such as ATP act as mediators of chemically induced nociception and pain and gases, such as hydrogen sulphide and nitric oxide, lead to TRPV1 activation. Finally, the products of lipoxygenases and omega-3 fatty acids among other molecules, such as divalent cations, have also been shown to endogenously regulate TRPV1 activity. Here we provide a comprehensive review of endogenous small molecules that regulate the function of TRPV1. Acting through mechanisms that lead to sensitization and desensitization of TRPV1, these molecules regulate pathways involved in pain and nociception. Understanding how these compounds modify TRPV1 activity will allow us to comprehend how some pathologies are associated with

  18. Carbon isotope ratio mass spectrometry for detection of endogenous steroid use: a testing strategy.

    PubMed

    Ahrens, Brian D; Butch, Anthony W

    2013-07-01

    Isotope ratio mass spectrometry (IRMS) testing is performed to determine if an atypical steroid profile is due to administration of an endogenous steroid. Androsterone (Andro) and etiocholanolone (Etio), and/or the androstanediols (5α- and 5β-androstane-3α,17β-diol) are typically analyzed by IRMS to determine the (13) C/(12) C ratio. The ratios of these target compounds are compared to the (13) C/(12) C ratio of an endogenous reference compound (ERC) such as 5β-pregnane-3α,20α-diol (Pdiol). Concentrations of Andro and Etio are high so (13) C/(12) C ratios can easily be measured in most urine samples. Despite the potentially improved sensitivity of the androstanediols for detecting the use of some testosterone formulations, additional processing steps are often required that increase labour costs and turnaround times. Since this can be problematic when performing large numbers of IRMS measurements, we established thresholds for Andro and Etio that can be used to determine the need for additional androstanediol testing. Using these criteria, 105 out of 2639 urine samples exceeded the Andro and/or Etio thresholds, with 52 of these samples being positive based on Andro and Etio IRMS testing alone. The remaining 53 urine samples had androstanediol IRMS testing performed and 3 samples were positive based on the androstanediol results. A similar strategy was used to establish a threshold for Pdiol to identify athletes with relatively (13) C-depleted values so that an alternative ERC can be used to confirm or establish a true endogenous reference value. Adoption of a similar strategy by other laboratories can significantly reduce IRMS sample processing and analysis times, thereby increasing testing capacity.

  19. Clonidine-specific antisera recognize an endogenous clonidine-displacing substance in brain

    SciTech Connect

    Meeley, M.P.; Towle, A.C.; Ernsberger, P.; Char, L.K.; McCauley, P.M.; Reis, D.J.

    1989-04-01

    An endogenous substance in brain, clonidine-displacing substance, binds to the same receptor populations as clonidine and is biologically active. Since receptor binding sites can be modeled by using specific antiligand antibodies, we tested the hypothesis that polyclonal antibodies raised in rat and rabbit against the clonidine analog p-aminoclonidine coupled to hemocyanin would recognize compounds structurally related to clonidine, including clonidine-displacing substance. Binding to anti-p-aminoclonidine antibodies was examined by using a competitive radioimmunoassay with tritiated p-aminoclonidine as the radioligand. Central vasodepressor agents that, like clonidine, are known to bind with high affinity to both imidazole sites and alpha 2-adrenergic receptors in brain inhibited radioligand binding to anti-p-aminoclonidine antibodies. All of these agents contain imidazol(in)e and phenyl ring moieties as part of their chemical structures (e.g., oxymetazoline); a number of other compounds without one or both of these rings failed to cross-react with the antisera. Clonidine-displacing substance, partially purified from bovine brain, also inhibited specific radioligand binding to anti-p-aminoclonidine antibodies. The inhibition was dose dependent and high affinity (IC50, 4 Units). The endogenous substance had no effect on the apparent affinity of the antibodies for the radioligand, but blocked a specific number of binding sites. Immunoprecipitation experiments showed that authentic clonidine-displacing substance, that which displaces tritiated p-aminoclonidine binding to membrane receptors, is recognized by anti-p-aminoclonidine antibodies.

  20. Increase in Endogenous and Exogenous Cyclic AMP Levels Inhibits Sclerotial Development in Sclerotinia sclerotiorum

    PubMed Central

    Rollins, Jeffrey A.; Dickman, Martin B.

    1998-01-01

    Growth and development of a wild-type Sclerotinia sclerotiorum isolate were examined in the presence of various pharmacological compounds to investigate signal transduction pathways that influence the development of sclerotia. Compounds known to increase endogenous cyclic AMP (cAMP) levels in other organisms by inhibiting phosphodiesterase activity (caffeine and 3-isobutyl-1-methyl xanthine) or by activating adenylate cyclase (NaF) reduced or eliminated sclerotial development in S. sclerotiorum. Growth in the presence of 5 mM caffeine correlated with increased levels of endogenous cAMP in mycelia. In addition, incorporation of cAMP into the growth medium decreased or eliminated the production of sclerotia in a concentration-dependent manner and increased the accumulation of oxalic acid. Inhibition of sclerotial development was cAMP specific, as exogenous cyclic GMP, AMP, and ATP did not influence sclerotial development. Transfer of developing cultures to cAMP-containing medium at successive time points demonstrated that cAMP inhibits development prior to or during sclerotial initiation. Together, these results indicate that cAMP plays a role in the early transition between mycelial growth and sclerotial development. PMID:9647827

  1. Ketoconazole and endogenous Cushing's syndrome. Effective but tricky to use.

    PubMed

    2016-03-01

    Endogenous Cushing's syndrome is a rare but serious disease. Ketoconazole was effective in over 50% of cases in non-comparative series in a total of 800 patients. However, ketoconazole is hepatotoxic and interacts with many other drugs. PMID:27152395

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

    PubMed

    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.

  3. Dietary compounds in relation to dietary diversity and human health.

    PubMed

    Hughes, Claude L; Dhiman, Tilak R

    2002-01-01

    The human diet contains numerous endocrine-active compounds that influence mammalian physiology. The effects of these dietary compounds may be mediated by interaction with well-characterized intracellular hormone receptors or by other effects on patterns of endogenous hormone production, metabolism, target tissue signaling, growth, or differentiation. Because humans evolved as omnivores, the spectrum of dietary compounds that can be tolerated at modest levels of intake without frank toxicity is broad. Modest intake of these diverse nonnutritive endocrine-active compounds offers potential human health benefits through modulation of metabolic and hormonal responses, especially in sedentary individuals consuming a highly refined diet.

  4. The endogenous opioid system in Gilles de la Tourette syndrome.

    PubMed

    Gillman, M A; Sandyk, R

    1986-04-01

    The various neurotransmitter systems postulated to be involved in the pathogenesis of Gilles de la Tourette syndrome(GTS) are described with special reference to the endogenous opioid system(EOS). Malfunction of the opioid system is proposed as the underlying disturbance in this disease causing secondary dysfunction of the other systems. Furthermore, the various symptoms of the illness are examined also in terms of dysfunction of the endogenous opioid system.

  5. Method for the Purification of Endogenous Unanchored Polyubiquitin Chains.

    PubMed

    Scott, Daniel; Strachan, Jo; Krishna, Varun Gopala; Shaw, Barry; Tooth, David J; Searle, Mark S; Oldham, Neil J; Layfield, Rob

    2016-01-01

    Unanchored polyubiquitin chains are endogenous non-substrate linked ubiquitin polymers which have emerging roles in the control of cellular physiology. We describe an affinity purification method based on an isolated ubiquitin-binding domain, the ZnF_UBP domain of the deubiquitinating enzyme USP5, which permits the selective purification of mixtures of endogenous unanchored polyubiquitin chains that are amenable to downstream molecular analyses. Further, we present methods for detection of unanchored polyubiquitin chains in purified fractions. PMID:27613037

  6. Magnesium compounds

    USGS Publications Warehouse

    Kramer, D.A.

    2002-01-01

    Seawater and natural brines accounted for about 60% of US magnesium compounds production in 2001. Dead-burned and caustic-calcined magnesias were recovered from seawater in Florida by Premier Chemicals. They were also recovered from Michigan well brines by Dow Chemical, Martin Marietta Magnesia Specialties and Rohm & Haas. And Premier Chemicals recovered dead-burned and caustic-calcined magnesias from magnesite in Nevada. Reilly Industries and Great Salt Lake Minerals recovered magnesium chloride brines from the Great Salt Lake in Utah.

  7. Magnesium compounds

    USGS Publications Warehouse

    Kramer, D.A.

    2010-01-01

    Seawater and natural brines accounted for about 40 percent of U.S. magnesium compounds production in 2009. Dead-burned magnesia was produced by Martin Marietta Magnesia Specialties from well brines in Michigan. Caustic-calcined magnesia was recovered from seawater by Premier Chemicals in Florida, from well brines in Michigan by Martin Marietta and from magnesite in Nevada by Premier Chemicals. Intrepid Potash-Wendover, and Great Salt Lake Minerals Corp. recovered magnesium chloride brines from the Great Salt Lake in Utah. Magnesium hydroxide was produced from seawater by SPI Pharma in Delaware and Premier Chemicals in Florida, and by Martin Marietta from its operation mentioned above.

  8. Magnesium compounds

    USGS Publications Warehouse

    Kramer, D.A.

    2011-01-01

    Seawater and natural brines accounted for about 54 percent of U.S. magnesium compounds production in 2010. Dead-burned magnesia was produced by Martin Marietta Magnesia Specialties from well brines in Michigan. Caustic-calcined magnesia was recovered from seawater by Premier Magnesia in Florida, from well brines in Michigan by Martin Marietta and from magnesite in Nevada by Premier Magnesia. Intrepid Potash-Wendover and Great Salt Lake Minerals Corp. recovered magnesium chloride brines from the Great Salt Lake in Utah. Magnesium hydroxide was produced from seawater by SPI Pharma in Delaware and Premier Magnesia in Florida, and by Martin Marietta from its operation mentioned above.

  9. Remarkable diversity of endogenous viruses in a crustacean genome.

    PubMed

    Thézé, Julien; Leclercq, Sébastien; Moumen, Bouziane; Cordaux, Richard; Gilbert, Clément

    2014-08-01

    Recent studies in paleovirology have uncovered myriads of endogenous viral elements (EVEs) integrated in the genome of their eukaryotic hosts. These fragments result from endogenization, that is, integration of the viral genome into the host germline genome followed by vertical inheritance. So far, most studies have used a virus-centered approach, whereby endogenous copies of a particular group of viruses were searched in all available sequenced genomes. Here, we follow a host-centered approach whereby the genome of a given species is comprehensively screened for the presence of EVEs using all available complete viral genomes as queries. Our analyses revealed that 54 EVEs corresponding to 10 different viral lineages belonging to 5 viral families (Bunyaviridae, Circoviridae, Parvoviridae, and Totiviridae) and one viral order (Mononegavirales) became endogenized in the genome of the isopod crustacean Armadillidium vulgare. We show that viral endogenization occurred recurrently during the evolution of isopods and that A. vulgare viral lineages were involved in multiple host switches that took place between widely divergent taxa. Furthermore, 30 A. vulgare EVEs have uninterrupted open reading frames, suggesting they result from recent endogenization of viruses likely to be currently infecting isopod populations. Overall, our work shows that isopods have been and are still infected by a large variety of viruses. It also extends the host range of several families of viruses and brings new insights into their evolution. More generally, our results underline the power of paleovirology in characterizing the viral diversity currently infecting eukaryotic taxa.

  10. Remarkable diversity of endogenous viruses in a crustacean genome.

    PubMed

    Thézé, Julien; Leclercq, Sébastien; Moumen, Bouziane; Cordaux, Richard; Gilbert, Clément

    2014-08-01

    Recent studies in paleovirology have uncovered myriads of endogenous viral elements (EVEs) integrated in the genome of their eukaryotic hosts. These fragments result from endogenization, that is, integration of the viral genome into the host germline genome followed by vertical inheritance. So far, most studies have used a virus-centered approach, whereby endogenous copies of a particular group of viruses were searched in all available sequenced genomes. Here, we follow a host-centered approach whereby the genome of a given species is comprehensively screened for the presence of EVEs using all available complete viral genomes as queries. Our analyses revealed that 54 EVEs corresponding to 10 different viral lineages belonging to 5 viral families (Bunyaviridae, Circoviridae, Parvoviridae, and Totiviridae) and one viral order (Mononegavirales) became endogenized in the genome of the isopod crustacean Armadillidium vulgare. We show that viral endogenization occurred recurrently during the evolution of isopods and that A. vulgare viral lineages were involved in multiple host switches that took place between widely divergent taxa. Furthermore, 30 A. vulgare EVEs have uninterrupted open reading frames, suggesting they result from recent endogenization of viruses likely to be currently infecting isopod populations. Overall, our work shows that isopods have been and are still infected by a large variety of viruses. It also extends the host range of several families of viruses and brings new insights into their evolution. More generally, our results underline the power of paleovirology in characterizing the viral diversity currently infecting eukaryotic taxa. PMID:25084787

  11. Remarkable Diversity of Endogenous Viruses in a Crustacean Genome

    PubMed Central

    Thézé, Julien; Leclercq, Sébastien; Moumen, Bouziane; Cordaux, Richard; Gilbert, Clément

    2014-01-01

    Recent studies in paleovirology have uncovered myriads of endogenous viral elements (EVEs) integrated in the genome of their eukaryotic hosts. These fragments result from endogenization, that is, integration of the viral genome into the host germline genome followed by vertical inheritance. So far, most studies have used a virus-centered approach, whereby endogenous copies of a particular group of viruses were searched in all available sequenced genomes. Here, we follow a host-centered approach whereby the genome of a given species is comprehensively screened for the presence of EVEs using all available complete viral genomes as queries. Our analyses revealed that 54 EVEs corresponding to 10 different viral lineages belonging to 5 viral families (Bunyaviridae, Circoviridae, Parvoviridae, and Totiviridae) and one viral order (Mononegavirales) became endogenized in the genome of the isopod crustacean Armadillidium vulgare. We show that viral endogenization occurred recurrently during the evolution of isopods and that A. vulgare viral lineages were involved in multiple host switches that took place between widely divergent taxa. Furthermore, 30 A. vulgare EVEs have uninterrupted open reading frames, suggesting they result from recent endogenization of viruses likely to be currently infecting isopod populations. Overall, our work shows that isopods have been and are still infected by a large variety of viruses. It also extends the host range of several families of viruses and brings new insights into their evolution. More generally, our results underline the power of paleovirology in characterizing the viral diversity currently infecting eukaryotic taxa. PMID:25084787

  12. Magnesium compounds

    USGS Publications Warehouse

    Kramer, D.A.

    2007-01-01

    Seawater and natural brines accounted for about 52 percent of U.S. magnesium compounds production in 2006. Dead-burned magnesia was produced by Martin Marietta Magnesia Specialties from well brines in Michigan. Caustic-calcined magnesia was recovered from sea-water by Premier Chemicals in Florida; from well brines in Michigan by Martin Marietta and Rohm and Haas; and from magnesite in Nevada by Premier Chemicals. Intrepid Potash-Wendover and Great Salt Lake Minerals recovered magnesium chloride brines from the Great Salt Lake in Utah. Magnesium hydroxide was produced from brucite by Applied Chemical Magnesias in Texas, from seawater by SPI Pharma in Delaware and Premier Chemicals in Florida, and by Martin Marietta and Rohm and Haas from their operations mentioned above. About 59 percent of the magnesium compounds consumed in the United States was used for refractories that are used mainly to line steelmaking furnaces. The remaining 41 percent was consumed in agricultural, chemical, construction, environmental and industrial applications.

  13. SAMPLE EXTRACTION AND GC-MS ANALYSIS FOR POLAR VOLATILE ORGANIC COMPOUNDS (PVOCS) IN LIQUID BIOLOGICAL MEDIA

    EPA Science Inventory

    Current approaches for assessing the cumulative exposures and effects from broad classes of environmental stressors incorporate the measurement of specific groups of endogenous compounds in human biological fluids. Recent focus has been on interpreting patterns of differentially...

  14. Bismaleimide compounds

    DOEpatents

    Adams, J.E.; Jamieson, D.R.

    1986-01-14

    Bismaleimides of the formula shown in the diagram wherein R[sub 1] and R[sub 2] each independently is H, C[sub 1-4]-alkyl, C[sub 1-4]-alkoxy, Cl or Br, or R[sub 1] and R[sub 2] together form a fused 6-membered hydrocarbon aromatic ring, with the proviso that R[sub 1] and R[sub 2] are not t-butyl or t-butoxy; X is O, S or Se; n is 1--3; and the alkylene bridging group, optionally, is substituted by 1--3 methyl groups or by fluorine, form polybismaleimide resins which have valuable physical properties. Uniquely, these compounds permit extended cure times, i.e., they remain fluid for a time sufficient to permit the formation of a homogeneous melt prior to curing.

  15. Bismaleimide compounds

    DOEpatents

    Adams, Johnnie E.; Jamieson, Donald R.

    1986-01-14

    Bismaleimides of the formula ##STR1## wherein R.sub.1 and R.sub.2 each independently is H, C.sub.1-4 -alkyl, C.sub.1-4 -alkoxy, C1 or Br, or R.sub.1 and R.sub.2 together form a fused 6-membered hydrocarbon aromatic ring, with the proviso that R.sub.1 and R.sub.2 are not t-butyl or t-butoxy; X is O, S or Se; n is 1-3; and the alkylene bridging group, optionally, is substituted by 1-3 methyl groups or by fluorine, form polybismaleimide resins which have valuable physical properties. Uniquely, these compounds permit extended cure times, i.e., they remain fluid for a time sufficient to permit the formation of a homogeneous melt prior to curing.

  16. Magnesium compounds

    USGS Publications Warehouse

    Kramer, D.A.

    2012-01-01

    Seawater and natural brines accounted for about 57 percent of magnesium compounds produced in the United States in 2011. Dead-burned magnesia was produced by Martin Marietta Magnesia Specialties LLC from well brines in Michigan. Caustic-calcined magnesia was recovered from seawater by Premier Magnesia LLC in Florida, from well brines in Michigan by Martin Marietta and from magnesite in Nevada by Premier Magnesia. Intrepid Potash Wendover LLC and Great Salt Lake Minerals Corp. recovered magnesium chloride brines from the Great Salt Lake in Utah. Magnesium hydroxide was produced from seawater by SPI Pharma Inc. in Delaware and Premier Magnesia in Florida, and by Martin Marietta from its brine operation in Michigan.

  17. Preliminary study on the occurrence of brominated organic compounds in Dutch marine organisms.

    PubMed

    Kotterman, Michiel; van der Veen, Ike; van Hesselingen, Judith; Leonards, Pim; Osinga, Ronald; de Boer, Jacob

    2003-07-01

    The extracts of three marine organisms; the ascidian Ciona intestinalis, the brown seaweed Sargassum muticum and the sponge Halichondria panicea, all elicited a number of brominated compounds, some of which were tentatively identified. Tribromophenol was observed in all species. This compound, also industrially produced as flame retardant and fungicide, was likely due to endogenous production. PMID:12919829

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

    PubMed Central

    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

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

    PubMed Central

    Koles, Kate; Yeh, Anna R.; Rodal, Avital A.

    2016-01-01

    ABSTRACT 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. PMID:26700726

  20. Design and synthesis of a series of piperazine-1-carboxamidine derivatives with antifungal activity resulting from accumulation of endogenous reactive oxygen species.

    PubMed

    François, Isabelle E; Thevissen, Karin; Pellens, Klaartje; Meert, Els M; Heeres, Jan; Freyne, Eddy; Coesemans, Erwin; Viellevoye, Marcel; Deroose, Frederik; Martinez Gonzalez, Sonia; Pastor, Joaquin; Corens, David; Meerpoel, Lieven; Borgers, Marcel; Ausma, Jannie; Dispersyn, Gerrit D; Cammue, Bruno P

    2009-10-01

    In this study, we screened a library of 500 compounds for fungicidal activity via induction of endogenous reactive oxygen species (ROS) accumulation. Structure-activity relationship studies showed that piperazine-1-carboxamidine analogues with large atoms or large side chains substituted on the phenyl group at the R(3) and R(5) positions are characterized by a high ROS accumulation capacity in Candida albicans and a high fungicidal activity. Moreover, we could link the fungicidal mode of action of the piperazine-1-carboxamidine derivatives to the accumulation of endogenous ROS. PMID:19705386

  1. Recognition of Endogenous Nucleic Acids by the Innate Immune System.

    PubMed

    Roers, Axel; Hiller, Björn; Hornung, Veit

    2016-04-19

    Recognition of DNA and RNA by endosomal and cytosolic sensors constitutes a central element in the detection of microbial invaders by the innate immune system. However, the capacity of these sensors to discriminate between microbial and endogenous nucleic acids is limited. Over the past few years, evidence has accumulated to suggest that endogenous DNA or RNA species can engage nucleic-acid-sensing pattern-recognition receptors that can trigger or sustain detrimental pathology. Here, we review principles of how the activation of innate sensors by host nucleic acids is prevented in the steady state and discuss four important determinants of whether a nucleic-acid-driven innate response is mounted. These include structural features of the ligand being sensed, the subcellular location and quantity of pathogen-derived or endogenous nucleic acids, and the regulation of sensor-activation thresholds. Furthermore, we emphasize disease mechanisms initiated by failure to discriminate self from non-self in nucleic acid detection.

  2. Expression of baboon endogenous virus in exogenously infected baboon cells.

    PubMed

    Lavelle, G; Foote, L; Heberling, R L; Kalter, S S

    1979-04-01

    Strains of low-passage, fetal diploid, baboon (Papio cynocephalus) fibroblasts were susceptible to exogenous infection with three independent isolates of baboon endogenous virus, as measured by an immunofluorescence assay specific for viral p28. Infectivity of the M7 strain of baboon endogenous virus for baboon cells of fetal skin muscle origin was equivalent to that for human and dog cells in that similar, linear, single-hit titration patterns were obtained. The assay for supernatant RNA-dependent DNA polymerase, however, showed that baboon cells produced only low levels of virus after infection compared with the production by heterologous cells. The results showed that baboon endogenous virus was capable of penetrating baboon cells and that viral genes were expressed in infected cells. Replication of complete infectious virus was restricted, however, indicating that in this primate system homologous cells differentially regulated the expression of viral genes.

  3. Endogenous Lentiviral Elements in the Weasel Family (Mustelidae)

    PubMed Central

    Han, Guan-Zhu; Worobey, Michael

    2012-01-01

    Endogenous retroviruses provide molecular fossils for studying the ancient evolutionary history of retroviruses. Here, we report our independent discovery and analysis of endogenous lentiviral insertions (Mustelidae endogenous lentivirus [MELV]) within the genomes of weasel family (Mustelidae). Genome-scale screening identified MELV elements in the domestic ferret (Mustela putorius furo) genome (MELVmpf). MELVmpf exhibits a typical lentiviral genomic organization. Phylogenetic analyses position MELVmpf basal to either primate lentiviruses or feline immunodeficiency virus. Moreover, we verified the presence of MELV insertions in the genomes of several species of the Lutrinae and Mustelinae subfamilies but not the Martinae subfamily, suggesting that the invasion of MELV into the Mustelidae genomes likely took place between 8.8 and 11.8 Ma. The discovery of MELV in weasel genomes extends the host range of lentiviruses to the Caniformia (order Carnivora) and provides important insights into the prehistoric diversity of lentiviruses. PMID:22522310

  4. Purification and analysis of endogenous human RNA exosome complexes

    PubMed Central

    Domanski, Michal; Upla, Paula; Rice, William J.; Molloy, Kelly R.; Ketaren, Natalia E.; Stokes, David L.; Jensen, Torben Heick; Rout, Michael P.

    2016-01-01

    As a result of its importance in key RNA metabolic processes, the ribonucleolytic RNA exosome complex has been the focus of intense study for almost two decades. Research on exosome subunit assembly, cofactor and substrate interaction, enzymatic catalysis and structure have largely been conducted using complexes produced in the yeast Saccharomyces cerevisiae or in bacteria. Here, we examine different populations of endogenous exosomes from human embryonic kidney (HEK) 293 cells and test their enzymatic activity and structural integrity. We describe methods to prepare EXOSC10-containing, enzymatically active endogenous human exosomes at suitable yield and purity for in vitro biochemistry and negative stain transmission electron microscopy. This opens the door for assays designed to test the in vitro effects of putative cofactors on human exosome activity and will enable structural studies of preparations from endogenous sources. PMID:27402899

  5. Endogenous cardiac stem cells for the treatment of heart failure

    PubMed Central

    Fuentes, Tania; Kearns-Jonker, Mary

    2013-01-01

    Stem cell-based therapies hold promise for regenerating the myocardium after injury. Recent data obtained from phase I clinical trials using endogenous cardiovascular progenitors isolated directly from the heart suggest that cell-based treatment for heart patients using stem cells that reside in the heart provides significant functional benefit and an improvement in patient outcome. Methods to achieve improved engraftment and regeneration may extend this therapeutic benefit. Endogenous cardiovascular progenitors have been tested extensively in small animals to identify cells that improve cardiac function after myocardial infarction. However, the relative lack of large animal models impedes translation into clinical practice. This review will exclusively focus on the latest research pertaining to humans and large animals, including both endogenous and induced sources of cardiovascular progenitors. PMID:24426784

  6. Endogenous lentiviral elements in the weasel family (Mustelidae).

    PubMed

    Han, Guan-Zhu; Worobey, Michael

    2012-10-01

    Endogenous retroviruses provide molecular fossils for studying the ancient evolutionary history of retroviruses. Here, we report our independent discovery and analysis of endogenous lentiviral insertions (Mustelidae endogenous lentivirus [MELV]) within the genomes of weasel family (Mustelidae). Genome-scale screening identified MELV elements in the domestic ferret (Mustela putorius furo) genome (MELVmpf). MELVmpf exhibits a typical lentiviral genomic organization. Phylogenetic analyses position MELVmpf basal to either primate lentiviruses or feline immunodeficiency virus. Moreover, we verified the presence of MELV insertions in the genomes of several species of the Lutrinae and Mustelinae subfamilies but not the Martinae subfamily, suggesting that the invasion of MELV into the Mustelidae genomes likely took place between 8.8 and 11.8 Ma. The discovery of MELV in weasel genomes extends the host range of lentiviruses to the Caniformia (order Carnivora) and provides important insights into the prehistoric diversity of lentiviruses.

  7. Residential water demand with endogenous pricing: The Canadian Case

    NASA Astrophysics Data System (ADS)

    Reynaud, Arnaud; Renzetti, Steven; Villeneuve, Michel

    2005-11-01

    In this paper, we show that the rate structure endogeneity may result in a misspecification of the residential water demand function. We propose to solve this endogeneity problem by estimating a probabilistic model describing how water rates are chosen by local communities. This model is estimated on a sample of Canadian local communities. We first show that the pricing structure choice reflects efficiency considerations, equity concerns, and, in some cases, a strategy of price discrimination across consumers by Canadian communities. Hence estimating the residential water demand without taking into account the pricing structures' endogeneity leads to a biased estimation of price and income elasticities. We also demonstrate that the pricing structure per se plays a significant role in influencing price responsiveness of Canadian residential consumers.

  8. Cinnabarinic acid, an endogenous metabolite of the kynurenine pathway, activates type 4 metabotropic glutamate receptors.

    PubMed

    Fazio, F; Lionetto, L; Molinaro, G; Bertrand, H O; Acher, F; Ngomba, R T; Notartomaso, S; Curini, M; Rosati, O; Scarselli, P; Di Marco, R; Battaglia, G; Bruno, V; Simmaco, M; Pin, J P; Nicoletti, F; Goudet, C

    2012-05-01

    Cinnabarinic acid is an endogenous metabolite of the kynurenine pathway that meets the structural requirements to interact with glutamate receptors. We found that cinnabarinic acid acts as a partial agonist of type 4 metabotropic glutamate (mGlu4) receptors, with no activity at other mGlu receptor subtypes. We also tested the activity of cinnabarinic acid on native mGlu4 receptors by examining 1) the inhibition of cAMP formation in cultured cerebellar granule cells; 2) protection against excitotoxic neuronal death in mixed cultures of cortical cells; and 3) protection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in mice after local infusion into the external globus pallidus. In all these models, cinnabarinic acid behaved similarly to conventional mGlu4 receptor agonists, and, at least in cultured neurons, the action of low concentrations of cinnabarinic acid was largely attenuated by genetic deletion of mGlu4 receptors. However, high concentrations of cinnabarinic acid were still active in the absence of mGlu4 receptors, suggesting that the compound may have off-target effects. Mutagenesis and molecular modeling experiments showed that cinnabarinic acid acts as an orthosteric agonist interacting with residues of the glutamate binding pocket of mGlu4. Accordingly, cinnabarinic acid did not activate truncated mGlu4 receptors lacking the N-terminal Venus-flytrap domain, as opposed to the mGlu4 receptor enhancer, N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC). Finally, we could detect endogenous cinnabarinic acid in brain tissue and peripheral organs by high-performance liquid chromatography-tandem mass spectrometry analysis. Levels increased substantially during inflammation induced by lipopolysaccharide. We conclude that cinnabarinic acid is a novel endogenous orthosteric agonist of mGlu4 receptors endowed with neuroprotective activity. PMID:22311707

  9. Identification, characterization and comparative genomics of chimpanzee endogenous retroviruses

    PubMed Central

    Polavarapu, Nalini; Bowen, Nathan J; McDonald, John F

    2006-01-01

    Background Retrotransposons, the most abundant and widespread class of eukaryotic transposable elements, are believed to play a significant role in mutation and disease and to have contributed significantly to the evolution of genome structure and function. The recent sequencing of the chimpanzee genome is providing an unprecedented opportunity to study the functional significance of these elements in two closely related primate species and to better evaluate their role in primate evolution. Results We report here that the chimpanzee genome contains at least 42 separate families of endogenous retroviruses, nine of which were not previously identified. All but two (CERV 1/PTERV1 and CERV 2) of the 42 families of chimpanzee endogenous retroviruses were found to have orthologs in humans. Molecular analysis (PCR and Southern hybridization) of CERV 2 elements demonstrates that this family is present in chimpanzee, bonobo, gorilla and old-world monkeys but absent in human, orangutan and new-world monkeys. A survey of endogenous retroviral positional variation between chimpanzees and humans determined that approximately 7% of all chimpanzee-human INDEL variation is associated with endogenous retroviral sequences. Conclusion Nine families of chimpanzee endogenous retroviruses have been transpositionally active since chimpanzees and humans diverged from a common ancestor. Seven of these transpositionally active families have orthologs in humans, one of which has also been transpositionally active in humans since the human-chimpanzee divergence about six million years ago. Comparative analyses of orthologous regions of the human and chimpanzee genomes have revealed that a significant portion of INDEL variation between chimpanzees and humans is attributable to endogenous retroviruses and may be of evolutionary significance. PMID:16805923

  10. SNIPER peptide-mediated degradation of endogenous proteins.

    PubMed

    Fan, Xuelai; Wang, Yu Tian

    2015-03-02

    Rapid and reversible methods for altering the function of endogenous proteins are not only indispensable tools for probing complex biological systems, but may potentially drive the development of new therapeutics for the treatment of human diseases. Genetic approaches have provided insights into protein function, but are limited in speed, reversibility and spatiotemporal control. To overcome these limitations, we have developed a peptide-based method (SNIPER: Selective Native Protein Eradication) to degrade any given endogenous protein at the post-translational level by harnessing chaperone-mediated autophagy, a major intracellular protein degradation pathway. This unit presents a typical strategy in the design and validation of a protein-knockdown peptide.

  11. The first full-length endogenous hepadnaviruses: identification and analysis.

    PubMed

    Liu, Wei; Pan, Shaokun; Yang, Huijuan; Bai, Weiya; Shen, Zhongliang; Liu, Jing; Xie, Youhua

    2012-09-01

    In silico screening of metazoan genome data identified multiple endogenous hepadnaviral elements in the budgerigar (Melopsittacus undulatus) genome, most notably two elements comprising about 1.3 × and 1.0 × the full-length genome. Phylogenetic and molecular dating analyses show that endogenous budgerigar hepatitis B viruses (eBHBV) share an ancestor with extant avihepadnaviruses and infiltrated the budgerigar genome millions of years ago. Identification of full-length genomes with preserved key features like ε signals could enable resurrection of ancient BHBV. PMID:22718817

  12. New HPLC evidence on endogenous tauret in retina and pigment epithelium.

    PubMed

    Petrosian, A M; Haroutounian, J E; Gundersen, T E; Blomhoff, R; Fugelli, K; Kanli, H

    2000-01-01

    This investigation was improve the separation for tauret (retinylidene taurine) and to compare its content in the retina under dark and light adaptation. To prevent tauret hydrolysis, retinal samples were quickly frozen and lyophilized. Methanol extracts of dried retina and pigment epithelium from both dark- or light-adapted frogs, Rana ridibunda, were injected onto HPLC. Synthetic standard tauret appeared at 4.7 min after the solvent front. At the same time, an endogenous substance was eluted from the mixed retinal and pigment epithelial samples. The UV spectra of this endogenous compound matched with the spectra of synthetic tauret obtained under identical conditions, with lambda(max) = 446 nm at peak. We conclude that the HPLC system used permitted full separation of tauret from the methanol extracts of the retina and pigment epithelium. TLC and further HPLC analysis have shown that tauret quantities were several times higher in the retina and pigment epithelium of the frogs adapted to dark compared with those light-adapted (about 4 h under 1000 1x illumination). Tauret based vitamin A transport is probably involved in other systems as well, where along with its other known beneficial effects taurine probably is necessary to facilitate vitamin A transport.

  13. Endogenous generation of hydrogen sulfide and its regulation in Shewanella oneidensis

    PubMed Central

    Wu, Genfu; Li, Ning; Mao, Yinting; Zhou, Guangqi; Gao, Haichun

    2015-01-01

    Hydrogen sulfide (H2S) has been recognized as a physiological mediator with a variety of functions across all domains of life. In this study, mechanisms of endogenous H2S generation in Shewanella oneidensis were investigated. As a research model with highly diverse anaerobic respiratory pathways, the microorganism is able to produce H2S by respiring on a variety of sulfur-containing compounds with SirACD and PsrABC enzymatic complexes, as well as through cysteine degradation with three enzymes, MdeA, SO_1095, and SseA. We showed that the SirACD and PsrABC complexes, which are predominantly, if not exclusively, responsible for H2S generation via respiration of sulfur species, do not interplay with each other. Strikingly, a screen for regulators controlling endogenous H2S generation by transposon mutagenesis identified global regulator Crp to be essential to all H2S-generating processes. In contrast, Fnr and Arc, two other global regulators that have a role in respiration, are dispensable in regulating H2S generation via respiration of sulfur species. Interestingly, Arc is involved in the H2S generation through cysteine degradation by repressing expression of the mdeA gene. We further showed that expression of the sirA and psrABC operons is subjected to direct regulation of Crp, but the mechanisms underlying the requirement of Crp for H2S generation through cysteine degradation remain elusive. PMID:25972854

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

    PubMed Central

    Font, Laura; Luján, Miguel Á.; Pastor, Raúl

    2013-01-01

    Significant evidence implicates the endogenous opioid system (EOS) (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 (CPP). 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 (DA). 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. PMID:23914161

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

    PubMed

    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. PMID:19803329

  16. Natural Compounds: DNA Methyltransferase Inhibitors in Oral Squamous Cell Carcinoma.

    PubMed

    Jha, Meenakshi; Aggarwal, Ruchi; Jha, Abhimanyu Kumar; Shrivastava, Anju

    2015-10-01

    Oral squamous cell carcinoma (OSCC) is a multistep process which is modulated by several endogenous and environmental factors. Epigenetic changes have been found to be equally responsible for OSCC as genetic changes. A plethora of genes showing hypermethylation have been discovered in OSCC. Since these changes are reversible, a lot of emphasis is on using the natural compounds for their ability to cause demethylation which could lead to reactivation of the inactivated tumor suppressor genes. This review encompasses the promoter hypermethylation of tumor suppressor genes in OSCC and its possible reversal using natural compounds. In addition, new compounds which could be screened for their demethylating ability have also been proposed. PMID:26210787

  17. Lasting impacts of prenatal cannabis exposure and the role of endogenous cannabinoids in the developing brain.

    PubMed

    Wu, Chia-Shan; Jew, Christopher P; Lu, Hui-Chen

    2011-07-01

    Cannabis is the most commonly used illicit substance among pregnant women. Human epidemiological and animal studies have found that prenatal cannabis exposure influences brain development and can have long-lasting impacts on cognitive functions. Exploration of the therapeutic potential of cannabis-based medicines and synthetic cannabinoid compounds has given us much insight into the physiological roles of endogenous ligands (endocannabinoids) and their receptors. In this article, we examine human longitudinal cohort studies that document the long-term influence of prenatal exposure to cannabis, followed by an overview of the molecular composition of the endocannabinoid system and the temporal and spatial changes in their expression during brain development. How endocannabinoid signaling modulates fundamental developmental processes such as cell proliferation, neurogenesis, migration and axonal pathfinding are also summarized.

  18. RELIABLE ASSAYS FOR DETERMINING ENDOGENOUS COMPONENTS OF HUMAN MILK

    EPA Science Inventory

    Healthy women from 18-38 years old (N=25) fasted for several hours and twice donated blood and milk (postpartum 2-7 weeks and 3-4 months) for the EPA's Methods Advancement for Milk Analysis study, a pilot for the National Children's Study (NCS). Endogenous components were chosen...

  19. Isolating Exogenous and Endogenous Modes of Temporal Attention

    ERIC Educational Resources Information Center

    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 report seeks to ameliorate this…

  20. Endogenous opioid peptides as neurotransmitters in the rat hippocampus

    SciTech Connect

    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 ({sup 3}H)-diprenorphine binding in a transient, calcium-dependent, and peptidase-sensitive manner. Autoradiographic localization of the sites of ({sup 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 ({sup 3}H)-ditolylguanidine in a transient and calcium-dependent manner with no apparent direct effects on sigma receptor affinity.

  1. Endogenous Depression in the Elderly: Prevalence and Agreement among Measures.

    ERIC Educational Resources Information Center

    Gallagher-Thompson, Dolores; And Others

    1992-01-01

    Examined agreement among diagnoses made according to 5 definitions of endogenous depression in 99 depressed elders. Poor to fair agreement was generally demonstrated, except for Research Diagnostic Criteria and Diagnostic and Statistical Manual of Mental Disorders, which demonstrated excellent agreement. Mostly, demographic and clinical variables…

  2. Evolutionary Systems Theory, Universities, and Endogenous Regional Economic Development

    ERIC Educational Resources Information Center

    Bowen, William M.

    2007-01-01

    Universities today are increasingly being viewed in terms of serving the purpose of economic development. This paper postulates that their chief purpose is to advance knowledge and that in doing so they effectuate regional economic growth and development through processes specified in the endogenous economic growth model. To achieve this purpose…

  3. [Exploration of the Essence of "Endogenous Turbidity" in Chinese Medicine].

    PubMed

    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.

  4. [Exploration of the Essence of "Endogenous Turbidity" in Chinese Medicine].

    PubMed

    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. PMID:26485920

  5. A population of endogenous pararetrovirus genomes in carrizo citrange

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The complete genomes of three related endogenous pararetroviruses (EPRVs) were obtained by 454 sequencing of nucleic acid extracts from ‘Carrizo’citrange, used as a citrus rootstock. Numerous homologous sequences have been found in the sweet orange genome. The new EPRVs are most closely related to...

  6. New horizons for newborn brain protection: enhancing endogenous neuroprotection.

    PubMed

    Hassell, K Jane; Ezzati, Mojgan; Alonso-Alconada, Daniel; Hausenloy, Derek J; Robertson, Nicola J

    2015-11-01

    Intrapartum-related events are the third leading cause of childhood mortality worldwide and result in one million neurodisabled survivors each year. Infants exposed to a perinatal insult typically present with neonatal encephalopathy (NE). The contribution of pure hypoxia-ischaemia (HI) to NE has been debated; over the last decade, the sensitising effect of inflammation in the aetiology of NE and neurodisability is recognised. Therapeutic hypothermia is standard care for NE in high-income countries; however, its benefit in encephalopathic babies with sepsis or in those born following chorioamnionitis is unclear. It is now recognised that the phases of brain injury extend into a tertiary phase, which lasts for weeks to years after the initial insult and opens up new possibilities for therapy.There has been a recent focus on understanding endogenous neuroprotection and how to boost it or to supplement its effectors therapeutically once damage to the brain has occurred as in NE. In this review, we focus on strategies that can augment the body's own endogenous neuroprotection. We discuss in particular remote ischaemic postconditioning whereby endogenous brain tolerance can be activated through hypoxia/reperfusion stimuli started immediately after the index hypoxic-ischaemic insult. Therapeutic hypothermia, melatonin, erythropoietin and cannabinoids are examples of ways we can supplement the endogenous response to HI to obtain its full neuroprotective potential. Achieving the correct balance of interventions at the correct time in relation to the nature and stage of injury will be a significant challenge in the next decade. PMID:26063194

  7. Improving access to endogenous DNA in ancient bones and teeth

    PubMed Central

    Damgaard, Peter B.; Margaryan, Ashot; Schroeder, Hannes; Orlando, Ludovic; Willerslev, Eske; Allentoft, Morten E.

    2015-01-01

    Poor DNA preservation is the most limiting factor in ancient genomic research. In the majority of ancient bones and teeth, endogenous DNA molecules represent a minor fraction of the whole DNA extract, rendering shot-gun sequencing inefficient for obtaining genomic data. Based on ancient human bone samples from temperate and tropical environments, we show that an EDTA-based enzymatic ‘pre-digestion’ of powdered bone increases the proportion of endogenous DNA several fold. By performing the pre-digestion step between 30 min and 6 hours on five bones, we observe an asymptotic increase in endogenous DNA content, with a 2.7-fold average increase reached at 1 hour. We repeat the experiment using a brief pre-digestion (15 or 30 mins) on 21 ancient bones and teeth from a variety of archaeological contexts and observe an improvement in 16 of these. We here advocate the implementation of a brief pre-digestion step as a standard procedure in ancient DNA extractions. Finally, we demonstrate on 14 ancient teeth that by targeting the outer layer of the roots we obtain up to 14 times more endogenous DNA than when using the inner dentine. Our presented methods are likely to increase the proportion of ancient samples that are suitable for genome-scale characterization. PMID:26081994

  8. Conceptual Understanding of Multiplicative Properties through Endogenous Digital Game Play

    ERIC Educational Resources Information Center

    Denham, Andre

    2012-01-01

    This study purposed to determine the effect of an endogenously designed instructional game on conceptual understanding of the associative and distributive properties of multiplication. Additional this study sought to investigate if performance on measures of conceptual understanding taken prior to and after game play could serve as predictors of…

  9. RXR function requires binding to an endogenous terpenoid ligand

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The issue of whether the nuclear receptor RXR must bind to an endogenous, nanomolar affinity ligand in order to perform its natural function is still unsettled (1). On the basis of our previous studies establishing that the Drosophilamelanogaster ortholog of the retinoid X receptor ("ultraspiracle,"...

  10. Health and Wages: Panel Data Estimates Considering Selection and Endogeneity

    ERIC Educational Resources Information Center

    Jackle, Robert; Himmler, Oliver

    2010-01-01

    This paper complements previous studies on the effects of health on wages by addressing the problems of unobserved heterogeneity, sample selection, and endogeneity in one comprehensive framework. Using data from the German Socio-Economic Panel (GSOEP), we find the health variable to suffer from measurement error and a number of tests provide…

  11. Role of endogenous angiogenesis inhibitors in Down syndrome.

    PubMed

    Ryeom, Sandra; Folkman, Judah

    2009-03-01

    New blood vessel growth via angiogenesis is a fundamental process in both physiological and pathological conditions. Physiological angiogenesis is critical during embryogenesis and placental development, whereas pathological angiogenesis plays an important role in the progression of many diseases, most notably tumor growth. Tumor angiogenesis is well accepted to be regulated by a balance of proangiogenic and antiangiogenic factors produced both by tumor cells and surrounding stromal cells. For many years, investigation of antiangiogenic therapies for cancer has focused on the proangiogenic cytokine, vascular endothelial growth factor; its receptors; or downstream signaling pathways. However, more recently with the identification of endogenous angiogenesis inhibitors, studies have turned toward understanding the role of endogenous antiangiogenic proteins in preventing disease progression. Clinical clues have suggested that specific populations may have dysregulated angiogenesis due to differential expression of endogenous angiogenesis regulators. For example, individuals with Down syndrome may possess a systemic antiangiogenic state with a significantly decreased incidence of angiogenesis-dependent diseases. Our work suggests that endogenous angiogenesis inhibitors may be the master regulators controlling progression of angiogenesis-dependent diseases such as vascular anomalies and cancer. The molecular regulation of angiogenesis is not yet fully understood; however, the Down syndrome population may give us insights toward novel therapies for controlling angiogenesis in disease.

  12. Optical Control of Mammalian Endogenous Transcription and Epigenetic States

    PubMed Central

    Trevino, Alexandro; Hsu, Patrick D.; Heidenreich, Matthias; Cong, Le; Platt, Randall J.; Scott, David A.; Church, George M.; Zhang, Feng

    2013-01-01

    The dynamic nature of gene expression enables cellular programming, homeostasis, and environmental adaptation in living systems. Dissection of causal gene functions in cellular and organismal processes therefore necessitates approaches that enable spatially and temporally precise modulation of gene expression. Recently, a variety of microbial and plant-derived light-sensitive proteins have been engineered as optogenetic actuators, enabling high precision spatiotemporal control of many cellular functions1-11. However, versatile and robust technologies that enable optical modulation of transcription in the mammalian endogenous genome remain elusive. Here, we describe the development of Light-Inducible Transcriptional Effectors (LITEs), an optogenetic two-hybrid system integrating the customizable TALE DNA-binding domain12-14 with the light-sensitive cryptochrome 2 protein and its interacting partner CIB1 from Arabidopsis thaliana. LITEs do not require additional exogenous chemical co-factors, are easily customized to target many endogenous genomic loci, and can be activated within minutes with reversibility3,4,6,7,15. LITEs can be packaged into viral vectors and genetically targeted to probe specific cell populations. We have applied this system in primary mouse neurons, as well as in the brain of awake mice in vivo to mediate reversible modulation of mammalian endogenous gene expression as well as targeted epigenetic chromatin modifications. The LITE system establishes a novel mode of optogenetic control of endogenous cellular processes and enables direct testing of the causal roles of genetic and epigenetic regulation in normal biological processes and disease states. PMID:23877069

  13. New horizons for newborn brain protection: enhancing endogenous neuroprotection

    PubMed Central

    Hassell, K Jane; Ezzati, Mojgan; Alonso-Alconada, Daniel; Hausenloy, Derek J; Robertson, Nicola J

    2015-01-01

    Intrapartum-related events are the third leading cause of childhood mortality worldwide and result in one million neurodisabled survivors each year. Infants exposed to a perinatal insult typically present with neonatal encephalopathy (NE). The contribution of pure hypoxia-ischaemia (HI) to NE has been debated; over the last decade, the sensitising effect of inflammation in the aetiology of NE and neurodisability is recognised. Therapeutic hypothermia is standard care for NE in high-income countries; however, its benefit in encephalopathic babies with sepsis or in those born following chorioamnionitis is unclear. It is now recognised that the phases of brain injury extend into a tertiary phase, which lasts for weeks to years after the initial insult and opens up new possibilities for therapy. There has been a recent focus on understanding endogenous neuroprotection and how to boost it or to supplement its effectors therapeutically once damage to the brain has occurred as in NE. In this review, we focus on strategies that can augment the body's own endogenous neuroprotection. We discuss in particular remote ischaemic postconditioning whereby endogenous brain tolerance can be activated through hypoxia/reperfusion stimuli started immediately after the index hypoxic-ischaemic insult. Therapeutic hypothermia, melatonin, erythropoietin and cannabinoids are examples of ways we can supplement the endogenous response to HI to obtain its full neuroprotective potential. Achieving the correct balance of interventions at the correct time in relation to the nature and stage of injury will be a significant challenge in the next decade. PMID:26063194

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

    SciTech Connect

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

    1989-11-01

    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-{sup 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.

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

    ERIC Educational Resources Information Center

    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…

  16. Endogenous methicillin-resistant Staphylococcus aureus endophthalmitis after leg trauma.

    PubMed

    Larson, Katie E; Carrillo-Marquez, Maria

    2015-08-01

    We present a case of endogenous endophthalmitis in a 13-year-old boy with methicillin-resistant Staphylococcus aureus sepsis. The patient underwent magnetic resonance imaging of the brain after intermittent anisocoria was noted on examination, leading to a diagnosis of endophthalmitis with a chorodial abscess.

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

    PubMed

    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. PMID:26607312

  18. Inhibition of cellular respiration by endogenously produced carbon monoxide.

    PubMed

    D'Amico, Gabriela; Lam, Francis; Hagen, Thilo; Moncada, Salvador

    2006-06-01

    Endogenously produced nitric oxide (NO) interacts with mitochondrial cytochrome c oxidase, leading to inhibition of cellular respiration. This interaction has been shown to have important physiological and pathophysiological consequences. Exogenous carbon monoxide (CO) is also known to inhibit cytochrome c oxidase in vitro; however, it is not clear whether endogenously produced CO can inhibit cellular respiration and, if so, what the significance of this might be. In this study, we show that exogenous CO inhibits respiration in a moderate but persistent manner in HEK293 cells under ambient (21%) oxygen concentrations (K(i) = 1.44 microM). This effect of CO was increased (K(i) = 0.35 microM) by incubation in hypoxic conditions (1% oxygen). Endogenous CO, generated by HEK293 cells transfected with the inducible isoform of haem oxygenase (haem oxygenase-1; HO-1), also inhibited cellular respiration moderately (by 12%) and this was accompanied by inhibition (23%) of cytochrome c oxidase activity. When the cells were incubated in hypoxic conditions during HO-1 induction, the inhibitory effect of CO on cell respiration was markedly increased to 70%. Furthermore, endogenously produced CO was found to be responsible for the respiratory inhibition that occurs in RAW264.7 cells activated in hypoxic conditions with lipopolysaccharide and interferon-gamma, in the presence of N-(iminoethyl)-L-ornithine to prevent the synthesis of NO. Our results indicate that CO contributes significantly to the respiratory inhibition in activated cells, particularly under hypoxic conditions. Inhibition of cell respiration by endogenous CO through its interaction with cytochrome c oxidase might have an important role in inflammatory and hypoxic conditions.

  19. LC/MS/MS analysis of the endogenous dimethyltryptamine hallucinogens, their precursors, and major metabolites in rat pineal gland microdialysate.

    PubMed

    Barker, Steven A; Borjigin, Jimo; Lomnicka, Izabela; Strassman, Rick

    2013-12-01

    We report a qualitative liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for the simultaneous analysis of the three known N,N-dimethyltryptamine endogenous hallucinogens, their precursors and metabolites, as well as melatonin and its metabolic precursors. The method was characterized using artificial cerebrospinal fluid (aCSF) as the matrix and was subsequently applied to the analysis of rat brain pineal gland-aCSF microdialysate. The method describes the simultaneous analysis of 23 chemically diverse compounds plus a deuterated internal standard by direct injection, requiring no dilution or extraction of the samples. The results demonstrate that this is a simple, sensitive, specific and direct approach to the qualitative analysis of these compounds in this matrix. The protocol also employs stringent MS confirmatory criteria for the detection and confirmation of the compounds examined, including exact mass measurements. The excellent limits of detection and broad scope make it a valuable research tool for examining the endogenous hallucinogen pathways in the central nervous system. We report here, for the first time, the presence of N,N-dimethyltryptamine in pineal gland microdialysate obtained from the rat.

  20. Relevance of tryptophan and tyrosine availability in endogenous and 'non-endogenous' depressives treated with imipramine or clomipramine.

    PubMed

    Møller, S E; Reisby, N; Ortmann, J; Elley, J; Krautwald, O

    1981-09-01

    This study was performed on 65 depressed in-patients who were included in previously reported trials of imipramine and clomipramine. Before and during treatment, blood samples were collected for estimation of the availability of tryptophan and tyrosine by measurement of their plasma ratios to competing amino acids, and for determination of plasma steady-state concentrations of imipramine, clomipramine and their demethylated metabolites. The patients were classified as endogenous or 'non-endogenous' depressives by means of diagnostic rating scales, and therapeutic efficacy was evaluated by means of the Hamilton rating scales. Neither imipramine nor clomipramine increased the availability of tryptophan or tyrosine. Three biochemical regions were defined: a low region including mostly patients with subnormal availability of both tryptophan and tyrosine, a medium region, and a high region including mostly patients with supernormal precursor availabilities. Endogenous depressives showed about the same biochemical distribution as controls whereas there tended to be a proportionately higher number of 'non-endogenous' depressives within the low region. Patients in the low region, irrespective of diagnostic classification, improved faster and more on imipramine than patients in the medium and high regions with comparable plasma drug levels. Patients on clomipramine tended to show a relationship between precursor availabilities and clinical response but no definite conclusion could be drawn from these data. The results suggest that determination of the pre-treatment tryptophan and tyrosine availability may be superior to diagnostic classification in predicting response to imipramine. The possible mode of action of tricyclic antidepressants is briefly discussed. PMID:6456290

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

    PubMed

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

    2016-07-01

    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/.

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

    PubMed Central

    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/. PMID:27131375

  3. The influence of endogenous and exogenous sex hormones in adolescents with attention to oral contraceptives and anabolic steroids.

    PubMed

    Lane, J R; Connor, J D

    1994-12-01

    The endogenous sex hormones produce dispositional changes in the developing child as well as imparting unique male and female dispositional patterns. Age-related changes have been observed for digoxin disposition and caffeine and theophylline metabolism. These age-related dispositional changes have led to age-dependent dosing recommendations. Studies with caffeine and antipyrine indicate that this change in drug disposition occurs over a short period of time, is seen earlier in girls than in boys, and is related to pubertal (Tanner) stage and the "growth spurt". Significant changes in endogenous sex hormone concentrations occur during the menstrual cycle and during pregnancy, leading to alterations in drug binding, distribution, and clearance. Oral contraceptives (OCs) inhibit the metabolism of certain drugs resulting in toxicity or lack of efficacy. Rifampin induces the OC metabolism, resulting in decreased clinical effectiveness. Most studies did not examine these kinetic and dynamic interactions between adult and adolescent users. It is estimated that there are over 45 anabolic steroid compounds available for abuse by athletes, and their use is increasing among male and female adolescents. Although the adolescent is at increased risk of developing adverse effects from these agents, a systematic evaluation of the long-term effects of anabolic steroid abuse has not been undertaken in this population. Further research is needed regarding the influence of endogenous and exogenous hormones on adolescent drug kinetics and dynamics. Because of their frequency of use among adolescents, OCs and anabolic steroids require particular emphasis.

  4. Assays for endogenous components of human milk: comparison of fresh and frozen samples and corresponding analytes in serum.

    PubMed

    Hines, Erin P; Rayner, Jennifer L; Barbee, Randy; Moreland, Rae Ann; Valcour, Andre; Schmid, Judith E; Fenton, Suzanne E

    2007-05-01

    Breast milk is a primary source of nutrition that contains many endogenous compounds that may affect infant development. The goals of this study were to develop reliable assays for selected endogenous breast milk components and to compare levels of those in milk and serum collected from the same mother twice during lactation (2-7 weeks and 3-4 months). Reliable assays were developed for glucose, secretory IgA, interleukin-6, tumor necrosis factor-a, triglycerides, prolactin, and estradiol from participants in a US EPA study called Methods Advancement in Milk Analysis (MAMA). Fresh and frozen (-20 degrees C) milk samples were assayed to determine effects of storage on endogenous analytes. The source effect (serum vs milk) seen in all 7 analytes indicates that serum should not be used as a surrogate for milk in children's health studies. The authors propose to use these assays in studies to examine relationships between the levels of milk components and children's health. PMID:17478867

  5. Competition between endogenous and exogenous orienting of visual attention.

    PubMed

    Berger, Andrea; Henik, Avishai; Rafal, Robert

    2005-05-01

    The relation between reflexive and voluntary orienting of visual attention was investigated with 4 experiments: a simple detection task, a localization task, a saccade toward the target task, and a target identification task in which discrimination difficulty was manipulated. Endogenous and exogenous orienting cues were presented in each trial and their validity was manipulated orthogonally to examine whether attention mechanisms are mediated by separate systems and whether they have additive and independent effects on visual detection and discrimination. The results showed that each orienting mechanism developed its typical and independent effect in every case except for the difficult identification task. A theoretical framework for understanding the relationship between endogenous and exogenous orienting of attention is proposed, tested, and confirmed.

  6. Activation of endogenous neural stem cells for multiple sclerosis therapy.

    PubMed

    Michailidou, Iliana; de Vries, Helga E; Hol, Elly M; van Strien, Miriam E

    2014-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, leading to severe neurological deficits. Current MS treatment regimens, consist of immunomodulatory agents aiming to reduce the rate of relapses. However, these agents are usually insufficient to treat chronic neurological disability. A promising perspective for future therapy of MS is the regeneration of lesions with replacement of the damaged oligodendrocytes or neurons. Therapies targeting to the enhancement of endogenous remyelination, aim to promote the activation of either the parenchymal oligodendrocyte progenitor cells or the subventricular zone-derived neural stem cells (NSCs). Less studied but highly potent, is the strategy of neuronal regeneration with endogenous NSCs that although being linked to numerous limitations, is anticipated to ameliorate cognitive disability in MS. Focusing on the forebrain, this review highlights the role of NSCs in the regeneration of MS lesions.

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

    PubMed

    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.

  8. Endogenous RNAi and adaptation to environment in C. elegans

    PubMed Central

    Grishok, Alla

    2012-01-01

    The contributions of short RNAs to the control of repetitive elements are well documented in animals and plants. Here, the role of endogenous RNAi and AF10 homolog ZFP-1 in the adaptation of C. elegans to the environment is discussed. First, modulation of insulin signaling through regulation of transcription of the PDK-1 kinase (Mansisidor et al., PLoS Genetics, 2011) is reviewed. Second, an siRNA-based natural selection model is proposed in which variation in endogenous siRNA pools between individuals is subject to natural selection similarly to DNA-based genetic variation. The value of C. elegans for the research of siRNA-based epigenetic variation and adaptation is highlighted. PMID:24058837

  9. Endogenous K-ras signaling in erythroid differentiation.

    PubMed

    Zhang, Jing; Lodish, Harvey F

    2007-08-15

    K-ras is one of the most frequently mutated genes in virtually all types of human cancers. Using mouse fetal liver erythroid progenitors as a model system, we studied the role of endogenous K-ras signaling in erythroid differentiation. When oncogenic K-ras is expressed from its endogenous promoter, it hyperactivates cytokine-dependent signaling pathways and results in a partial block in erythroid differentiation. In erythroid progenitors deficient in K-ras, cytokine-dependent Akt activation is greatly reduced, leading to delays in erythroid differentiation. Thus, both loss- and gain-of-Kras functions affect erythroid differentiation through modulation of cytokine signaling. These results support the notion that in human cancer patients oncogenic Ras signaling might be controlled by antagonizing essential cytokines.

  10. Immunomodulatory effects of endogenous and synthetic peptides activating opioid receptors.

    PubMed

    Pomorska, Dorota K; Gach, Katarzyna; Janecka, Anna

    2014-01-01

    The main role of endogenous opioid peptides is the modulation of pain. Opioid peptides exert their analgesic activity by binding to the opioid receptors distributed widely in the central nervous system (CNS). However, opioid receptors are also found on tissues and organs outside the CNS, including the cells of the immune system, indicating that opioids are capable of exerting additional effects in periphery. Morphine, which is a gold standard in the treatment of chronic pain, is well-known for its immunosuppressive effects. Much less is known about the immunomodulatory effects exerted by endogenous (enkephalins, endorphins, dynorphins and endomorphins) and synthetic peptides activating opioid receptors. In this review we tried to summarize opioid peptide-mediated modulation of immune cell functions which can be stimulatory as well as inhibitory. PMID:25553430

  11. Exogenic and endogenic albedo and color patterns on Europa

    NASA Technical Reports Server (NTRS)

    Mcewen, A. S.

    1986-01-01

    New global and high-resolution multispectral mosaics of Europa have been produced from the Voyager imaging data. Photometric normalizations are based on multiple-image techniques that explicitly account for intrinsic albedo variations through pixel-by-pixel solutions. The exogenic color and albedo pattern on Europa is described by a second-order function of the cosine of the angular distance from the apex of orbital motion. On the basis of this second-order function and of color trends that are different on the leading and trailing hemispheres, the exogenic pattern is interpreted as being due to equilibrium between two dominant processes: (1) impact gardening and (2) magnetospheric interactions, including sulfur-ion implantation and sputtering redistribution. Removal of the model exogenic pattern in the mosaics reveals the endogenic variations, consisting of only two major units: darker (redder) and bright materials. Therefore Europa's visual spectral reflectivity is simple, having one continuous exogenic pattern and two discrete endogenic units.

  12. [Proposal of endogenous anticholinergic hypothesis in Alzheimer disease].

    PubMed

    Hori, Koji; Konishi, Kimiko; Akita, Ryo; Tani, Masayuki; Tomioka, Hiroi; Kitajima, Yuka; Yokoyama, Sachiko; Azuma, Kazunari; Ikuse, Daisuke; Akashi, Norinao; Yuda, Hajime; Hachisu, Mitsugu

    2013-06-01

    We previously speculated that anticholinergic activity (AA) endogenously appeared in Alzheimer's disease (AD) and accelerated AD pathology. In this article we introduce manuscripts supporting the endogenous appearance of AA in AD and the acceleration of AD pathology. We speculate that acethylcholine (ACh) not only is related to cognitive functions but also regulates the inflammatory system. Therefore in AD, in which the ACh system is down-regulated, the hyperactivity of the inflammatory system may be caused and among cyctokines, substances having anticholinergic properties may appear. We also refer to a case in which serum anticholinergic activity (SAA) disappeared with the prescription of memantine (an antidementia agent that has the property of the N-methyl-D-aspartate (NMDA) receptor blocker) and speculate that because the hyperactivity of the inflammatory system occurs by way of the hyperactivity of NMDA receptor, memantine could abolish the AA.

  13. Diet-induced obese mice retain endogenous leptin action.

    PubMed

    Ottaway, Nickki; Mahbod, Parinaz; Rivero, Belen; Norman, Lee Ann; Gertler, Arieh; D'Alessio, David A; Perez-Tilve, Diego

    2015-06-01

    Obesity is characterized by hyperleptinemia and decreased response to exogenous leptin. This has been widely attributed to the development of leptin resistance, a state of impaired leptin signaling proposed to contribute to the development and persistence of obesity. To directly determine endogenous leptin activity in obesity, we treated lean and obese mice with a leptin receptor antagonist. The antagonist increased feeding and body weight (BW) in lean mice, but not in obese models of leptin, leptin receptor, or melanocortin-4 receptor deficiency. In contrast, the antagonist increased feeding and BW comparably in lean and diet-induced obese (DIO) mice, an increase associated with decreased hypothalamic expression of Socs3, a primary target of leptin. These findings demonstrate that hyperleptinemic DIO mice retain leptin suppression of feeding comparable to lean mice and counter the view that resistance to endogenous leptin contributes to the persistence of DIO in mice.

  14. Activation of endogenous neural stem cells for multiple sclerosis therapy

    PubMed Central

    Michailidou, Iliana; de Vries, Helga E.; Hol, Elly M.; van Strien, Miriam E.

    2015-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, leading to severe neurological deficits. Current MS treatment regimens, consist of immunomodulatory agents aiming to reduce the rate of relapses. However, these agents are usually insufficient to treat chronic neurological disability. A promising perspective for future therapy of MS is the regeneration of lesions with replacement of the damaged oligodendrocytes or neurons. Therapies targeting to the enhancement of endogenous remyelination, aim to promote the activation of either the parenchymal oligodendrocyte progenitor cells or the subventricular zone-derived neural stem cells (NSCs). Less studied but highly potent, is the strategy of neuronal regeneration with endogenous NSCs that although being linked to numerous limitations, is anticipated to ameliorate cognitive disability in MS. Focusing on the forebrain, this review highlights the role of NSCs in the regeneration of MS lesions. PMID:25653584

  15. THE PRESENCE OF ENDOGENOUS PYROGEN IN NORMAL RABBIT TISSUES

    PubMed Central

    Snell, E. S.; Atkins, Elisha

    1965-01-01

    Saline extracts of homogenized, uninfected, rabbit tissues produced febrile responses when injected intravenously into rabbits. Extracts of muscle, lung, and heart evoked fevers that were similar to those induced by leucocyte pyrogen; extracts of spleen, liver, and kidney caused more sustained fevers. The minimal pyrogenic dose appeared to be between 1.5 and 3 gm wet weight of tissue. Evidence is presented that neither Gram-negative bacterial endotoxin nor polymorphonuclear leucocytes (circulating or sequestered in the tissues) can be implicated as the source of pyrogen in tissue extracts. It seems likely, therefore, that a pyrogenic material of truly endogenous origin is widely distributed in tissues. Tissue pyrogen appears to be a large molecule which is relatively resistant to treatment with acid but not with alkali. Possible pathological roles for this endogenous agent (or agents) are briefly indicated. PMID:14319400

  16. Endogenous CO dynamics monitoring in breath by tunable diode laser

    NASA Astrophysics Data System (ADS)

    Kouznetsov, Andrian I.; Stepanov, Eugene V.; Shulagin, Yurii A.; Skrupskii, Vladimir A.

    1996-04-01

    High sensitive CO gas analyzer based on tunable diode laser (TDL) was used as a real time monitor of endogenous carbon monoxide in a set of breath physiology experiments. The measurements of the CO content dynamics in exhaled air with 10 ppb sensitivity were attended with detection of carbon dioxide and O2 in breath, lung ventilation parameters, heart rate and blood analysis using conventional techniques. Variations of endogenous CO in human breath caused by hyperoxia, hypoxia, hyperventilation as well as sport loading were studied in real time. Scattering of the CO variation time constants was observed for different tested persons. Possible reasons for this scattering related with the organisms' physiology peculiarities are discussed.

  17. Salusin-β as a powerful endogenous antidipsogenic neuropeptide

    PubMed Central

    Suzuki-Kemuriyama, Noriko; Nakano-Tateno, Tae; Tani, Yuji; Hirata, Yukio; Shichiri, Masayoshi

    2016-01-01

    Salusin-β is an endogenous parasympathomimetic peptide, predominantly localized to the hypothalamus and posterior pituitary. Subcutaneously administered salusin-β (50 nmol/mouse) significantly increased water intake but did not affect locomotor activity or food intake. The salusin-β-induced increase in water intake was completely abrogated by pretreatment with muscarinic antagonist, atropine sulphate. In contrast, intracerebroventricular injection of salusin-β, at lower doses (10–100 fmol/mouse) caused a long-lasting decrease in water intake and locomotor activity throughout the entire dark phase of the diurnal cycle. Pre-injection of intracerebroventricular anti-salusin-β IgG completely abrogated the central salusin-β mediated suppression of water intake and locomotor activity. These results demonstrate contrasting actions of salusin-β in the control of water intake via the central and peripheral systems and highlight it as a potent endogenous antidipsogenic neuropeptide. PMID:26869388

  18. The Negative Effects of Volatile Sulphur Compounds.

    PubMed

    Milella, Lisa

    2015-01-01

    Oral malodor has been studied extensively in humans but not necessarily to the same degree in our veterinary patients where malodor constitutes a significant problem. Breath malodor may originate from the mouth, or from an extra oral source, originating from other organ systems such as gastrointestinal, respiratory, or even systemic disease. Oral malodor is a result of microbial metabolism of exogenous and endogenous proteinaceous substrates leading to the production of compounds such as indole, skatole, tyramine, cadaverine, puterescine, mercaptans, and sulphides. Volatile sulphur compounds have been shown to be the main cause of oral malodor. Although most clients perceive oral malodor to be primarily a cosmetic problem, there is an increasing volume of evidence in human dental literature demonstrating that volatile sulphur compounds produced by bacteria, even at low concentrations, are toxic to tissues and play a role in the pathogenesis of periodontitis. This article reviews the current available literature in human dentistry looking at these negative effects. No veterinary studies have been conducted looking at the negative effects of volatile sulphur compounds specifically, but as this article highlights, we should be aware of the potential negative effects of volatile sulphur compounds and consider this an area of future research. PMID:26415386

  19. Excretion of biliary compounds during intrauterine life

    PubMed Central

    Macias, Rocio IR; Marin, Jose JG; Serrano, Maria A

    2009-01-01

    In adults, the hepatobiliary system, together with the kidney, constitute the main routes for the elimination of several endogenous and xenobiotic compounds into bile and urine, respectively. However, during intrauterine life the biliary route of excretion for cholephilic compounds, such as bile acids and biliary pigments, is very poor. Although very early in pregnancy the fetal liver produces bile acids, bilirubin and biliverdin, these compounds cannot be efficiently eliminated by the fetal hepatobiliary system, owing to the immaturity of the excretory machinery in the fetal liver. Therefore, the potentially harmful accumulation of cholephilic compounds in the fetus is prevented by their elimination across the placenta. Owing to the presence of detoxifying enzymes and specific transport systems at different locations of the placental barrier, such as the endothelial cells of chorionic vessels and trophoblast cells, this organ plays an important role in the hepatobiliary-like function during intrauterine life. The relevance of this excretory function in normal fetal physiology is evident in situations where high concentrations of biliary compounds are accumulated in the mother. This may result in oxidative stress and apoptosis, mainly in the placenta and fetal liver, which might affect normal fetal development and challenge the fate of the pregnancy. The present article reviews current knowledge of the mechanisms underlying the hepatobiliary function of the fetal-placental unit and the repercussions of several pathological conditions on this tandem. PMID:19230042

  20. Endogenous Protease Nexin-1 Protects against Cerebral Ischemia

    PubMed Central

    Mirante, Osvaldo; Price, Melanie; Puentes, Wilfredo; Castillo, Ximena; Benakis, Corinne; Thevenet, Jonathan; Monard, Denis; Hirt, Lorenz

    2013-01-01

    The serine protease thrombin plays a role in signalling ischemic neuronal death in the brain. Paradoxically, endogenous neuroprotective mechanisms can be triggered by preconditioning with thrombin (thrombin preconditioning, TPC), leading to tolerance to cerebral ischemia. Here we studied the role of thrombin’s endogenous potent inhibitor, protease nexin-1 (PN-1), in ischemia and in tolerance to cerebral ischemia induced by TPC. Cerebral ischemia was modelled in vitro in organotypic hippocampal slice cultures from rats or genetically engineered mice lacking PN-1 or with the reporter gene lacZ knocked into the PN-1 locus PN-1HAPN-1-lacZ/HAPN-1-lacZ (PN-1 KI) exposed to oxygen and glucose deprivation (OGD). We observed increased thrombin enzyme activity in culture homogenates 24 h after OGD. Lack of PN-1 increased neuronal death in the CA1, suggesting that endogenous PN-1 inhibits thrombin-induced neuronal damage after ischemia. OGD enhanced β-galactosidase activity, reflecting PN-1 expression, at one and 24 h, most strikingly in the stratum radiatum, a glial cell layer adjacent to the CA1 layer of ischemia sensitive neurons. TPC, 24 h before OGD, additionally increased PN-1 expression 1 h after OGD, compared to OGD alone. TPC failed to induce tolerance in cultures from PN-1−/− mice confirming PN-1 as an important TPC target. PN-1 upregulation after TPC was blocked by the c-Jun N-terminal kinase (JNK) inhibitor, L-JNKI1, known to block TPC. This work suggests that PN-1 is an endogenous neuroprotectant in cerebral ischemia and a potential target for neuroprotection. PMID:23949634

  1. Endogenous protease nexin-1 protects against cerebral ischemia.

    PubMed

    Mirante, Osvaldo; Price, Melanie; Puentes, Wilfredo; Castillo, Ximena; Benakis, Corinne; Thevenet, Jonathan; Monard, Denis; Hirt, Lorenz

    2013-08-14

    The serine protease thrombin plays a role in signalling ischemic neuronal death in the brain. Paradoxically, endogenous neuroprotective mechanisms can be triggered by preconditioning with thrombin (thrombin preconditioning, TPC), leading to tolerance to cerebral ischemia. Here we studied the role of thrombin's endogenous potent inhibitor, protease nexin-1 (PN-1), in ischemia and in tolerance to cerebral ischemia induced by TPC. Cerebral ischemia was modelled in vitro in organotypic hippocampal slice cultures from rats or genetically engineered mice lacking PN-1 or with the reporter gene lacZ knocked into the PN-1 locus PN-1HAPN-1-lacZ/HAPN-1-lacZ (PN-1 KI) exposed to oxygen and glucose deprivation (OGD). We observed increased thrombin enzyme activity in culture homogenates 24 h after OGD. Lack of PN-1 increased neuronal death in the CA1, suggesting that endogenous PN-1 inhibits thrombin-induced neuronal damage after ischemia. OGD enhanced β-galactosidase activity, reflecting PN-1 expression, at one and 24 h, most strikingly in the stratum radiatum, a glial cell layer adjacent to the CA1 layer of ischemia sensitive neurons. TPC, 24 h before OGD, additionally increased PN-1 expression 1 h after OGD, compared to OGD alone. TPC failed to induce tolerance in cultures from PN-1(-/-) mice confirming PN-1 as an important TPC target. PN-1 upregulation after TPC was blocked by the c-Jun N-terminal kinase (JNK) inhibitor, L-JNKI1, known to block TPC. This work suggests that PN-1 is an endogenous neuroprotectant in cerebral ischemia and a potential target for neuroprotection.

  2. Stochastic resonance in neuron models: Endogenous stimulation revisited

    NASA Astrophysics Data System (ADS)

    Plesser, Hans E.; Geisel, Theo

    2001-03-01

    The paradigm of stochastic resonance (SR)-the idea that signal detection and transmission may benefit from noise-has met with great interest in both physics and the neurosciences. We investigate here the consequences of reducing the dynamics of a periodically driven neuron to a renewal process (stimulation with reset or endogenous stimulation). This greatly simplifies the mathematical analysis, but we show that stochastic resonance as reported earlier occurs in this model only as a consequence of the reduced dynamics.

  3. [The immunological mechanisms of the tissue lesions in endogenous uveitis].

    PubMed

    Todea, V

    1994-01-01

    The endogenous uveitis is essentially an immunologic disease, although it has a very variable immunology. During the immune response are implied the reactions of tardive hypersensibility (by immune complexes), hypersensibility through antibodies produced intraocularly or transported by the overall circulation and rarely, immediate hypersensibility reaction. The absence of lymphatics in the eye and of the antigenic cells in the tissues which limit the anterior chamber, implies an active, deviated immunity response, denoted by the term ACAID. PMID:8060956

  4. Pseudogene-derived endogenous siRNAs and their function.

    PubMed

    Chan, Wen-Ling; Chang, Jan-Gowth

    2014-01-01

    Pseudogenes were once considered genomic fossils, but recent studies indicate that they may function as gene regulators through the generation of endogenous small interfering RNAs (esiRNAs), antisense RNAs, and decoys for microRNAs. In this review, we summarize pseudogene study methods, emphasizing relevant publicly available resources, and we describe a systematic pipeline to identify pseudogene-derived esiRNAs and their targets, which can lead to a deeper understanding of pseudogene function.

  5. Endogenous protease nexin-1 protects against cerebral ischemia.

    PubMed

    Mirante, Osvaldo; Price, Melanie; Puentes, Wilfredo; Castillo, Ximena; Benakis, Corinne; Thevenet, Jonathan; Monard, Denis; Hirt, Lorenz

    2013-01-01

    The serine protease thrombin plays a role in signalling ischemic neuronal death in the brain. Paradoxically, endogenous neuroprotective mechanisms can be triggered by preconditioning with thrombin (thrombin preconditioning, TPC), leading to tolerance to cerebral ischemia. Here we studied the role of thrombin's endogenous potent inhibitor, protease nexin-1 (PN-1), in ischemia and in tolerance to cerebral ischemia induced by TPC. Cerebral ischemia was modelled in vitro in organotypic hippocampal slice cultures from rats or genetically engineered mice lacking PN-1 or with the reporter gene lacZ knocked into the PN-1 locus PN-1HAPN-1-lacZ/HAPN-1-lacZ (PN-1 KI) exposed to oxygen and glucose deprivation (OGD). We observed increased thrombin enzyme activity in culture homogenates 24 h after OGD. Lack of PN-1 increased neuronal death in the CA1, suggesting that endogenous PN-1 inhibits thrombin-induced neuronal damage after ischemia. OGD enhanced β-galactosidase activity, reflecting PN-1 expression, at one and 24 h, most strikingly in the stratum radiatum, a glial cell layer adjacent to the CA1 layer of ischemia sensitive neurons. TPC, 24 h before OGD, additionally increased PN-1 expression 1 h after OGD, compared to OGD alone. TPC failed to induce tolerance in cultures from PN-1(-/-) mice confirming PN-1 as an important TPC target. PN-1 upregulation after TPC was blocked by the c-Jun N-terminal kinase (JNK) inhibitor, L-JNKI1, known to block TPC. This work suggests that PN-1 is an endogenous neuroprotectant in cerebral ischemia and a potential target for neuroprotection. PMID:23949634

  6. Peptic ulcer disease in endogenous hypercortisolism: myth or reality?

    PubMed

    Hatipoglu, Esra; Caglar, Asli Sezgin; Caglar, Erkan; Ugurlu, Serdal; Tuncer, Murat; Kadioglu, Pinar

    2015-11-01

    Many clinicians believe hypercortisolism is ulcerogenic. However, data from clinical studies show that prophylaxis for peptic ulcer disease is no longer recommended in patients receiving corticosteroid treatment. This has not yet been verified in endogenous hypercortisolism by controlled clinical studies. The purpose of the current study was to evaluate the relationship between endogenous Cushing's syndrome (CS) and peptic ulcer disease and Helicobacter pylori infection. The study group contained 20 cases with CS resulting from ACTH-dependent endogenous hypercortisolism. The control groups consisted of 14 age- and gender-matched cases receiving exogenous corticosteroid therapy and 100 cases of dyspepsia with non-cushingoid features. Upper gastrointestinal endoscopy was performed on all cases. Biopsies were taken from five different points: two samples from the antrum, two samples from the corpus, and one sample from the fundus. A histological diagnosis of Helicobacter pylori infection was also obtained from evaluation of biopsy specimens. The frequency of stomach and duodenal ulcers did not vary between the groups (p = 0.5 and p = 0.7). Antral gastritis was less frequent and pangastritis was more common in cases with CS compared to the healthy controls (p = 0.001 and p < 0.001). The incidence of Candida esophagitis was more frequent in cases with CS compared to cases with corticosteroid treatment and healthy controls (p = 0.03). Histopathological findings and frequency of Helicobacter pylori based on pathology results did not vary between the three groups. It is possible that neither exogenous nor endogenous corticosteroid excess directly causes peptic ulcer or Helicobacter pylori infection. Prophylactic use of proton pump inhibitors is not compulsory for hypercortisolism of any type.

  7. Myelin regeneration in multiple sclerosis: targeting endogenous stem cells.

    PubMed

    Huang, Jeffrey K; Fancy, Stephen P J; Zhao, Chao; Rowitch, David H; Ffrench-Constant, Charles; Franklin, Robin J M

    2011-10-01

    Regeneration of myelin sheaths (remyelination) after central nervous system demyelination is important to restore saltatory conduction and to prevent axonal loss. In multiple sclerosis, the insufficiency of remyelination leads to the irreversible degeneration of axons and correlated clinical decline. Therefore, a regenerative strategy to encourage remyelination may protect axons and improve symptoms in multiple sclerosis. We highlight recent studies on factors that influence endogenous remyelination and potential promising pharmacological targets that may be considered for enhancing central nervous system remyelination.

  8. Behavioral fractality in marine copepods: Endogenous rhythms versus exogenous stressors

    NASA Astrophysics Data System (ADS)

    Seuront, Laurent

    2011-01-01

    The presence of endogenous rhythms in the swimming behavior of five common species of copepods (i.e. minute marine crustaceans) was investigated through comparisons of the scaling properties of their three-dimensional trajectories and cumulative probability distribution functions of move lengths recorded during the day and at night. Beside clear inter-specific differences in their behavioral scaling properties, the five species exhibited an increase in path tortuosity at night, consistent with an increase in food foraging activity. Given the absence of food under all experimental conditions, this suggests the presence of an endogenous swimming rhythm consistent with the widely reported pattern of ascent at dusk resulting in copepods entering the food-rich surface layer at night. The impact of the stress exerted on swimming behavior by changes in the light regime (i.e. light and dark conditions respectively experienced at night and during the day) and the related copepod behavioral adaptivity was also investigated. The low and high fractal dimensions respectively observed during daytime in the dark and during night-time under conditions of simulated daytime indicate that these organisms have the ability to adjust the complexity of their swimming path depending on exogenous factors, independent of their actual endogenous rhythms. The scaling exponents of the cumulative probability distribution function of move lengths exhibit a significant decrease during daylight hours under simulated night-time conditions and during the night under simulated daytime conditions, suggesting an increase in the stress levels experienced by the five species considered. It is finally shown that the stress exerted on endogenous behavioral diel variability by exogenous cues has a species-specific effect on copepods.

  9. Two-Stage Bayesian Model Averaging in Endogenous Variable Models.

    PubMed

    Lenkoski, Alex; Eicher, Theo S; Raftery, Adrian E

    2014-01-01

    Economic modeling in the presence of endogeneity is subject to model uncertainty at both the instrument and covariate level. We propose a Two-Stage Bayesian Model Averaging (2SBMA) methodology that extends the Two-Stage Least Squares (2SLS) estimator. By constructing a Two-Stage Unit Information Prior in the endogenous variable model, we are able to efficiently combine established methods for addressing model uncertainty in regression models with the classic technique of 2SLS. To assess the validity of instruments in the 2SBMA context, we develop Bayesian tests of the identification restriction that are based on model averaged posterior predictive p-values. A simulation study showed that 2SBMA has the ability to recover structure in both the instrument and covariate set, and substantially improves the sharpness of resulting coefficient estimates in comparison to 2SLS using the full specification in an automatic fashion. Due to the increased parsimony of the 2SBMA estimate, the Bayesian Sargan test had a power of 50 percent in detecting a violation of the exogeneity assumption, while the method based on 2SLS using the full specification had negligible power. We apply our approach to the problem of development accounting, and find support not only for institutions, but also for geography and integration as development determinants, once both model uncertainty and endogeneity have been jointly addressed.

  10. ENDOGENOUS CARDIOTONIC STEROIDS AND SALT-SENSITIVE HYPERTENSION

    PubMed Central

    Fedorova, Olga V.; Shapiro, Joseph I.; Bagrov, Alexei Y.

    2010-01-01

    Endogenous cardiotonic steroids (CTS), also called digitalis like factors, have been postulated to play important roles in pathogenesis of hypertension for nearly half of a century. For the past 50 years biomedical scientists have been in quest of an unidentified factor or hormone that both increases blood pressure and renal sodium excretion; this “natriuretic hormone” was, in fact, postulated to interact with the Na/K-ATPase. Recent discoveries have led to the identification of steroid molecules which are present in humans, rodents and amphibians, and which, in a complex manner, interact with each other and with the other systems that regulate renal salt handling and contribute to the salt-sensitivity of blood pressure. Recent findings include the specific identification of endogenous cardenolide (endogenous ouabain) and bufadienolide (marinobufagenin) CTS in humans along with the delineation of mechanisms by which CTS can signal through the Na/K-ATPase. Although CTS were first considered important in the regulation of renal sodium transport and arterial pressure, more recent work implicates these hormones in the central regulation of blood pressure and regulation of cell growth, and development of cardiovascular and renal fibrosis in particular. PMID:20347967

  11. Control of RFM strain endogenous retrovirus in RFM mouse cells.

    PubMed

    Tennant, R W; Otten, J A; Wang, T W; Liou, R S; Brown, A; Yang, W K

    1983-01-01

    RFM/Un mice express an endogenous type C retrovirus throughout their life span in many tissues; primary or established embryo fibroblast cell cultures do not express a virus but can be induced by exposure to 5-iodo-2'-deoxyuridine. All of our sources yielded a single ecotropic virus (RFV) which appeared to be related more closely to the endogenous N-tropic virus (WN1802N) of BALB/c mice than to Gross leukemia virus on the basis of two-dimensional gel electropherograms of virion proteins. No xenotropic or recombinant viruses were isolated by cocultivation techniques. RFV is N-tropic, and RFM/Un cells possess the Fv-1n allele, as indicated by restriction of B-tropic virus and susceptibility to Gross strain N-tropic virus. However, RFM cells are highly resistant to RFV and other endogenous N-tropic viruses. This resistance is expressed by two-hit titration kinetics and by inhibition of viral linear duplex DNA formation. This is similar to the effects of the Fv-1 locus, but preliminary work has shown no apparent genetic linkage between the two restrictions. The relative strength of the restriction, the presence of a single class of ecotropic virus, and the absence of recombinant viruses suggest that in RFM mice virus is expressed only in cells in which it is induced and not by cell-to-cell transmission.

  12. Endogenous Cardioprotective Agents: Role in Pre and Postconditioning.

    PubMed

    Penna, Claudia; Granata, Riccarda; Tocchetti, Carlo Gabriele; Gallo, Maria Pia; Alloatti, Giuseppe; Pagliaro, Pasquale

    2015-01-01

    Cardiovascular diseases (CVD) are the leading cause of death, chronic illness and disability in Western countries. The most common cause of CVD derives from the harmful effects of acute myocardial ischemia and subsequent reperfusion injury. Cardioprotection against acute ischemia/ reperfusion injury is made possible by the "conditioning protocols." Conditioning is obtained by applying a few periods of brief ischemia and reperfusion in the event of prolonged (index) ischemia that may cause myocardial infarction. Whilst the conditioning stimulus is applied before the index ischemia in ischemic pre-conditioning, it is applied after the event in post-conditioning. Pre and post- conditioning stimuli can be applied in a different/remote organ (remote pre- and post-conditioning); in this case conditioning stimulus can also be applied during the index event, in the so called remote per-conditioning. All these endogenous cardioprotective strategies recruit endogenous cytoprotective agents and factors that elicit specific cardioprotective pathways. Here, we discuss many of these cardioprotective factors compared to literature and highlight their main characteristics and mechanisms of action. Enphasis is given to endogenous cardioprotective agents acting or not on surface receptors, including chromogranin A derivatives, ghrelin-associated peptides, growth factors and cytokines, and to microvesicles and exosomes. Moreover the cardioprotective effects of gasotransmitters nitric oxide, hydrogen sulphide and carbon monoxide are reviewed. The possible clinical translation of these knowledge for future successful therapies is briefly and critically discussed.

  13. Circulating Hepcidin-25 Is Reduced by Endogenous Estrogen in Humans

    PubMed Central

    Lehtihet, Mikael; Bonde, Ylva; Beckman, Lena; Berinder, Katarina; Hoybye, Charlotte; Rudling, Mats; Sloan, John H.; Konrad, Robert J.; Angelin, Bo

    2016-01-01

    Objective Hepcidin reduces iron absorption by binding to the intestinal iron transporter ferroportin, thereby causing its degradation. Although short-term administration of testosterone or growth hormone (GH) has been reported to decrease circulating hepcidin levels, little is known about how hepcidin is influenced in human endocrine conditions associated with anemia. Research design and methods We used a sensitive and specific dual–monoclonal antibody sandwich immunoassay to measure hepcidin-25 in patients (a) during initiation of in vitro fertilization when endogenous estrogens were elevated vs. suppressed, (b) with GH deficiency before and after 12 months substitution treatment, (c) with hyperthyroidism before and after normalization, and (d) with hyperprolactinemia before and after six months of treatment with a dopamine agonist. Results In response to a marked stimulation of endogenous estrogen production, median hepcidin levels decreased from 4.85 to 1.43 ng/mL (p < 0.01). Hyperthyroidism, hyperprolactinemia, or GH substitution to GH-deficient patients did not influence serum hepcidin-25 levels. Conclusions In humans, gonadotropin-stimulated endogenous estrogen markedly decreases circulating hepcidin-25 levels. No clear and stable correlation between iron biomarkers and hepcidin-25 was seen before or after treatment of hyperthyroidism, hyperprolactinemia or growth hormone deficiency. PMID:26866603

  14. Determination of endogenous faecal phosphorus loss in goats.

    PubMed

    Tayo, Grace Oluwatoyin; Tang, Shao Xun; Tan, Zhi Liang; Sun, Zhi Hong; Wang, Min; Zhou, Chuan She; Han, Xue Feng

    2009-04-01

    Four black Liuyang wether goats were fed with corn stover and concentrate formulated to contain four levels of dietary phosphorus (P), including 0.129, 0.140, 0.162 and 0.180% of P. In a 4 x 4 Latin square experiment the endogenous faecal P loss was determined by the regression technique and the substitution method. Treatment effects on faecal and urinary P output, apparent P digestibility and P retention, and saliva P secretion were not significant. A linear relationship was observed between apparent faecal digestible P (Y, g/kg DMI) and P intake (X, g/kg DMI), which was described by the equation: Y = 0.4799 X -0.9209, r2 = 0.9869, (p < 0.05). The true P digestibility determined by the regression technique and the substitution method amounted to 48.0 and 48.9%, respectively; the recorded endogenous faecal P losses were 0.92 and 0.93 g/kg DMI, respectively. The study demonstrated the potential of the regression method as well as the substitution method for estimation of true P digestibility and endogenous faecal P losses in goats.

  15. Two-Stage Bayesian Model Averaging in Endogenous Variable Models.

    PubMed

    Lenkoski, Alex; Eicher, Theo S; Raftery, Adrian E

    2014-01-01

    Economic modeling in the presence of endogeneity is subject to model uncertainty at both the instrument and covariate level. We propose a Two-Stage Bayesian Model Averaging (2SBMA) methodology that extends the Two-Stage Least Squares (2SLS) estimator. By constructing a Two-Stage Unit Information Prior in the endogenous variable model, we are able to efficiently combine established methods for addressing model uncertainty in regression models with the classic technique of 2SLS. To assess the validity of instruments in the 2SBMA context, we develop Bayesian tests of the identification restriction that are based on model averaged posterior predictive p-values. A simulation study showed that 2SBMA has the ability to recover structure in both the instrument and covariate set, and substantially improves the sharpness of resulting coefficient estimates in comparison to 2SLS using the full specification in an automatic fashion. Due to the increased parsimony of the 2SBMA estimate, the Bayesian Sargan test had a power of 50 percent in detecting a violation of the exogeneity assumption, while the method based on 2SLS using the full specification had negligible power. We apply our approach to the problem of development accounting, and find support not only for institutions, but also for geography and integration as development determinants, once both model uncertainty and endogeneity have been jointly addressed. PMID:24223471

  16. Endogenous Cardiotonic Steroids: Physiology, Pharmacology, and Novel Therapeutic Targets

    PubMed Central

    Bagrov, Alexei Y.; Shapiro, Joseph I.; Fedorova, Olga V.

    2009-01-01

    Endogenous cardiotonic steroids (CTS), also called digitalis-like factors, have been postulated to play important roles in health and disease for nearly half a century. Recent discoveries, which include the specific identification of endogenous cardenolide (endogenous ouabain) and bufadienolide (marinobufagenin) CTS in humans along with the delineation of an alternative mechanism by which CTS can signal through the Na+/K+-ATPase, have increased the interest in this field substantially. Although CTS were first considered important in the regulation of renal sodium transport and arterial pressure, more recent work implicates these hormones in the regulation of cell growth, differentiation, apoptosis, and fibrosis, the modulation of immunity and of carbohydrate metabolism, and the control of various central nervous functions and even behavior. This review focuses on the physiological interactions between CTS and other regulatory systems that may be important in the pathophysiology of essential hypertension, preeclampsia, end-stage renal disease, congestive heart failure, and diabetes mellitus. Based on our increasing understanding of the regulation of CTS as well as the molecular mechanisms of these hormone increases, we also discuss potential therapeutic strategies. PMID:19325075

  17. Drawing a fine line on endogenous retroelement activity

    PubMed Central

    Castro-Diaz, Nathaly; Friedli, Marc; Trono, Didier

    2015-01-01

    Endogenous retroelements (EREs) are essential motors of evolution yet require careful control to prevent genomic catastrophes, notably during the vulnerable phases of epigenetic reprogramming that occur immediately after fertilization and in germ cells. Accordingly, a variety of mechanisms restrict these mobile genetic units. Previous studies have revealed the importance of KRAB-containing zinc finger proteins (KRAB-ZFPs) and their cofactor, KAP1, in the early embryonic silencing of endogenous retroviruses and so-called SVAs, but the implication of this transcriptional repression system in the control of LINE-1, the only known active autonomous retrotransposon in the human genome, was thought to be marginal. Two recent studies straighten the record by revealing that the KRAB/KAP system is key to the control of L1 in embryonic stem (ES) cells, and go further in demonstrating that DNA methylation and KRAB/KAP1-induced repression contribute to this process in an evolutionally dynamic fashion. These results shed light on the delicate equilibrium between higher vertebrates and endogenous retroelements, which are not just genetic invaders calling for strict control but rather a constantly renewed and nicely exploitable source of evolutionary potential. PMID:26442176

  18. Effects of endogenous formaldehyde in nasal tissues on inhaled formaldehyde dosimetry predictions in the rat, monkey, and human nasal passages.

    PubMed

    Schroeter, Jeffry D; Campbell, Jerry; Kimbell, Julia S; Conolly, Rory B; Clewell, Harvey J; Andersen, Melvin E

    2014-04-01

    Formaldehyde is a nasal carcinogen in rodents at high doses and is an endogenous compound that is present in all living cells. Due to its high solubility and reactivity, quantitative risk estimates for inhaled formaldehyde have relied on internal dose estimates in the upper respiratory tract. Dosimetry calculations are complicated by the presence of endogenous formaldehyde concentrations in the respiratory mucosa. Anatomically accurate computational fluid dynamics (CFD) models of the rat, monkey, and human nasal passages were used to simulate uptake of inhaled formaldehyde. An epithelial structure was implemented in the nasal CFD models to estimate formaldehyde absorption from air:tissue partitioning, species-specific metabolism, first-order clearance, DNA binding, and endogenous formaldehyde production. At an exposure concentration of 1 ppm, predicted formaldehyde nasal uptake was 99.4, 86.5, and 85.3% in the rat, monkey, and human, respectively. Endogenous formaldehyde in nasal tissues did not significantly affect wall mass flux or nasal uptake predictions at exposure concentrations > 500 ppb; however, reduced nasal uptake was predicted at lower exposure concentrations. At an exposure concentration of 1 ppb, predicted nasal uptake was 17.5 and 42.8% in the rat and monkey; net desorption of formaldehyde was predicted in the human model. The nonlinear behavior of formaldehyde nasal absorption will affect the dose-response analysis and subsequent risk estimates at low exposure concentrations. Updated surface area partitioning of nonsquamous epithelium and average flux values in regions where DNA-protein cross-links and cell proliferation rates were measured in rats and monkeys are reported for use in formaldehyde risk models of carcinogenesis.

  19. Fourth-Generation Progestins Inhibit 3β-Hydroxysteroid Dehydrogenase Type 2 and Modulate the Biosynthesis of Endogenous Steroids

    PubMed Central

    Louw-du Toit, Renate; Perkins, Meghan S.; Snoep, Jacky L.; Storbeck, Karl-Heinz; Africander, Donita

    2016-01-01

    Progestins used in contraception and hormone replacement therapy are synthetic compounds designed to mimic the actions of the natural hormone progesterone and are classed into four consecutive generations. The biological actions of progestins are primarily determined by their interactions with steroid receptors, and factors such as metabolism, pharmacokinetics, bioavailability and the regulation of endogenous steroid hormone biosynthesis are often overlooked. Although some studies have investigated the effects of select progestins on a few steroidogenic enzymes, studies comparing the effects of progestins from different generations are lacking. This study therefore explored the putative modulatory effects of progestins on de novo steroid synthesis in the adrenal by comparing the effects of select progestins from the respective generations, on endogenous steroid hormone production by the H295R human adrenocortical carcinoma cell line. Ultra-performance liquid chromatography/tandem mass spectrometry analysis showed that the fourth-generation progestins, nestorone (NES), nomegestrol acetate (NoMAC) and drospirenone (DRSP), unlike the progestins selected from the first three generations, modulate the biosynthesis of several endogenous steroids. Subsequent assays performed in COS-1 cells expressing human 3βHSD2, suggest that these progestins modulate the biosynthesis of steroid hormones by inhibiting the activity of 3βHSD2. The Ki values determined for the inhibition of human 3βHSD2 by NES (9.5 ± 0.96 nM), NoMAC (29 ± 7.1 nM) and DRSP (232 ± 38 nM) were within the reported concentration ranges for the contraceptive use of these progestins in vivo. Taken together, our results suggest that newer, fourth-generation progestins may exert both positive and negative physiological effects via the modulation of endogenous steroid hormone biosynthesis. PMID:27706226

  20. Endogenous hepadnaviruses in the genome of the budgerigar (Melopsittacus undulatus) and the evolution of avian hepadnaviruses.

    PubMed

    Cui, Jie; Holmes, Edward C

    2012-07-01

    Endogenous hepadnaviruses (hepatitis B viruses [HBVs]) were recently discovered in the genomes of passerine birds. We mined six additional avian genomes and discovered multiple copies of endogenous HBVs in the budgerigar (order Psittaciformes), designated eBHBV. A phylogenetic analysis reveals that the endogenous hepadnaviruses are more diverse than their exogenous counterparts and that the endogenous and exogenous hepadnaviruses form distinct lineages even when sampled from the same avian order, indicative of multiple genomic integration events. PMID:22553337

  1. Endogenous Hepadnaviruses in the Genome of the Budgerigar (Melopsittacus undulatus) and the Evolution of Avian Hepadnaviruses

    PubMed Central

    Cui, Jie

    2012-01-01

    Endogenous hepadnaviruses (hepatitis B viruses [HBVs]) were recently discovered in the genomes of passerine birds. We mined six additional avian genomes and discovered multiple copies of endogenous HBVs in the budgerigar (order Psittaciformes), designated eBHBV. A phylogenetic analysis reveals that the endogenous hepadnaviruses are more diverse than their exogenous counterparts and that the endogenous and exogenous hepadnaviruses form distinct lineages even when sampled from the same avian order, indicative of multiple genomic integration events. PMID:22553337

  2. Evidence for Arginine as the Endogenous Precursor of Necines in Heliotropium1

    PubMed Central

    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

  3. Radioprotective Action of Low-Intensity Light into the Red Absorption Band of Endogenous Molecular Oxygen

    NASA Astrophysics Data System (ADS)

    Ivanov, A. V.; Mashalov, A. A.; Zakharov, S. D.

    2016-08-01

    Application of ionizing radiation in oncology (radiation therapy) is a widespread way to eliminate malignant tumors. Normal tissues are inevitable included in any radiation field, and their reliable protection is actual till now. All attempts to solve the problem are based on search of effective radioprotectors, i.e. chemical compounds of various classes, which should be entered into the patient. To date about 50,000 compounds with some radioprotection properties had been tested, but the most effective of them have been simultaneously the most toxic. Here the preliminary results of researches devoted to development of an optical technique on basis of the light-oxygen effect for the protection of women with breast cancer from side effects of the radiation therapy are presented. A low intensity emission of the semiconductor laser in a red spectral interval was used to excite a very small quantity of endogenous molecular oxygen in O2(1Δg) state. It is shown, that application of the method at occurrence of earliest signs of radiation injury allows notably reducing dangerous breaks in radiation therapy course.

  4. Endogenous technological and population change under increasing water scarcity

    NASA Astrophysics Data System (ADS)

    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

  5. Endogenous technological and demographic change under increasing water scarcity

    NASA Astrophysics Data System (ADS)

    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

  6. Compounding in Ukraine.

    PubMed

    Zdoryk, Oleksandr A; Georgiyants, Victoriya A; Gryzodub, Oleksandr I; Schnatz, Rick

    2013-01-01

    Pharmaceutical compounding in modern Ukraine has a rich history and goes back to ancient times. Today in the Ukraine, there is a revival of compounding practice, the opening of private compounding pharmacies, updating of legislative framework and requirements of the State Pharmacopeia of Ukraine for compounding preparations, and the introduction of Good Pharmaceutical Practice. PMID:23696172

  7. Endogenous concentrations of GHB in postmortem blood from deaths unrelated to GHB use.

    PubMed

    Korb, Ann-Sophie; Cooper, Gail

    2014-10-01

    Gamma-hydroxybutyrate (GHB) is an endogenous compound, but its presence in postmortem blood presents a challenge when interpreting elevated levels as GHB is misused as a recreational drug and is also produced postmortem. A total of 387 postmortem cases (273 male and 114 female) submitted to the toxicology laboratory between 2010 and 2012 specifically requested the analysis of the ketoacidosis biomarker, beta-hydroxybutyrate (BHB). No reference to GHB use was identified in any of the case files; however, BHB and GHB are measured simultaneously using deuterated GHB as the internal standard (GHB-d6) within a calibration range of 5-500 mg/L. GHB was not detected or <10 mg/L in 18% of the cases (n = 68), between 10 and 50 mg/L in 73% of the cases (n = 283) and between 51 and 193 mg/L in 9% of the cases (n = 36). The manner of death was classified as accidental (n = 11), alcohol-related (n = 237), drug-related (n = 23), homicide (n = 1), natural (n = 91), suicide (n = 9), medical-related (n = 1) and undetermined (n = 14). Six cases had GHB concentrations in excess of 100 mg/L with advanced decomposition changes noted in five of these cases. Moderate-to-advanced decomposition was also noted in 50% (n = 15) of the cases with GHB concentrations in excess of 50 mg/L but <100 mg/L. Approximately one-third of the blood samples tested contained a preservative and although a higher proportion of these samples had GHB concentrations <10 mg/L or not detected (∼30% preserved versus 11% unpreserved), there were still cases with GHB concentrations >51 mg/L (∼6% preserved versus 11% unpreserved). This study highlights the danger of only using a cutoff to establish endogenous levels compared with exogenous use of GHB in postmortem blood.

  8. Effect of carbon source type on intracellular stored polymers during endogenous denitritation (ED) treating landfill leachate.

    PubMed

    Miao, Lei; Wang, Shuying; Li, Baikun; Cao, Tianhao; Zhang, Fangzhai; Wang, Zhong; Peng, Yongzhen

    2016-09-01

    Glycogen accumulating organisms (GAOs) capable of storing organic compounds as polyhydroxyalkanoate (PHA) have been used for endogenous denitritation (ED), but the effect of carbon sources type on nitrogen removal performance of GAOs treating landfill leachate is unclear. In this study, a successful ED system treating landfill leachate (COD/NH4(+)-N (C/N): 4) without external carbon source addition was applied. The mature leachate with C/N of 1 was used as the feeding base solution, with acetate, propionate, and glucose examined as the carbon sources, and their effects on yields and compositions of PHA produced by GAOs were determined and associated with nitrogen removal performance. In the case of sole carbon source, acetate was much easier to be stored than propionate and glucose, which led to a higher nitrogen removal efficiency. Glucose had the lowest amount of PHA storage and led to the lowest performance. In the case of composite carbon sources (two scenarios: acetate + propionate; acetate + propionate + glucose), GAOs stored sufficient PHA and exhibited similar nitrogen removal efficiencies. Moreover, type of carbon source influenced the compositions of PHA. The polyhydroxybutyrate (PHB) fraction in PHA was far more than polyhydroxyvalerate (PHV) in all tests. PHV was synthesized only when acetate existed in carbon source. The microbial diversity analysis revealed that Proteobacteria was the most abundant phylum. Among the 108 genera detected in this ED system, the genera responsible for denitritation were Thauera, Paracoccus, Ottowia and Comamonadaceae_unclassified, accounting for 46.21% of total bacteria. Especially, Paracoccus and Comamonadaceae_unclassified transformed the carbon source into PHA for denitritation, and carried out endogenous denitritation. PMID:27232984

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

    PubMed

    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

  10. Pharmacy compounding urban legends.

    PubMed

    Kastango, Eric S

    2006-01-01

    This article reviews and clarifies a small sampling of the myths, or urban legends, about compounding. Included are comments on United sTates Pharmacopeia Chapter 797, environmental issues related to sterile compounding, and suggested resources for clarification of some of these myths. This article recommends a knowledge-based partnership between compounding pharmacists and pharmaceutical manufacturers to improve compounding activities and quality assurance methods to ensure that compounded medications are safe.

  11. Phytodegradation of organic compounds.

    PubMed

    Newman, Lee A; Reynolds, Charles M

    2004-06-01

    The phytodegradation of organic compounds can take place inside the plant or within the rhizosphere of the plant. Many different compounds and classes of compounds can be removed from the environment by this method, including solvents in groundwater, petroleum and aromatic compounds in soils, and volatile compounds in the air. Although still a relatively new area of research, there are many laboratories studying the underlying science necessary for a wide range of applications for plant-based remediation of organic contaminants.

  12. Endogenous technological and demographic change under increasing water scarcity

    NASA Astrophysics Data System (ADS)

    Pande, S.; Ertsen, M.; Sivapalan, M.

    2013-12-01

    Many ancient civilizations such as the Indus Valley civilization dispersed under extreme dry conditions. Even contemporary societies such as the one in Murrumbidgee river basin, Australia, have started to witness a decline in overall population under increasing water scarcity. Skeptics of hydroclimatic determinism have often cautioned against the use of hydroclimatic change as the sole predictor of the fate of contemporary societies in water scarce regions by suggesting that technological change may ameliorate the effects of increasing water scarcity. We here develop a simple overlapping generations model of endogenous technological and demographic change. It models technological change not as an exogenous random sequence of events but as an endogenous process (as is widely accepted in contemporary literature) 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, individuals' patience in terms of its present consumption versus future consumption, the production technology and the (endogenous) interaction of these factors. The population growth rate is modeled to decline once consumption per capita crosses a ';survival' threshold. The model demonstrates that technological change may ameliorate the effects of increasing water scarcity but only to a certain extent in many cases. It is possible that technological change may allow a society to escape the effect of increasing water society, leading to an exponential rise in technology and population. However, such cases require that the rate of success of investment in technological advancement is high. In other more realistic cases of technological success, we find that endogenous technology change has an effect delaying the peak of population before it starts to decline. While the model is a rather simple model of societal growth, it is capable of replicating (not to scale) patterns of technological

  13. Microbial cycling of volatile organic sulfur compounds.

    PubMed

    Lomans, B P; van der Drift, C; Pol, A; Op den Camp, H J M

    2002-04-01

    Microbial cycling of volatile organic sulfur compounds (VOSCs), especially dimethyl sulfide (DMS) and methanethiol (MT), is intensively studied because these compounds play an important role in the processes of global warming, acid precipitation, and the global sulfur cycle. VOSC concentrations in freshwater sediments are low due to the balance between the formation and degradation of these compounds. These reactions occur for the greater part at the oxic/anoxic interphase of sediment and water column. In contrast to marine ecosystems, where dimethylsulfoniopropionate is the main precursor of MT and DMS, in freshwater ecosystems, VOSCs are formed mainly by methylation of sulfide and to a lesser extent from the degradation of S-containing amino acids. One of the major routes for DMS and MT formation through sulfide methylation is anaerobic O-demethylation of methoxylated aromatic compounds. Inhibition studies have revealed that the major part of the endogenously produced MT and DMS is degraded anaerobically by methanogens. The major bacterial groups involved in formation and consumption of VOSCs are described. PMID:12022467

  14. A comparative assessment of endogenous water institutional change

    NASA Astrophysics Data System (ADS)

    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.

  15. Trafficking of an endogenous potassium channel in adult ventricular myocytes

    PubMed Central

    Wang, Tiantian; Cheng, Yvonne; Dou, Ying; Goonesekara, Charitha; David, Jens-Peter; Steele, David F.; Huang, Chen

    2012-01-01

    The roles of several small GTPases in the expression of an endogenous potassium current, Ito,f, in adult rat ventricular myocytes have been investigated. The results indicate that forward trafficking of newly synthesized Kv4.2, which underlies Ito,f in these cells, requires both Rab1 and Sar1 function. Expression of a Rab1 dominant negative (DN) reduced Ito,f current density by roughly one-half relative to control, mCherry-transfected myocytes. Similarly, expression of a Sar1DN nearly halved Ito,f current density. Rab11 is not essential to trafficking of Kv4.2, as expression of a Rab11DN had no effect on Ito,f over the time frames investigated here. In a process dependent on intact endoplasmic reticulum (ER)-to-Golgi transport, however, overexpression of wild-type Rab11 resulted in a doubling of Ito,f density; block of ER-to-Golgi traffic by Brefeldin A completely abrogated the effect. Also implicated in the trafficking of Kv4.2 are Rab5 and Rab4. Rab5DN expression increased endogenous Ito,f by two- to threefold, nonadditively with inhibition of dynamin-dependent endocytosis. And, in a phenomenon similar to that previously reported for myoblast-expressed Kv1.5, Rab4DN expression roughly doubled endogenous peak transient currents. Colocalization experiments confirmed the involvement of Rab4 in postinternalization trafficking of Kv4.2. There was little role evident for the lysosome in the degradation of internalized Kv4.2, as overexpression of neither wild-type nor DN isoforms of Rab7 had any effect on Ito,f. Instead, degradation may depend largely on the proteasome; the proteasome inhibitor MG132 significantly increased Ito,f density. PMID:22914645

  16. Visualization of an endogenous retinoic acid gradient across embryonic development.

    PubMed

    Shimozono, Satoshi; Iimura, Tadahiro; Kitaguchi, Tetsuya; Higashijima, Shin-Ichi; Miyawaki, Atsushi

    2013-04-18

    In vertebrate development, the body plan is determined by primordial morphogen gradients that suffuse the embryo. Retinoic acid (RA) is an important morphogen involved in patterning the anterior-posterior axis of structures, including the hindbrain and paraxial mesoderm. RA diffuses over long distances, and its activity is spatially restricted by synthesizing and degrading enzymes. However, gradients of endogenous morphogens in live embryos have not been directly observed; indeed, their existence, distribution and requirement for correct patterning remain controversial. Here we report a family of genetically encoded indicators for RA that we have termed GEPRAs (genetically encoded probes for RA). Using the principle of fluorescence resonance energy transfer we engineered the ligand-binding domains of RA receptors to incorporate cyan-emitting and yellow-emitting fluorescent proteins as fluorescence resonance energy transfer donor and acceptor, respectively, for the reliable detection of ambient free RA. We created three GEPRAs with different affinities for RA, enabling the quantitative measurement of physiological RA concentrations. Live imaging of zebrafish embryos at the gastrula and somitogenesis stages revealed a linear concentration gradient of endogenous RA in a two-tailed source-sink arrangement across the embryo. Modelling of the observed linear RA gradient suggests that the rate of RA diffusion exceeds the spatiotemporal dynamics of embryogenesis, resulting in stability to perturbation. Furthermore, we used GEPRAs in combination with genetic and pharmacological perturbations to resolve competing hypotheses on the structure of the RA gradient during hindbrain formation and somitogenesis. Live imaging of endogenous concentration gradients across embryonic development will allow the precise assignment of molecular mechanisms to developmental dynamics and will accelerate the application of approaches based on morphogen gradients to tissue engineering and

  17. Prostanoids inhibit release of endogenous norepinephrine from rat isolated trachea.

    PubMed

    Racké, K; Bähring, J; Langer, C; Bräutigam, M; Wessler, I

    1992-11-01

    Prostanoids, of epithelial origin, are known as modulators of several processes in the airways. The present study examined whether prostanoids are involved in the local control of sympathetic neurotransmission. The release of endogenous norepinephrine from rat isolated tracheae was evoked by electrical field stimulation (3 Hz, 540 pulses) in the presence of yohimbine, desipramine, and tyrosine. In different series of experiments, indomethacin (3 mumol/L) increased the evoked release of endogenous norepinephrine by 70 to 80%. In the presence of indomethacin, prostaglandin E2 (PGE2) and several prostanoid receptor agonists inhibited the evoked release of norepinephrine in a concentration-dependent manner, maximally by 60 to 70%. According to the concentration producing 35% inhibition of norepinephrine release (half-maximal effect), the following rank order of potencies was observed (EC35): nocloprost (8 nmol/L), sulprostone (30 nmol/L), PGE2 (308 nmol/L), iloprost (2 mumol/L), and U46619 (> 10 mumol/L). The EP1 receptor antagonist AH 6809 (3 mumol/L) had no effect on the evoked norepinephrine release and did not affect the inhibitory effect of 1 mumol/L of sulprostone. In the absence of indomethacin, the inhibitory effect of PGE2 was similar to that observed in the presence of indomethacin. After removal of the epithelium, the evoked norepinephrine release was markedly reduced. However, no significant effect of indomethacin was observed in epithelium-denuded tracheae. In conclusion, norepinephrine release in the rat trachea is inhibited via prostaglandin receptors that have the pharmacologic characteristics of the EP3 subtype. Endogenous eicosanoids, most likely of epithelial origin, are involved in the local control of the release of norepinephrine. PMID:1443867

  18. Endogenous Bioactive Lipids and the Regulation of Conventional Outflow Facility

    PubMed Central

    Wan, Zhou; Woodward, David F.; Stamer, W. Daniel

    2009-01-01

    Summary Perturbation of paracrine signaling within the human conventional outflow pathway influences tissue homeostasis and outflow function. For example, exogenous introduction of the bioactive lipids, sphingosine-1-phosphate, anandamide or prostaglandin F2α, to conventional outflow tissues alters the rate of drainage of aqueous humor through the trabecular meshwork, and into Schlemm’s canal. This review summarizes recent data that characterizes endogenous bioactive lipids, their receptors and associated signaling partners in the conventional outflow tract. We also discuss the potential of targeting such signaling pathways as a strategy for the development of therapeutics to treat ocular hypertension and glaucoma. PMID:19381354

  19. Endogenous RNA viruses of plants in insect genomes

    PubMed Central

    Cui, Jie; Holmes, Edward C.

    2013-01-01

    Endogenous viral elements (EVEs) derived from RNA viruses with no DNA stage are rare, especially those where the parental viruses possess single-strand positive-sense (ssRNA+) genomes. Here we provide evidence that EVEs that share a sequence similarity to ssRNA+viruses of plants are integrated into the genomes of a number of insects, including mosquito, fruit flies, bees, ant, silkworm, pea aphid, Monarch butterfly, and wasps. A preliminary phylogenetic analysis places these EVEs as divergent relatives of the Virgaviridae and three currently unclassified plant viral species. PMID:22410578

  20. Imaging of endogenous RNA using genetically encoded probes.

    PubMed

    Ozawa, Takeaki; Umezawa, Yoshio

    2011-03-01

    Imaging of RNAs in single cells revealed their localized transcription and specific function. Such information cannot be obtained from bulk measurements. This unit contains a protocol of an imaging method capable of visualizing endogenous RNAs bound to genetically encoded fluorescent probes in single living cells. The protocol includes methods of design and construction of the probes, their characterization, and imaging a target RNA in living cells. The methods for RNA imaging are generally applicable to many kinds of RNAs and may allow for elucidating novel functions of localized RNAs and understanding their dynamics in living cells. Curr. Protoc. Chem. Biol. 3:27-37 © 2011 by John Wiley & Sons, Inc.

  1. Evaluation of the endogenous glucocorticoid hypothesis of denervation atrophy

    NASA Technical Reports Server (NTRS)

    Konagaya, Masaaki; Konagaya, Yoko; Max, Stephen R.

    1988-01-01

    The effects are studied of the oral administration of RU38486, a potent selective glucocorticoid antagonist, on muscle weight, non-collagen protein content, and selected enzyme activities (choline acetyltransferase, glucose 6-phosphate dehydrogenase, and glutamine synthetase) following denervation of rat skeletal muscle. Neither decreases in muscle weight, protein content, and choline acetyltransferase activity, nor increases in the activities of glucose 6-phosphate dehydrogernase and glutamine synthetase were affected by RU38486. These data do not support the hypothesis that denervation atrophy results from enhanced sensitivity of muscle to endogenous glucocorticoids.

  2. Endogenous hydrogen sulfide enhances salt tolerance by coupling the reestablishment of redox homeostasis and preventing salt-induced K⁺ loss in seedlings of Medicago sativa.

    PubMed

    Lai, Diwen; Mao, Yu; Zhou, Heng; Li, Feng; Wu, Mingzhu; Zhang, Jing; He, Ziyi; Cui, Weiti; Xie, Yanjie

    2014-08-01

    Despite the external application of hydrogen sulfide (H2S) conferring plant tolerance against various environmental cues, the physiological significance of l-cysteine desulfhydrase (L-DES)-associated endogenous H2S production involved in salt-stress signaling was poorly understood. To address this gap, the participation of in planta changes of H2S homeostasis involved in alfalfa salt tolerance was investigated. The increasing concentration of NaCl (from 50 to 300 mM) progressively caused the induction of total l-DES activity and the increase of endogenous H2S production. NaCl-triggered toxicity symptoms (175 mM), including seedling growth inhibition and lipid peroxidation, were alleviated by sodium hydrosulfide (NaHS; 100 μM), a H2S donor, whereas aggravated by an inhibitor of l-DES or a H2S scavenger. A weaker or negative response was observed in lower or higher dose of NaHS. Further results showed that endogenous l-DES-related H2S modulated several genes/activities of antioxidant defence enzymes, and also regulated the contents of antioxidant compounds, thus counterbalancing the NaCl-induced lipid peroxidation. Moreover, H2S maintained K(+)/Na(+) homeostasis by preventing the NaCl-triggered K(+) efflux, which might be result form the impairment of SKOR expression. Together, our findings indicated that endogenous H2S homeostasis enhance salt tolerance by coupling the reestablishment of redox balance and restraining K(+) efflux in alfalfa seedlings.

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

    PubMed Central

    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

  4. Vascular responses to compound 48/80 in rat mesenteric vascular beds.

    PubMed

    Jin, Honghua; Li, Zhen; Takatori, Shingo; Koyama, Toshihiro; Jin, Xin; Zamami, Yoshito; Kawasaki, Hiromu; Sun, Pengyuan

    2016-06-01

    A further investigation was performed on the vascular effect of endogenous histamine using the histamine releaser, compound 48/80, in rat mesenteric vascular beds with active tone. In preparations with intact endothelium, low concentrations of compound 48/80 (1.53 × 10(-5) - 3 × 1.53 × 10(-5) mg/mL) perfusion for 1 min only induced a small vasodilation. High concentrations of compound 48/80 (1.53 × 10(-4) - 3 × 1.53 × 10(-2) mg/mL) induced a biphasic vascular responses, an initial vasoconstriction followed a subsequent long-lasting vasodilation. The vasodilation induced by low concentrations of compound 48/80 and the vasoconstriction induced by high concentration of compound 48/80 was inhibited by olopatadine. However, cimetidine did not affect the responses induced by compound 48/80. Endothelium removal enlarged the compound 48/80-induced phase-2 vasoconstriction, while it attenuated the phase-3 vasodilation. Additionally, indomethacin and seratrodast significantly inhibited vasoconstriction but it did not affect the long-lasting vasodilation induced by high concentrations of compound 48/80. Ruthenium red inhibited the vasodilation induced by low concentrations and high concentrations of compound 48/80. These results suggest that the vasoconstriction induce by high concentrations of compound 48/80 is mediated by endogenous histamine released from mast cells. It is also suggested that thromboxane A2 released from mast cells is related to the vasoconstriction. PMID:26991394

  5. Surfactant treatments alter endogenous surfactant metabolism in rabbit lungs

    SciTech Connect

    Oetomo, S.B.; Lewis, J.; Ikegami, M.; Jobe, A.H. )

    1990-04-01

    The effect of exogenous surfactant on endogenous surfactant metabolism was evaluated using a single-lobe treatment strategy to compare effects of treated with untreated lung within the same rabbit. Natural rabbit surfactant, Survanta, or 0.45% NaCl was injected into the left main stem bronchus by use of a Swan-Ganz catheter. Radiolabeled palmitic acid was then given by intravascular injection at two times after surfactant treatment, and the ratios of label incorporation and secretion in the left lower lobe to label incorporation and secretion in the right lung were compared. The treatment procedure resulted in a reasonably uniform surfactant distribution and did not disrupt lobar pulmonary blood flow. Natural rabbit surfactant increased incorporation of palmitate into saturated phosphatidylcholine (Sat PC) approximately 2-fold (P less than 0.01), and secretion of labeled Sat PC increased approximately 2.5-fold in the surfactant-treated left lower lobe relative to the right lung (P less than 0.01). Although Survanta did not alter incorporation, it did increase secretion but not to the same extent as rabbit surfactant (P less than 0.01). Alteration of endogenous surfactant Sat PC metabolism in vivo by surfactant treatments was different from that which would have been predicted by previous in vitro studies.

  6. Intergenerational redistribution in a small open economy with endogenous fertility.

    PubMed

    Kolmar, M

    1997-08-01

    The literature comparing fully funded (FF) and pay-as-you-go (PAYG) financed public pension systems in small, open economies stresses the importance of the Aaron condition as an empirical measure to decide which system can be expected to lead to a higher long-run welfare. A country with a PAYG system has a higher level of utility than a country with a FF system if the growth rate of total wage income exceeds the interest rate. Endogenizing population growth makes one determinant of the growth rate of wage incomes endogenous. The author demonstrates why the Aaron condition ceases to be a good indicator in this case. For PAYG-financed pension systems, claims can be calculated according to individual contributions or the number of children in a family. Analysis determined that for both structural determinants there is no interior solution of the problem of intergenerational utility maximization. Pure systems are therefore always welfare maximizing. Moreover, children-related pension claims induce a fiscal externality which tends to be positive. The determination of the optimal contribution rate shows that the Aaron condition is generally a misleading indicator for the comparison of FF and PAYG-financed pension systems.

  7. Presynaptic Control of Corticostriatal Synapses by Endogenous GABA

    PubMed Central

    Logie, Christopher; Bagetta, Vincenza

    2013-01-01

    Corticostriatal terminals have presynaptic GABAB receptors that limit glutamate release, but how these receptors are activated by endogenous GABA released by different types of striatal neurons is still unknown. To address this issue, we used single and paired whole-cell recordings combined with stimulation of corticostriatal fibers in rats and mice. In the presence of opioid, GABAA, and NK1 receptor antagonists, antidromic stimulation of a population of striatal projection neurons caused suppression of subsequently evoked EPSPs in projection neurons. These effects were larger at intervals of 500 ms than 1 or 2 s, and were fully blocked by the selective GABAB receptor antagonist CGP 52432. Bursts of spikes in individual projection neurons were not able to inhibit evoked EPSPs. Similarly, spikes in fast spiking interneurons and low-threshold spike interneurons failed to elicit detectable effects mediated by GABAB receptors. Conversely, spikes in individual neurogliaform interneurons suppressed evoked EPSPs, and these effects were blocked by CGP 52432. These results provide the first demonstration of how GABAB receptors are activated by endogenous GABA released by striatal neuronal types. PMID:24068811

  8. Human neuromelanin: an endogenous microglial activator for dopaminergic neuron death

    PubMed Central

    Zhang, Wei; Zecca, Luigi; Wilson, Belinda; Ren, RW; Wang, Yong-jun; Wang, Xiao-min; Hong, Jau-Shyong

    2013-01-01

    Substantial evidence indicates that neuroinflammation caused by over-activation of microglial in the substantia nigra is critical in the pathogenesis of dopaminergic neurodegeneration in Parkinson’s disease (PD). Increasing data demonstrates that environmental factors such as rotenone, paraquat play pivotal roles in the death of dopaminergic neurons. Here, potential role and mechanism of neuromelanin (NM), a major endogenous component in dopaminergic neurons of the substantia nigra, on microglial activation and associated dopaminergic neurotoxicity were investigated. Using multiple well-established primary mesencephalic cultures, we tested whether human NM (HNM) could activate microglia, thereby provoking dopaminergic neurodegeneration. The results demonstrated that in primary mesencephalic neuron-glia cultures, HNM caused dopaminergic neuronal damage characterized by the decreased dopamine uptake and reduced numbers and shorted dendrites of dopaminergic neurons. HNM-induced degeneration was relatively selective to dopaminergic neurons since the other types of neurons determined by either gamma-aminobutyric acid uptake and total neuronal numbers after staining showed smaller decrease. We demonstrated that HNM produced modest dopaminergic neurotoxicity in neuron-enriched cultures; in contrast, much greater neurotoxicity was observed in the presence of microglia. HNM-induced microglial activation was shown by morphological changes and production of proinflammatory and neurotoxic factors. These results suggest that HNM, once released from damaged dopaminergic neurons, can be an potent endogenous activator involved in the reactivation of microglia, which may mediate disease progression. Thus, inhibition of reactive microglia can be a useful strategy for PD therapy. PMID:23276965

  9. Endogenous change: on cooperation and water in ancient history

    NASA Astrophysics Data System (ADS)

    Pande, S.; Ertsen, M.

    2013-04-01

    We propose and test the theory of endogenous change based on historical reconstructions of two ancient civilizations, Indus and Hohokam, in two water scarce basins, the Indus basin in the Indian subcontinent and the Lower Colorado basin in Southwestern United States. The endogenous institutional change sees changes in institutions as a sequence of equilibria brought about by changes in "quasi-parameters" such as rainfall, population density, soil and land use induced water resource availability. In the historical reconstructions of ancient civilizations, institutions are proximated by the scale of cooperation be it in the form of the extent of trade, sophisticated irrigation network, a centrally planned state or a loosely held state with a common cultural identity. The "quasi-parameters" either change naturally or are changed by humans and the changes affect the stability of cooperative structures over time. However, human influenced changes in the quasi-parameters itself are conditioned on the scale of existing cooperative structures. We thus provide insights into the quantitative dimensions of water access by ancient populations and its co-evolution with the socioeconomic and sociopolitical organization of the human past. We however do not suggest that water manipulation was the single most significant factor in stimulating social development and complexity - clearly this has been shown as highly reductionist, even misleading. The paper cautiously contributes to proximate prediction of hydrological change by attempting to understand the complexity of coupled human-hydrological systems.

  10. Endogenous Mouse Dicer Is an Exclusively Cytoplasmic Protein

    PubMed Central

    Much, Christian; Pavlinic, Dinko; Buness, Andreas; Rappsilber, Juri; Benes, Vladimir; Allshire, Robin; O’Carroll, Dónal

    2016-01-01

    Dicer is a large multi-domain protein responsible for the ultimate step of microRNA and short-interfering RNA biogenesis. In human and mouse cell lines, Dicer has been shown to be important in the nuclear clearance of dsRNA as well as the establishment of chromatin modifications. Here we set out to unambiguously define the cellular localization of Dicer in mice to understand if this is a conserved feature of mammalian Dicer in vivo. To this end, we utilized an endogenously epitope tagged Dicer knock-in mouse allele. From primary mouse cell lines and adult tissues, we determined with certainty by biochemical fractionation and confocal immunofluorescence microscopy that endogenous Dicer is exclusively cytoplasmic. We ruled out the possibility that a fraction of Dicer shuttles to and from the nucleus as well as that FGF or DNA damage signaling induce Dicer nuclear translocation. We also explored Dicer localization during the dynamic and developmental context of embryogenesis, where Dicer is ubiquitously expressed and strictly cytoplasmic in all three germ layers as well as extraembryonic tissues. Our data exclude a direct role for Dicer in the nuclear RNA processing in the mouse. PMID:27254021

  11. Salidroside inhibits endogenous hydrogen peroxide induced cytotoxicity of endothelial cells.

    PubMed

    Zhao, Xingyu; Jin, Lianhai; Shen, Nan; Xu, Bin; Zhang, Wei; Zhu, Hongli; Luo, Zhengli

    2013-01-01

    Salidroside, a phenylpropanoid glycoside isolated from Rhodiola rosea L., shows potent antioxidant property. Herein, we investigated the protective effects of salidroside against hydrogen peroxide (H2O2)-induced oxidative damage in human endothelial cells (EVC-304). EVC-304 cells were incubated in the presence or absence of low steady states of H2O2 (3-4 µM) generated by glucose oxidase (GOX) with or without salidroside. 3(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) assays were performed, together with Hoechst 33258 staining and flow cytometric analysis using Annexin-V and propidium iodide (PI) label. The results indicated that salidroside pretreatment attenuated endogenous H2O2 induced apoptotic cell death in EVC-304 cells in a dose-dependent pattern. Furthermore, Western blot data revealed that salidroside inhibited activation of caspase-3, 9 and cleavage of poly(ADP-ribose) polymerase (PARP) induced by endogenous H2O2. It also decreased the expression of Bax and rescued the balance of pro- and anti-apoptotic proteins. All these results demonstrated that salidroside may present a potential therapy for oxidative stress in cardiovascular and cerebrovascular diseases.

  12. Discovery and characterization of an endogenous CXCR4 antagonist.

    PubMed

    Zirafi, Onofrio; Kim, Kyeong-Ae; Ständker, Ludger; Mohr, Katharina B; Sauter, Daniel; Heigele, Anke; Kluge, Silvia F; Wiercinska, Eliza; Chudziak, Doreen; Richter, Rudolf; Moepps, Barbara; Gierschik, Peter; Vas, Virag; Geiger, Hartmut; Lamla, Markus; Weil, Tanja; Burster, Timo; Zgraja, Andreas; Daubeuf, Francois; Frossard, Nelly; Hachet-Haas, Muriel; Heunisch, Fabian; Reichetzeder, Christoph; Galzi, Jean-Luc; Pérez-Castells, Javier; Canales-Mayordomo, Angeles; Jiménez-Barbero, Jesus; Giménez-Gallego, Guillermo; Schneider, Marion; Shorter, James; Telenti, Amalio; Hocher, Berthold; Forssmann, Wolf-Georg; Bonig, Halvard; Kirchhoff, Frank; Münch, Jan

    2015-05-01

    CXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPI-X4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation. PMID:25921529

  13. Endogenous cortisol levels influence exposure therapy in spider phobia.

    PubMed

    Lass-Hennemann, Johanna; Michael, Tanja

    2014-09-01

    Previous research in patients with phobia showed that the administration of glucocorticoids reduces fear in phobic situations and enhances exposure therapy. Glucocorticoids underlie a daily cycle with a peak in the morning and low levels during the evening and night. The aim of the present study was to investigate whether exposure is more effective when conducted in the morning when endogenous cortisol levels are high. Sixty patients meeting DSM IV criteria for specific phobia (animal type) were randomly assigned to one-session exposure treatment either at 08.00 a.m. (high cortisol group) or at 06.00 p.m. (low cortisol group). Participants returned for a posttreatment assessment one week after therapy and a follow-up assessment three months after therapy. Both groups showed good outcome, but patients treated in the morning exhibited significantly less fear of spiders in the behavioral approach test (BAT) and a trend for lower scores on the Fear of Spiders Questionnaire (FSQ) than patients treated in the evening. This effect was present at posttreatment and follow-up. Our findings indicate that exposure therapy is more effective in the morning than in the evening. We suggest that this may be due to higher endogenous cortisol levels in the morning group that enhance extinction memory.

  14. Spatial models of political competition with endogenous political parties.

    PubMed

    Laver, Michael; Schilperoord, Michel

    2007-09-29

    Two important human action selection processes are the choice by citizens of parties to support in elections and the choice by party leaders of policy 'packages' offered to citizens in order to attract this support. Having reviewed approaches analysing these choices and the reasons for doing this using the methodology of agent-based modelling, we extend a recent agent-based model of party competition to treat the number and identity of political parties as an output of, rather than an input to, the process of party competition. Party birth is modelled as an endogenous change of agent type from citizen to party leader, which requires describing citizen dissatisfaction with the history of the system. Endogenous birth and death of parties transforms into a dynamic system even in an environment where all agents have otherwise non-responsive adaptive rules. A key parameter is the survival threshold, with lower thresholds leaving citizens on average less dissatisfied. Paradoxically, the adaptive rule most successful for party leaders in winning votes makes citizens on average less happy than under other policy-selection rules.

  15. Coevolution of endogenous Betaretroviruses of sheep and their host

    PubMed Central

    Arnaud, F.; Varela, M.; Spencer, T. E.

    2014-01-01

    Sheep betaretroviruses offer a unique model system to study the complex interaction between retroviruses and their host. Jaagsiekte sheep retrovirus (JSRV) is a pathogenic exogenous retrovirus and the causative agent of ovine pulmonary adenocarcinoma. The sheep genome contains at least 27 copies of endogenous retroviruses (enJSRVs) highly related to JSRV. enJSRVs have played several roles in the evolution of the domestic sheep as they are able to block the JSRV replication cycle and play a critical role in sheep conceptus development and placental morphogenesis. Available data strongly suggest that some dominant negative enJSRV proviruses (i.e. able to block JSRV replication) have been positively selected during evolution. Interestingly, viruses escaping the transdominant enJSRV loci have recently emerged (less than 200 years ago). Thus, endogenization of these retroviruses may still be occurring today. Therefore, sheep provide an exciting and unique system to study retrovirus-host coevolution. (Part of a Multi-author Review) PMID:18818869

  16. Dynamic nuclear polarization of nucleic acid with endogenously bound manganese.

    PubMed

    Wenk, Patricia; Kaushik, Monu; Richter, Diane; Vogel, Marc; Suess, Beatrix; Corzilius, Björn

    2015-09-01

    We report the direct dynamic nuclear polarization (DNP) of (13)C nuclei of a uniformly [(13)C,(15)N]-labeled, paramagnetic full-length hammerhead ribozyme (HHRz) complex with Mn(2+) where the enhanced polarization is fully provided by the endogenously bound metal ion and no exogenous polarizing agent is added. A (13)C enhancement factor of ε = 8 was observed by intra-complex DNP at 9.4 T. In contrast, "conventional" indirect and direct DNP experiments were performed using AMUPol as polarizing agent where we obtained a (1)H enhancement factor of ε ≈ 250. Comparison with the diamagnetic (Mg(2+)) HHRz complex shows that the presence of Mn(2+) only marginally influences the (DNP-enhanced) NMR properties of the RNA. Furthermore two-dimensional correlation spectra ((15)N-(13)C and (13)C-(13)C) reveal structural inhomogeneity in the frozen, amorphous state indicating the coexistence of several conformational states. These demonstrations of intra-complex DNP using an endogenous metal ion as well as DNP-enhanced MAS NMR of RNA in general yield important information for the development of new methods in structural biology. PMID:26219517

  17. Endogenous ouabain in renal Na(+) handling and related diseases.

    PubMed

    Manunta, Paolo; Messaggio, Elisabetta; Casamassima, Nunzia; Gatti, Guido; Carpini, Simona Delli; Zagato, Laura; Hamlyn, John M

    2010-12-01

    The Na(+) pump and its Endogenous modulator Ouabain (EO) can be considered as an ancestral enzymatic system, conserved among species ranging from Drosophila to humans, related to Na handling. In this review, we examine how EO is linked with vascular function in hypertension and if it impacts the pathogenesis of heart and renal failure. Moreover, the molecular mechanism of endogenous ouabain-linked hypertension involves the sodium pump/sodium-calcium exchanger duet. Biosynthesis of EO occurs in adrenal glands and is under the control of angiotensin II, ACTH and epinephrine. Elevated concentrations of EO and in the sub-nanomolar concentration range were found to stimulate proliferation and differentiation of cardiac and smooth muscle cells. They may have a primary role in the development of cardiac dysfunction and failure. Experimental data suggest that the Na/K-ATPase α(2)-catalytic subunit causes EO-induced vasoconstriction. Finally, maneuvers that promote Na depletion, as diuretic therapy or reduced Na intake, raise the EO levels. Taken together, these findings suggest a key role for EO in body Na homeostasis.

  18. Endogenous triacylglycerol utilization by the isolated rat atria.

    PubMed

    Varela, A; Savino, E A

    1988-03-01

    The isolated atria from 24 h fasted rats, either in the presence of glucose or in a substrate-free medium containing 2-deoxyglucose, mobilized the endogenous triacylglycerol (TG) to a greater extent than those from fed rats. The TG of the fasted atria had almost disappeared at the end of the 90 min incubation in the substrate-free plus 2-deoxyglucose medium, whereas in those from fed rats a mobilization-resistant portion of about 40% of the TG pool remained. This finding coincided with a lower decay of the contractile and pacemaker activities in the atria from fasted rats. Insulin abolished the TG mobilization in the atria from fed rats in the presence of glucose, but it was ineffective in the fasted atria. These data suggest that the endogenous-TG and glucose share in supporting the atrial functions, that insulin is involved in the control of TG consumption only in the fed state and that the greater TG mobilization in the fasted atria, at least partly, meets the energy requirements of the tissue.

  19. Harnessing endogenous stem/progenitor cells for tendon regeneration

    PubMed Central

    Lee, Chang H.; Lee, Francis Y.; Tarafder, Solaiman; Kao, Kristy; Jun, Yena; Yang, Guodong; Mao, Jeremy J.

    2015-01-01

    Current stem cell–based strategies for tissue regeneration involve ex vivo manipulation of these cells to confer features of the desired progenitor population. Recently, the concept that endogenous stem/progenitor cells could be used for regenerating tissues has emerged as a promising approach that potentially overcomes the obstacles related to cell transplantation. Here we applied this strategy for the regeneration of injured tendons in a rat model. First, we identified a rare fraction of tendon cells that was positive for the known tendon stem cell marker CD146 and exhibited clonogenic capacity, as well as multilineage differentiation ability. These tendon-resident CD146+ stem/progenitor cells were selectively enriched by connective tissue growth factor delivery (CTGF delivery) in the early phase of tendon healing, followed by tenogenic differentiation in the later phase. The time-controlled proliferation and differentiation of CD146+ stem/progenitor cells by CTGF delivery successfully led to tendon regeneration with densely aligned collagen fibers, normal level of cellularity, and functional restoration. Using siRNA knockdown to evaluate factors involved in tendon generation, we demonstrated that the FAK/ERK1/2 signaling pathway regulates CTGF-induced proliferation and differentiation of CD146+ stem/progenitor cells. Together, our findings support the use of endogenous stem/progenitor cells as a strategy for tendon regeneration without cell transplantation and suggest this approach warrants exploration in other tissues. PMID:26053662

  20. MALDI imaging mass spectrometry and analysis of endogenous peptides.

    PubMed

    Chatterji, Bijon; Pich, Andreas

    2013-08-01

    In recent years, MALDI imaging mass spectrometry (MALDI-IMS) has developed as a promising tool to investigate the spatial distribution of biomolecules in intact tissue specimens. Ion densities of various molecules can be displayed as heat maps while preserving anatomical structures. In this short review, an overview of different biomolecules that can be analyzed by MALDI-IMS is given. Many reviews have covered imaging of lipids, small metabolites, whole proteins and enzymatically digested proteins in the past. However, little is known about imaging of endogenous peptides, for example, in the rat brain, and this will therefore be highlighted in this review. Furthermore, sample preparation of frozen or formalin-fixed, paraffin-embedded (FFPE) tissue is crucial for imaging experiments. Therefore, some aspects of sample preparation will be addressed, including washing and desalting, the choice of MALDI matrix and its deposition. Apart from mapping endogenous peptides, their reliable identification in situ still remains challenging and will be discussed as well. PMID:23992420

  1. Effects of endogenous antidiuretic hormone (ADH) on macrophage phagocytosis

    SciTech Connect

    Fernandez-Repollet, E.; Opava-Stitzer, S.; Tiffany, S.; Schwartz, A.

    1983-07-01

    Although several studies have indicated that antidiuretic hormone (ADH) enhances the phagocytic function of the reticuloendothelial system (RES) in shock syndromes, it remains unknown what influence ADH exerts upon the individual phagocytic components of this system. The present investigation was designed to evaluate the effects of endogenous ADH on the phagocytic activity of peritoneal macrophage cells. As a phagocytic stimuli, fluorescent methacrylate microbeads were injected intraperitoneally into Brattleboro (ADH deficient) and normal Long Evans rats in the presence and absence of exogenous ADH. Peritoneal cells were harvested 19-22 hr after the administration of the microbeads and the percent phagocytosis was determined in macrophage cells using a fluorescence-activated cell sorter (FACS II). Our results indicate that the percentage of peritoneal macrophages ingesting the fluorescent methacrylate microbeads was significantly reduced in the absence of ADH (Brattleboro rats: 5.4 +/- 0.6% versus Long Evans rats: 16.8 +/- 2.3%; p less than 0.001). In addition, our data demonstrate that exogenous administration of ADH significantly enhanced macrophage phagocytosis in Brattleboro (14.7 +/- 2.2%) and normal Long Evans (49.6 +/- 4.5%) rats. These data suggest, for the first time, that endogenous ADH might play a modulatory role in the phagocytic activity of a specific component of the RES, namely, the macrophage cell.

  2. Endogenous repair after spinal cord contusion injuries in the rat.

    PubMed

    Beattie, M S; Bresnahan, J C; Komon, J; Tovar, C A; Van Meter, M; Anderson, D K; Faden, A I; Hsu, C Y; Noble, L J; Salzman, S; Young, W

    1997-12-01

    Contusion injuries of the rat thoracic spinal cord were made using a standardized device developed for the Multicenter Animal Spinal Cord Injury Study (MASCIS). Lesions of different severity were studied for signs of endogenous repair at times up to 6 weeks following injury. Contusion injuries produced a typical picture of secondary damage resulting in the destruction of the cord center and the chronic sparing of a peripheral rim of fibers which varied in amount depending upon the injury magnitude. It was noted that the cavities often developed a dense cellular matrix that became partially filled with nerve fibers and associated Schwann cells. The amount of fiber and Schwann cell ingrowth was inversely related to the severity of injury and amount of peripheral fiber sparing. The source of the ingrowing fibers was not determined, but many of them clearly originated in the dorsal roots. In addition to signs of regeneration, we noted evidence for the proliferation of cells located in the ependymal zone surrounding the central canal at early times following contusion injuries. These cells may contribute to the development of cellular trabeculae that provide a scaffolding within the lesion cavity that provides the substrates for cellular infiltration and regeneration of axons. Together, these observations suggest that the endogenous reparative response to spinal contusion injury is substantial. Understanding the regulation and restrictions on the repair processes might lead to better ways in which to encourage spontaneous recovery after CNS injury. PMID:9417825

  3. Silent no more: Endogenous small RNA pathways promote gene expression.

    PubMed

    Wedeles, Christopher J; Wu, Monica Z; Claycomb, Julie M

    2014-01-01

    Endogenous small RNA pathways related to RNA interference (RNAi) play a well-documented role in protecting host genomes from the invasion of foreign nucleic acids. In C. elegans, the PIWI type Argonaute, PRG-1, through an association with 21U-RNAs, mediates a genome surveillance process by constantly scanning the genome for potentially deleterious invading elements. Upon recognition of foreign nucleic acids, PRG-1 initiates a cascade of cytoplasmic and nuclear events that results in heritable epigenetic silencing of these transcripts and their coding genomic loci. If the PRG-1/21U-RNA genome surveillance pathway has the capacity to target most of the C. elegans transcriptome, what mechanisms exist to protect endogenous transcripts from being silenced by this pathway? In this commentary, we discuss three recent publications that implicate the CSR-1 small RNA pathway in the heritable activation of germline transcripts, propose a model as to why not all epialleles behave similarly, and touch on the practical implications of these findings.

  4. Endogenous patterns of mechanical stress are required for branching morphogenesis

    PubMed Central

    Gjorevski, Nikolce; Nelson, Celeste M.

    2011-01-01

    Spatial patterning of cell behaviors establishes the regional differences within tissues that collectively develop branched organs into their characteristic treelike shapes. Here we show that the pattern of branching morphogenesis of three-dimensional (3D) engineered epithelial tissues is controlled in part by gradients of endogenous mechanical stress. We used microfabrication to build model mammary epithelial tissues of defined geometry that branched in a stereotyped pattern when induced with growth factors. Branches initiated from sites of high mechanical stress within the tissues, as predicted numerically and measured directly using 3D traction force microscopy. Branch sites were defined by activation of focal adhesion kinase (FAK), inhibition of which disrupted morphogenesis. Stress, FAK activation, and branching were all altered by manipulating cellular contractility, matrix stiffness, intercellular cohesion and tissue geometry. These data suggest that the pattern and magnitude of mechanical stress across epithelial tissues cooperate with biochemical signals to specify branching pattern. Insight, innovation, integration Morphogenesis is ultimately a physical process wherein tissues are sculpted into their final three-dimensional (3D) patterns. Mechanical stresses from the microenvironment can also play regulatory roles, but their influence on pattern is difficult to ascertain in 3D systems in vivo. Here we integrate 3D microscale engineered tissues with insight from biological mechanics to understand the role of endogenous mechanical stresses in patterning tissue development. The innovation lies in the use of numerical modeling to design experiments that can predict the stress distribution and resulting morphogenesis of model tissues. PMID:20717570

  5. Bilirubin is an Endogenous Antioxidant in Human Vascular Endothelial Cells

    PubMed Central

    Ziberna, Lovro; Martelanc, Mitja; Franko, Mladen; Passamonti, Sabina

    2016-01-01

    Bilirubin is a standard serum biomarker of liver function. Inexplicably, it is inversely correlated with cardiovascular disease risk. Given the role of endothelial dysfunction in originating cardiovascular diseases, direct analysis of bilirubin in the vascular endothelium would shed light on these relationships. Hence, we used high-performance liquid chromatography coupled with thermal lens spectrometric detection and diode array detection for the determination of endogenous cellular IXα-bilirubin. To confirm the isomer IXα-bilirubin, we used ultra-performance liquid chromatography coupled with a high-resolution mass spectrometer using an electrospray ionization source, as well as tandem mass spectrometric detection. We measured bilirubin in both arterial and venous rat endothelium (0.9–1.5 pmol mg−1 protein). In the human endothelial Ea.hy926 cell line, we demonstrated that intracellular bilirubin (3–5 pmol mg−1 protein) could be modulated by either extracellular bilirubin uptake, or by up-regulation of heme oxygenase-1, a cellular enzyme related to endogenous bilirubin synthesis. Moreover, we determined intracellular antioxidant activity by bilirubin, with EC50 = 11.4 ± 0.2 nM, in the range of reported values of free serum bilirubin (8.5–13.1 nM). Biliverdin showed similar antioxidant properties as bilirubin. We infer from these observations that intra-endothelial bilirubin oscillates, and may thus be a dynamic factor of the endothelial function. PMID:27381978

  6. Why do cannabinoid receptors have more than one endogenous ligand?

    PubMed Central

    Di Marzo, Vincenzo; De Petrocellis, Luciano

    2012-01-01

    The endocannabinoid system was revealed following the understanding of the mechanism of action of marijuana's major psychotropic principle, Δ9-tetrahydrocannabinol, and includes two G-protein-coupled receptors (GPCRs; the cannabinoid CB1 and CB2 receptors), their endogenous ligands (the endocannabinoids, the best studied of which are anandamide and 2-arachidonoylglycerol (2-AG)), and the proteins that regulate the levels and activity of these receptors and ligands. However, other minor lipid metabolites different from, but chemically similar to, anandamide and 2-AG have also been suggested to act as endocannabinoids. Thus, unlike most other GPCRs, cannabinoid receptors appear to have more than one endogenous agonist, and it has been often wondered what could be the physiological meaning of this peculiarity. In 1999, it was proposed that anandamide might also activate other targets, and in particular the transient receptor potential of vanilloid type-1 (TRPV1) channels. Over the last decade, this interaction has been shown to occur both in peripheral tissues and brain, during both physiological and pathological conditions. TRPV1 channels can be activated also by another less abundant endocannabinoid, N-arachidonoyldopamine, but not by 2-AG, and have been proposed by some authors to act as ionotropic endocannabinoid receptors. This article will discuss the latest discoveries on this subject, and discuss, among others, how anandamide and 2-AG differential actions at TRPV1 and cannabinoid receptors contribute to making this signalling system a versatile tool available to organisms to fine-tune homeostasis. PMID:23108541

  7. Endogenous Mouse Dicer Is an Exclusively Cytoplasmic Protein.

    PubMed

    Much, Christian; Auchynnikava, Tania; Pavlinic, Dinko; Buness, Andreas; Rappsilber, Juri; Benes, Vladimir; Allshire, Robin; O'Carroll, Dónal

    2016-06-01

    Dicer is a large multi-domain protein responsible for the ultimate step of microRNA and short-interfering RNA biogenesis. In human and mouse cell lines, Dicer has been shown to be important in the nuclear clearance of dsRNA as well as the establishment of chromatin modifications. Here we set out to unambiguously define the cellular localization of Dicer in mice to understand if this is a conserved feature of mammalian Dicer in vivo. To this end, we utilized an endogenously epitope tagged Dicer knock-in mouse allele. From primary mouse cell lines and adult tissues, we determined with certainty by biochemical fractionation and confocal immunofluorescence microscopy that endogenous Dicer is exclusively cytoplasmic. We ruled out the possibility that a fraction of Dicer shuttles to and from the nucleus as well as that FGF or DNA damage signaling induce Dicer nuclear translocation. We also explored Dicer localization during the dynamic and developmental context of embryogenesis, where Dicer is ubiquitously expressed and strictly cytoplasmic in all three germ layers as well as extraembryonic tissues. Our data exclude a direct role for Dicer in the nuclear RNA processing in the mouse. PMID:27254021

  8. Elevations of Endogenous Kynurenic Acid Produce Spatial Working Memory Deficits

    PubMed Central

    Chess, Amy C.; Simoni, Michael K.; Alling, Torey E.; Bucci, David J.

    2007-01-01

    Kynurenic acid (KYNA) is a tryptophan metabolite that is synthesized and released by astrocytes and acts as a competitive antagonist of the glycine site of N-methyl-D-aspartate receptors at high concentrations and as a noncompetitive antagonist of the α7-nicotinic acetylcholine receptor at low concentrations. The discovery of increased cortical KYNA levels in schizophrenia prompted the hypothesis that elevated KYNA concentration may underlie the working memory dysfunction observed in this population that has been attributed to altered glutamatergic and/or cholinergic transmission. The present study investigated the effect of elevated endogenous KYNA on spatial working memory function in rats. Increased KYNA levels were achieved with intraperitoneal administration of kynurenine (100 mg/kg), the precursor of KYNA synthesis. Rats were treated with either kynurenine or a vehicle solution prior to testing in a radial arm maze task at various delays. Elevations of endogenous KYNA resulted in increased errors in the radial arm maze. In separate experiments, assessment of locomotor activity in an open field and latency to retrieve food reward from one of the maze arms ruled out the possibility that deficits in the maze were attributable to altered locomotor activity or motivation to consume food. These results provide evidence that increased KYNA levels produce spatial working memory deficits and are among the first to demonstrate the influence of glia-derived molecules on cognitive function. The implications for psychopathological conditions such as schizophrenia are discussed. PMID:16920787

  9. Endogenous allergens in the regulatory assessment of genetically engineered crops.

    PubMed

    Graf, Lynda; Hayder, Hikmat; Mueller, Utz

    2014-11-01

    A scientific approach to the assessment of foods derived from genetically engineered (GE) crops is critical to maintaining objectivity and public confidence in regulatory decisions. Principles developed at the international level support regulators and enable robust and transparent safety assessments. A comparison of key constituents in the GE crop with a suitable comparator is an important element of an assessment. In Europe, endogenous allergens would be included in the comparative analysis, however this approach has been hindered by technical limitations on the ability to accurately measure identified allergenic proteins. Over recent years, improved proteomic methods have enabled researchers to focus on major allergenic proteins in conventional food crops, as information on natural variability is largely lacking. Emerging data for soybean indicate that variability in levels of major allergens already in the food supply is broad. This raises questions about the biological interpretation of differences between a GE plant and its conventional counterpart, in particular, whether any conclusions about altered allergenicity could be inferred. This paper discusses the scientific justification for requiring proteomic analysis of endogenous allergens as part of the evaluation. Ongoing scientific review and corresponding international discussion are integral to ensuring that data requirements address legitimate risk assessment questions.

  10. Dinitroso and polynitroso compounds

    PubMed Central

    Gowenlock, Brian G.; Richter-Addo, George B.

    2005-01-01

    The growing interest in the chemistry of C-nitroso compounds (RN=O; R = alkyl or aryl group) is due in part to the recognition of their participation in various metabolic processes of nitrogen-containing compounds. C-Nitroso compounds have a rich organic chemistry in their own right, displaying interesting intra- and intermolecular dimerization processes and addition reactions with unsaturated compounds. In addition, they have a fascinating coordination chemistry. While most of the attention has been directed towards C-nitroso compounds containing a single –NO moiety, there is an emerging area of research dealing with dinitroso and polynitroso compounds. In this critical review, we present and discuss the synthetic routes and properties of these relatively unexplored dinitroso and polynitroso compounds, and suggest areas of further development involving these compounds. (126 references.) PMID:16100619

  11. Compounds affecting cholesterol absorption

    NASA Technical Reports Server (NTRS)

    Hua, Duy H. (Inventor); Koo, Sung I. (Inventor); Noh, Sang K. (Inventor)

    2004-01-01

    A class of novel compounds is described for use in affecting lymphatic absorption of cholesterol. Compounds of particular interest are defined by Formula I: ##STR1## or a pharmaceutically acceptable salt thereof.

  12. Reaction of homopiperazine with endogenous formaldehyde: a carbon hydrogen addition metabolite/product identified in rat urine and blood.

    PubMed

    Martin, Scott; Lenz, Eva M; Temesi, Dave; Wild, Martin; Clench, Malcolm R

    2012-08-01

    Drug reactivity and bioactivation are of major concern to the development of potential drug candidates in the pharmaceutical industry (Chem Res Toxicol 17:3-16, 2004; Chem Res Toxicol 19:889-893, 2006). Identifying potentially problematic compounds as soon as possible in the discovery process is of great importance, so often early in vitro screening is used to speed up attrition. Identification of reactive moieties is relatively straightforward with appropriate in vitro trapping experiments; however, on occasion unexpected reactive intermediates can be found later during more detailed in vivo studies. Here, we present one such example involving a series of compounds from an early drug discovery campaign. These compounds were found to react with endogenous formaldehyde from a rat in vivo study, resulting in the formation of novel +13-Da bridged homopiperazine products (equivalent to the addition of one carbon and one hydrogen atom), which were detected in urine and blood. The identification of these +13-Da products and their origin and mechanism of formation are described in detail through analyses of a representative homopiperazine compound [N-(3-(3-fluorophenyl)-1,2,4-thiadiazol-5-yl)-4-(4-isopropyl-1,4-diaze-pane-2-carbonyl)piperazine-1-carboxamide (AZX)] by liquid chromatography-UV-mass spectrometry, (1)H NMR, and chemical tests. PMID:22550270

  13. Regulating compounding pharmacies.

    PubMed

    Noble, Ashley

    2015-06-01

    (1) The Pew Charitable Trusts identified 27 compounding incidents that resulted in 89 deaths since 2001. (2) Unlike drug manufacturers, compounding pharmacies are generally not required to report adverse events associated with their products to the FDA. (3) Federal law on drug compounding was updated in 2013 to create a new group of compounders called "outsourcing facilities." Over 50 facilities in 23 states are now registered with the FDA.

  14. Effect of canrenone on the digitalis site of Na+/K(+)-ATPase in human placental membranes and in erythrocytes.

    PubMed

    Balzan, S; Nicolini, G; Bellitto, L; Ghione, S; Biver, P; Montali, U

    2003-07-01

    It has been reported that canrenone, which is used in hypertensive therapy as an antialdosteronic drug, may also act as a blocker of ouabain effects. Several studies suggest that human plasma contains an endogenous ouabain-like factor similar to ouabain, which may be increased in hypertension, in pregnancy, and in the neonatal state. This study evaluated (1) the effect of canrenone on Na+/K(+)-ATPase in relation to ouabain in human placental membranes and erythrocytes by 3H-ouabain binding assay; (2) the capacity of canrenone (10 microM) to reverse the inhibition of Na+/K(+)-ATPase by ouabain and by ouabain-like factor (from umbilical cord plasma) in human erythrocytes employing a 86Rb uptake assay. Increasing concentrations of canrenone (0-350 microM) partially competed with 3H-ouabain binding in placental membrane (40%) and erythrocytes (60%). Scatchard plot from radioreceptor assay in placental membrane showed that ouabain and canrenone compete for the same binding site. In erythrocytes, canrenone completely reversed the inhibition caused by ouabain (5 x 10(-9) M) and ouabain-like factor (2 x 10(-9) M ouabain equivalents). A reduction of inhibition of about 50% was observed with ouabain and ouabain-like factor respectively at a concentration of 5 x 10(-8) M and 2 x 10(-8) M (ouabain equivalents). Our results thus provide evidence that canrenone, at therapeutical concentrations, is a partial competitive agonist of ouabain and of ouabain-like factor in human placental membranes and erythrocytes. PMID:12827023

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

    PubMed

    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.

  16. Upregulating endogenous genes by an RNA-programmable artificial transactivator

    PubMed Central

    Fimiani, Cristina; Goina, Elisa; Mallamaci, Antonello

    2015-01-01

    To promote expression of endogenous genes ad libitum, we developed a novel, programmable transcription factor prototype. Kept together via an MS2 coat protein/RNA interface, it includes a fixed, polypeptidic transactivating domain and a variable RNA domain that recognizes the desired gene. Thanks to this device, we specifically upregulated five genes, in cell lines and primary cultures of murine pallial precursors. Gene upregulation was small, however sufficient to robustly inhibit neuronal differentiation. The transactivator interacted with target gene chromatin via its RNA cofactor. Its activity was restricted to cells in which the target gene is normally transcribed. Our device might be useful for specific applications. However for this purpose, it will require an improvement of its transactivation power as well as a better characterization of its target specificity and mechanism of action. PMID:26152305

  17. [Evaluation of the endogenous intoxication syndrome in food toxic infections].

    PubMed

    Marzhokhova, M Iu; Zhelikhazheva, Zh M

    2009-01-01

    To study the endogenous intoxication syndrome in patients with food toxic infections is essential in revealing the pathogenetic mechanisms underlying this disease. For this, the authors measured the level of low and average molecular weight, as well as their protein component--oligopeptides in plasma, red blood cells, and urine in the course of the disease. There were increased levels of the study parameters, which depended on the stage and degree of a pathological process. The determination of the level of low and average molecular weight and oligopeptides in plasma, red blood cells, and urine may serve as a marker of the intoxication syndrome; the level of the study parameters may be used as additional criteria for the severity of the process, the prediction of disease development and comorbidity, and as a criterion for recovery completeness.

  18. Natural mutagenesis of human genomes by endogenous retrotransposons

    PubMed Central

    Iskow, Rebecca C.; McCabe, Michael T.; Mills, Ryan E.; Torene, Spencer; Pittard, W. Stephen; Neuwald, Andrew F.; Van Meir, Erwin G.; Vertino, Paula M.; Devine, Scott E.

    2010-01-01

    SUMMARY Two abundant classes of mobile elements, namely Alu and L1 elements, continue to generate new retrotransposon insertions in human genomes. Estimates suggest that these elements have generated millions of new germline insertions in individual human genomes worldwide. Unfortunately, current technologies are not capable of detecting most of these young insertions, and the true extent of germline mutagenesis by endogenous human retrotransposons has been difficult to examine. Here, we describe new technologies for detecting these young retrotransposon insertions and demonstrate that such insertions indeed are abundant in human populations. We also found that new somatic L1 insertions occur at high frequencies in human lung cancer genomes. Genome-wide analysis suggests that altered DNA methylation may be responsible for the high levels of L1 mobilization observed in these tumors. Our data indicate that transposon-mediated mutagenesis is extensive in human genomes, and is likely to have a major impact on human biology and diseases. PMID:20603005

  19. Endogenous opioids: a proximate reward mechanism for kin selection?

    PubMed

    D'Amato, F R; Pavone, F

    1993-07-01

    The kin selection theory predicts that individuals would behave differently toward one another, depending on their genetic relatedness. Proximate mechanisms have been postulated to exist helping the individual to discriminate what is good or bad for him. Opioids have been discovered to be involved in the mediation of reinforcement, in particular they underlay social emotion. In this study it is shown that pain sensitivity decreased in male mice interacting with siblings following 2 months of separation; this analgesic response was antagonized by naloxone administration. Interaction with unknown and unrelated subjects did not change the nociceptive threshold. These results suggest that interacting with kin is an adaptive situation reinforced, at the neural level, by the release of endogenous opioids.

  20. Pluripotency and the endogenous retrovirus HERVH: Conflict or serendipity?

    PubMed

    Izsvák, Zsuzsanna; Wang, Jichang; Singh, Manvendra; Mager, Dixie L; Hurst, Laurence D

    2016-01-01

    Remnants of ancient retroviral infections during evolution litter all mammalian genomes. In modern humans, such endogenous retroviral (ERV) sequences comprise at least 8% of the genome. While ERVs and other types of transposable elements undoubtedly contribute to the genomic "junk yard", functions for some ERV sequences have been demonstrated, with growing evidence that ERVs can be important players in gene regulatory processes. Here we focus on one particular large family of human ERVs, termed HERVH, which several recent studies suggest has a key regulatory role in human pluripotent stem cells. Remarkably, this is not the first instance of an ERV controlling pluripotency. We speculate as to why this convergent evolution might have come about, suggesting that it may reflect selection on the virus to extend the time available for transposition. Alternatively it may reflect serendipity alone. PMID:26735931

  1. Human endogenous retrovirus K10 encodes a functional integrase.

    PubMed Central

    Kitamura, Y; Ayukawa, T; Ishikawa, T; Kanda, T; Yoshiike, K

    1996-01-01

    We cloned a human endogenous retrovirus K1O DNA fragment encoding integrase and expressed it as a fusion protein with Escherichia coli maltose-binding protein. Integrase activities were measured in vitro by using a double-stranded oligonucleotide as a substrate mimicking viral long terminal repeats (LTR). The fusion protein was highly active for both terminal cleavage and strand transfer in the presence of Mn2+ on the K1O LTR substrate. It was also active on both Rous sarcoma virus and human immunodeficiency virus type 1 LTR substrates, whereas Rous sarcoma virus and human immunodeficiency virus type 1 integrases were active only on their corresponding LTR substrates. The results strongly suggest that K1O encodes a functional integrase with relaxed substrate specificity. PMID:8627815

  2. Light-induced suppression of endogenous circadian amplitude in humans

    NASA Technical Reports Server (NTRS)

    Jewett, Megan; Czeisler, Charles A.; Kronauer, Richard E.

    1991-01-01

    A recent demonstration that the phase of the human circadian pacemaker could be inverted using an unconventional three-cycle stimulus has led to an investigation of whether critically timed exposure to a more moderate stimulus could drive that oscillator toward its singularity, a phaseless position at which the amplitude of circadian oscillation is zero. It is reported here that exposure of humans to fewer cycles of bright light, centered around the time at which the human circadian pacemaker is most sensitive to light-induced phase shifts, can markedly attenuate endogenous cicadian amplitude. In some cases this results in an apparent loss of rhythmicity, as expected to occur in the region of singularity.

  3. Serratia marcescens endogenous endophthalmitis in an immunocompetent host.

    PubMed

    Memon, Muhammad; Raman, Vasant

    2016-01-01

    A systemically well 66-year-old white Caucasian man presented to the urgent care department with a short history of progressive pain and blurring of vision in his left eye. He denied a history of trauma, intraocular surgery or use of illicit drugs. He was diagnosed with endogenous endophthalmitis. Vitreous biopsy grew Serratia marcescens, a Gram negative bacteria. In spite of extensive investigation, there was no obvious source of infection. He had an indwelling urine catheter for prostate hypertrophy, but urine culture was negative. There was no evidence of immunocompromise. He was treated with systemic as well as intravitreal antibiotics. In spite of appropriate treatment, the patient lost vision. S. marcescens endophthalmitis, seen even in immunocompetent people, carries a poor visual prognosis. PMID:26791115

  4. Endogenous siRNAs, regulators of internal affairs

    PubMed Central

    Piatek, Monica J; Werner, Andreas

    2015-01-01

    Endogenous short interfering RNAs (endo-siRNAs) have recently emerged as versatile regulators of gene expression. They derive from double stranded intrinsic transcripts and are processed by Dicer and associate with Argonaute proteins. In Caenorhabditis elegans, endo-siRNAs are known as 22G and 26G RNAs and are involved in genome protection and gene regulation. Drosophila melanogaster endo-siRNAs are produced with the help of specific Dicer and Argonaute isoforms and play an essential role in transposon control and the protection from viral infections. Biological functions of endo-siRNAs in vertebrates include repression of transposable elements, chromatin organisation as well as gene regulation at transcriptional and post-transcriptional level. PMID:25110021

  5. Generation of neutralising antibodies against porcine endogenous retroviruses (PERVs)

    SciTech Connect

    Kaulitz, Danny; Fiebig, Uwe; Eschricht, Magdalena; Wurzbacher, Christian; Kurth, Reinhard; Denner, Joachim

    2011-03-01

    Antibodies neutralising porcine endogenous retroviruses (PERVs) were induced in different animal species by immunisation with the transmembrane envelope protein p15E. These antibodies recognised epitopes, designated E1, in the fusion peptide proximal region (FPPR) of p15E, and E2 in the membrane proximal external region (MPER). E2 is localised in a position similar to that of an epitope in the transmembrane envelope protein gp41 of the human immunodeficiency virus-1 (HIV-1), recognised by the monoclonal antibody 4E10 that is broadly neutralising. To detect neutralising antibodies specific for PERV, a novel assay was developed, which is based on quantification of provirus integration by real-time PCR. In addition, for the first time, highly effective neutralising antibodies were obtained by immunisation with the surface envelope protein of PERV. These data indicate that neutralising antibodies can be induced by immunisation with both envelope proteins.

  6. CYTOCHEMICAL LOCALIZATION OF ENDOGENOUS PEROXIDASE IN THYROID FOLLICULAR CELLS

    PubMed Central

    Strum, Judy M.; Karnovsky, Morris J.

    1970-01-01

    Endogenous peroxidase activity in rat thyroid follicular cells is demonstrated cytochemically. Following perfusion fixation of the thyroid gland, small blocks of tissue are incubated in a medium containing substrate for peroxidase, before being postfixed in osmium tetroxide, and processed for electron microscopy. Peroxidase activity is found in thyroid follicular cells in the following sites: (a) the perinuclear cisternae, (b) the cisternae of the endoplasmic reticulum, (c) the inner few lamellae of the Golgi complex, (d) within vesicles, particularly those found apically, and (e) associated with the external surfaces of the microvilli that project apically from the cell into the colloid. In keeping with the radioautographic evidence of others and the postulated role of thyroid peroxidase in iodination, it is suggested that the microvillous apical cell border is the major site where iodination occurs. However, that apical vesicles also play a role in iodination cannot be excluded. The in vitro effect of cyanide, aminotriazole, and thiourea is also discussed. PMID:4190069

  7. Genome-wide reexamination of endogenous retroviruses in Rattus norvegicus.

    PubMed

    Garcia-Etxebarria, Koldo; Jugo, Begoña M

    2016-07-01

    Endogenous retroviruses (ERVs) are remnants of retroviral infections that are present in a large number of vertebrate genomes. Based on the proposal that the rat could act as a reservoir of retroviruses, rat ERVs were analysed in silico using a whole-genome approach. To enrich the detected ERV groups, we applied an upgraded approach based on the hidden Markov model. We found 2637 elements that were classified into the following groups: 9 groups of Class I; 15 of Class II, 7 of them previously described; 1 of Class III; and 3 groups whose classification was unclear but were distantly related to Class I. Sixteen ERV groups seemed to be specific to rat. The high number of rat-specific groups might be related to the contact of rats with retroviruses and their role as a reservoir. In addition, the env gene of the more extended groups seemed to be undetectable.

  8. Endogenous coresidence and program incidence: South Africa's Old Age Pension.

    PubMed

    Hamoudi, Amar; Thomas, Duncan

    2014-07-01

    We investigate whether living arrangements respond to an arguably exogenous shift in the distribution of power in family economic decision-making. In the early 1990s, the South African Old Age Pension was expanded to cover most black South Africans above a sex-specific age cut-off resulting in a substantial increase in the income of older South Africans and potentially their say in the economic decisions of their families. Beneficiaries of the program are more likely to coreside with adults who have less human capital as measured by height and education. Since height and education are fixed for adults, this cannot be an effect of the pension income but reflects selective changes in living arrangements resulting from the pension. The findings highlight the endogeneity of living arrangements and illustrate the potential value of moving beyond theory and data that are confined to a spatially determined definition of the household.

  9. Serratia marcescens endogenous endophthalmitis in an immunocompetent host.

    PubMed

    Memon, Muhammad; Raman, Vasant

    2016-01-20

    A systemically well 66-year-old white Caucasian man presented to the urgent care department with a short history of progressive pain and blurring of vision in his left eye. He denied a history of trauma, intraocular surgery or use of illicit drugs. He was diagnosed with endogenous endophthalmitis. Vitreous biopsy grew Serratia marcescens, a Gram negative bacteria. In spite of extensive investigation, there was no obvious source of infection. He had an indwelling urine catheter for prostate hypertrophy, but urine culture was negative. There was no evidence of immunocompromise. He was treated with systemic as well as intravitreal antibiotics. In spite of appropriate treatment, the patient lost vision. S. marcescens endophthalmitis, seen even in immunocompetent people, carries a poor visual prognosis.

  10. Endogenously determined cycles: empirical evidence from livestock industries.

    PubMed

    McCullough, Michael P; Huffaker, Ray; Marsh, Thomas L

    2012-04-01

    This paper applies the techniques of phase space reconstruction and recurrence quantification analysis to investigate U.S. livestock cycles in relation to recent literature on the business cycle. Results are presented for pork and cattle cycles, providing empirical evidence that the cycles themselves have slowly diminished. By comparing the evolution of production processes for the two livestock cycles we argue that the major cause for this moderation is largely endogenous. The analysis suggests that previous theoretical models relying solely on exogenous shocks to create cyclical patterns do not fully capture changes in system dynamics. Specifically, the biological constraint in livestock dynamics has become less significant while technology and information are relatively more significant. Concurrently, vertical integration of the supply chain may have improved inventory management, all resulting in a small, less deterministic, cyclical effect.

  11. Human Endogenous Retrovirus Group E and Its Involvement in Diseases

    PubMed Central

    Le Dantec, Christelle; Vallet, Sophie; Brooks, Wesley H.; Renaudineau, Yves

    2015-01-01

    Human endogenous retrovirus group E (HERV-E) elements are stably integrated into the human genome, transmitted vertically in a Mendelian manner, and are endowed with transcriptional activity as alternative promoters or enhancers. Such effects are under the control of the proviral long terminal repeats (LTR) that are organized into three HERV-E phylogenetic subgroups, namely LTR2, LTR2B, and LTR2C. Moreover, HERV-E expression is tissue-specific, and silenced by epigenetic constraints that may be disrupted in cancer, autoimmunity, and human placentation. Interest in HERV-E with regard to these conditions has been stimulated further by concerns regarding the capacity of HERV-E elements to modify the expression of neighboring genes and/or to produce retroviral proteins, including immunosuppressive env peptides, which in turn may induce (auto)-antibody (Ab) production. Finally, better understanding of HERV-E elements may have clinical applications for prevention, diagnosis, prognosis, and therapy. PMID:25785516

  12. Unusual productions of endogenous alcohol: report of two autopsy cases.

    PubMed

    Moriya, F; Ishizu, H; Miyaishi, S

    1991-10-01

    We experienced two autopsy cases in which endogenous alcohol productions by saprogens had been unusual. Case 1 is a victim found in a mountain stream 3 to 4 weeks after his death. Since ethanol and n-propanol concentrations in the right intrathoracic bloody fluid, pericardial sac fluid, and blood in the right side of the heart were 0.41 mg/g and 0.052 mg/g, 0.42 mg/g and 0.032 mg/g, and 0.45 mg/g and 0.025 mg/g, respectively. The ethanol detected in those specimens appeared to have been produced postmortem. The femoral muscle and urine, however, contained very little n-propanol though the ethanol levels were 0.21 mg/g and 0.05 mg/g, respectively. Thus, we judged the victim might have died soon after drinking a little alcohol. Case 2 is a victim who was stabbed in the abdomen (liver) with a knife and died due to hemorrhagic shock after 26.5 hours in spite of a peritoneotomy. It was probable that metabolic activities of the liver had decreased significantly after getting a wound. Almost 1 mg/g of ethanol and little n-propanol were detected in the heart blood. In the intraabdominal bloody fluid, however, 2.45 mg/g of ethanol and 0.079 mg/g of n-propanol were detected. n-Propanol level in the bloody fluid is equal to that in severely decomposed body and indicates that a large amount of ethanol was endogenously produced. It may be considered that the unusual ethanol production was caused by the severe peritonitis after the operation.

  13. Endogenous nociceptin modulates diet preference independent of motivation and reward.

    PubMed

    Koizumi, Miwako; Cagniard, Barbara; Murphy, Niall P

    2009-04-20

    Previous studies show that the opioid peptide nociceptin stimulates food intake. Here, we studied nociceptin receptor knockout (NOP KO) mice in various behavioral paradigms designed to differentiate psychological and physiological loci at which endogenous nociceptin might control feeding. When presented a choice under food restriction, NOP KO mice displayed reduced preference for high sucrose diet, but lower intake of high fat diet under no-choice conditions. These responses were absent under ad libitum feeding conditions. Conditioned place preference to high fat diet under food-deprived conditions was unaltered in NOP KO mice, suggesting no difference in reward responses. Furthermore, operant food self-administration under a variety of conditions showed no genotype-dependent differences, suggesting no differences in the motivational properties of food. Taste reactivity to sucrose was unchanged in NOP KO mice, though NOP KO mice had altered aversive reactions to quinine solutions under ad libitum feeding, suggesting minor differences in the affective impact of palatable and unpalatable tastants. Although NOP KO mice re-fed following food-deprivation showed normal increases in plasma glucose and insulin, multidimensional scaling analysis showed that the relationship between these measures, body weight and plasma leptin was substantially disrupted in NOP KO, particularly in fasted mice. Additionally, the typical positive relationship between body weight and plasma leptin was considerably weaker in NOP KO mice. Together, these findings suggest that endogenous nociceptin differentially modulates diet preference depending on macronutrient content and homeostatic state, independently of the motivating, rewarding or orosensory properties of food, but may involve metabolic or postingestive processes. PMID:19138695

  14. Endogenous technological and population change under increasing water scarcity

    NASA Astrophysics Data System (ADS)

    Pande, S.; Ertsen, M.; Sivapalan, M.

    2014-08-01

    Ancient civilizations may have dispersed or collapsed under extreme dry conditions. There are indications that the same may hold for modern societies. However, hydroclimatic change cannot be the sole predictor of the fate of contemporary societies in water-scarce regions. This paper focuses on technological change as a factor that may ameliorate the effects of increasing water scarcity and as such counter the effects of hydroclimatic changes. We study the role of technological change on the dynamics of coupled human-water systems, and model technological change as an endogenous process that depends on many factors intrinsic to coupled human-water dynamics. We do not treat technology as an exogenous random sequence of events, but assume that it results from societal actions. While the proposed model is a rather simple model of a coupled human-water system, it is shown to be capable of replicating patterns of technological, population, production and consumption per capita changes. 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. In general we find that endogenous technology change under increasing water scarcity helps to delay the peak of population size before it inevitably starts to decline. We also analyze the case when water remains constant over time and find that co-evolutionary trajectories can never grow at a constant rate; rather the rate itself grows with time. Thus our model does not predict a co-evolutionary trajectory of a socio-hydrological system where technological innovation harmoniously provides for a growing population. It allows either for an explosion or an eventual dispersal of population. The latter occurs only under increasing water scarcity. As a result, we draw the conclusion that declining consumption per capita despite technological advancement and increase in aggregate production may serve as a useful predictor of upcoming

  15. Endogenous DNA Damage and Risk of Testicular Germ Cell Tumors

    SciTech Connect

    Cook, M B; Sigurdson, A J; Jones, I M; Thomas, C B; Graubard, B I; Korde, L; Greene, M H; McGlynn, K A

    2008-01-18

    Testicular germ cell tumors (TGCT) are comprised of two histologic groups, seminomas and nonseminomas. We postulated that the possible divergent pathogeneses of these histologies may be partially explained by variable endogenous DNA damage. To assess our hypothesis, we conducted a case-case analysis of seminomas and nonseminomas using the alkaline comet assay to quantify single-strand DNA breaks and alkali-labile sites. The Familial Testicular Cancer study and the U.S. Radiologic Technologists cohort provided 112 TGCT cases (51 seminomas & 61 nonseminomas). A lymphoblastoid cell line was cultured for each patient and the alkaline comet assay was used to determine four parameters: tail DNA, tail length, comet distributed moment (CDM) and Olive tail moment (OTM). Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using logistic regression. Values for tail length, tail DNA, CDM and OTM were modeled as categorical variables using the 50th and 75th percentiles of the seminoma group. Tail DNA was significantly associated with nonseminoma compared to seminoma (OR{sub 50th percentile} = 3.31, 95%CI: 1.00, 10.98; OR{sub 75th percentile} = 3.71, 95%CI: 1.04, 13.20; p for trend=0.039). OTM exhibited similar, albeit statistically non-significant, risk estimates (OR{sub 50th percentile} = 2.27, 95%CI: 0.75, 6.87; OR{sub 75th percentile} = 2.40, 95%CI: 0.75, 7.71; p for trend=0.12) whereas tail length and CDM showed no association. In conclusion, the results for tail DNA and OTM indicate that endogenous DNA damage levels are higher in patients who develop nonseminoma compared with seminoma. This may partly explain the more aggressive biology and younger age-of-onset of this histologic subgroup compared with the relatively less aggressive, later-onset seminoma.

  16. Remodeling of Endogenous Mammary Epithelium by Breast Cancer Stem Cells

    PubMed Central

    Parashurama, Natesh; Lobo, Neethan A.; Ito, Ken; Mosley, Adriane R.; Habte, Frezghi G.; Zabala, Maider; Smith, Bryan R.; Lam, Jessica; Weissman, Irving L.; Clarke, Michael F.; Gambhir, Sanjiv S.

    2014-01-01

    Poorly regulated tissue remodeling results in increased breast cancer risk, yet how breast cancer stem cells (CSC) participate in remodeling is unknown. We performed in vivo imaging of changes in fluorescent, endogenous duct architecture as a metric for remodeling. First, we quantitatively imaged physiologic remodeling of primary branches of the developing and regenerating mammary tree. To assess CSC-specific remodeling events, we isolated CSC from MMTV-Wnt1 (mouse mammary tumor virus long-term repeat enhancer driving Wnt1 oncogene) breast tumors, a well studied model in which tissue remodeling affects tumorigenesis. We confirm that CSC drive tumorigenesis, suggesting a link between CSC and remodeling. We find that normal, regenerating, and developing gland maintain a specific branching pattern. In contrast, transplantation of CSC results in changes in the branching patterns of endogenous ducts while non-CSC do not. Specifically, in the presence of CSC, we identified an increased number of branches, branch points, ducts which have greater than 40 branches (5/33 for CSC and 0/39 for non-CSC), and histological evidence of increased branching. Moreover, we demonstrate that only CSC implants invade into surrounding stroma with structures similar to developing mammary ducts (nine for CSC and one for non-CSC). Overall, we demonstrate a novel approach for imaging physiologic and pathological remodeling. Furthermore, we identify unique, CSC-specific, remodeling events. Our data suggest that CSC interact with the microenvironment differently than non-CSC, and that this could eventually be a therapeutic approach for targeting CSC. PMID:22899386

  17. Remodeling of endogenous mammary epithelium by breast cancer stem cells.

    PubMed

    Parashurama, Natesh; Lobo, Neethan A; Ito, Ken; Mosley, Adriane R; Habte, Frezghi G; Zabala, Maider; Smith, Bryan R; Lam, Jessica; Weissman, Irving L; Clarke, Michael F; Gambhir, Sanjiv S

    2012-10-01

    Poorly regulated tissue remodeling results in increased breast cancer risk, yet how breast cancer stem cells (CSC) participate in remodeling is unknown. We performed in vivo imaging of changes in fluorescent, endogenous duct architecture as a metric for remodeling. First, we quantitatively imaged physiologic remodeling of primary branches of the developing and regenerating mammary tree. To assess CSC-specific remodeling events, we isolated CSC from MMTV-Wnt1 (mouse mammary tumor virus long-term repeat enhancer driving Wnt1 oncogene) breast tumors, a well studied model in which tissue remodeling affects tumorigenesis. We confirm that CSC drive tumorigenesis, suggesting a link between CSC and remodeling. We find that normal, regenerating, and developing gland maintain a specific branching pattern. In contrast, transplantation of CSC results in changes in the branching patterns of endogenous ducts while non-CSC do not. Specifically, in the presence of CSC, we identified an increased number of branches, branch points, ducts which have greater than 40 branches (5/33 for CSC and 0/39 for non-CSC), and histological evidence of increased branching. Moreover, we demonstrate that only CSC implants invade into surrounding stroma with structures similar to developing mammary ducts (nine for CSC and one for non-CSC). Overall, we demonstrate a novel approach for imaging physiologic and pathological remodeling. Furthermore, we identify unique, CSC-specific, remodeling events. Our data suggest that CSC interact with the microenvironment differently than non-CSC, and that this could eventually be a therapeutic approach for targeting CSC. PMID:22899386

  18. Nilotinib exacerbates diabetes mellitus by decreasing secretion of endogenous insulin.

    PubMed

    Ito, Yoshikiyo; Miyamoto, Toshihiro; Chong, Yong; Maki, Toshinobu; Akashi, Koichi; Kamimura, Tomohiko

    2013-01-01

    We report a 74-year-old female with chronic myelogenous leukemia (CML) in accelerated phase with pre-existing severe type 2 diabetes (T2D) and hemorrhagic gastric ulcers who was successfully treated with nilotinib. We first considered second-generation tyrosine kinase inhibitors for the treatment of this patient, as they elicit a superior response compared with imatinib. We next selected nilotinib, rather than dasatinib, since the increased risk of bleeding associated with dasatinib represented a greater risk of fatality than aggravation of T2D with nilotinib. After improvement of hemorrhagic gastric ulcers and T2D with exogenous insulin therapy, we began nilotinib administration; insulin dose was increased to maintain her glucose levels whereas urine C-peptide level decreased. Conversely, when nilotinib was discontinued due to liver dysfunction, the dosage of injected insulin was decreased and urine C-peptide levels increased. After re-starting nilotinib, the required dose of insulin gradually increased again, and urine C-peptide level decreased, indicating that nilotinib may have impaired secretion of endogenous insulin. The patient obtained a complete cytogenetic response after 3 months of nilotinib treatment. Her T2D has since been well controlled by insulin therapy. To our knowledge, this is the first report that nilotinib treatment for patients with severe T2D may induce a reversible decrease in endogenous insulin secretion, although the precise underlying mechanisms remain unknown. We highly recommend sufficient screening and early intervention with exogenous insulin therapy for diabetic CML patients who receive nilotinib.

  19. Relationship between endogenous 3-methylhistidine excretion and body composition.

    PubMed

    Lukaski, H C; Mendez, J; Buskirk, E R; Cohn, S H

    1981-03-01

    Fourteen healthy men (aged 20-30 yr) consumed two isocaloric, isonitrogenous diets in the sequence of a 4-day meat diet (MD) followed by a 7-day meal-free diet (MFD). Urinary 3-methylhistidine (3MH) excretion during the MD (513 +/- 21 mumol . day-1, mean +/- SE) was significantly higher (P less than 0.01) than day 3 of the MFD (230 +/- 10 mumol . day-1), after which the mean daily 3MH output was constant with a mean coefficient of variation of 4.5%. There was no change in fat-free body mass (FFBM) determined by densitometry at the start (62.3 +/- 1.8 kg) and the end (62.2 +/- 1.9 kg) of the 11-day dietary period. Mean muscle mass (MM) calculated from measurements of total-body potassium and nitrogen was 23.4 +/- 1.3 kg. Endogenous 3MH excretion was related more closely to MM (r = 0.91, P less than 0.001) than to FFBM measured by densitometry (r = 0.81, P less than 0.001). Only a low correlation coefficient (r = 0.33, P less than 0.05) was observed between 3MH and the nonmuscle component of FFBM. Urinary creatinine output also was correlated significantly with 3MH (r = 0.87; P less than 0.001) and MM (r = 0.79; P less than 0.01). It is concluded that because endogenous 3MH is significantly related to MM in man, it can be used as a marker to study in vivo total-body muscle protein degradation provided that the necessary dietary restrictions are observed.

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

    PubMed

    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.

  1. Evidences for Chlorogenic Acid--A Major Endogenous Polyphenol Involved in Regulation of Ripening and Senescence of Apple Fruit.

    PubMed

    Xi, Yu; Cheng, Dai; Zeng, Xiangquan; Cao, Jiankang; Jiang, Weibo

    2016-01-01

    To learn how the endogenous polyphenols may play a role in fruit ripening and senescence, apple pulp discs were used as a model to study the influences of chlorogenic acid (CHA, a major polyphenol in apple pulp) on fruit ripening and senescence. Apple ('Golden Delicious') pulp discs prepared from pre-climacteric fruit were treated with 50 mg L(-1) CHA and incubated in flasks with 10 mM MES buffer (pH 6.0, 11% sorbitol). Compared to the control samples, treatment with CHA significantly reduced ethylene production and respiration rate, and enhanced levels of firmness and soluble solids content of the pulp discs during incubation at 25°C. These results suggested that CHA could retard senescence of the apple pulp discs. Proteomics analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometry (MALDI-TOF/TOF) revealed that the expressions of several key proteins correlated to fruit ripening and senescence were affected by the treatment with CHA. Further study showed that treating the pulp discs with CHA remarkably reduced levels of lipoxygenase, β-galactosidase, NADP-malic enzyme, and enzymatic activities of lipoxygenase and UDP-glucose pyrophosphorylase, all of which are known as promoters of fruit ripening and senescence. These results could provide new insights into the functions of endogenous phenolic compounds in fruit ripening and senescence.

  2. Evidences for Chlorogenic Acid — A Major Endogenous Polyphenol Involved in Regulation of Ripening and Senescence of Apple Fruit

    PubMed Central

    Xi, Yu; Cheng, Dai; Zeng, Xiangquan; Cao, Jiankang; Jiang, Weibo

    2016-01-01

    To learn how the endogenous polyphenols may play a role in fruit ripening and senescence, apple pulp discs were used as a model to study the influences of chlorogenic acid (CHA, a major polyphenol in apple pulp) on fruit ripening and senescence. Apple (‘Golden Delicious’) pulp discs prepared from pre-climacteric fruit were treated with 50 mg L-1 CHA and incubated in flasks with 10 mM MES buffer (pH 6.0, 11% sorbitol). Compared to the control samples, treatment with CHA significantly reduced ethylene production and respiration rate, and enhanced levels of firmness and soluble solids content of the pulp discs during incubation at 25°C. These results suggested that CHA could retard senescence of the apple pulp discs. Proteomics analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometry (MALDI-TOF/TOF) revealed that the expressions of several key proteins correlated to fruit ripening and senescence were affected by the treatment with CHA. Further study showed that treating the pulp discs with CHA remarkably reduced levels of lipoxygenase, β-galactosidase, NADP-malic enzyme, and enzymatic activities of lipoxygenase and UDP-glucose pyrophosphorylase, all of which are known as promoters of fruit ripening and senescence. These results could provide new insights into the functions of endogenous phenolic compounds in fruit ripening and senescence. PMID:26756813

  3. Evidences for Chlorogenic Acid--A Major Endogenous Polyphenol Involved in Regulation of Ripening and Senescence of Apple Fruit.

    PubMed

    Xi, Yu; Cheng, Dai; Zeng, Xiangquan; Cao, Jiankang; Jiang, Weibo

    2016-01-01

    To learn how the endogenous polyphenols may play a role in fruit ripening and senescence, apple pulp discs were used as a model to study the influences of chlorogenic acid (CHA, a major polyphenol in apple pulp) on fruit ripening and senescence. Apple ('Golden Delicious') pulp discs prepared from pre-climacteric fruit were treated with 50 mg L(-1) CHA and incubated in flasks with 10 mM MES buffer (pH 6.0, 11% sorbitol). Compared to the control samples, treatment with CHA significantly reduced ethylene production and respiration rate, and enhanced levels of firmness and soluble solids content of the pulp discs during incubation at 25°C. These results suggested that CHA could retard senescence of the apple pulp discs. Proteomics analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometry (MALDI-TOF/TOF) revealed that the expressions of several key proteins correlated to fruit ripening and senescence were affected by the treatment with CHA. Further study showed that treating the pulp discs with CHA remarkably reduced levels of lipoxygenase, β-galactosidase, NADP-malic enzyme, and enzymatic activities of lipoxygenase and UDP-glucose pyrophosphorylase, all of which are known as promoters of fruit ripening and senescence. These results could provide new insights into the functions of endogenous phenolic compounds in fruit ripening and senescence. PMID:26756813

  4. Ammonium Activates Ouabain-Activated Signalling Pathway in Astrocytes: Therapeutic Potential of Ouabain Antagonist

    PubMed Central

    Song, Dan; Du, Ting

    2014-01-01

    The causal role of ammonium in hepatic encephalopathy was identified in 1930s. Astroglial cells are primary cellular elements of hepatic encephalopathy which conceptually, can be considered a toxic astrogliopathology. Previously we have reported that acute exposure to ammonium activated ouabain/Na,K-ATPase signalling pathway, which includes Src, EGF receptor, Raf, Ras, MEK and ERK1/2. Chronic incubation of astrocytes with ammonium increased production of endogenous ouabain-like compound. Ouabain antagonist canrenone abolished effects of ammonium on astrocytic swelling, ROS production, and upregulation of gene expression and function of TRPC1 and Cav1.2. However, ammonium induces multiple pathological modifications in astrocytes, and some of them may be not related to this signalling pathway. In this review, we focus on the effect of ammonium on ouabain/Na,K-ATPase signalling pathway and its involvement in ammonium-induced ROS production, cell swelling and aberration of Ca2+ signals in astrocytes. We also briefly discuss Na,K-ATPase, EGF receptor, endogenous ouabain and ouabain antagonist. PMID:25342941

  5. Ammonium activates ouabain-activated signalling pathway in astrocytes: therapeutic potential of ouabain antagonist.

    PubMed

    Song, Dan; Du, Ting

    2014-07-01

    The causal role of ammonium in hepatic encephalopathy was identified in 1930s. Astroglial cells are primary cellular elements of hepatic encephalopathy which conceptually, can be considered a toxic astrogliopathology. Previously we have reported that acute exposure to ammonium activated ouabain/Na,K-ATPase signalling pathway, which includes Src, EGF receptor, Raf, Ras, MEK and ERK1/2. Chronic incubation of astrocytes with ammonium increased production of endogenous ouabain-like compound. Ouabain antagonist canrenone abolished effects of ammonium on astrocytic swelling, ROS production, and upregulation of gene expression and function of TRPC1 and Cav1.2. However, ammonium induces multiple pathological modifications in astrocytes, and some of them may be not related to this signalling pathway. In this review, we focus on the effect of ammonium on ouabain/Na,K-ATPase signalling pathway and its involvement in ammonium-induced ROS production, cell swelling and aberration of Ca(2+) signals in astrocytes. We also briefly discuss Na,K-ATPase, EGF receptor, endogenous ouabain and ouabain antagonist. PMID:25342941

  6. Ecotoxicology of organofluorous compounds.

    PubMed

    Murphy, Margaret B; Loi, Eva I H; Kwok, Karen Y; Lam, Paul K S

    2012-01-01

    Organofluorous compounds have been developed for myriad purposes in a variety of fields, including manufacturing, industry, agriculture, and medicine. The widespread use and application of these compounds has led to increasing concern about their potential ecological toxicity, particularly because of the stability of the C-F bond, which can result in chemical persistence in the environment. This chapter reviews the chemical properties and ecotoxicology of four groups of organofluorous compounds: fluorinated refrigerants and propellants, per- and polyfluorinated compounds (PFCs), fluorinated pesticides, and fluoroquinolone antibiotics. These groups vary in their environmental fate and partitioning, but each raises concern in terms of ecological risk on both the regional and global scale, particularly those compounds with long environmental half-lives. Further research on the occurrence and toxicities of many of these compounds is needed for a more comprehensive understanding of their ecological effects.

  7. XAFS Model Compound Library

    DOE Data Explorer

    Newville, Matthew

    The XAFS Model Compound Library contains XAFS data on model compounds. The term "model" compounds refers to compounds of homogeneous and well-known crystallographic or molecular structure. Each data file in this library has an associated atoms.inp file that can be converted to a feff.inp file using the program ATOMS. (See the related Searchable Atoms.inp Archive at http://cars9.uchicago.edu/~newville/adb/) This Library exists because XAFS data on model compounds is useful for several reasons, including comparing to unknown data for "fingerprinting" and testing calculations and analysis methods. The collection here is currently limited, but is growing. The focus to date has been on inorganic compounds and minerals of interest to the geochemical community. [Copied, with editing, from http://cars9.uchicago.edu/~newville/ModelLib/

  8. Preparation of uranium compounds

    DOEpatents

    Kiplinger, Jaqueline L; Montreal, Marisa J; Thomson, Robert K; Cantat, Thibault; Travia, Nicholas E

    2013-02-19

    UI.sub.3(1,4-dioxane).sub.1.5 and UI.sub.4(1,4-dioxane).sub.2, were synthesized in high yield by reacting turnings of elemental uranium with iodine dissolved in 1,4-dioxane under mild conditions. These molecular compounds of uranium are thermally stable and excellent precursor materials for synthesizing other molecular compounds of uranium including alkoxide, amide, organometallic, and halide compounds.

  9. Nitrodifluoraminoterphenyl compounds and processes

    DOEpatents

    Lerom, M.W.; Peters, H.M.

    1975-07-08

    This patent relates to the nitrodifluoraminoterphenyl compounds: 3,3''-bis (difluoramino)-2,2'' 4,4', 4'',6,6',6''-octanitro-m-terphenyl (DDONT) and 3,3''-bis(difluoramino)-2,2',2''4,4',4'',6,6',6''-nonanitro-m-terphenyl (DDNONA). Procedures are described wherein diamino precursors of the indicated compounds are prepared and the final compounds are obtained by a fluorination operation. The compounds are highly energetic and suitable for use as explosives and particularly in exploding bridge wire (EBW) detonators. (auth)

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

    PubMed

    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. PMID:26456389

  11. Block of NMDA receptor channels by endogenous neurosteroids: implications for the agonist induced conformational states of the channel vestibule

    PubMed Central

    Vyklicky, Vojtech; Krausova, Barbora; Cerny, Jiri; Balik, Ales; Zapotocky, Martin; Novotny, Marian; Lichnerova, Katarina; Smejkalova, Tereza; Kaniakova, Martina; Korinek, Miloslav; Petrovic, Milos; Kacer, Petr; Horak, Martin; Chodounska, Hana; Vyklicky, Ladislav

    2015-01-01

    N-methyl-D-aspartate receptors (NMDARs) mediate synaptic plasticity, and their dysfunction is implicated in multiple brain disorders. NMDARs can be allosterically modulated by numerous compounds, including endogenous neurosteroid pregnanolone sulfate. Here, we identify the molecular basis of the use-dependent and voltage-independent inhibitory effect of neurosteroids on NMDAR responses. The site of action is located at the extracellular vestibule of the receptor’s ion channel pore and is accessible after receptor activation. Mutations in the extracellular vestibule in the SYTANLAAF motif disrupt the inhibitory effect of negatively charged steroids. In contrast, positively charged steroids inhibit mutated NMDAR responses in a voltage-dependent manner. These results, in combination with molecular modeling, characterize structure details of the open configuration of the NMDAR channel. Our results provide a unique opportunity for the development of new therapeutic neurosteroid-based ligands to treat diseases associated with dysfunction of the glutamate system. PMID:26086919

  12. Myo-inositol esters of indole-3-acetic acid are endogenous components of Zea mays L. shoot tissue

    NASA Technical Reports Server (NTRS)

    Chisnell, J. R.

    1984-01-01

    Indole-3-acetyl-myo-inositol esters have been demonstrated to be endogenous components of etiolated Zea mays shoots tissue. This was accomplished by comparison of the putative compounds with authentic, synthetic esters. The properties compared were liquid and gas-liquid chromatographic retention times and the 70-ev mass spectral fragmentation pattern of the pentaacetyl derivative. The amount of indole-3-acetyl-myo-inositol esters in the shoots was determined to be 74 nanomoles per kilogram fresh weight as measured by isotope dilution, accounting for 19% of the ester indole-3-acetic acid of the shoot. This work is the first characterization of an ester conjugate of indole-3-acetate acid from vegetative shoot tissue using multiple chromatographic properties and mass spectral identification. The kernel and the seedling shoot both contain indole-3-acetyl-myo-inositol esters, and these esters comprise approximately the same percentage of the total ester content of the kernel and of the shoot.

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

    PubMed

    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

  14. Taurine Bromamine: Reactivity of an Endogenous and Exogenous Anti-Inflammatory and Antimicrobial Amino Acid Derivative

    PubMed Central

    Bertozo, Luiza De Carvalho; Morgon, Nelson Henrique; De Souza, Aguinaldo Robinson; Ximenes, Valdecir Farias

    2016-01-01

    Taurine bromamine (Tau-NHBr) is produced by the reaction between hypobromous acid (HOBr) and the amino acid taurine. There are increasing number of applications of Tau-NHBr as an anti-inflammatory and microbicidal drug for topical usage. Here, we performed a comprehensive study of the chemical reactivity of Tau-NHBr with endogenous and non-endogenous compounds. Tau-NHBr reactivity was compared with HOBr, hypochlorous acid (HOCl) and taurine chloramine (Tau-NHCl). The second-order rate constants (k2) for the reactions between Tau-NHBr and tryptophan (7.7 × 102 M−1s−1), melatonin (7.3 × 103 M−1s−1), serotonin (2.9 × 103 M−1s−1), dansylglycine (9.5 × 101 M−1s−1), tetramethylbenzidine (6.4 × 102 M−1s−1) and H2O2 (3.9 × M−1s−1) were obtained. Tau-NHBr demonstrated the following selectivity regarding its reactivity with free amino acids: tryptophan > cysteine ~ methionine > tyrosine. The reactivity of Tau-NHBr was strongly affected by the pH of the medium (for instance with dansylglycine: pH 5.0, 1.1 × 104 M−1s−1, pH 7.0, 9.5 × 10 M−1s−1 and pH 9.0, 1.7 × 10 M−1s−1), a property that is related to the formation of the dibromamine form at acidic pH (Tau-NBr2). The formation of singlet oxygen was observed in the reaction between Tau-NHBr and H2O2. Tau-NHBr was also able to react with linoleic acid, but with low efficiency compared with HOBr and HOCl. Compared with HOBr, Tau-NHBr was not able to react with nucleosides. In conclusion, the following reactivity sequence was established: HOBr > HOCl > Tau-NHBr > Tau-NHCl. These findings can be very helpful for researchers interested in biological applications of taurine haloamines. PMID:27110829

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

    PubMed Central

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

    2015-01-01

    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 (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 exposure

  16. Taurine Bromamine: Reactivity of an Endogenous and Exogenous Anti-Inflammatory and Antimicrobial Amino Acid Derivative.

    PubMed

    De Carvalho Bertozo, Luiza; Morgon, Nelson Henrique; De Souza, Aguinaldo Robinson; Ximenes, Valdecir Farias

    2016-01-01

    Taurine bromamine (Tau-NHBr) is produced by the reaction between hypobromous acid (HOBr) and the amino acid taurine. There are increasing number of applications of Tau-NHBr as an anti-inflammatory and microbicidal drug for topical usage. Here, we performed a comprehensive study of the chemical reactivity of Tau-NHBr with endogenous and non-endogenous compounds. Tau-NHBr reactivity was compared with HOBr, hypochlorous acid (HOCl) and taurine chloramine (Tau-NHCl). The second-order rate constants (k₂) for the reactions between Tau-NHBr and tryptophan (7.7 × 10² M(-1)s(-1)), melatonin (7.3 × 10³ M(-1)s(-1)), serotonin (2.9 × 10³ M(-1)s(-1)), dansylglycine (9.5 × 10¹ M(-1)s(-1)), tetramethylbenzidine (6.4 × 10² M(-1)s(-1)) and H₂O₂ (3.9 × M(-1)s(-1)) were obtained. Tau-NHBr demonstrated the following selectivity regarding its reactivity with free amino acids: tryptophan > cysteine ~ methionine > tyrosine. The reactivity of Tau-NHBr was strongly affected by the pH of the medium (for instance with dansylglycine: pH 5.0, 1.1 × 10⁴ M(-1)s(-1), pH 7.0, 9.5 × 10 M(-1)s(-1) and pH 9.0, 1.7 × 10 M(-1)s(-1)), a property that is related to the formation of the dibromamine form at acidic pH (Tau-NBr₂). The formation of singlet oxygen was observed in the reaction between Tau-NHBr and H₂O₂. Tau-NHBr was also able to react with linoleic acid, but with low efficiency compared with HOBr and HOCl. Compared with HOBr, Tau-NHBr was not able to react with nucleosides. In conclusion, the following reactivity sequence was established: HOBr > HOCl > Tau-NHBr > Tau-NHCl. These findings can be very helpful for researchers interested in biological applications of taurine haloamines. PMID:27110829

  17. Expression of UDP-Glucuronosyltransferase 1 (UGT1) and Glucuronidation Activity toward Endogenous Substances in Humanized UGT1 Mouse Brain

    PubMed Central

    Kutsuno, Yuki; Hirashima, Rika; Sakamoto, Masaya; Ushikubo, Hiroko; Michimae, Hirofumi; Itoh, Tomoo; Tukey, Robert H.

    2015-01-01

    Although UDP-glucuronosyltransferases (UGTs) are important phase II drug-metabolizing enzymes, they are also involved in the metabolism of endogenous compounds. Certain substrates of UGTs, such as serotonin and estradiol, play important roles in the brain. However, the expression of UGTs in the human brain has not been fully clarified. Recently, humanized UGT1 mice (hUGT1 mice) in which the original Ugt1 locus was disrupted and replaced with the human UGT1 locus have been developed. In the present study, the expression pattern of UGT1As in brains from humans and hUGT1 mice was examined. We found that UGT1A1, 1A3, 1A6, and 1A10 were expressed in human brains. The expression pattern of UGT1As in hUGT1 mouse brains was similar to that in human brains. In addition, we examined the expression of UGT1A1 and 1A6 in the cerebellum, olfactory bulbs, midbrain, hippocampus, and cerebral cortex of hUGT1 mice. UGT1A1 in all brain regions and UGT1A6 in the cerebellum and cerebral cortex of 6-month-old hUGT1 mice were expressed at a significantly higher rate than those of 2-week-old hUGT1 mice. A difference in expression levels between brain regions was also observed. Brain microsomes exhibited glucuronidation activities toward estradiol and serotonin, with mean values of 0.13 and 5.17 pmol/min/mg, respectively. In conclusion, UGT1A1 and UGT1A6 might play an important role in function regulation of endogenous compounds in a region- and age-dependent manner. Humanized UGT1 mice might be useful to study the importance of brain UGTs in vivo. PMID:25953521

  18. Melatonin and farm animals: endogenous rhythms and exogenous applications.

    PubMed

    Paterson, A M; Foldes, A

    1994-05-01

    Studies on farm animals have contributed significantly to our increased understanding of basic melatonin-related physiological mechanisms, as well as to the regulation of reproduction and pelage in individual domestic species. This review concentrates on recent work on the role of melatonin in the regulation of porcine reproduction, cervine endocrine, and behavioral cycles and wool and cashmere production which has added to this knowledge base. Early studies of the domestic pig indicated that melatonin secretion in this species differed markedly from that in other domestic and laboratory animals. There is now clear evidence that this is not the case and that the domestic pig uses a circadian rhythm of melatonin release for the transduction of photoperiodic information. Apparent inconsistencies among reports may be due, in part, to differences in the conditions under which the experiments were performed and to the assay systems employed to measure circulating melatonin, the concentrations of which are much lower than in other domestic species. Appropriately administered exogenous melatonin advances the onset of puberty in gilts, and may prove to be effective in overcoming seasonal infertility in female pigs. Appropriately timed melatonin and/or photoperiod treatments, administered to ruminants in utero, influence the reproductive physiology of the offspring, indicating that even in species which don't develop an endogenous melatonin rhythm till some weeks postnatally, awareness of photoenvironment, presumably via maternal melatonin, predates birth. Pre- or early postnatal melatonin-related treatments also influence the development/cycle frequency of pelage. Areas requiring further investigation include the hormonal/growth factors involved, reasons for the transient nature of the effects in sheep and goats, and the reason for similar effects on pelage of augmenting or inactivating melatonin. Aspects of endogenous melatonin rhythms in farm species which require

  19. Endogenous ethanol production in trauma victims associated with medical treatment.

    PubMed

    Moriya, F; Hashimoto, Y

    1996-08-01

    Four cases of trauma, where endogenous ethanol production was suspected to have been occurred in association with medical treatment, are reported. To discriminate endogenous ethanol produced de novo by bacteria from exogenous ethanol by drinking, various tissues and body fluids, such as brain and cerebrospinal fluid, together with blood obtained from various locations, were subjected to analysis for both ethanol and n-propanol. The first individual was a 40-year-old man who had been stabbed in the abdomen with a knife and had died of bleeding about 12 h after peritoneotomy, and autopsied 12 h later. In the heart blood, 0.44 mg/g ethanol and 0.005 mg/g n-propanol were detected. Ethanol levels in the cerebrospinal fluid, vitreous humor and brain, reflecting exogenous ethanol levels, were 0.08-0.16 mg/g, and no n-propanol was detected in any of the specimens. The second individual was a 45-year-old man who had been punched hard in the head and face and had died of traumatic shock about 12 h after hospitalization, and autopsied 12 h later. The heart blood concentrations of ethanol and n-propanol were 0.15 and 0.008 mg/g respectively, and a subdural hematoma contained only 0.05 mg/g ethanol and non n-propanol. The third individual was a 34-year-old man who suffered incised wounds of the left arm and head with a sickle and had died of hemorrhagic shock. In the heart blood, 0.30 mg/g ethanol and 0.026 mg/g n-propanol were detected; there was 0.04 mg/g ethanol and no n-propanol in the brain. The fourth individual was a 76-year-old woman who had been hit by a motorcycle and had died of liver rupture about 1 h after admission to a hospital. The heart blood contained 0.22 mg/g ethanol and 0.002 mg/g n-propanol. Only a trace of ethanol and no n-propanol were detected in the pericardial sac fluid and cerebrospinal fluid.

  20. Endogenous and exogenous progesterone influence body temperature in dairy cows.

    PubMed

    Suthar, V S; Burfeind, O; Bonk, S; Dhami, A J; Heuwieser, W

    2012-05-01

    Three experiments were conducted to determine the effect of endogenous progesterone (P4) on body temperature comparing lactating, pregnant with lactating, nonpregnant cows, and to study the effect of exogenous P4 administered via a controlled internal drug release (CIDR) insert on body temperature in lactating dairy cows. Body temperature was measured vaginally and rectally using temperature loggers and a digital thermometer, respectively. In experiment 1, 10 cyclic lactating cows (3 primiparous, 7 multiparous) and 10 lactating, pregnant cows (3 primiparous, 7 multiparous) were included. Vaginal temperatures and serum P4 concentrations were greater in pregnant cows (vaginal: 0.3±0.01°C; P4: 5.5±0.4 ng/mL) compared with nonpregnant cows. In experiment 2, estrous cycles of 14 postpartum healthy, cyclic, lactating cows (10 primiparous, 4 multiparous) were synchronized, and cows were assigned randomly to 1 of 2 treatments (CIDR-P4 or CIDR-blank). A temperature logger was inserted 1 d after ovulation using a P4-free CIDR (CIDR-blank) and a CIDR containing 1.38g of P4 (CIDR-P4) in the control (n=7) and the P4-treated group (n=7), respectively. On d 3 after P4 treatment, vaginal temperature was 0.3±0.03°C greater compared with that on d 1 and d 5. In experiment 3, 9 cyclic multiparous lactating cows were enrolled 1±1 d after confirmed ovulation and a temperature logger inserted. Two days later, a CIDR-P4 was inserted on top of the CIDR-blank. On d 5±1 and d 7±1, respectively, the CIDR-P4 and CIDR-blank with the temperature logger were removed. During the CIDR-P4 treatment (48h), vaginal temperature was 0.2±0.05°C and 0.1±0.05°C greater than during the pre- and post-treatment periods (48h), respectively. Serum P4 concentration peaked during CIDR-P4 treatment (2.2±0.8 ng/mL) and was greater than during the pre-treatment period (0.2±0.2 ng/mL) for 48h. An increase in vaginal temperature could be due to endogenous and exogenous P4. However, a correlation between

  1. Melatonin in Children with Autism Spectrum Disorders: Endogenous and Pharmacokinetic Profiles in Relation to Sleep

    ERIC Educational Resources Information Center

    Goldman, Suzanne E.; Adkins, Karen W.; Calcutt, M. Wade; Carter, Melissa D.; Goodpaster, Robert L.; Wang, Lily; Shi, Yaping; Burgess, Helen J.; Hachey, David L.; Malow, Beth A.

    2014-01-01

    Supplemental melatonin has been used to treat sleep onset insomnia in children with autism spectrum disorders (ASD), although the mechanism of action is uncertain. We assessed endogenous and supplemental melatonin profiles in relation to sleep in nine children with ASD. In endogenous samples, maximal melatonin concentration (C[subscript max]) and…

  2. [Do enkephalins and other endogenous opioids participate in regulation of cancer growth?].

    PubMed

    Kajdaniuk, D; Marek, B; Buntner, B; Zwirska-Korczala, K

    2000-01-01

    Attempts are interesting exploratory trend to define precisely relations between endogenous opioid system and neoplastic process development. Mechanism in which enkephalins and other endogenous opioides could influence on cancer growth is not clear. Several hypothesis were put and presented in the paper.

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

    ERIC Educational Resources Information Center

    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…

  4. Endogenous and exogenous ocular and systemic silver deposition.

    PubMed

    Spencer, W H; Garron, L K; Contreras, F; Hayes, T L; Lai, C

    1980-04-01

    The ocular distribution of particulate silver after prolonged ingestion and the topical application of an organic silver compound (argyrol) are described and compared with the distribution after long-term occupational contact with refined silver. The deposits appear to be inert and to cause no functional visual deficit.

  5. The Pharmacological Effects of S-Propargyl-Cysteine, a Novel Endogenous H2S-Producing Compound.

    PubMed

    Wen, Ya-Dan; Zhu, Yi-Zhun

    2015-01-01

    S-propargyl-cysteine (SPRC), also named as ZYZ-802, is a structural analog of S-allylcysteine (SAC), the most abundant constituent of aged garlic extract. SPRC becomes a derivative of the amino acid cysteine, which contains sulfur atom, by changing allyl group in SAC to propargyl group in SPRC. Another analog of SPRC and SAC is S-propyl cysteine (SPC), which has propyl group instead in its cysteine structure. Drug formulation of SPRC has been investigated in the mixture of extenders, such as lactose, microcrystalline cellulose, and cross-linked povidone, showing good fluidity and scale-up production possibility. Controlled release formulation of SPRC (CR-SPRC) and leonurine-SPRC were invented and shown the decent pharmacological effects in heart failure and hypoxia injury, respectively. The pharmacological effects of SPRC have been shown that cardioprotection and proangiogenesis in several ischemic heart models, neuroprotection in Alzheimer's disease, proapoptosis in gastric cancer and anti-inflammation in acute pancreatitis. Moreover, CR-SPRC reduced infarct size and recovered partial cardiac function in heart failure rat model. Leonurine-SPRC protected hypoxic neonatal rat ventricular myocytes in much lower dose. Interestingly, since the propagyl group in SPRC has the stronger chemical bond in the cysteine structure than allyl group in SAC and propyl group in SPC, SPRC showed more extensive cardioprotection in ischemic rat hearts model compared to SAC and SPC. The mechanisms of pharmacological effects of SPRC have been unveiled that SPRC reduced Ca2+ accumulation, activated antioxidants, inhibited STAT3, decreased inflammatory cytokines, and elevated p53 and Bax. More pharmacological effects and mechanisms of SPRC will be discovered in atherosclerosis, hypertension, and other diseases.

  6. The Pharmacological Effects of S-Propargyl-Cysteine, a Novel Endogenous H2S-Producing Compound.

    PubMed

    Wen, Ya-Dan; Zhu, Yi-Zhun

    2015-01-01

    S-propargyl-cysteine (SPRC), also named as ZYZ-802, is a structural analog of S-allylcysteine (SAC), the most abundant constituent of aged garlic extract. SPRC becomes a derivative of the amino acid cysteine, which contains sulfur atom, by changing allyl group in SAC to propargyl group in SPRC. Another analog of SPRC and SAC is S-propyl cysteine (SPC), which has propyl group instead in its cysteine structure. Drug formulation of SPRC has been investigated in the mixture of extenders, such as lactose, microcrystalline cellulose, and cross-linked povidone, showing good fluidity and scale-up production possibility. Controlled release formulation of SPRC (CR-SPRC) and leonurine-SPRC were invented and shown the decent pharmacological effects in heart failure and hypoxia injury, respectively. The pharmacological effects of SPRC have been shown that cardioprotection and proangiogenesis in several ischemic heart models, neuroprotection in Alzheimer's disease, proapoptosis in gastric cancer and anti-inflammation in acute pancreatitis. Moreover, CR-SPRC reduced infarct size and recovered partial cardiac function in heart failure rat model. Leonurine-SPRC protected hypoxic neonatal rat ventricular myocytes in much lower dose. Interestingly, since the propagyl group in SPRC has the stronger chemical bond in the cysteine structure than allyl group in SAC and propyl group in SPC, SPRC showed more extensive cardioprotection in ischemic rat hearts model compared to SAC and SPC. The mechanisms of pharmacological effects of SPRC have been unveiled that SPRC reduced Ca2+ accumulation, activated antioxidants, inhibited STAT3, decreased inflammatory cytokines, and elevated p53 and Bax. More pharmacological effects and mechanisms of SPRC will be discovered in atherosclerosis, hypertension, and other diseases. PMID:26162842

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

    PubMed

    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.

  8. Endogenous and exogenous ligands of aryl hydrocarbon receptor: current state of art.

    PubMed

    Stejskalova, Lucie; Dvorak, Zdenek; Pavek, Petr

    2011-02-01

    Aryl hydrocarbon receptor (AhR) is an important transcriptional regulator of drug metabolizing enzymes that dominantly controls the expression of cytochrome P450 CYP1 family genes and some phase II enzymes. AhR also has many endogenous functions including cell cycle control, immune response, and cell differentiation. In addition, AhR is well-known to be involved in chemically-induced carcinogenesis. AhR is activated by a variety of endogenous and exogenous ligands. While exogenous activation of AhR has deleterious effects on human organism, sustained activation of AhR by endogenous ligands is indispensable for proper cell functions. Therefore, the effects of exogenous and endogenous ligands on AhR resemble the Dr. Jekyll and Mr. Hyde story. The aim of the current paper is to summarize and update the knowledge on exogenous and endogenous AhR ligands. PMID:21395538

  9. A novel endogenous betaretrovirus group characterized from polar bears (Ursus maritimus) and giant pandas (Ailuropoda melanoleuca).

    PubMed

    Mayer, Jens; Tsangaras, Kyriakos; Heeger, Felix; Avila-Arcos, María; Stenglein, Mark D; Chen, Wei; Sun, Wei; Mazzoni, Camila J; Osterrieder, Nikolaus; Greenwood, Alex D

    2013-08-15

    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. 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 history within the HERV-K group. All individual remnants of proviral sequences contain numerous frameshifts and stop codons and thus, the virus is likely non-infectious.

  10. Endogenous Asymmetric Dimethylarginine Pathway in High Altitude Adapted Yaks

    PubMed Central

    Mizuno, Shiro; Ishizaki, Takeshi; Toga, Hirohisa; Sakai, Akio; Isakova, Jainagul; Taalaibekova, Elnura; Baiserkeev, Zamirbek; Kojonazarov, Baktybek; Aldashev, Almaz

    2015-01-01

    Hypoxia-induced and high altitude pulmonary hypertension are a major problem in the mountain areas of the world. The asymmetric methylarginines (ADMA) inhibit nitric oxide (NO) synthesis by competing with L-arginine, and high levels of plasma ADMA predict adverse outcomes in pulmonary hypertension. However, little is known about the regulation of the ADMA-NO pathway in animals adapted to high altitudes. We measured the plasma ADMA concentration, endothelial NO synthase (eNOS), dimethylarginine dimethylaminohydrolases (DDAH) protein expression, and DDAH activities in the lungs from yaks. Although the yaks are hypoxemic, cardiac function and pulmonary arterial pressures are almost normal, and we found decreased DDAH expression and activity in association with reduced plasma ADMA concentrations. The eNOS expression was significantly higher in yaks. These results indicate that augmented endogenous NO activity in yaks through the ADMA-DDAH pathway and eNOS upregulation account for the low pulmonary vascular tone observed in high altitude adapted yaks. PMID:26380264

  11. Glucose Oscillations Can Activate an Endogenous Oscillator in Pancreatic Islets

    PubMed Central

    Mukhitov, Nikita; Roper, Michael G.; Bertram, Richard

    2016-01-01

    Pancreatic islets manage elevations in blood glucose level by secreting insulin into the bloodstream in a pulsatile manner. Pulsatile insulin secretion is governed by islet oscillations such as bursting electrical activity and periodic Ca2+ entry in β-cells. In this report, we demonstrate that although islet oscillations are lost by fixing a glucose stimulus at a high concentration, they may be recovered by subsequently converting the glucose stimulus to a sinusoidal wave. We predict with mathematical modeling that the sinusoidal glucose signal’s ability to recover islet oscillations depends on its amplitude and period, and we confirm our predictions by conducting experiments with islets using a microfluidics platform. Our results suggest a mechanism whereby oscillatory blood glucose levels recruit non-oscillating islets to enhance pulsatile insulin output from the pancreas. Our results also provide support for the main hypothesis of the Dual Oscillator Model, that a glycolytic oscillator endogenous to islet β-cells drives pulsatile insulin secretion. PMID:27788129

  12. Ethanol Tolerance Affects Endogenous Adenosine Signaling in Mouse Hippocampus.

    PubMed

    Zhang, Dali; Xiong, Wei; Jackson, Michael F; Parkinson, Fiona E

    2016-07-01

    Ethanol has many pharmacological effects, including increases in endogenous adenosine levels and adenosine receptor activity in brain. Ethanol consumption is associated with both positive and negative health outcomes, but tolerance to the behavioral effects of ethanol can lead to increased consumption, which increases the risk of negative health outcomes. The present study was performed to test whether a 7-day treatment with ethanol is linked to reduced adenosine signaling and whether this is a consequence of reduced ecto-5'-nucleotidase activity. Wild-type (CD73(+/+)) and ecto-5'-nucleotidase-deficient (CD73(-/-)) mice were treated with ethanol (2 g/kg) or saline for 7 days. In CD73(+/+) mice, repeated ethanol treatment reduced the hypothermic and ataxic effects of acute ethanol, indicating the development of tolerance to the acute effects of ethanol. In CD73(+/+) mice, this 7-day ethanol treatment led to increased hippocampal synaptic activity and reduced adenosine A1 receptor activity under both basal and low Mg(2+) conditions. These effects of ethanol tolerance were associated with an 18% decrease in activity of ecto-5'-nucleotidase activity in hippocampal cell membranes. In contrast, ethanol treatment was not associated with changes in synaptic activity or adenosine signaling in hippocampus from CD73(-/-) mice. These data indicate that ethanol treatment is associated with a reduction in adenosine signaling through adenosine A1 receptors in hippocampus, mediated, at least in part, via reduced ecto-5'-nucleotidase activity. PMID:27189965

  13. [Neuropeptide thyroliberin--an endogenous anticonvulsant in the brain].

    PubMed

    Chepurnov, S A; Chepurnova, N E; Abbasova, K R; Goncharov, O B

    2002-01-01

    Thyroliberin (TRH) promoting endogenous antidepressive effect is the most general regulator of the central mechanisms and visceral functions (especially respiration). Our group pioneered in applying the anticonvulsant action of TRH after local intranasal application. This application TRH in ultra-low doses contrast the method of systemic TRH administration (i.v., i.m. or oral in the large doses--mg). In our experiments intranasal application of 10(-9) M, 10(-10) M and 10(-12) M TRH significantly inhibited the severe epileptic motor fits in rats induced by pentylenetetrazole (PTZ). Beneficent effect of TRH is also confirmed by EEG (TRH suppressed SWD in cortex, amygdala and hippocamp). In the experiment that follows compared effects of TRH (pyroGlu-His-Pro-NH2) and its metabolite dipeptide cHis-Pro-NH2 (10(-10) M, 10(-5) M). The experiments make more precise that only TRH but not His-Pro posses the anticonvulsant properties. There is a good believe that medical potentialities of TRH have not been exhausted and its new possibilities of its usage will be revealed in epileptology. PMID:11881332

  14. Endogenous nociceptin system involvement in stress responses and anxiety behavior.

    PubMed

    Fulford, Allison Jane

    2015-01-01

    The mechanisms underpinning stress-related behavior and dysfunctional events leading to the expression of neuropsychiatric disorders remain incompletely understood. Novel candidates involved in the neuromodulation of stress, mediated both peripherally and centrally, provide opportunities for improved understanding of the neurobiological basis of stress disorders and may represent targets for novel therapeutic development. This chapter provides an overview of the mechanisms by which the opioid-related peptide, nociceptin, regulates the neuroendocrine stress response and stress-related behavior. In our research, we have employed nociceptin receptor antagonists to investigate endogenous nociceptin function in tonic control over stress-induced activity of the hypothalamo-pituitary-adrenal axis. Nociceptin demonstrates a wide range of functions, including modulation of psychological and inflammatory stress responses, modulation of neurotransmitter release, immune homeostasis, in addition to anxiety and cognitive behaviors. Greater appreciation of the complexity of limbic-hypothalamic neuronal networks, together with attention toward gender differences and the roles of steroid hormones, provides an opportunity for deeper understanding of the importance of the nociceptin system in the context of the neurobiology of stress and behavior.

  15. Copper is an endogenous modulator of neural circuit spontaneous activity

    PubMed Central

    Dodani, Sheel C.; Firl, Alana; Chan, Jefferson; Nam, Christine I.; Aron, Allegra T.; Onak, Carl S.; Ramos-Torres, Karla M.; Paek, Jaeho; Webster, Corey M.; Feller, Marla B.; Chang, Christopher J.

    2014-01-01

    For reasons that remain insufficiently understood, the brain requires among the highest levels of metals in the body for normal function. The traditional paradigm for this organ and others is that fluxes of alkali and alkaline earth metals are required for signaling, but transition metals are maintained in static, tightly bound reservoirs for metabolism and protection against oxidative stress. Here we show that copper is an endogenous modulator of spontaneous activity, a property of functional neural circuitry. Using Copper Fluor-3 (CF3), a new fluorescent Cu+ sensor for one- and two-photon imaging, we show that neurons and neural tissue maintain basal stores of loosely bound copper that can be attenuated by chelation, which define a labile copper pool. Targeted disruption of these labile copper stores by acute chelation or genetic knockdown of the CTR1 (copper transporter 1) copper channel alters the spatiotemporal properties of spontaneous activity in developing hippocampal and retinal circuits. The data identify an essential role for copper neuronal function and suggest broader contributions of this transition metal to cell signaling. PMID:25378701

  16. Two endogenous proteins that induce cell wall extension in plants

    NASA Technical Reports Server (NTRS)

    McQueen-Mason, S.; Durachko, D. M.; Cosgrove, D. J.

    1992-01-01

    Plant cell enlargement is regulated by wall relaxation and yielding, which is thought to be catalyzed by elusive "wall-loosening" enzymes. By employing a reconstitution approach, we found that a crude protein extract from the cell walls of growing cucumber seedlings possessed the ability to induce the extension of isolated cell walls. This activity was restricted to the growing region of the stem and could induce the extension of isolated cell walls from various dicot stems and the leaves of amaryllidaceous monocots, but was less effective on grass coleoptile walls. Endogenous and reconstituted wall extension activities showed similar sensitivities to pH, metal ions, thiol reducing agents, proteases, and boiling in methanol or water. Sequential HPLC fractionation of the active wall extract revealed two proteins with molecular masses of 29 and 30 kD associated with the activity. Each protein, by itself, could induce wall extension without detectable hydrolytic breakdown of the wall. These proteins appear to mediate "acid growth" responses of isolated walls and may catalyze plant cell wall extension by a novel biochemical mechanism.

  17. An Eleven-Year Retrospective Study of Endogenous Bacterial Endophthalmitis

    PubMed Central

    Nishida, Takashi; Ishida, Kyoko; Niwa, Yoshiaki; Kawakami, Hideaki; Mochizuki, Kiyofumi; Ohkusu, Kiyofumi

    2015-01-01

    Purpose. To determine the clinical features, microbial profiles, treatment outcomes, and prognostic factors for endogenous bacterial endophthalmitis (EBE). Methods. The medical records of 27 eyes of 21 patients diagnosed with EBE for 11 years were reviewed. Collected data included age, site of infection, visual acuities (VAs), microbial profiles, and treatment regimen. Results. The mean age was 68.5 years. Gram-positive organisms accounted for 76.2%, while gram-negative ones accounted for 19.0%. Staphylococcus aureus was the most common causative organism (52.3%) of which 72.7% was methicillin-resistant S. aureus. A final VA of ≥20/40 was achieved in 44% and 20/200 or better was in 64%. Eyes with initial VA of ≥20/200 (P = 0.003) and focal involvements (P = 0.011) had significantly better final VA. Initial VA (P = 0.001) and the interval between onset of ocular symptoms and intravitreal antibiotic injection (P = 0.097) were associated with final VA in eyes receiving intravitreal antibiotics. Conclusions. EBE is generally associated with poor visual outcome; however the prognosis may depend on initial VA, extent of ocular involvement, and an interval between onset of ocular symptoms and intravitreal antibiotic injection. Early diagnosis and early intravitreal injection supplement to systemic antibiotics might lead to a relatively good visual outcome. PMID:25802752

  18. Endogenous lipolytic activities during autolysis of highly enriched hepatic lysosomes.

    PubMed

    Beckman, J K; Owens, K; Weglicki, W B

    1981-11-01

    High enriched (50- to 70-fold) fractions of "native" lysosomes were isolated using continuous flow electrophoresis from livers of rats which had not been pretreated with Triton WR-1339. Incubation of lysosomes for 30 min at pH 5.0 in the presence of 5 mM EDTA resulted in a dramatic loss in the content of fatty acids bound to triacylglycerols (137 down to 10 mumol/mg protein) and to phospholipids and an elevation in the level of unesterified fatty acid. Phosphatidylcholine, phosphatidylethanolamine and sphingomyelin concentrations decreased whereas those of lysophosphatidylethanolamine (0.8 up to 8.5% of total lipid-P) and lysophosphatidylcholine (1.9 up to 16.7%) rose in a manner parallel to their respective, fully acylated lipids. Other phospholipids, including phosphatidylinositol, did not change in concentration during incubation. These results indicate that lysosomal phospholipase A, sphingomyelin and triacylglycerol lipase are activated by incubation at acid pH, enabling them to hydrolyze endogenous lysosomal lipids. However, lysosomal phosphatidylinositol-directed phospholipase C is apparently unable to interact with phosphatidylinositol of the lysosomal membrane. PMID:7311738

  19. Endogenous Groups and Dynamic Selection in Mechanism Design*

    PubMed Central

    Madeira, Gabriel A.; Townsend, Robert M.

    2010-01-01

    We create a dynamic theory of endogenous risk sharing groups, with good internal information, and their coexistence with relative performance, individualistic regimes, which are informationally more opaque. Inequality and organizational form are determined simultaneously. Numerical techniques and succinct re-formulations of mechanism design problems with suitable choice of promised utilities allow the computation of a stochastic steady state and its transitions. Regions of low inequality and moderate to high wealth (utility promises) produce the relative performance regime, while regions of high inequality and low wealth produce the risk sharing group regime. If there is a cost to prevent coalitions, risk sharing groups emerge at high wealth levels also. Transitions from the relative performance regime to the group regime tend to occur when rewards to observed outputs exacerbate inequality, while transitions from the group regime to the relative performance regime tend to come with a decrease in utility promises. Some regions of inequality and wealth deliver long term persistence of organization form and inequality, while other regions deliver high levels of volatility. JEL Classification Numbers: D23,D71,D85,O17. PMID:20107614

  20. Lung Regeneration: Endogenous and Exogenous Stem Cell Mediated Therapeutic Approaches.

    PubMed

    Akram, Khondoker M; Patel, Neil; Spiteri, Monica A; Forsyth, Nicholas R

    2016-01-19

    The tissue turnover of unperturbed adult lung is remarkably slow. However, after injury or insult, a specialised group of facultative lung progenitors become activated to replenish damaged tissue through a reparative process called regeneration. Disruption in this process results in healing by fibrosis causing aberrant lung remodelling and organ dysfunction. Post-insult failure of regeneration leads to various incurable lung diseases including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. Therefore, identification of true endogenous lung progenitors/stem cells, and their regenerative pathway are crucial for next-generation therapeutic development. Recent studies provide exciting and novel insights into postnatal lung development and post-injury lung regeneration by native lung progenitors. Furthermore, exogenous application of bone marrow stem cells, embryonic stem cells and inducible pluripotent stem cells (iPSC) show evidences of their regenerative capacity in the repair of injured and diseased lungs. With the advent of modern tissue engineering techniques, whole lung regeneration in the lab using de-cellularised tissue scaffold and stem cells is now becoming reality. In this review, we will highlight the advancement of our understanding in lung regeneration and development of stem cell mediated therapeutic strategies in combating incurable lung diseases.

  1. Involvement of endogenous neuromedin U and neuromedin S in thermoregulation.

    PubMed

    Nakahara, Keiko; Akagi, Ai; Shimizu, Seiya; Tateno, Satoshi; Qattali, Abdul Wahid; Mori, Kenji; Miyazato, Mikiya; Kangawa, Kenji; Murakami, Noboru

    2016-02-19

    We investigated the possible involvement of neuromedin U (NMU) and neuromedin S (NMS) in thermoregulation in rats. Intracerebroventricular (icv) injection of NMU or NMS increased the back surface temperature (BS-T) in a dose-dependent manner during both the light and dark periods. Pre-treatment with the β3 blocker SR59230A, and the cyclooxygenase blocker indomethacin, inhibited the increase in BS-T induced by NMS. Icv injection of NMS and NMU increased the expression of mRNAs for prostaglandin E synthase and cyclooxygenase 2 (COX2) in the hypothalamus, and that of mRNA for uncoupling protein 1 (UCP1) in the brown adipose tissue. Comparison of thermogenesis in terms of body temperature under normal and cold conditions revealed that NMS-KO and double-KO mice had a significantly low BS-T during the active phase, whereas NMU-KO mice did not. Exposure to low temperature decreased the BS temperature in all KO mice, but BS-T was lower in NMS-KO and double-KO mouse than in NMU-KO mice. Calorie and oxygen consumption was also significantly lower in all KO mice than in wild-type mice during the dark period. These results suggest that NMU and NMS are involved in thermoregulation via the prostaglandin E2 and β3 adrenergic receptors, but that endogenous NMS might play a more predominant role than NMU.

  2. Opening of Iris flowers is regulated by endogenous auxins.

    PubMed

    van Doorn, Wouter G; Dole, Isabelle; Celikel, Fisun G; Harkema, Harmannus

    2013-01-15

    Flower opening in Iris (Iris×hollandica) requires elongation of the pedicel and ovary. This moves the floral bud upwards, thereby allowing the tepals to move laterally. Flower opening is requires with elongation of the pedicel and ovary. In cv. Blue Magic, we investigated the possible role of hormones other than ethylene in pedicel and ovary elongation and flower opening. Exogenous salicylic acid (SA) and the cytokinins benzyladenine (N6-benzyladenine, BA) and zeatin did not affect opening. Jasmonic acid (JA) and abscisic acid (ABA) were slightly inhibitory, but an inhibitor of ABA synthesis (norflurazon) was without effect. Flower opening was promoted by gibberellic acid (GA(3)), but two inhibitors of gibberellin synthesis (4-hydroxy-5-isopropyl-2-methylphenyltrimethyl ammonium chloride-1-piperidine carboxylate, AMO-1618; ancymidol) did not change opening. The auxins indoleacetic acid (IAA) and naphthaleneacetic acid (NAA) strongly promoted elongation and opening. An inhibitor of auxin transport (2,3,5-triodobenzoic acid, TIBA) and an inhibitor of auxin effects [α-(p-chlorophenoxy)-isobutyric acid; PCIB] inhibited elongation and opening. The data suggest that endogenous auxins are among the regulators of the pedicel and ovary elongation and thus of flower opening in Iris. PMID:23218543

  3. Endogenous ethanol affects biopolyester molecular weight in recombinant Escherichia coli.

    PubMed

    Hiroe, Ayaka; Hyakutake, Manami; Thomson, Nicholas M; Sivaniah, Easan; Tsuge, Takeharu

    2013-11-15

    In biopolyester synthesis, polyhydroxyalkanoate (PHA) synthase (PhaC) catalyzes the polymerization of PHA in bacterial cells, followed by a chain transfer (CT) reaction in which the PHA polymer chain is transferred from PhaC to a CT agent. Accordingly, the frequency of CT reaction determines PHA molecular weight. Previous studies have shown that exogenous alcohols are effective CT agents. This study aimed to clarify the effect of endogenous ethanol as a CT agent for poly[(R)-3-hydroxybutyrate] [P(3HB)] synthesis in recombinant Escherichia coli, by comparing with that of exogenous ethanol. Ethanol supplementation to the culture medium reduced P(3HB) molecular weights by up to 56% due to ethanol-induced CT reaction. NMR analysis of P(3HB) polymers purified from the culture supplemented with (13)C-labeled ethanol showed the formation of a covalent bond between ethanol and P(3HB) chain at the carboxyl end. Cultivation without ethanol supplementation resulted in the reduction of P(3HB) molecular weight with increasing host-produced ethanol depending on culture aeration. On the other hand, production in recombinant BW25113(ΔadhE), an alcohol dehydrogenase deletion strain, resulted in a 77% increase in molecular weight. Analysis of five E. coli strains revealed that the estimated number of CT reactions was correlated with ethanol production. These results demonstrate that host-produced ethanol acts as an equally effective CT agent as exogenous ethanol, and the control of ethanol production is important to regulate the PHA molecular weight.

  4. Curbing Inflammation through Endogenous Pathways: Focus on Melanocortin Peptides

    PubMed Central

    Ahmed, Tazeen J.; Montero-Melendez, Trinidad; Perretti, Mauro; Pitzalis, Costantino

    2013-01-01

    The resolution of inflammation is now known to be an active process, armed with a multitude of mediators both lipid and protein in nature. Melanocortins are peptides endowed with considerable promise with their proresolution and anti-inflammatory effects in preclinical models of inflammatory disease, with tissue protective effects. These peptides and their targets are appealing because they can be seen as a natural way of inducing these effects as they harness endogenous pathways of control. Whereas most of the information generated about these mediators derives from several acute models of inflammation (such as zymosan induced peritonitis), there is some indication that these mediators may inhibit chronic inflammation by modulating cytokines, chemokines, and leukocyte apoptosis. In addition, proresolving mediators and their mimics have often been tested alongside therapeutic protocols, hence have been tested in settings more relevant to real life clinical scenarios. We provide here an overview on some of these mediators with a focus on melanocortin peptides and receptors, proposing that they may unveil new opportunities for innovative treatments of inflammatory arthritis. PMID:23738228

  5. Interchromosomal gene conversion at an endogenous human cell locus.

    PubMed Central

    Quintana, P J; Neuwirth, E A; Grosovsky, A J

    2001-01-01

    To examine the relationship between gene conversion and reciprocal exchange at an endogenous chromosomal locus, we developed a reversion assay in a thymidine kinase deficient mutant, TX545, derived from the human lymphoblastoid cell line TK6. Selectable revertants of TX545 can be generated through interchromosomal gene conversion at the site of inactivating mutations on each tk allele or by reciprocal exchange that alters the linkage relationships of inactivating polymorphisms within the tk locus. Analysis of loss of heterozygosity (LOH) at intragenic polymorphisms and flanking microsatellite markers was used to initially evaluate allelotypes in TK(+) revertants for patterns associated with either gene conversion or crossing over. The linkage pattern in a subset of convertants was then unambiguously established, even in the event of prereplicative recombinational exchanges, by haplotype analysis of flanking microsatellite loci in tk(-/-) LOH mutants collected from the tk(+/-) parental convertant. Some (7/38; 18%) revertants were attributable to easily discriminated nonrecombinational mechanisms, including suppressor mutations within the tk coding sequence. However, all revertants classified as a recombinational event (28/38; 74%) were attributed to localized gene conversion, representing a highly significant preference (P < 0.0001) over gene conversion with associated reciprocal exchange, which was never observed. PMID:11404339

  6. Endogenous and exogenous control of gametogenesis and spawning in echinoderms.

    PubMed

    Mercier, Annie; Hamel, Jean-François

    2009-01-01

    Most echinoderms display seasonal or other temporal cycles of reproduction that presumably result from the complex interplay of endogenous and exogenous signals. Various environmental, chemical and hormonal factors, acting directly or indirectly, individually or in combination, have been proposed to cue, favour or modulate a suite of reproductive functions from the onset of gametogenesis to gamete release. From as early as the nineteenth century, an astonishing array of studies has been published on topics related to the control of reproduction in echinoderms, ranging from fortuitous behavioural observations to complex experimental demonstrations and molecular analyses. Although the exact pathways involved in the perception of external signals and their transduction into coordinated spawning events remain obscure for most species, significant advances have been made that shed new light on the information gathered over decades of research. By compiling the existing literature (over 1000 references), interpreting the main results, critically assessing the methodologies used and reviewing the emerging hypotheses, we endeavour to draw a clearer picture of the existing knowledge and to provide a framework for future investigation of the mechanisms that underlie reproductive strategies in echinoderms and, by extension, in other marine invertebrates.

  7. Discovery of unfixed endogenous retrovirus insertions in diverse human populations

    PubMed Central

    Wildschutte, Julia Halo; Williams, Zachary H.; Montesion, Meagan; Subramanian, Ravi P.; Kidd, Jeffrey M.; Coffin, John M.

    2016-01-01

    Endogenous retroviruses (ERVs) have contributed to more than 8% of the human genome. The majority of these elements lack function due to accumulated mutations or internal recombination resulting in a solitary (solo) LTR, although members of one group of human ERVs (HERVs), HERV-K, were recently active with members that remain nearly intact, a subset of which is present as insertionally polymorphic loci that include approximately full-length (2-LTR) and solo-LTR alleles in addition to the unoccupied site. Several 2-LTR insertions have intact reading frames in some or all genes that are expressed as functional proteins. These properties reflect the activity of HERV-K and suggest the existence of additional unique loci within humans. We sought to determine the extent to which other polymorphic insertions are present in humans, using sequenced genomes from the 1000 Genomes Project and a subset of the Human Genome Diversity Project panel. We report analysis of a total of 36 nonreference polymorphic HERV-K proviruses, including 19 newly reported loci, with insertion frequencies ranging from <0.0005 to >0.75 that varied by population. Targeted screening of individual loci identified three new unfixed 2-LTR proviruses within our set, including an intact provirus present at Xq21.33 in some individuals, with the potential for retained infectivity. PMID:27001843

  8. Copper is an endogenous modulator of neural circuit spontaneous activity.

    PubMed

    Dodani, Sheel C; Firl, Alana; Chan, Jefferson; Nam, Christine I; Aron, Allegra T; Onak, Carl S; Ramos-Torres, Karla M; Paek, Jaeho; Webster, Corey M; Feller, Marla B; Chang, Christopher J

    2014-11-18

    For reasons that remain insufficiently understood, the brain requires among the highest levels of metals in the body for normal function. The traditional paradigm for this organ and others is that fluxes of alkali and alkaline earth metals are required for signaling, but transition metals are maintained in static, tightly bound reservoirs for metabolism and protection against oxidative stress. Here we show that copper is an endogenous modulator of spontaneous activity, a property of functional neural circuitry. Using Copper Fluor-3 (CF3), a new fluorescent Cu(+) sensor for one- and two-photon imaging, we show that neurons and neural tissue maintain basal stores of loosely bound copper that can be attenuated by chelation, which define a labile copper pool. Targeted disruption of these labile copper stores by acute chelation or genetic knockdown of the CTR1 (copper transporter 1) copper channel alters the spatiotemporal properties of spontaneous activity in developing hippocampal and retinal circuits. The data identify an essential role for copper neuronal function and suggest broader contributions of this transition metal to cell signaling.

  9. Influence of endogenous prostaglandins on mTAL injury.

    PubMed

    Silva, P; Rosen, S; Spokes, K; Taylor, M; Epstein, F H

    1990-11-01

    We altered renal prostaglandin production by isolated rat kidneys in several ways to see if this would influence the susceptibility of cells lining the medullary thick ascending limb to injury. Rats were fed a diet containing either safflower oil (high in linoleic acid) or fish oil (low in arachidonate precursors) as a source of fat. After 90 min of perfusion, the kidneys of rats fed safflower oil showed only 32.7 +/- 6.7% of medullary thick ascending limb cells near the inner medulla with severe damage, whereas the same zone in perfused kidneys of rats fed fish oil showed 96.6 +/- 1.3% severely damaged cells (P less than 0.01). The protection afforded by safflower oil was accompanied by a doubling of urinary excretion of PGE2 and 6-keto-PGF1 alpha, and was eliminated by indomethacin, which suppressed prostaglandin synthesis. Perfusion with bradykinin also greatly increased prostaglandin excretion and reduced severe medullary thick ascending limb damage in the deepest zone of the outer medulla from 51.3 +/- 6.6% in controls to 28.5 +/- 5.9% (P less than 0.02). The protection provided by bradykinin was also completely reversed by indomethacin. The results suggest that endogenous prostaglandins serve a protective function against hypoxic injury for cells of the medullary thick ascending limb.

  10. Deletion of endogenous Tau proteins is not detrimental in Drosophila.

    PubMed

    Burnouf, Sylvie; Grönke, Sebastian; Augustin, Hrvoje; Dols, Jacqueline; Gorsky, Marianna Karina; Werner, Jennifer; Kerr, Fiona; Alic, Nazif; Martinez, Pedro; Partridge, Linda

    2016-01-01

    Human Tau (hTau) is a highly soluble and natively unfolded protein that binds to microtubules within neurons. Its dysfunction and aggregation into insoluble paired helical filaments is involved in the pathogenesis of Alzheimer's disease (AD), constituting, together with accumulated β-amyloid (Aβ) peptides, a hallmark of the disease. Deciphering both the loss-of-function and toxic gain-of-function of hTau proteins is crucial to further understand the mechanisms leading to neurodegeneration in AD. As the fruit fly Drosophila melanogaster expresses Tau proteins (dTau) that are homologous to hTau, we aimed to better comprehend dTau functions by generating a specific tau knock-out (KO) fly line using homologous recombination. We observed that the specific removal of endogenous dTau proteins did not lead to overt, macroscopic phenotypes in flies. Indeed, survival, climbing ability and neuronal function were unchanged in tau KO flies. In addition, we did not find any overt positive or negative effect of dTau removal on human Aβ-induced toxicity. Altogether, our results indicate that the absence of dTau proteins has no major functional impact on flies, and suggests that our tau KO strain is a relevant model to further investigate the role of dTau proteins in vivo, thereby giving additional insights into hTau functions.

  11. Endogenous lipoid pneumonia in a cachectic patient after brain injury.

    PubMed

    Zhang, Ji; Mu, Jiao; Lin, Wei; Dong, Hongmei

    2015-01-01

    Endogenous lipoid pneumonia (EnLP) is an uncommon non-life-threatening inflammatory lung disease that usually occurs in patients with conditions such as lung cancers, primary sclerosing cholangitis, and undifferentiated connective tissue disease. Here we report a case of EnLP in a paralytic and cachectic patient with bronchopneumonia after brain injury. A 40-year-old man experienced a severe brain injury in an automobile accident. He was treated for 1 month and his status plateaued. However, he became paralyzed and developed cachexia and ultimately died 145 days after the accident. Macroscopically, multifocal yellowish firm nodules were visible on scattered gross lesions throughout the lungs. Histologically, many foam cells had accumulated within the alveoli and alveolar walls accompanied by a surrounding interstitial infiltration of lymphocytes. The findings were in accordance with a diagnosis of EnLP. Bronchopneumonia was also noted. To our knowledge, there have been few reports of EnLP associated with bronchopneumonia and cachexia after brain injury. This uncommon pathogenesis should be well recognized by clinicians and forensic pathologists. The case reported here should prompt medical staff to increase the nutritional status and fight pulmonary infections in patients with brain injury to prevent the development of EnLP. PMID:26097618

  12. Ethanol Tolerance Affects Endogenous Adenosine Signaling in Mouse Hippocampus

    PubMed Central

    Zhang, Dali; Xiong, Wei; Jackson, Michael F.

    2016-01-01

    Ethanol has many pharmacological effects, including increases in endogenous adenosine levels and adenosine receptor activity in brain. Ethanol consumption is associated with both positive and negative health outcomes, but tolerance to the behavioral effects of ethanol can lead to increased consumption, which increases the risk of negative health outcomes. The present study was performed to test whether a 7-day treatment with ethanol is linked to reduced adenosine signaling and whether this is a consequence of reduced ecto-5′-nucleotidase activity. Wild-type (CD73+/+) and ecto-5′-nucleotidase-deficient (CD73−/−) mice were treated with ethanol (2 g/kg) or saline for 7 days. In CD73+/+ mice, repeated ethanol treatment reduced the hypothermic and ataxic effects of acute ethanol, indicating the development of tolerance to the acute effects of ethanol. In CD73+/+ mice, this 7-day ethanol treatment led to increased hippocampal synaptic activity and reduced adenosine A1 receptor activity under both basal and low Mg2+ conditions. These effects of ethanol tolerance were associated with an 18% decrease in activity of ecto-5′-nucleotidase activity in hippocampal cell membranes. In contrast, ethanol treatment was not associated with changes in synaptic activity or adenosine signaling in hippocampus from CD73−/− mice. These data indicate that ethanol treatment is associated with a reduction in adenosine signaling through adenosine A1 receptors in hippocampus, mediated, at least in part, via reduced ecto-5′-nucleotidase activity. PMID:27189965

  13. Protein Prenylation Constitutes an Endogenous Brake on Axonal Growth.

    PubMed

    Li, Hai; Kuwajima, Takaaki; Oakley, Derek; Nikulina, Elena; Hou, Jianwei; Yang, Wan Seok; Lowry, Emily Rhodes; Lamas, Nuno Jorge; Amoroso, Mackenzie Weygandt; Croft, Gist F; Hosur, Raghavendra; Wichterle, Hynek; Sebti, Said; Filbin, Marie T; Stockwell, Brent; Henderson, Christopher E

    2016-07-12

    Suboptimal axonal regeneration contributes to the consequences of nervous system trauma and neurodegenerative disease, but the intrinsic mechanisms that regulate axon growth remain unclear. We screened 50,400 small molecules for their ability to promote axon outgrowth on inhibitory substrata. The most potent hits were the statins, which stimulated growth of all mouse- and human-patient-derived neurons tested, both in vitro and in vivo, as did combined inhibition of the protein prenylation enzymes farnesyltransferase (PFT) and geranylgeranyl transferase I (PGGT-1). Compensatory sprouting of motor axons may delay clinical onset of amyotrophic lateral sclerosis (ALS). Accordingly, elevated levels of PGGT1B, which would be predicted to reduce sprouting, were found in motor neurons of early- versus late-onset ALS patients postmortem. The mevalonate-prenylation pathway therefore constitutes an endogenous brake on axonal growth, and its inhibition provides a potential therapeutic approach to accelerate neuronal regeneration in humans. PMID:27373155

  14. Deletion of endogenous Tau proteins is not detrimental in Drosophila

    PubMed Central

    Burnouf, Sylvie; Grönke, Sebastian; Augustin, Hrvoje; Dols, Jacqueline; Gorsky, Marianna Karina; Werner, Jennifer; Kerr, Fiona; Alic, Nazif; Martinez, Pedro; Partridge, Linda

    2016-01-01

    Human Tau (hTau) is a highly soluble and natively unfolded protein that binds to microtubules within neurons. Its dysfunction and aggregation into insoluble paired helical filaments is involved in the pathogenesis of Alzheimer’s disease (AD), constituting, together with accumulated β-amyloid (Aβ) peptides, a hallmark of the disease. Deciphering both the loss-of-function and toxic gain-of-function of hTau proteins is crucial to further understand the mechanisms leading to neurodegeneration in AD. As the fruit fly Drosophila melanogaster expresses Tau proteins (dTau) that are homologous to hTau, we aimed to better comprehend dTau functions by generating a specific tau knock-out (KO) fly line using homologous recombination. We observed that the specific removal of endogenous dTau proteins did not lead to overt, macroscopic phenotypes in flies. Indeed, survival, climbing ability and neuronal function were unchanged in tau KO flies. In addition, we did not find any overt positive or negative effect of dTau removal on human Aβ-induced toxicity. Altogether, our results indicate that the absence of dTau proteins has no major functional impact on flies, and suggests that our tau KO strain is a relevant model to further investigate the role of dTau proteins in vivo, thereby giving additional insights into hTau functions. PMID:26976084

  15. Do polyunsaturated fatty acids behave like an endogenous "polypill"?

    PubMed

    Das, Undurti N

    2008-01-01

    Lowering plasma low density lipoprotein-cholesterol (LDL-C), blood pressure, homocysteine, and preventing platelet aggregation using a combination of a statin, three blood pressure lowering drugs such as a thiazide, a beta blocker, and an angiotensin converting enzyme (ACE) inhibitor each at half standard dose; folic acid; and aspirin - called as polypill - was estimated to reduce cardiovascular events by approximately 80%. Essential fatty acids (EFAs) and their long-chain metabolites and other products prevent platelet aggregation, lower blood pressure, reduce LDL-C, and ameliorate the adverse actions of homocysteine. Thus, EFAs and their metabolites show all the actions expected of the "polypill". Unlike the proposed "polypill", EFAs are endogenous molecules, have no significant side effects, can be taken orally for long periods of time even by pregnant women, lactating mothers, and children; and have been shown to reduce the incidence cardiovascular diseases. I propose that a rational combination of omega-3 and omega-6 fatty acids is as beneficial as that of the "polypill"; and may even show additional benefit in the prevention of depression, schizophrenia, Alzheimer's disease, and enhance cognitive function. PMID:17624683

  16. Lung Regeneration: Endogenous and Exogenous Stem Cell Mediated Therapeutic Approaches.

    PubMed

    Akram, Khondoker M; Patel, Neil; Spiteri, Monica A; Forsyth, Nicholas R

    2016-01-01

    The tissue turnover of unperturbed adult lung is remarkably slow. However, after injury or insult, a specialised group of facultative lung progenitors become activated to replenish damaged tissue through a reparative process called regeneration. Disruption in this process results in healing by fibrosis causing aberrant lung remodelling and organ dysfunction. Post-insult failure of regeneration leads to various incurable lung diseases including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. Therefore, identification of true endogenous lung progenitors/stem cells, and their regenerative pathway are crucial for next-generation therapeutic development. Recent studies provide exciting and novel insights into postnatal lung development and post-injury lung regeneration by native lung progenitors. Furthermore, exogenous application of bone marrow stem cells, embryonic stem cells and inducible pluripotent stem cells (iPSC) show evidences of their regenerative capacity in the repair of injured and diseased lungs. With the advent of modern tissue engineering techniques, whole lung regeneration in the lab using de-cellularised tissue scaffold and stem cells is now becoming reality. In this review, we will highlight the advancement of our understanding in lung regeneration and development of stem cell mediated therapeutic strategies in combating incurable lung diseases. PMID:26797607

  17. Endogenous or exogenous origin of vaginal candidiasis in Polish women?

    PubMed

    Mnichowska-Polanowskai, Magdalena; Wojciechowska-Koszko, Iwona; Klimowicz, Bogumia; Szymaniak, Ludmia; Krasnodebska-Szponder, Barbara; Szych, Zbigniew; Giedrys-Kalemba, Stefania

    2013-01-01

    Vaginal candidiasis is a common problem of clinical practice. Many studies have been conducted to explain its origin but only a few have included Polish women. The aim of the study was to determine the prevalence and similarity of oral, anal and vaginal Candida albicans strains isolated from Polish women with vaginal candidiasis. The study involved 20 from 37 recruited women. Swab samples were collected from their vagina, anus, and oral cavity at two-month intervals. All the women were treated with nystatin. Yeast were recovered and identified by the germ-tube test, API /Vitek system, typed by API ZYM and RAPD-PCR. Chi-square test was used to analyze the data. A total of 170 Candida albicans isolates were recovered from 180 samples collected 3 times from 3 sites of 20 women. Positive yeast vaginal cultures were found in all patients before administration of nystatin. Vaginal yeast recovery rate was decreased statistically significant in both follow-up visits (p= 0.001; p= 0.003). The same and different genotypes/biotypes were found concomitantly in a few body sites and/ or repeatedly at time interval from the same body site. The results support the concept of dynamic exchange of yeast within one woman and endogenous or exogenous origin of vaginal candidiasis.

  18. Discovery of unfixed endogenous retrovirus insertions in diverse human populations.

    PubMed

    Wildschutte, Julia Halo; Williams, Zachary H; Montesion, Meagan; Subramanian, Ravi P; Kidd, Jeffrey M; Coffin, John M

    2016-04-19

    Endogenous retroviruses (ERVs) have contributed to more than 8% of the human genome. The majority of these elements lack function due to accumulated mutations or internal recombination resulting in a solitary (solo) LTR, although members of one group of human ERVs (HERVs), HERV-K, were recently active with members that remain nearly intact, a subset of which is present as insertionally polymorphic loci that include approximately full-length (2-LTR) and solo-LTR alleles in addition to the unoccupied site. Several 2-LTR insertions have intact reading frames in some or all genes that are expressed as functional proteins. These properties reflect the activity of HERV-K and suggest the existence of additional unique loci within humans. We sought to determine the extent to which other polymorphic insertions are present in humans, using sequenced genomes from the 1000 Genomes Project and a subset of the Human Genome Diversity Project panel. We report analysis of a total of 36 nonreference polymorphic HERV-K proviruses, including 19 newly reported loci, with insertion frequencies ranging from <0.0005 to >0.75 that varied by population. Targeted screening of individual loci identified three new unfixed 2-LTR proviruses within our set, including an intact provirus present at Xq21.33 in some individuals, with the potential for retained infectivity.

  19. Endogenous surfactant turnover in preterm infants measured with stable isotopes.

    PubMed

    Bunt, J E; Zimmermann, L J; Wattimena, J L; van Beek, R H; Sauer, P J; Carnielli, V P

    1998-03-01

    We studied surfactant synthesis and turnover in vivo in preterm infants using the stable isotope [U-13C]glucose, as a precursor for the synthesis of palmitic acid in surfactant phosphatidylcholine (PC). Six preterm infants (birth weight, 916 +/- 244 g; gestational age, 27.7 +/- 1.7 wk) received a 24-h [U-13C]glucose infusion on the first day of life. The 13C-enrichment of palmitic acid in surfactant PC, obtained from tracheal aspirates, was measured by gas chromatography-combustion interface-isotope ratio mass spectrometry. We observed a significant incorporation of carbon-13 from glucose into surfactant PC palmitate. PC palmitate became enriched after 19.4 +/- 2.3 (16.5 to 22.3) h and reached maximum enrichment at 70 +/- 18 (48 to 96) h after the start of the label infusion. The fractional synthesis rate (FSR) of surfactant PC palmitate from glucose was 2.7 +/- 1.3%/d. We calculated the absolute production rate of surfactant PC to be 4.2 mg/kg/d, and the half-life to be 113 +/- 25 (87 to 144) h. Data on endogenous surfactant production and turnover were obtained for the first time in human infants with the use of stable isotopes. This novel and safe method could be applied to address many important issues concerning surfactant metabolism in preterm infants, children, and adults.

  20. Strategies to Detect Endogenous Ubiquitination of a Target Mammalian Protein.

    PubMed

    Sigismund, Sara; Polo, Simona

    2016-01-01

    Different biochemical techniques are well established to investigate target's ubiquitination in mammals without overexpressing a tagged version of ubiquitin (Ub). The simplest and more direct approach is to immunoprecipitate (IP) your target protein from cell lysate (stimulated and/or properly treated), followed by western blot analysis utilizing specific antibodies against Ub (see Subheading 3.1). This approach requires a good antibody against the target working in IP; alternatively, one could express a tagged version of the protein, possibly at the endogenous level. Another approach consists in IP ubiquitinated proteins from total cell lysate followed by detection with the antibody against the protein of interest. This second method relies on the availability of specific and very efficient antibodies against Ub (see Subheading 3.2). A more quantitative approach is the DELFIA assay (Perkin Elmer), an ELISA-based assay, which allows comparing more samples and conditions (see Subheading 3.3). Cross-validation with more than one approach is usually recommended in order to prove that your protein is modified by ubiquitin.Here we will use the EGFR as model system but protocols can be easily modified according to the protein of interest. PMID:27613032

  1. Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses

    PubMed Central

    Tönjes, Ralf R.

    2012-01-01

    Summary: Xenotransplantation may be a solution to overcome the shortage of organs for the treatment of patients with organ failure, but it may be associated with the transmission of porcine microorganisms and the development of xenozoonoses. Whereas most microorganisms may be eliminated by pathogen-free breeding of the donor animals, porcine endogenous retroviruses (PERVs) cannot be eliminated, since these are integrated into the genomes of all pigs. Human-tropic PERV-A and -B are present in all pigs and are able to infect human cells. Infection of ecotropic PERV-C is limited to pig cells. PERVs may adapt to host cells by varying the number of LTR-binding transcription factor binding sites. Like all retroviruses, they may induce tumors and/or immunodeficiencies. To date, all experimental, preclinical, and clinical xenotransplantations using pig cells, tissues, and organs have not shown transmission of PERV. Highly sensitive and specific methods have been developed to analyze the PERV status of donor pigs and to monitor recipients for PERV infection. Strategies have been developed to prevent PERV transmission, including selection of PERV-C-negative, low-producer pigs, generation of an effective vaccine, selection of effective antiretrovirals, and generation of animals transgenic for a PERV-specific short hairpin RNA inhibiting PERV expression by RNA interference. PMID:22491774

  2. Inhibition of cyclic gonadotropin secretion by endogenous human prolactin.

    PubMed

    Tyson, J E; Khojandi, M; Huth, J; Smith, B; Thomas, P

    1975-02-01

    The resumption of cyclic uterine bleeding reportedly accompanies the use of human prolactin (HPRL)-suppressing agents in postpill galactorrhea-amenorrhea. In this laboratory, HPRL suppression with L-dopa was variable and short lived. Basal plasma HPRL levels were elevated before and after as much as five months of therapy. Galactorrhea persisted and mean gonadotropin concentrations were subnormal. An immediate and sustained attenuation of HPRL secretion ( less than 200 per cent) followed the use of 2-Br-alpha-ergocryptine (CB-154). Cyclic gonadotropin secretion resumed and was accompanied by ovulation and, in one instance, pregnancy. The cessation of galactorrhea was positively correlated with the rise in the daily concentration of 17 beta-estradiol. Cyclic postovulatory menstruation continued after the cessation of CB-154 treatment. HPRL levels remained normal. The daily patterns of human follicle-stimulating hormone (HFSH) and human tuteinizing hormone (HLH) secretion created by the suppression of HPRL displayed an inherent rhythmicity identical to that observed at the time of menarche. The inhibitory effects of HPRL appeared directed at cyclic rather than tonic gonadotropin secretion. At the same time, diminished ovarian estrogen production seemed to increase mammary gland sensitivity to HPRL, leading to lactation. One may postulate, therefore, that the ingestion of sex steroids is associated with an over-all suppression of endogenous cyclic and, to a lesser extent, tonic gonadotropin secretion secondary to which ovarian function is attenuated. Without physiologic concentration of circulating estrogen, HPRL induces mammary alveolar function with the production of a milklike secretion.

  3. Local properties of patterned vegetation: quantifying endogenous and exogenous effects.

    PubMed

    Penny, Gopal G; Daniels, Karen E; Thompson, Sally E

    2013-12-13

    Dryland ecosystems commonly exhibit periodic bands of vegetation, thought to form due to competition between individual plants for heterogeneously distributed water. In this paper, we develop a Fourier method for locally identifying the pattern wavenumber and orientation, and apply it to aerial images from a region of vegetation patterning near Fort Stockton, TX, USA. We find that the local pattern wavelength and orientation are typically coherent, but exhibit both rapid and gradual variation driven by changes in hillslope gradient and orientation, the potential for water accumulation, or soil type. Endogenous pattern dynamics, when simulated for spatially homogeneous topographic and vegetation conditions, predict pattern properties that are much less variable than the orientation and wavelength observed in natural systems. Our local pattern analysis, combined with ancillary datasets describing soil and topographic variation, highlights a largely unexplored correlation between soil depth, pattern coherence, vegetation cover and pattern wavelength. It also, surprisingly, suggests that downslope accumulation of water may play a role in changing vegetation pattern properties.

  4. Local properties of patterned vegetation: quantifying endogenous and exogenous effects.

    PubMed

    Penny, Gopal G; Daniels, Karen E; Thompson, Sally E

    2013-01-01

    Dryland ecosystems commonly exhibit periodic bands of vegetation, thought to form due to competition between individual plants for heterogeneously distributed water. In this paper, we develop a Fourier method for locally identifying the pattern wavenumber and orientation, and apply it to aerial images from a region of vegetation patterning near Fort Stockton, TX, USA. We find that the local pattern wavelength and orientation are typically coherent, but exhibit both rapid and gradual variation driven by changes in hillslope gradient and orientation, the potential for water accumulation, or soil type. Endogenous pattern dynamics, when simulated for spatially homogeneous topographic and vegetation conditions, predict pattern properties that are much less variable than the orientation and wavelength observed in natural systems. Our local pattern analysis, combined with ancillary datasets describing soil and topographic variation, highlights a largely unexplored correlation between soil depth, pattern coherence, vegetation cover and pattern wavelength. It also, surprisingly, suggests that downslope accumulation of water may play a role in changing vegetation pattern properties.

  5. [Correlations between endogenous intoxication and excessive body weight].

    PubMed

    Abylaĭuly, Zh; Oshakbaev, K P; Kozhabekova, B N; Erdesova, G E; Imantaeva, G M; Uberbaeva, G K

    2005-01-01

    The aim of the study was to analyze correlations between endogenous intoxication (EI) and lipid peroxidation (LP) indices in patients with cardiovascular and endocrine diseases and healthy individuals, taking into account the presence of excessive body weight (EBW), as well as to compare EI and LP indices in practically healthy people with and without excessive body weight (EBW). The subjects were 165 people, including 36 healthy individuals and 129 patients with cardiovascular and endocrine disease. The healthy ones were divided into two groups: 20 with and 16 without EBW. To evaluate the degree of EI, the concentration of middle-molecular-weight peptides (MMWP) was measured by the method offered by N. I. Gabrielyan et al. in 1984. To evaluate LP processes, serum levels of the secondary LP product, malonic dialdehyde, and two antioxidative enzymes, superoxide dismutase and catalase, were measured. The results show that treatment aimed at LP suppression is not appropriate; it should be aimed at the cause of LP activation instead, which is the increase of MMWP level due to EBW. LP activation significantly correlates with increase of MMWP blood level (p < 0.05). EBW worsens EI and activates LP in healthy people, thus being a stress factor to the organism. Increased MMWP level and LP activation in healthy individuals with EBW may be a premorbid diagnostic marker.

  6. Optogenetic control of endogenous Ca(2+) channels in vivo.

    PubMed

    Kyung, Taeyoon; Lee, Sangkyu; Kim, Jung Eun; Cho, Taesup; Park, Hyerim; Jeong, Yun-Mi; Kim, Dongkyu; Shin, Anna; Kim, Sungsoo; Baek, Jinhee; Kim, Jihoon; Kim, Na Yeon; Woo, Doyeon; Chae, Sujin; Kim, Cheol-Hee; Shin, Hee-Sup; Han, Yong-Mahn; Kim, Daesoo; Heo, Won Do

    2015-10-01

    Calcium (Ca(2+)) signals that are precisely modulated in space and time mediate a myriad of cellular processes, including contraction, excitation, growth, differentiation and apoptosis. However, study of Ca(2+) responses has been hampered by technological limitations of existing Ca(2+)-modulating tools. Here we present OptoSTIM1, an optogenetic tool for manipulating intracellular Ca(2+) levels through activation of Ca(2+)-selective endogenous Ca(2+) release-activated Ca(2+) (CRAC) channels. Using OptoSTIM1, which combines a plant photoreceptor and the CRAC channel regulator STIM1 (ref. 4), we quantitatively and qualitatively controlled intracellular Ca(2+) levels in various biological systems, including zebrafish embryos and human embryonic stem cells. We demonstrate that activating OptoSTIM1 in the CA1 hippocampal region of mice selectively reinforced contextual memory formation. The broad utility of OptoSTIM1 will expand our mechanistic understanding of numerous Ca(2+)-associated processes and facilitate screening for drug candidates that antagonize Ca(2+) signals.

  7. Biofortification of rice with lysine using endogenous histones.

    PubMed

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

    2015-02-01

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

  8. Lung Regeneration: Endogenous and Exogenous Stem Cell Mediated Therapeutic Approaches

    PubMed Central

    Akram, Khondoker M.; Patel, Neil; Spiteri, Monica A.; Forsyth, Nicholas R.

    2016-01-01

    The tissue turnover of unperturbed adult lung is remarkably slow. However, after injury or insult, a specialised group of facultative lung progenitors become activated to replenish damaged tissue through a reparative process called regeneration. Disruption in this process results in healing by fibrosis causing aberrant lung remodelling and organ dysfunction. Post-insult failure of regeneration leads to various incurable lung diseases including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. Therefore, identification of true endogenous lung progenitors/stem cells, and their regenerative pathway are crucial for next-generation therapeutic development. Recent studies provide exciting and novel insights into postnatal lung development and post-injury lung regeneration by native lung progenitors. Furthermore, exogenous application of bone marrow stem cells, embryonic stem cells and inducible pluripotent stem cells (iPSC) show evidences of their regenerative capacity in the repair of injured and diseased lungs. With the advent of modern tissue engineering techniques, whole lung regeneration in the lab using de-cellularised tissue scaffold and stem cells is now becoming reality. In this review, we will highlight the advancement of our understanding in lung regeneration and development of stem cell mediated therapeutic strategies in combating incurable lung diseases. PMID:26797607

  9. Fungal laccases degradation of endocrine disrupting compounds.

    PubMed

    Macellaro, Gemma; Pezzella, Cinzia; Cicatiello, Paola; Sannia, Giovanni; Piscitelli, Alessandra

    2014-01-01

    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. PMID:24829908

  10. Fungal Laccases Degradation of Endocrine Disrupting Compounds

    PubMed Central

    Macellaro, Gemma; Cicatiello, Paola; Sannia, Giovanni

    2014-01-01

    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. PMID:24829908

  11. Exogenous and endogenous contributions to nitrogen fluxes in the digestive tract of pigs fed a casein diet. III. Recycling of endogenous nitrogen.

    PubMed

    Souffrant, W B; Rérat, A; Laplace, J P; Darcy-Vrillon, B; Köhler, R; Corring, T; Gebhardt, G

    1993-01-01

    The aim of the present study was to measure the incorporation of infused 15N in blood fractions, urine, digesta, faeces and in the exocrine pancreatic and biliary secretions, in order to estimate the endogenous part of nitrogen in the ileal digesta and in the faeces of pigs fed a casein diet and to calculate the total endogenous nitrogen secretion as well as its recycling in the digestive tract. For 8 d 11 Large White female pigs (50.1 +/- 1.8 kg) received a continuous infusion of L-[15N]leucine via a catheter in the jugular vein. The 15N-enrichment was measured in several fractions. The 15N-level of the pancreatic juice was higher than that in the biliary secretion, TCA-blood fractions, and urine during the whole experimental period. Using the 15N-isotope dilution method it was found that casein was completely digested up to the terminal ileum and that all the nitrogen in the ileal digesta was of endogenous origin. The total endogenous secretion was estimated at approximately 11 g N/d. The reabsorption of endogenous nitrogen amounted to 79% up to the end of the small intestine and 88% over the whole digestive tract. PMID:8240681

  12. Endogenous Market-Clearing Prices and Reference Point Adaptation

    NASA Astrophysics Data System (ADS)

    Dragicevic, Arnaud Z.

    When prices depend on the submitted bids, i.e. with endogenous market-clearing prices in repeated-round auction mechanisms, the assumption of independent private values that underlines the property of incentive-compatibility is to be brought into question; even if these mechanisms provide active involvement and market learning. In its orthodox view, adaptive bidding behavior imperils incentive-compatibility. We relax the assumption of private values' independence in the repeated-round auctions, when the market-clearing prices are made public at the end of each round. Instead of using game-theory learning models, we introduce a behavioral model that shows that bidders bid according to the anchoring-and-adjustment heuristic, which neither ignores the rationality and incentive-compatibility constraints, nor rejects the posted prices issued from others' bids. Bidders simply weight information at their disposal and adjust their discovered value using reference points encoded in the sequential price weighting function. Our model says that bidders and offerers are sincere boundedly rational utility maximizers. It lies between evolutionary dynamics and adaptive heuristics and we model the concept of inertia as high weighting of the anchor, which stands for truthful bidding and high regard to freshly discovered preferences. Adjustment means adaptive rule based on adaptation of the reference point in the direction of the posted price. It helps a bidder to maximize her expected payoff, which is after all the only purpose that matters to rationality. The two components simply suggest that sincere bidders are boundedly rational. Furthermore, by deviating from their anchor in the direction of the public signal, bidders operate in a correlated equilibrium. The correlation between bids comes from the commonly observed history of play and each bidder's actions are determined by the history. Bidders are sincere if they have limited memory and confine their reference point adaptation

  13. Can Neural Activity Propagate by Endogenous Electrical Field?

    PubMed

    Qiu, Chen; Shivacharan, Rajat S; Zhang, Mingming; Durand, Dominique M

    2015-12-01

    It is widely accepted that synaptic transmissions and gap junctions are the major governing mechanisms for signal traveling in the neural system. Yet, a group of neural waves, either physiological or pathological, share the same speed of ∼0.1 m/s without synaptic transmission or gap junctions, and this speed is not consistent with axonal conduction or ionic diffusion. The only explanation left is an electrical field effect. We tested the hypothesis that endogenous electric fields are sufficient to explain the propagation with in silico and in vitro experiments. Simulation results show that field effects alone can indeed mediate propagation across layers of neurons with speeds of 0.12 ± 0.09 m/s with pathological kinetics, and 0.11 ± 0.03 m/s with physiologic kinetics, both generating weak field amplitudes of ∼2-6 mV/mm. Further, the model predicted that propagation speed values are inversely proportional to the cell-to-cell distances, but do not significantly change with extracellular resistivity, membrane capacitance, or membrane resistance. In vitro recordings in mice hippocampi produced similar speeds (0.10 ± 0.03 m/s) and field amplitudes (2.5-5 mV/mm), and by applying a blocking field, the propagation speed was greatly reduced. Finally, osmolarity experiments confirmed the model's prediction that cell-to-cell distance inversely affects propagation speed. Together, these results show that despite their weak amplitude, electric fields can be solely responsible for spike propagation at ∼0.1 m/s. This phenomenon could be important to explain the slow propagation of epileptic activity and other normal propagations at similar speeds.

  14. Visualization of Epicardial Cryoablation Lesions using Endogenous Tissue Fluorescence

    PubMed Central

    Swift, Luther; Gil, Daniel A.B.; Jaimes, Rafael; Kay, Matthew; Mercader, Marco; Sarvazyan, Narine

    2014-01-01

    Background Percutaneous cryoballoon ablation is a commonly used procedure to treat atrial fibrillation. One of the major limitations of the procedure is the inability to directly visualize tissue damage and functional gaps between the lesions. We seek to develop an approach that will enable real-time visualization of tissue necrosis during cryo- or radiofrequency ablation procedures. Methods and Results Cryoablation of either blood-perfused or saline-perfused hearts was associated with a marked decrease in NADH fluorescence leading to a 60-70% loss of signal intensity at the lesion site. The total lesion area observed on the NADH channel exhibited a strong correlation with the area identified by triphenyl tetrazolium staining (r=0.89, p<0.001). At physiological temperatures, loss of NADH became visually apparent within 26±8 sec after detachment of the cryoprobe from the epicardial surface and plateaued within minutes after which the boundaries of the lesions remained stable for several hours. The loss of electrical activity within the cryoablation site exhibited a close spatial correlation with the loss of NADH (r=0.84±0.06, p<0.001). Cryoablation led to a decrease in diffuse reflectance across the entire visible spectrum which was in stark contrast to radiofrequency ablation that markedly increased the intensity of reflected light at the lesion sites. Conclusions We confirmed the feasibility of using endogenous NADH fluorescence for the real-time visualization of cryoablation lesions in blood-perfused cardiac muscle preparations and revealed similarities and differences between imaging cryo- and radiofrequency ablation lesions when using ultraviolet and visible light illumination. PMID:25141861

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

    PubMed

    Hadjiconstantinou, Maria; Neff, Norton H

    2011-06-01

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

  16. Effective Delivery of Endogenous Antioxidants Ameliorates Diabetic Nephropathy

    PubMed Central

    Park, Yongsoo; Kim, Hyunok; Park, Leejin; Min, Dongsoo; Park, Jinseu; Choi, Sooyoung; Park, Moon Hyang

    2015-01-01

    Background Diabetic nephropathy (DN) is thought to be partially due to the injury of renal cells and the renal micro-environment by free radicals. Free radial scavenging agents that inhibit free radical damage may well prevent the development of underlying conditions such as mesangial expansion (by inhibiting extracellular matrix expression) in these patients. Methods Using techniques for intra-cellular delivery of peptides, we made metallothionein (MT) and superoxide dismutase (SOD), potent endogenous antioxidants, readily transducible into cell membrane and tested their protective effect against the development of DN in OLETF rats. Herein, we study antioxidant peptides for their ability to prevent oxidative damage to primary rat mesangial cells (MCs), which are important constituents of renal glomeruli. Results Intraperitoneal administration of these antioxidants resulted in delivery to the kidney and decreased ROS and the expression of downstream signals in renal cells and postponed the usual progression to DN. In in vitro experiments, MT and SOD were efficiently transferred to MCs, and the increased removal of ROS by MT and SOD was proportional to the degree of scavenging enzymes delivered. MT and SOD decreased three major oxidative injuries (hyperglycemia, AGE and ROS exposure) and also injuries directly mediated by angiotensin II in MCs while changing downstream signal transduction. Conclusions The protective effects of MT and SOD for the progression of DN in experimental animals may be associated with the scavenging of ROS by MT and SOD and correlated changes in signal transduction downstream. Concomitant administration of these antioxidant peptides may prove to be a new approach for the prevention and therapy of DN. PMID:26114547

  17. The endogenous cannabinoid system protects against colonic inflammation

    PubMed Central

    Massa, Federico; Marsicano, Giovanni; Hermann, Heike; Cannich, Astrid; Monory, Krisztina; Cravatt, Benjamin F.; Ferri, Gian-Luca; Sibaev, Andrei; Storr, Martin; Lutz, Beat

    2004-01-01

    Excessive inflammatory responses can emerge as a potential danger for organisms’ health. Physiological balance between pro- and anti-inflammatory processes constitutes an important feature of responses against harmful events. Here, we show that cannabinoid receptors type 1 (CB1) mediate intrinsic protective signals that counteract proinflammatory responses. Both intrarectal infusion of 2,4-dinitrobenzene sulfonic acid (DNBS) and oral administration of dextrane sulfate sodium induced stronger inflammation in CB1-deficient mice (CB1–/–) than in wild-type littermates (CB1+/+). Treatment of wild-type mice with the specific CB1 antagonist N-(piperidino-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-pyrazole-3-carboxamide (SR141716A) mimicked the phenotype of CB1–/– mice, showing an acute requirement of CB1 receptors for protection from inflammation. Consistently, treatment with the cannabinoid receptor agonist R(-)-7-hydroxy-Δ6-tetra-hydrocannabinol-dimethylheptyl (HU210) or genetic ablation of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) resulted in protection against DNBS-induced colitis. Electrophysiological recordings from circular smooth muscle cells, performed 8 hours after DNBS treatment, revealed spontaneous oscillatory action potentials in CB1–/– but not in CB1+/+ colons, indicating an early CB1-mediated control of inflammation-induced irritation of smooth muscle cells. DNBS treatment increased the percentage of myenteric neurons expressing CB1 receptors, suggesting an enhancement of cannabinoid signaling during colitis. Our results indicate that the endogenous cannabinoid system represents a promising therapeutic target for the treatment of intestinal disease conditions characterized by excessive inflammatory responses. PMID:15085199

  18. Endogenous 2-oxoacids differentially regulate expression of oxygen sensors.

    PubMed Central

    Dalgard, Clifton Lee; Lu, Huasheng; Mohyeldin, Ahmed; Verma, Ajay

    2004-01-01

    Adaptations to change in oxygen availability are crucial for survival of multi-cellular organisms and are also implicated in several disease states. Such adaptations rely upon gene expression regulated by the heterodimeric transcription factors HIFs (hypoxia-inducible factors). Enzymes that link changes in oxygen tensions with the stability and transcriptional activity of HIFs are considered as oxygen sensors. These enzymes are oxygen-, iron- and 2-oxoglutarate-dependent dioxygenases that hydroxylate key proline and asparagine residues in HIFalpha subunits. The constitutive inhibitory action of these enzymes on HIFs is relieved by hypoxia and by agents that displace iron or 2-oxoglutarate. Two of the enzymes, HPH (HIF prolyl hydroxylase)-1 and HPH-2, are known to be inducible by hypoxia in a HIF-dependent manner. This suggests the existence of a novel feedback loop for adjusting hypoxia-regulated gene expression. We have recently shown that HIF-1alpha stability, HIF-1 nuclear translocation and HIF-mediated gene expression in human glioma cell lines can be stimulated by pyruvate independently of hypoxia. In the present study we show that the endogenous 2-oxoacid oxaloacetate can also activate HIF-mediated gene expression. Pyruvate and oxaloacetate treatment of cells also up-regulates HPH-1 and HPH-2, but not HPH-3 or the HIF asparaginyl hydroxylase FIH-1 (factor inhibiting HIF). Regulation of HIF-1 and the expression of HPH homologue genes can thus be influenced by specific glycolytic and tricarboxylic acid cycle metabolites. These findings may underlie important interactions between oxygen homoeostasis, glycolysis, the tricarboxylic acid cycle and gluconeogenesis. PMID:14984367

  19. Estimating endogenous changes in task performance from EEG

    PubMed Central

    Touryan, Jon; Apker, Gregory; Lance, Brent J.; Kerick, Scott E.; Ries, Anthony J.; McDowell, Kaleb

    2014-01-01

    Brain wave activity is known to correlate with decrements in behavioral performance as individuals enter states of fatigue, boredom, or low alertness.Many BCI technologies are adversely affected by these changes in user state, limiting their application and constraining their use to relatively short temporal epochs where behavioral performance is likely to be stable. Incorporating a passive BCI that detects when the user is performing poorly at a primary task, and adapts accordingly may prove to increase overall user performance. Here, we explore the potential for extending an established method to generate continuous estimates of behavioral performance from ongoing neural activity; evaluating the extended method by applying it to the original task domain, simulated driving; and generalizing the method by applying it to a BCI-relevant perceptual discrimination task. Specifically, we used EEG log power spectra and sequential forward floating selection (SFFS) to estimate endogenous changes in behavior in both a simulated driving task and a perceptual discrimination task. For the driving task the average correlation coefficient between the actual and estimated lane deviation was 0.37 ± 0.22 (μ ± σ). For the perceptual discrimination task we generated estimates of accuracy, reaction time, and button press duration for each participant. The correlation coefficients between the actual and estimated behavior were similar for these three metrics (accuracy = 0.25 ± 0.37, reaction time = 0.33 ± 0.23, button press duration = 0.36 ± 0.30). These findings illustrate the potential for modeling time-on-task decrements in performance from concurrent measures of neural activity. PMID:24994968

  20. Novel endogenous glycan therapy for retinal diseases: safety, in vitro stability, ocular pharmacokinetic modeling, and biodistribution.

    PubMed

    Swaminathan, Shankar; Li, Huiling; Palamoor, Mallika; de Obarrio, Walter T Luchsinger; Madhura, Dorababu; Meibohm, Bernd; Jablonski, Monica M

    2014-03-01

    Asialo, tri-antennary oligosaccharide (NA3 glycan) is an endogenous compound, which supports proper folding of outer segment membranes, promotes normal ultrastructure, and maintains protein expression patterns of photoreceptors and Müller cells in the absence of retinal pigment epithelium support. It is a potential new therapeutic for atrophic age-related macular degeneration (AMD) and other retinal degenerative disorders. Herein, we evaluate the safety, in vitro stability, ocular pharmacokinetics and biodistribution of NA3. NA3 was injected into the vitreous of New Zealand white rabbits at two concentrations viz. 1 nM (minimum effective concentration (MEC)) and 100 nM (100XMEC) at three time points. Safety was evaluated using routine clinical and laboratory tests. Ocular pharmacokinetics and biodistribution of [(3)H]NA3 were estimated using scintillation counting in various parts of the eye, multiple peripheral organs, and plasma. Pharmacokinetic parameters were estimated by non-compartmental modeling. A 2-aminobenzamide labeling and hydrophilic interaction liquid interaction chromatography were used to assess plasma and vitreous stability. NA3 was well tolerated by the eye. The concentration of NA3 in eye tissues was in the order: vitreous > retina > sclera/choroid > aqueous humor > cornea > lens. Area under the curve (0 to infinity) (AUC∞) was the highest in the vitreous thereby providing a positive concentration gradient for NA3 to reach the retina. Half-lives in critical eye tissues ranged between 40 and 60 h. NA3 concentrations were negligible in peripheral organs. Radioactivity from [(3)H]NA3 was excreted via urine and feces. NA3 was stable at 37°C in vitreous over a minimum of 6 days, while it degraded rapidly in plasma. Collectively, these results document that NA3 shows a good safety profile and favorable ocular pharmacokinetics.

  1. Endogenous retrovirus induces leukemia in a xenograft mouse model for primary myelofibrosis

    PubMed Central

    Triviai, Ioanna; Ziegler, Marion; Bergholz, Ulla; Oler, Andrew J.; Stübig, Thomas; Prassolov, Vladimir; Fehse, Boris; Kozak, Christine A.; Kröger, Nicolaus; Stocking, Carol

    2014-01-01

    The compound immunodeficiencies in nonobese diabetic (NOD) inbred mice homozygous for the Prkdcscid and Il2rgnull alleles (NSG mice) permit engraftment of a wide-range of primary human cells, enabling sophisticated modeling of human disease. In studies designed to define neoplastic stem cells of primary myelofibrosis (PMF), a myeloproliferative neoplasm characterized by profound disruption of the hematopoietic microenvironment, we observed a high frequency of acute myeloid leukemia (AML) in NSG mice. AML was of mouse origin, confined to PMF-xenografted mice, and contained multiple clonal integrations of ecotropic murine leukemia virus (E-MuLV). Significantly, MuLV replication was not only observed in diseased mice, but also in nontreated NSG controls. Furthermore, in addition to the single ecotropic endogenous retrovirus (eERV) located on chromosome 11 (Emv30) in the NOD genome, multiple de novo germ-line eERV integrations were observed in mice from each of four independent NSG mouse colonies. Analysis confirmed that E-MuLV originated from the Emv30 provirus and that recombination events were not necessary for virus replication or AML induction. Pathogenicity is thus likely attributable to PMF-mediated paracrine stimulation of mouse myeloid cells, which serve as targets for retroviral infection and transformation, as evidenced by integration into the Evi1 locus, a hotspot for retroviral-induced myeloid leukemia. This study thus corroborates a role of paracrine stimulation in PMF disease progression, underlines the importance of target cell type and numbers in MuLV-induced disease, and mandates awareness of replicating MuLV in NOD immunodeficient mice, which can significantly influence experimental results and their interpretation. PMID:24912157

  2. Endogenous retrovirus induces leukemia in a xenograft mouse model for primary myelofibrosis.

    PubMed

    Triviai, Ioanna; Ziegler, Marion; Bergholz, Ulla; Oler, Andrew J; Stübig, Thomas; Prassolov, Vladimir; Fehse, Boris; Kozak, Christine A; Kröger, Nicolaus; Stocking, Carol

    2014-06-10

    The compound immunodeficiencies in nonobese diabetic (NOD) inbred mice homozygous for the Prkdc(scid) and Il2rg(null) alleles (NSG mice) permit engraftment of a wide-range of primary human cells, enabling sophisticated modeling of human disease. In studies designed to define neoplastic stem cells of primary myelofibrosis (PMF), a myeloproliferative neoplasm characterized by profound disruption of the hematopoietic microenvironment, we observed a high frequency of acute myeloid leukemia (AML) in NSG mice. AML was of mouse origin, confined to PMF-xenografted mice, and contained multiple clonal integrations of ecotropic murine leukemia virus (E-MuLV). Significantly, MuLV replication was not only observed in diseased mice, but also in nontreated NSG controls. Furthermore, in addition to the single ecotropic endogenous retrovirus (eERV) located on chromosome 11 (Emv30) in the NOD genome, multiple de novo germ-line eERV integrations were observed in mice from each of four independent NSG mouse colonies. Analysis confirmed that E-MuLV originated from the Emv30 provirus and that recombination events were not necessary for virus replication or AML induction. Pathogenicity is thus likely attributable to PMF-mediated paracrine stimulation of mouse myeloid cells, which serve as targets for retroviral infection and transformation, as evidenced by integration into the Evi1 locus, a hotspot for retroviral-induced myeloid leukemia. This study thus corroborates a role of paracrine stimulation in PMF disease progression, underlines the importance of target cell type and numbers in MuLV-induced disease, and mandates awareness of replicating MuLV in NOD immunodeficient mice, which can significantly influence experimental results and their interpretation.

  3. Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo

    PubMed Central

    Najm, Fadi J.; Madhavan, Mayur; Zaremba, Anita; Shick, Elizabeth; Karl, Robert T.; Factor, Daniel C.; Miller, Tyler E.; Nevin, Zachary S.; Kantor, Christopher; Sargent, Alex; Quick, Kevin L.; Schlatzer, Daniela M.; Tang, Hong; Papoian, Ruben; Brimacombe, Kyle R.; Shen, Min; Boxer, Matthew B.; Jadhav, Ajit; Robinson, Andrew P.; Podojil, Joseph R.; Miller, Stephen D.; Miller, Robert H.; Tesar, Paul J.

    2015-01-01

    Multiple sclerosis (MS) involves an aberrant autoimmune response and progressive failure of remyelination in the central nervous system (CNS). Prevention of neural degeneration and subsequent disability requires remyelination through the generation of new oligodendrocytes, but current treatments exclusively target the immune system. Oligodendrocyte progenitor cells (OPCs) are stem cells in the CNS and the principal source of myelinating oligodendrocytes1. OPCs are abundant in demyelinated regions of MS patients, yet fail to differentiate, thereby representing a cellular target for pharmacological intervention2. To discover therapeutic compounds for enhancing myelination from endogenous OPCs, we screened a library of bioactive small molecules on mouse pluripotent epiblast stem cell (EpiSC)-derived OPCs3–5. We identified seven drugs that functioned at nanomolar doses to selectively enhance the generation of mature oligodendrocytes from OPCs in vitro. Two drugs, miconazole and clobetasol, were effective in promoting precocious myelination in organotypic cerebellar slice cultures, and in vivo in early postnatal mouse pups. Systemic delivery of each of the two drugs significantly increased the number of new oligodendrocytes and enhanced remyelination in a lysolecithin-induced mouse model of focal demyelination. Administering each of the two drugs at the peak of disease in the experimental autoimmune encephalomyelitis (EAE) mouse model of chronic progressive MS resulted in striking reversal of disease severity. Immune response assays showed that miconazole functioned directly as a remyelinating drug with no effect on the immune system, whereas clobetasol was a potent immunosuppressant as well as a remyelinating agent. Mechanistic studies showed that miconazole and clobetasol functioned in OPCs through mitogen-activated protein kinase (MAPK) and glucocorticoid receptor (GR) signaling, respectively. Furthermore, both drugs enhanced the generation of human

  4. Genetic variants of human organic anion transporter 4 demonstrate altered transport of endogenous substrates

    PubMed Central

    Shima, James E.; Komori, Takafumi; Taylor, Travis R.; Stryke, Doug; Kawamoto, Michiko; Johns, Susan J.; Carlson, Elaine J.; Ferrin, Thomas E.

    2010-01-01

    Apical reabsorption from the urine has been shown to be important for such processes as the maintenance of critical metabolites in the blood and the excretion of nephrotoxic compounds. The solute carrier (SLC) transporter OAT4 (SLC22A11) is expressed on the apical membrane of renal proximal tubule cells and is known to mediate the transport of a variety of xenobiotic and endogenous organic anions. Functional characterization of genetic variants of apical transporters thought to mediate reabsorption, such as OAT4, may provide insight into the genetic factors influencing the complex pathways involved in drug elimination and metabolite reclamation occurring in the kidney. Naturally occurring genetic variants of OAT4 were identified in public databases and by resequencing DNA samples from 272 individuals comprising 4 distinct ethnic groups. Nine total nonsynonymous variants were identified and functionally assessed using uptake of three radiolabeled substrates. A nonsense variant, R48Stop, and three other variants (R121C, V155G, and V155M) were found at frequencies of at least 2% in an ethnic group specific fashion. The L29P, R48Stop, and H469R variants displayed a complete loss of function, and kinetic analysis identified a reduced Vmax in the common nonsynonymous variants. Plasma membrane levels of OAT4 protein were absent or reduced in the nonfunctional variants, providing a mechanistic reason for the observed loss of function. Characterization of the genetic variants of reabsorptive transporters such as OAT4 is an important step in understanding variability in tubular reabsorption with important implications in innate homeostatic processes and drug disposition. PMID:20668102

  5. Heart testing compound

    DOEpatents

    Knapp, F.F. Jr.; Goodman, M.M.

    1983-06-29

    The compound 15-(p-(/sup 125/I)-iodophenyl)-6-tellurapentadecanoic acid is disclosed as a myocardial imaging agent having rapid and pronounced uptake, prolonged myocardial retention, and low in vivo deiodination.

  6. Heart testing compound

    DOEpatents

    Knapp, Jr., Furn F.; Goodman, Mark M.

    1985-01-01

    The compound 15-(p-[.sup.125 I]-iodophenyl)-6-tellurapentadecanoic acid is disclosed as a myocardial imaging agent having rapid and pronounced uptake, prolonged myocardial retention, and low in vivo deiodination.

  7. Anti-Fog Compound

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Tracer Chemical Corporation's TRX Anti-Fog Composition is an inexpensive product which prevents condensation on plastic and glass surfaces. It was the result from a Tech Briefs article detailing a Johnson Space Center compound.

  8. Influence of Glutamic Acid on the Endogenous Respiration of Bacillus subtilis

    PubMed Central

    Clifton, C. E.; Cherry, John

    1966-01-01

    Clifton, C. E. (Stanford University, Stanford, Calif.), and John Cherry. Influence of glutamic acid on the endogenous respiration of Bacillus subtilis. J. Bacteriol. 91:546–550. 1966.—Amino acids serve as the major initial endogenous substrate for Bacillus subtilis. The endogenous activity of freshly harvested washed cells is high and falls off rapidly with time of shaking at 30 C to lower but still significant levels. The rate of O2 consumption after the addition of glutamic acid also decreases as the cells age, but more slowly than noted for endogenous respiration. When cells were fed glutamate as soon as possible after harvesting, an apparent stimulation of endogenous respiration was noted. However, endogenous activity was inhibited if the cell suspensions were shaken for at least 1 hr before addition of the glutamate. Similar results were obtained with glycerol or glucose as exogenous substrates. Variation in rates of respiration with age of the cells, inherent instability of B. subtilis, and possible utilization of substances initially excreted by the cells appear to account for the variations noted regarding the influence of an exogenous substrate on endogenous respiration. PMID:4956754

  9. Compound composite odontoma

    PubMed Central

    Girish, G; Bavle, Radhika M; Singh, Manish Kumar; Prasad, Sahana N

    2016-01-01

    The term odontoma has been used as a descriptor for any tumor of odontogenic origin. It is a growth in which both epithelial and mesenchymal cells exhibits complete differentiation. Odontomas are considered as hamartomas rather than true neoplasm. They are usually discovered on routine radiographic examination. Odontomas, according to the World Health Organization, are classified into complex odontoma and compound odontomas. The present paper reports a case of compound composite odontomas. PMID:27194882

  10. Compound composite odontoma.

    PubMed

    Girish, G; Bavle, Radhika M; Singh, Manish Kumar; Prasad, Sahana N

    2016-01-01

    The term odontoma has been used as a descriptor for any tumor of odontogenic origin. It is a growth in which both epithelial and mesenchymal cells exhibits complete differentiation. Odontomas are considered as hamartomas rather than true neoplasm. They are usually discovered on routine radiographic examination. Odontomas, according to the World Health Organization, are classified into complex odontoma and compound odontomas. The present paper reports a case of compound composite odontomas.

  11. Chemistry of peroxide compounds

    NASA Technical Reports Server (NTRS)

    Volnov, I. I.

    1981-01-01

    The history of Soviet research from 1866 to 1967 on peroxide compounds is reviewed. This research dealt mainly with peroxide kinetics, reactivity and characteristics, peroxide production processes, and more recently with superoxides and ozonides and emphasis on the higher oxides of group 1 and 2 elements. Solid state fluidized bed synthesis and production of high purity products based on the relative solubilities of the initial, intermediate, and final compounds and elements in liquid ammonia are discussed.

  12. Compounding a Problem?

    PubMed

    Berlin, Joey

    2016-01-01

    Allergist-immunologists say a U.S. Pharmacopeia proposal will mess with an allergy treatment system that's worked for more than a century. The revised standards, if adopted, would remove a key exemption separating allergen extract preparations from the stricter requirements of other compounds. Immunologists say the exemption has allowed them to compound allergen extracts in their own offices, and they've done so safely and effectively millions of times a year.

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

    PubMed

    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.

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

    PubMed Central

    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. Degradation of endogenous and exogenous genes of roundup-ready soybean during food processing.

    PubMed

    Chen, Ying; Wang, Yuan; Ge, Yiqiang; Xu, Baoliang

    2005-12-28

    Roundup-Ready soybeans have been genetically modified to resist the effects of the herbicidal glyphosate and have become the most prevalent transgenic crop in the world. In this work, Roundup-Ready soybeans were used as raw material to study the effects of critical processing procedures such as grinding, cooking, blending, homogenization, sterilization, and spray-drying on the length of DNA fragments of an endogenous gene (lectin) and an exogenous gene (epsps) examined in material from three soybean foods of bean curd, soy milk, and soy powder and from samples taken during their processing. The results showed that various processing procedures caused degradations of both the endogenous and exogenous genes to different degrees. In the grinding procedure, endogenous gene DNA was degraded from 1883 to approximately 836 bp, and exogenous gene DNA was degraded from 1512 to approximately 408 bp. In the blending and squeeze-molding procedures, exogenous gene DNA was also degraded from about 408 to 190 bp, but there was no obvious action on the endogenous gene. After the endogenous and exogenous genes had been degraded to some degree, such as 836 and 408 bp, respectively, they were not evidently affected by cooking procedure at 100 degrees C for 15 min. However, the endogenous gene was further considerably degraded from around 836 to 162 bp in the sterilization procedure at 121 degrees C for 30 s. The effect of the homogenization step on endogenous and exogenous genes was similar to that of the cooking procedure. The coagulation procedure, principally a biochemical reaction, did not greatly affect the exogenous gene but did affect endogenous gene, reducing DNA size from about 836 to 407 bp. Furthermore, the spray-drying procedure, a process of physical shearing, high temperature, and sudden high pressure, distinctly caused degradation of both the lectin and epsps genes, rapidly decreasing the sizes from about 836 to 162 bp for the endogenous gene and from about 408 to 190

  16. Understanding medication compounding issues.

    PubMed

    Hicks, Rodney W

    2014-04-01

    The potential for contamination of compounded products and the resulting infections are a serious threat to patient safety. Immediate use products are used frequently in the perioperative department, and perioperative nurses should be familiar with the guidelines and practices that aim to reduce the contamination that can occur during the sterile compounding process. Four common themes lead to successful compounding: quality (eg, product identification, purity, stability, compatibility, risk level assessment), the environment (eg, using a segregated compounding area with specialized airflow capabilities, reducing particulate matter, practicing proper hand hygiene, performing gloved fingertip sampling, properly cleaning equipment and work areas), personnel activities (eg, familiarity with types of containers used and how often they can be accessed, following expiration dates and the number of times containers can be accessed), and the control process (eg, process monitoring, quality improvement). If a third-party vendor is contracted to handle compounding for a facility, perioperative personnel should be aware of the responsibilities for the facility and the vendor to ensure a quality compounding program. PMID:24674793

  17. Occupancy of dopamine D2/3 receptors in rat brain by endogenous dopamine measured with the agonist positron emission tomography radioligand [11C]MNPA.

    PubMed

    Seneca, Nicholas; Zoghbi, Sami S; Skinbjerg, Mette; Liow, Jeih-San; Hong, Jinsoo; Sibley, David R; Pike, Victor W; Halldin, Christer; Innis, Robert B

    2008-10-01

    Estimates of dopamine D(2/3) receptor occupancy by endogenous dopamine using positron emission tomography (PET) in animals have varied almost threefold. This variability may have been caused by incomplete depletion of dopamine or by the use of antagonist radioligands, which appear less sensitive than agonist radioligands to changes in endogenous dopamine. PET scans were performed in rats with the agonist PET radioligand [(11)C]MNPA ([O-methyl-(11)C]2-methoxy-N-propylnorapomorphine). [(11)C]MNPA was injected as a bolus plus constant infusion to achieve steady-state concentration in the body and equilibrium receptor binding in the brain. Radioligand binding was compared at baseline and after treatment with reserpine plus alpha-methyl-para-tyrosine, which cause approximately 95% depletion of endogenous dopamine. Depletion of dopamine increased radioligand binding in striatum but had little effect in cerebellum. Striatal [(11)C]MNPA binding potential was 0.93 +/- 0.12 at baseline and increased to 1.99 +/- 0.25 after dopamine depletion. Occupancy of D(2/3) receptors by endogenous dopamine at baseline was calculated to be approximately 53%. Striatal binding was displaceable with raclopride, but not with BP 897 (a selective D(3) compound), thus confirming the D(2) receptor specificity of [(11)C]MNPA binding. Radioactivity extracted from rat brain contained only 8-10% radiometabolites and was insignificantly altered by administration of reserpine plus alpha-methyl-para-tyrosine. Hence, dopamine depletion did not increase the PET measurements via an effect on radiotracer metabolism. Our in vivo estimate of dopamine's occupancy of D(2/3) receptors at baseline is higher than that previously reported using antagonist radioligands and PET, but is similar to that reported using agonist radioligands and ex vivo measurements.

  18. Endogenous DNA-directed DNA synthesising system in a microsomal fraction of embryonic chick brain.

    PubMed Central

    Smith, J; Soriano, L

    1977-01-01

    A DNA polymerising complex directed by endogenous DNA has been partially purified from 11-day-old embryonic chick brain microsomes by DEAE-cellulose and phosphocellulose column chromatography. The active fractions are eluted together with an exogenous DNA-directed DNA polymerase; after Sephadex gel filtration, the endogenous activity remains associated with a high molecular weight DNA-directed DNA polymerase. The endogenous activity of the complex has been shown to be RNase-resistant and actinomycin-sensitive. It requires potassium, an ATP-regenerating system and all four deoxyribonucleoside triphosphates for full activity. The significance of this activity with regard to the protovirus hypothesis is discussed. PMID:866184

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

    PubMed

    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.

  20. Isolated group B streptococcal endogenous endophthalmitis simulating retinoblastoma or persistent fetal vasculature in a healthy full-term infant.

    PubMed

    McCourt, Emily A; Hink, Eric M; Durairaj, Vikram D; Oliver, Scott C N

    2010-08-01

    Group B streptococcus (GBS) is a potentially devastating neonatal pathogen that most commonly causes meningitis, sepsis, and pneumonia. It is also a very rare cause of endogenous endophthalmitis. We present the second case of endogenous endophthalmitis caused by GBS in a healthy newborn and the first case of endogenous endophthalmitis by GBS in a newborn mimicking retinoblastoma and resulting in enucleation. PMID:20637664

  1. Nonpost mold cure compound

    NASA Astrophysics Data System (ADS)

    Hirata, Akihiro

    1997-08-01

    The recent low price trend of electronic products has made IC manufacturing efficiency a top priority in the semiconductor industry. Post mold cure (PMC) process, which generally involves heating the packages in the oven at 175 C for 4 to 8 hours, takes up much longer time than most other assembly processes. If this PMC process can be reduced or eliminated, semiconductor makers will be rewarded with a much higher cost merit. We define the purpose of Non-PMC as 'to get high reliability with suitable physical and electrical properties without PMC'. We compared carious properties of molding compound before and after PMC. We found that curing reaction has almost complete through DSC and C-NMR measurement, but several properties have not stabilized yet, and that not all properties after PMC were better than before PMC. We developed new grade of molding compound considering these facts. And we found that main factors to accomplish non-PMC compound are curability and flowability, and more, increasing of fundamental properties. To accomplish non-PMC, at first, molding compound need to have very high curability. Generally speaking, too high curability causes low flowability, and causes incomplete filing, wire sweep, pad shift, and weak adhesion to inner parts of IC packages. To prevent these failures, various compound properties were studied, and we achieved in adding good flowability to very high curable molding compound. Finally, anti-popcorn property was improved by adding low moisture, high adhesion, high Tg, and high flexural strengths at high temperature. Through this study, we developed new compound grade for various package, especially large QFP using standard ECN resin.

  2. Human Endogenous Retrovirus and Neuroinflammation in Chronic Inflammatory Demyelinating Polyradiculoneuropathy

    PubMed Central

    Faucard, Raphaël; Madeira, Alexandra; Gehin, Nadège; Authier, François-Jérôme; Panaite, Petrica-Adrian; Lesage, Catherine; Burgelin, Ingrid; Bertel, Mélanie; Bernard, Corinne; Curtin, François; Lang, Aloïs B.; Steck, Andreas J.; Perron, Hervé; Kuntzer, Thierry; Créange, Alain

    2016-01-01

    Background Human endogenous retroviruses HERV-W encode a pro-inflammatory protein, named MSRV-Env from its original identification in Multiple Sclerosis. Though not detected in various neurological controls, MSRV-Env was found in patients with chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs). This study investigated the expression of MSRV in CIDP and evaluated relevant MSRV-Env pathogenic effects. Methods 50 CIDP patients, 19 other neurological controls (ONDs) and 65 healthy blood donors (HBDs) were recruited from two different countries. MSRV-env and -pol transcripts, IL6 and CXCL10 levels were quantified from blood samples. MSRV-Env immunohistology was performed in distal sensory nerves from CIDP and neurological controls biopsies. MSRV-Env pathogenic effects and mode of action were assayed in cultured primary human Schwann cells (HSCs). Findings In both cohorts, MSRV-env and -pol transcripts, IL6 positivity prevalence and CXCL10 levels were significantly elevated in CIDP patients when compared to HBDs and ONDs (statistically significant in all comparisons). MSRV-Env protein was detected in Schwann cells in 5/7 CIDP biopsies. HSC exposed to or transfected with MSRV-env presented a strong increase of IL6 and CXCL10 transcripts and protein secretion. These pathogenic effects on HSC were inhibited by GNbAC1, a highly specific and neutralizing humanized monoclonal antibody targeting MSRV-Env. Interpretation The present study showed that MSRV-Env may trigger the release of critical immune mediators proposed as instrumental factors involved in the pathophysiology of CIDP. Significant MSRV-Env expression was detected in a significant proportion of patients with CIDP, in which it may play a role according to its presently observed effects on Schwann cells along with previously known effects on immune cells. Experimental results also suggest that a biomarker-driven therapeutic strategy targeting this protein with a neutralizing antibody such as GNbAC1

  3. Can Neural Activity Propagate by Endogenous Electrical Field?

    PubMed Central

    Qiu, Chen; Shivacharan, Rajat S.; Zhang, Mingming

    2015-01-01

    It is widely accepted that synaptic transmissions and gap junctions are the major governing mechanisms for signal traveling in the neural system. Yet, a group of neural waves, either physiological or pathological, share the same speed of ∼0.1 m/s without synaptic transmission or gap junctions, and this speed is not consistent with axonal conduction or ionic diffusion. The only explanation left is an electrical field effect. We tested the hypothesis that endogenous electric fields are sufficient to explain the propagation with in silico and in vitro experiments. Simulation results show that field effects alone can indeed mediate propagation across layers of neurons with speeds of 0.12 ± 0.09 m/s with pathological kinetics, and 0.11 ± 0.03 m/s with physiologic kinetics, both generating weak field amplitudes of ∼2–6 mV/mm. Further, the model predicted that propagation speed values are inversely proportional to the cell-to-cell distances, but do not significantly change with extracellular resistivity, membrane capacitance, or membrane resistance. In vitro recordings in mice hippocampi produced similar speeds (0.10 ± 0.03 m/s) and field amplitudes (2.5–5 mV/mm), and by applying a blocking field, the propagation speed was greatly reduced. Finally, osmolarity experiments confirmed the model's prediction that cell-to-cell distance inversely affects propagation speed. Together, these results show that despite their weak amplitude, electric fields can be solely responsible for spike propagation at ∼0.1 m/s. This phenomenon could be important to explain the slow propagation of epileptic activity and other normal propagations at similar speeds. SIGNIFICANCE STATEMENT Neural activity (waves or spikes) can propagate using well documented mechanisms such as synaptic transmission, gap junctions, or diffusion. However, the purpose of this paper is to provide an explanation for experimental data showing that neural signals can propagate by means other than synaptic

  4. Analytical approach for the determination of steroid profile of humans by gas chromatography isotope ratio mass spectrometry aimed at distinguishing between endogenous and exogenous steroids.

    PubMed

    Bulska, Ewa; Gorczyca, Damian; Zalewska, Izabela; Pokrywka, Andrzej; Kwiatkowska, Dorota

    2015-03-15

    The contamination of commonly used supplements by unknown steroids as well as their metabolites (parent compounds) become a challenge for the analytical laboratories. Although the determination of steroids profile is not trivial because of the complex matrix and low concentration of single compound, one of the most difficult current problem is to distinguish, during analytical procedure, endogenous androgens such as testosterone, dehydrotestosterone or dehydroepiandrosterone from their synthetic equivalents. The aim of this work was to develop and validate an analytical procedure for determination of the steroid profile in human urine by gas chromatography-combustion-isotope ratio mass spectrometry (GC/C/IRMS) toward distinguishing between endogenous and exogenous steroids. Beside the optimization of the experimental parameters for gas chromatography separation and mass spectrometry, attention was focused on urine sample preparation. Using an optimized sample preparation protocol it was possible to achieve better chromatographic resolutions and better sensitivity enabling the determination of 5 steroids, androsterone, etiocholanolone, testosterone, 5-androstandiol, 11-hydroxyandrdostane, pregnandiol, with the expanded uncertainty (k=2) below 1‰. This enable to evaluate the significant shift of the δ(13)C/(12)C [‰] values for each of examined steroids (excluding ERC). The analytical protocol described in this work was successfully used for the confirmation of positive founding urine by evaluation T/E ratio after GC/C/IRMS analysis.

  5. Analytical approach for the determination of steroid profile of humans by gas chromatography isotope ratio mass spectrometry aimed at distinguishing between endogenous and exogenous steroids.

    PubMed

    Bulska, Ewa; Gorczyca, Damian; Zalewska, Izabela; Pokrywka, Andrzej; Kwiatkowska, Dorota

    2015-03-15

    The contamination of commonly used supplements by unknown steroids as well as their metabolites (parent compounds) become a challenge for the analytical laboratories. Although the determination of steroids profile is not trivial because of the complex matrix and low concentration of single compound, one of the most difficult current problem is to distinguish, during analytical procedure, endogenous androgens such as testosterone, dehydrotestosterone or dehydroepiandrosterone from their synthetic equivalents. The aim of this work was to develop and validate an analytical procedure for determination of the steroid profile in human urine by gas chromatography-combustion-isotope ratio mass spectrometry (GC/C/IRMS) toward distinguishing between endogenous and exogenous steroids. Beside the optimization of the experimental parameters for gas chromatography separation and mass spectrometry, attention was focused on urine sample preparation. Using an optimized sample preparation protocol it was possible to achieve better chromatographic resolutions and better sensitivity enabling the determination of 5 steroids, androsterone, etiocholanolone, testosterone, 5-androstandiol, 11-hydroxyandrdostane, pregnandiol, with the expanded uncertainty (k=2) below 1‰. This enable to evaluate the significant shift of the δ(13)C/(12)C [‰] values for each of examined steroids (excluding ERC). The analytical protocol described in this work was successfully used for the confirmation of positive founding urine by evaluation T/E ratio after GC/C/IRMS analysis. PMID:25498150

  6. Mitochondria-Targeted Protective Compounds in Parkinson's and Alzheimer's Diseases

    PubMed Central

    Fernández-Moriano, Carlos; González-Burgos, Elena; Gómez-Serranillos, M. Pilar

    2015-01-01

    Mitochondria are cytoplasmic organelles that regulate both metabolic and apoptotic signaling pathways; their most highlighted functions include cellular energy generation in the form of adenosine triphosphate (ATP), regulation of cellular calcium homeostasis, balance between ROS production and detoxification, mediation of apoptosis cell death, and synthesis and metabolism of various key molecules. Consistent evidence suggests that mitochondrial failure is associated with early events in the pathogenesis of ageing-related neurodegenerative disorders including Parkinson's disease and Alzheimer's disease. Mitochondria-targeted protective compounds that prevent or minimize mitochondrial dysfunction constitute potential therapeutic strategies in the prevention and treatment of these central nervous system diseases. This paper provides an overview of the involvement of mitochondrial dysfunction in Parkinson's and Alzheimer's diseases, with particular attention to in vitro and in vivo studies on promising endogenous and exogenous mitochondria-targeted protective compounds. PMID:26064418

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

    NASA Technical Reports Server (NTRS)

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

    2016-01-01

    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.

  8. Induction of Endogenous Reactive Oxygen Species in Mitochondria by Fullerene-Based Photodynamic Therapy.

    PubMed

    Li, Qian; Liu, Chenguang; Li, Hongguang

    2016-06-01

    The production of ROS in mitochondria plays critical role in photodynamic therapy (PDT). The aim of this study was to investigate whether fullerene-based PDT can induce generation of additional endogenous ROS in mitochondria. Chitosan oligosaccharide grafted fullerene conjugate (CS-C60) was synthesized as a model water-soluble fullerene. The relationship among photodynamic cytotoxicity, intracellular ROS and CS-C60 amount demonstrated that low dose fullerene could induce generation of endogenous ROS in human malignant melanoma (A375) cells. Laser scanning microscope (LSM) image shows that considerable amount of endogenous ROS was generated in mitochondria even CS-C60 could not localize into mitochondria. Assay with rotenone shows that PDT-induced endogenous ROS was generated via electron transport chain (ETC).

  9. In between: Gypsy in Drosophila melanogaster Reveals New Insights into Endogenous Retrovirus Evolution

    PubMed Central

    Touret, Franck; Guiguen, François; Greenland, Timothy; Terzian, Christophe

    2014-01-01

    Retroviruses are RNA viruses that are able to synthesize a DNA copy of their genome and insert it into a chromosome of the host cell. Sequencing of different eukaryote genomes has revealed the presence of many such endogenous retroviral sequences. The mechanisms by which these retroviral sequences have colonized the genome are still unknown, and the endogenous retrovirus gypsy of Drosophila melanogaster is a powerful experimental model for deciphering this process in vivo. Gypsy is expressed in a layer of somatic cells, and then transferred into the oocyte by an unknown mechanism. This critical step is the start of the endogenization process. Moreover gypsy has been shown to have infectious properties, probably due to its envelope gene acquired from a baculovirus. Recently we have also shown that gypsy maternal transmission is reduced in the presence of the endosymbiotic bacterium Wolbachia. These studies demonstrate that gypsy is a unique and powerful model for understanding the endogenization of retroviruses. PMID:25502325

  10. Quantifying the time scales over which exogenous and endogenous conditions affect soil respiration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Understanding how exogenous and endogenous factors and aboveground-belowground linkages modulate carbon dynamics is difficult because of influences of antecedent conditions. For example, there are variable lags between aboveground assimilation and belowground efflux, and the duration of antecedent p...

  11. The validity of four definitions of endogenous depression. II. Clinical, demographic, familial, and psychosocial correlates.

    PubMed

    Zimmerman, M; Coryell, W; Pfohl, B; Stangl, D

    1986-03-01

    Based on a survey of the classic literature and studies examining the correlates of a clinical diagnosis of endogenous or nonendogenous depression, we found 14 variables that should discriminate endogenous and nonendogenous depressives. We applied four definitions of endogenous depression (Feinberg and Carroll, DSM-III, Research Diagnostic Criteria, and Newcastle) to a consecutive series of 152 unipolar major depressive inpatients. We examined the concordance between the definitions and the relationship between each definition and clinical, demographic, family history, and psychosocial factors. The DSM-III and Newcastle definitions were less inclusive than the other two definitions. We found some support for the validity of each of the four definitions. The validity of the Newcastle scale was the most frequently supported, with the endogenous depressives having a lower rate of personality disorder, marital separations and divorces, familial alcoholism, life events, and nonserious suicide attempts. PMID:3954543

  12. Lack of differences in blood and tissue concentrations of endogenous ethanol in conventional and germfree rats.

    PubMed

    Jones, A W; Ostrovsky YuM; Wallin, A; Midtvedt, T

    1984-01-01

    Headspace gas chromatography was used to determine the concentrations of endogenous ethanol in blood and tissue of conventional and germfree rats. In all biological specimens analysed, the four principal volatile endogenous substances were identified as methanol, acetaldehyde, ethanol and acetone. No statistically significant differences in the concentrations of endogenous ethanol were noted between conventional and germfree animals. In whole blood, liver, kidney, and brain of germfree rats the concentrations of endogenous ethanol were 4.2 +/- 0.19 microM, 5.1 +/- 0.55 microM, 8.2 +/- 0.59 microM and 4.4 +/- 0.17 microM (means +/- SE), respectively. The higher concentration in kidney was also observed in conventional rats. Our results suggest that ethanol is a normal metabolic intermediate in rats and does not exclusively arise from microbial fermentation reactions in the gastrointestinal tract.

  13. Lens regeneration using endogenous stem cells with gain of visual function.

    PubMed

    Lin, Haotian; Ouyang, Hong; Zhu, Jie; Huang, Shan; Liu, Zhenzhen; Chen, Shuyi; Cao, Guiqun; Li, Gen; Signer, Robert A J; Xu, Yanxin; Chung, Christopher; Zhang, Ying; Lin, Danni; Patel, Sherrina; Wu, Frances; Cai, Huimin; Hou, Jiayi; Wen, Cindy; Jafari, Maryam; Liu, Xialin; Luo, Lixia; Zhu, Jin; Qiu, Austin; Hou, Rui; Chen, Baoxin; Chen, Jiangna; Granet, David; Heichel, Christopher; Shang, Fu; Li, Xuri; Krawczyk, Michal; Skowronska-Krawczyk, Dorota; Wang, Yujuan; Shi, William; Chen, Daniel; Zhong, Zheng; Zhong, Sheng; Zhang, Liangfang; Chen, Shaochen; Morrison, Sean J; Maas, Richard L; Zhang, Kang; Liu, Yizhi

    2016-03-17

    The repair and regeneration of tissues using endogenous stem cells represents an ultimate goal in regenerative medicine. To our knowledge, human lens regeneration has not yet been demonstrated. Currently, the only treatment for cataracts, the leading cause of blindness worldwide, is to extract the cataractous lens and implant an artificial intraocular lens. However, this procedure poses notable risks of complications. Here we isolate lens epithelial stem/progenitor cells (LECs) in mammals and show that Pax6 and Bmi1 are required for LEC renewal. We design a surgical method of cataract removal that preserves endogenous LECs and achieves functional lens regeneration in rabbits and macaques, as well as in human infants with cataracts. Our method differs conceptually from current practice, as it preserves endogenous LECs and their natural environment maximally, and regenerates lenses with visual function. Our approach demonstrates a novel treatment strategy for cataracts and provides a new paradigm for tissue regeneration using endogenous stem cells.

  14. Induction of Endogenous Reactive Oxygen Species in Mitochondria by Fullerene-Based Photodynamic Therapy.

    PubMed

    Li, Qian; Liu, Chenguang; Li, Hongguang

    2016-06-01

    The production of ROS in mitochondria plays critical role in photodynamic therapy (PDT). The aim of this study was to investigate whether fullerene-based PDT can induce generation of additional endogenous ROS in mitochondria. Chitosan oligosaccharide grafted fullerene conjugate (CS-C60) was synthesized as a model water-soluble fullerene. The relationship among photodynamic cytotoxicity, intracellular ROS and CS-C60 amount demonstrated that low dose fullerene could induce generation of endogenous ROS in human malignant melanoma (A375) cells. Laser scanning microscope (LSM) image shows that considerable amount of endogenous ROS was generated in mitochondria even CS-C60 could not localize into mitochondria. Assay with rotenone shows that PDT-induced endogenous ROS was generated via electron transport chain (ETC). PMID:27427601

  15. Lens regeneration using endogenous stem cells with gain of visual function.

    PubMed

    Lin, Haotian; Ouyang, Hong; Zhu, Jie; Huang, Shan; Liu, Zhenzhen; Chen, Shuyi; Cao, Guiqun; Li, Gen; Signer, Robert A J; Xu, Yanxin; Chung, Christopher; Zhang, Ying; Lin, Danni; Patel, Sherrina; Wu, Frances; Cai, Huimin; Hou, Jiayi; Wen, Cindy; Jafari, Maryam; Liu, Xialin; Luo, Lixia; Zhu, Jin; Qiu, Austin; Hou, Rui; Chen, Baoxin; Chen, Jiangna; Granet, David; Heichel, Christopher; Shang, Fu; Li, Xuri; Krawczyk, Michal; Skowronska-Krawczyk, Dorota; Wang, Yujuan; Shi, William; Chen, Daniel; Zhong, Zheng; Zhong, Sheng; Zhang, Liangfang; Chen, Shaochen; Morrison, Sean J; Maas, Richard L; Zhang, Kang; Liu, Yizhi

    2016-03-17

    The repair and regeneration of tissues using endogenous stem cells represents an ultimate goal in regenerative medicine. To our knowledge, human lens regeneration has not yet been demonstrated. Currently, the only treatment for cataracts, the leading cause of blindness worldwide, is to extract the cataractous lens and implant an artificial intraocular lens. However, this procedure poses notable risks of complications. Here we isolate lens epithelial stem/progenitor cells (LECs) in mammals and show that Pax6 and Bmi1 are required for LEC renewal. We design a surgical method of cataract removal that preserves endogenous LECs and achieves functional lens regeneration in rabbits and macaques, as well as in human infants with cataracts. Our method differs conceptually from current practice, as it preserves endogenous LECs and their natural environment maximally, and regenerates lenses with visual function. Our approach demonstrates a novel treatment strategy for cataracts and provides a new paradigm for tissue regeneration using endogenous stem cells. PMID:26958831

  16. Differing effects of exogenous and endogenous hydrogen sulphide in carrageenan-induced knee joint synovitis in the rat

    PubMed Central

    Ekundi-Valentim, E; Santos, KT; Camargo, EA; Denadai-Souza, A; Teixeira, SA; Zanoni, CI; Grant, AD; Wallace, JL; Muscará, MN; Costa, SK

    2010-01-01

    Background and purpose: Recent findings suggest that the noxious gas H2S is produced endogenously, and that physiological concentrations of H2S are able to modulate pain and inflammation in rodents. This study was undertaken to evaluate the ability of endogenous and exogenous H2S to modulate carrageenan-induced synovitis in the rat knee. Experimental approach: Synovitis was induced in Wistar rats by intra-articular injection of carrageenan into the knee joint. Sixty minutes prior to carrageenan injection, the rats were pretreated with indomethacin, an inhibitor of H2S formation (dl-propargylglycine) or an H2S donor [Lawesson's reagent (LR)]. Key results: Injection of carrageenan evoked knee inflammation, pain as characterized by impaired gait, secondary tactile allodynia of the ipsilateral hindpaw, joint swelling, histological changes, inflammatory cell infiltration, increased synovial myeloperoxidase, protein nitrotyrosine residues, inducible NOS (iNOS) activity and NO production. Pretreatment with LR or indomethacin significantly attenuated the pain responses, and all the inflammatory and biochemical changes, except for the increased iNOS activity, NO production and 3-NT. Propargylglycine pretreatment potentiated synovial iNOS activity (and NO production), and enhanced macrophage infiltration, but had no effect on other inflammatory parameters. Conclusions and implications: Whereas exogenous H2S delivered to the knee joint can produce a significant anti-inflammatory and anti-nociceptive effect, locally produced H2S exerts little immunomodulatory effect. These data further support the development and use of H2S donors as potential alternatives (or complementary therapies) to the available anti-inflammatory compounds used for treatment of joint inflammation or relief of its symptoms. PMID:20136840

  17. Metalloid compounds as drugs

    PubMed Central

    Sekhon, B. S.

    2013-01-01

    The six elements commonly known as metalloids are boron, silicon, germanium, arsenic, antimony, and tellurium. Metalloid containing compounds have been used as antiprotozoal drugs. Boron-based drugs, the benzoxaboroles have been exploited as potential treatments for neglected tropical diseases. Arsenic has been used as a medicinal agent and arsphenamine was the main drug used to treat syphilis. Arsenic trioxide has been approved for the treatment of acute promyelocytic leukemia. Pentavalent antimonials have been the recommended drug for visceral leishmaniasis and cutaneous leishmaniasis. Tellurium (IV) compounds may have important roles in thiol redox biological activity in the human body, and ammonium trichloro (dioxoethylene-O, O’-)tellurate (AS101) may be a promising agent for the treatment of Parkinson’s disease. Organosilicon compounds have been shown to be effective in vitro multidrug-resistance reverting agents. PMID:24019824

  18. Sulfur compounds in coal

    NASA Technical Reports Server (NTRS)

    Attar, A.; Corcoran, W. H.

    1977-01-01

    The literature on the chemical structure of the organic sulfur compounds (or functional groups) in coal is reviewed. Four methods were applied in the literature to study the sulfur compounds in coal: direct spectrometric and chemical analysis, depolymerization in drastic conditions, depolymerization in mild conditions, and studies on simulated coal. The data suggest that most of the organic sulfur in coal is in the form of thiophenic structures and aromatic and aliphatic sulfides. The relative abundance of the sulfur groups in bituminous coal is estimated as 50:30:20%, respectively. The ratio changes during processing and during the chemical analysis. The main effects are the transformation during processing of sulfides to the more stable thiophenic compounds and the elimination of hydrogen sulfide.

  19. Compound management beyond efficiency.

    PubMed

    Burr, Ian; Winchester, Toby; Keighley, Wilma; Sewing, Andreas

    2009-06-01

    Codeveloping alongside chemistry and in vitro screening, compound management was one of the first areas in research recognizing the need for efficient processes and workflows. Material management groups have centralized, automated, miniaturized and, importantly, found out what not to do with compounds. While driving down cost and improving quality in storage and processing, researchers still face the challenge of interfacing optimally with changing business processes, in screening groups, and with external vendors and focusing on biologicals in many companies. Here we review our strategy to provide a seamless link between compound acquisition and screening operations and the impact of material management on quality of the downstream processes. Although this is driven in part by new technologies and improved quality control within material management, redefining team structures and roles also drives job satisfaction and motivation in our teams with a subsequent positive impact on cycle times and customer feedback.

  20. Organic compounds in meteorites

    NASA Technical Reports Server (NTRS)

    Anders, E.; Hayatsu, R.; Studier, M. H.

    1973-01-01

    The problem of whether organic compounds originated in meteorites as a primary condensate from a solar gas or whether they were introduced as a secondary product into the meteorite during its residence in a parent body is examined by initially attempting to reconstruct the physical conditions during condensation (temperature, pressure, time) from clues in the inorganic matrix of the meteorite. The condensation behavior of carbon under these conditions is then analyzed on the basis of thermodynamic calculations, and compounds synthesized in model experiments on the condensation of carbon are compared with those actually found in meteorites. Organic compounds in meteorites seem to have formed by catalytic reactions of carbon monoxide, hydrogen, and ammonia in the solar nebula at 360 to 400 K temperature and about 3 to 7.6 microtorr pressure. The onset of these reactions was triggered by the formation of suitable catalysts (magnetite, hydrated silicates) at these temperatures.

  1. [Antibodies to endogenous bioregulators and their association with age and sex in chronic pain syndrome].

    PubMed

    Myagkova, M A; Petrochenko, S N; Morozova, V S; Moseikin, I A; Shypitsin, V V; Polyvyanaya, O Yu

    2013-01-01

    Authors studied changes in the levels of antibodies to endogenous bioregulators (Ab) to Β-endorphin, orphanin, serotonin, dopamine and angiotensin in 36 healthy people and 109 patients with dorsopathy with chronic pain syndrome. The association of these immunological indicators with age and sex was found. It has been concluded that the levels of Ab to endogenous bioregulators may be considered as a marker of algic system pathology that does not depend on age and is sex-related.

  2. [Antibodies to endogenous bioregulators and their association with age and sex in chronic pain syndrome].

    PubMed

    Myagkova, M A; Petrochenko, S N; Morozova, V S; Moseikin, I A; Shypitsin, V V; Polyvyanaya, O Yu

    2013-01-01

    Authors studied changes in the levels of antibodies to endogenous bioregulators (Ab) to Β-endorphin, orphanin, serotonin, dopamine and angiotensin in 36 healthy people and 109 patients with dorsopathy with chronic pain syndrome. The association of these immunological indicators with age and sex was found. It has been concluded that the levels of Ab to endogenous bioregulators may be considered as a marker of algic system pathology that does not depend on age and is sex-related. PMID:23739439

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

    PubMed

    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. PMID:26013541

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

    PubMed

    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.

  5. Movement of endogenous calcium in the elongating zone of graviresponding roots of Zea mays

    NASA Technical Reports Server (NTRS)

    Moore, R.; Cameron, I. L.; Smith, N. K.

    1989-01-01

    Endogenous calcium (Ca) accumulates along the lower side of the elongating zone of horizontally oriented roots of Zea mays cv. Yellow Dent. This accumulation of Ca correlates positively with the onset of gravicurvature, and occurs in the cytoplasm, cell walls and mucilage of epidermal cells. Corresponding changes in endogenous Ca do not occur in cortical cells of the elongating zone of intact roots. These results indicate that the calcium asymmetries associated with root gravicurvature occur in the outermost layers of the root.

  6. The induction of free proline accumulation by endogenous ABA in Arabidopsis thaliana during drought

    SciTech Connect

    Gottlieb, M.L.; Bray, E.A. )

    1991-05-01

    Endogenous levels of abscisic acid (ABA) and free proline increase in response to drought stress. Exogenous ABA has been shown to induce proline accumulation, suggesting that ABA triggers the amino acid response. To determine if endogenous ABA induces free proline accumulation, increases in ABA and proline during drought stress were compared between wild type (WT), ABA-insensitive (abi) and ABA-deficient (aba) mutants of Arabidopsis thaliana. If elevated levels of endogenous ABA signal the proline response, then the mutants would not be expected to accumulate proline during stress. abi should be unable to respond to increased levels of endogenous ABA, while aba should be unable to accumulate sufficient ABA to elicit a proline response. Drought-stressed three week old shoots of WT, abi, and aba exhibited different patterns of endogenous ABA accumulation, but similar patterns of proline accumulation over 24 hours. Although the patterns of endogenous ABA accumulation differed, maximum levels were similar in WT and abi, but aba produced approximately 25% less. However, free proline accumulated in all three plant lines. abi exhibited a greater, more rapid increase in free proline over that in either WT or aba. aba, however, showed the same pattern and levels of accumulation as that in WT. Since free proline accumulated to at least similar levels in both WT and mutants, regardless of the levels of ABA accumulation, it may be that only a small endogenous ABA accumulation is required for proline accumulation. Alternatively, endogenous ABA may not be the direct signal for the proline response during drought stress.

  7. Microoptical compound lens

    DOEpatents

    Sweatt, William C.; Gill, David D.

    2007-10-23

    An apposition microoptical compound lens comprises a plurality of lenslets arrayed around a segment of a hollow, three-dimensional optical shell. The lenslets collect light from an object and focus the light rays onto the concentric, curved front surface of a coherent fiber bundle. The fiber bundle transports the light rays to a planar detector, forming a plurality of sub-images that can be reconstructed as a full image. The microoptical compound lens can have a small size (millimeters), wide field of view (up to 180.degree.), and adequate resolution for object recognition and tracking.

  8. Endogenization of mouse mammary tumor virus (MMTV)-like elements in genomes of pikas (Ochotona sp.).

    PubMed

    Lemos de Matos, Ana; de Sousa-Pereira, Patrícia; Lissovsky, Andrey A; van der Loo, Wessel; Melo-Ferreira, José; Cui, Jie; Esteves, Pedro J

    2015-12-01

    Despite the finding in European rabbit and other leporid genomes of the first ever described endogenous lentivirus and of a European rabbit exclusive endogenous gammaretrovirus, until now no exogenous retroviruses have been isolated in Lagomorpha species. Nevertheless, looking for the presence of endogenous retroviruses (ERVs) in the species genomes could lead to the discovery of retroviral lineages yet to be found in Lagomorpha. Different mammalian genomes harbor endogenous viral sequences phylogenetically close to the betaretrovirus mouse mammary tumor virus (MMTV), propelling us to look for such retroviral "fossil" in American pika (Ochotona princeps) and European rabbit (Oryctolagus cuniculus) genomes. By performing genomic mining using MMTV gag and LTR as query sequences, we found that such viral elements were absent from the European rabbit genome. Oppositely, significant matches were found in American pika, and more importantly, a nearly complete MMTV-like virus (Pika-BERV) was identified. Using Pika-BERV gag and LTR as templates, we found similar sequences endogenized in different pika (Ochotona sp.) species. The orthology of the LTR flanking region between some pika species supported shared ancestry of specific endogenous betaretroviruses, while in other pika species similar sequences, but not orthologous, should have resulted from independent insertions. Our study supports the possible existence of infecting exogenous betaretroviruses for a long term, after the divergence of Ochotonidae from Leporidae, but yet to be identified. PMID:26151606

  9. Endogenous field feedback promotes the detectability for exogenous electric signal in the hybrid coupled population

    SciTech Connect

    Wei, Xile; Zhang, Danhong; Wang, Jiang; Yu, Haitao; Lu, Meili; Che, Yanqiu

    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.

  10. Determination of endogenous ethanol in blood and breath by gas chromatography-mass spectrometry.

    PubMed

    Jones, A W; Mårdh, G; Anggård, E

    1983-01-01

    We describe methods for the determination of endogenous ethanol in biological specimens from healthy abstaining subjects. The analytical methods were headspace gas chromatography (GC) for plasma samples and gas chromatography-mass spectometry (GC/MS) with deuterium labelled species 2H3-ethanol and 2H5-ethanol as internal standards for breath analysis. Ethanol in rebreathed air was about 10% higher than in directly analysed end-expired alveolar air. Known volumes of rebreathed air were passed through a liquid-N2 freeze trap and the volatile constituents of breath were concentrated prior to analysis by GC or GC/MS. Besides endogenous ethanol, peaks were seen on the chromatograms for methanol, acetone and acetaldehyde as well as several as yet unidentified substances. The endogenous alcohols ethanol and methanol were confirmed from their mass chromatograms and the GC/MS profile also indicated the presence of endogenous propan-1-ol. The concentration of endogenous ethanol in plasma showed wide inter-subject variations ranging from below detection limits to 1.6 micrograms/ml (34.8 mumol/l) and with mean +/- SD of 0.39 +/- 0.45 micrograms/ml (8.5 +/- 9.8 mumol/l). We aim to characterise further the role of endogenous ethanol with the main focus on dynamic aspects such as the rate of formation and turnover.

  11. A threshold of endogenous stress is required to engage cellular response to protect against mutagenesis.

    PubMed

    Saintigny, Yannick; Chevalier, François; Bravard, Anne; Dardillac, Elodie; Laurent, David; Hem, Sonia; Dépagne, Jordane; Radicella, J Pablo; Lopez, Bernard S

    2016-07-11

    Endogenous stress represents a major source of genome instability, but is in essence difficult to apprehend. Incorporation of labeled radionuclides into DNA constitutes a tractable model to analyze cellular responses to endogenous attacks. Here we show that incorporation of [(3)H]thymidine into CHO cells generates oxidative-induced mutagenesis, but, with a peak at low doses. Proteomic analysis showed that the cellular response differs between low and high levels of endogenous stress. In particular, these results confirmed the involvement of proteins implicated in redox homeostasis and DNA damage signaling pathways. Induced-mutagenesis was abolished by the anti-oxidant N-acetyl cysteine and plateaued, at high doses, upon exposure to L-buthionine sulfoximine, which represses cellular detoxification. The [(3)H]thymidine-induced mutation spectrum revealed mostly base substitutions, exhibiting a signature specific for low doses (GC > CG and AT > CG). Consistently, the enzymatic activity of the base excision repair protein APE-1 is induced at only medium or high doses. Collectively, the data reveal that a threshold of endogenous stress must be reached to trigger cellular detoxification and DNA repair programs; below this threshold, the consequences of endogenous stress escape cellular surveillance, leading to high levels of mutagenesis. Therefore, low doses of endogenous local stress can jeopardize genome integrity more efficiently than higher doses.

  12. Discrepancy of neural response between exogenous and endogenous task switching: an event-related potentials study.

    PubMed

    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.

  13. A threshold of endogenous stress is required to engage cellular response to protect against mutagenesis

    PubMed Central

    Saintigny, Yannick; Chevalier, François; Bravard, Anne; Dardillac, Elodie; Laurent, David; Hem, Sonia; Dépagne, Jordane; Radicella, J. Pablo; Lopez, Bernard S.

    2016-01-01

    Endogenous stress represents a major source of genome instability, but is in essence difficult to apprehend. Incorporation of labeled radionuclides into DNA constitutes a tractable model to analyze cellular responses to endogenous attacks. Here we show that incorporation of [3H]thymidine into CHO cells generates oxidative-induced mutagenesis, but, with a peak at low doses. Proteomic analysis showed that the cellular response differs between low and high levels of endogenous stress. In particular, these results confirmed the involvement of proteins implicated in redox homeostasis and DNA damage signaling pathways. Induced-mutagenesis was abolished by the anti-oxidant N-acetyl cysteine and plateaued, at high doses, upon exposure to L-buthionine sulfoximine, which represses cellular detoxification. The [3H]thymidine-induced mutation spectrum revealed mostly base substitutions, exhibiting a signature specific for low doses (GC > CG and AT > CG). Consistently, the enzymatic activity of the base excision repair protein APE-1 is induced at only medium or high doses. Collectively, the data reveal that a threshold of endogenous stress must be reached to trigger cellular detoxification and DNA repair programs; below this threshold, the consequences of endogenous stress escape cellular surveillance, leading to high levels of mutagenesis. Therefore, low doses of endogenous local stress can jeopardize genome integrity more efficiently than higher doses. PMID:27406380

  14. PERSISTENT PERFLUORINATED ORGANIC COMPOUNDS

    EPA Science Inventory

    Perfluorinated compounds (PFCs) have gained notoriety in the recent past. Global distribution of PFCs in wildlife, environmental samples and humans has sparked a recent increase in new investigations concerning PFCs. Historically PFCs have been used in a wide variety of consume...

  15. 8-fluoropurine compounds

    DOEpatents

    Barrio, Jorge R.; Satyamurthy, Nagichettiar; Namavari, Mohammad; Phelps, Michael E.

    2001-01-01

    An efficient, regiocontrolled approach to the synthesis of 8-fluoropurines by direct fluorination of purines with dilute elemental fluorine, or acetyl hypofluorite, is provided. In a preferred embodiment, a purine compound is dissolved in a polar solvent and reacted with a dilute mixture of F.sub.2 in He or other inert gas.

  16. Fun with Ionic Compounds

    ERIC Educational Resources Information Center

    Logerwell, Mollianne G.; Sterling, Donna R.

    2007-01-01

    Ionic bonding is a fundamental topic in high school chemistry, yet it continues to be a concept that students struggle to understand. Even if they understand atomic structure and ion formation, it can be difficult for students to visualize how ions fit together to form compounds. This article describes several engaging activities that help…

  17. Boron and Compounds

    Integrated Risk Information System (IRIS)

    Boron and Compounds ; CASRN 7440 - 42 - 8 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinoge

  18. Beryllium and compounds

    Integrated Risk Information System (IRIS)

    Beryllium and compounds ; CASRN 7440 - 41 - 7 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarci

  19. Selenium and Compounds

    Integrated Risk Information System (IRIS)

    Selenium and Compounds ; CASRN 7782 - 49 - 2 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcin

  20. Zinc and Compounds

    Integrated Risk Information System (IRIS)

    Zinc and Compounds ; CASRN 7440 - 66 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogen

  1. Lead and compounds (inorganic)

    Integrated Risk Information System (IRIS)

    Lead and compounds ( inorganic ) ; CASRN 7439 - 92 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for

  2. Aminopropyl thiophene compounds

    DOEpatents

    Goodman, Mark M.; Knapp, Jr., Furn F.

    1990-01-01

    Radiopharmaceuticals useful in brain imaging comprising radiohalogenated thienylethylamine derivatives. The compounds are 5-halo-thiophene-2-isopropyl amines able to cross the blood-brain barrier and be retained for a sufficient length of time to allow the evaluation of regional blood flow by radioimaging of the brain.

  3. Energies of organic compounds

    SciTech Connect

    Wiberg, K.B.

    1995-07-01

    The studies included hydrolysis of ketals, hydration of alkenes, barrier to rotation about C-O bonds in esters and acids, hydrolysis of lactones, reduction of ketones, non-bonded interactions, and enthalpies of vaporization of ketones, ketals, and other compounds.

  4. Compound floating pivot micromechanisms

    DOEpatents

    Garcia, Ernest J.

    2001-04-24

    A new class of tilting micromechanical mechanisms have been developed. These new mechanisms use compound floating pivot structures to attain far greater tilt angles than are practical using other micromechanical techniques. The new mechanisms are also capable of bi-directional tilt about multiple axes.

  5. Aminopropyl thiophene compounds

    SciTech Connect

    Goodman, M.M.; Knapp, F.F.

    1990-04-03

    This patent describes radiopharmaceuticals useful in brain imaging comprising radiohalogenated thienylethylamine derivatives. The compounds are 5-halo-thiophene-2-isopropyl amines able to cross the blood-brain barrier and be retained for a sufficient length of time to allow the evaluation of regional blood flow by radioimaging of the brain.

  6. Urinary Compounds in Autism

    ERIC Educational Resources Information Center

    Alcorn, A.; Berney, T.; Bretherton, K.; Mills, M.; Savery, D.; Shattock, P.

    2004-01-01

    Although earlier claims to identify specific compounds in the urine of people with autism had been discredited, it was subsequently suggested that there might be biochemical characteristics that were specific to early childhood, particularly in those who also did not have a severe degree of intellectual disability This study was to establish…

  7. Barium and Compounds

    Integrated Risk Information System (IRIS)

    Barium and Compounds ; CASRN 7440 - 39 - 3 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinog

  8. Noun Compounding in Thai.

    ERIC Educational Resources Information Center

    Fasold, Ralph William August

    The present study, a slightly revised version of the author's 1968 Ph.D. thesis presented to the University of Chicago, investigates compound formation in Thai. Chapter 1 summarizes the transformational generative theory on which the study is based, discusses the concept that Thai is a "simple" language in comparison with English, and briefly…

  9. 2011 CCNP Heinz Lehman Award paper: Searching for an endogenous anti-Alzheimer molecule: identifying small molecules in the brain that slow Alzheimer disease progression by inhibition of β-amyloid aggregation

    PubMed Central

    Meek, Autumn R.; Simms, Gordon A.; Weaver, Donald F.

    2013-01-01

    Background Alzheimer disease is a neurodegenerative disorder that progresses with marked interindividual clinical variability. We postulate the existence of endogenous molecules within the human brain exerting an antiaggregant activity that will prevent/slow Alzheimer disease progression. Methods We performed in silico studies to determine if the small endogenous molecules L-phosphoserine (L-PS) and 3-hydroxyanthranilic acid (3-HAA) could bind to the target region of β-amyloid responsible for protein misfolding. In vitro assays measured the antiaggregation effect of these molecules at varying concentrations. Results In silico studies demonstrated that L-PS and 3-HAA, both endogenous brain molecules, were capable of binding to the histidine13–histidine–glutamine–lysine16 (HHQK) region of β-amyloid involved in misfolding: these interactions were energetically favoured. The in vitro assays showed that both L-PS and 3-HAA were capable of inhibiting β-amyloid aggregation in a dose-dependent manner, with 3-HAA being more potent than L-PS. Limitations Studies were performed in silico and in vitro but not in vivo. Conclusion We successfully identified 2 endogenous brain molecules, L-PS and 3-HAA, that were capable of binding to the region of β-amyloid that leads to protein misfolding and neurotoxicity. Both L-PS and 3-HAA were able to inhibit β-amyloid aggregation in varying concentrations; levels of these compounds in the brain may impact their effectiveness in slowing/preventing β-amyloid aggregation. PMID:23394811

  10. Toxicity of dipyridyl compounds and related compounds.

    PubMed

    Li, Shenggang; Crooks, Peter A; Wei, Xiaochen; de Leon, Jose

    2004-01-01

    Five dipyridyl isomers, 2,2'-, 2,3'-, 2,4'-, 3,3'-, and 4,4'-dipyridyl, are products resulting from the pyrolytic degradation of tobacco products and degradation of the herbicide paraquat, and therefore may be present in the environment. In this article, the toxicological properties of these dipyridyl isomers in humans and animals are reviewed. Epidemiological studies suggest that cancerous skin lesions in workers involved in the manufacturing of paraquat may be associated with exposure to dipyridyl compounds. Experimental animal studies suggest that dipyridyl isomers may have several toxicological effects. Three of the dipyridyl isomers (the 2,2', 2,4', and 4,4' isomers) appear to be inducers of some metabolic enzymes. The 2,2'-dipyridyl isomer, an iron chelator, appears to influence vasospasm in primate models of stroke. The cytotoxic effects of 2,2'-dipyridyl on several leukemia cell lines have been reported, and a potent teratogenic effect of 2,2'-dipyridyl has been observed in rats. Based on the results of paraquat studies in experimental animal models, it has been proposed that paraquat may have deleterious effects on dopaminergic neurons. These findings support the epidemiological evidence that paraquat exposure may be associated with the development of Parkinson's disease. Studies designed to determine an association between paraquat exposure and Parkinson's disease are complicated by the possibility that metabolic changes may influence the neurotoxicity of paraquat and/or its metabolites. Preliminary unpublished data in mice show that 300-mg/kg doses of 2,2'-dipyridyl are neurotoxic, and 300-mg/kg doses of 2,4'- and 4,4'-dipyridyls are lethal. These results are consistent with earlier studies in Sherman rats using high 2,2'- and 4,4'-dipyridyl doses. New studies are needed to further explore the toxicological properties of dipyridyls and their potential public health impact.

  11. Selenium inhibits root elongation by repressing the generation of endogenous hydrogen sulfide in Brassica rapa.

    PubMed

    Chen, Yi; Mo, Hai-Zhen; Zheng, Mei-Yu; Xian, Ming; Qi, Zhong-Qiang; Li, You-Qin; Hu, Liang-Bin; Chen, Jian; Yang, Li-Fei

    2014-01-01

    Selenium (Se) has been becoming an emerging pollutant causing severe phytotoxicity, which the biochemical mechanism is rarely known. Although hydrogen sulfide (H2S) has been suggested as an important exogenous regulator modulating plant physiological adaptions in response to heavy metal stress, whether and how the endogenous H2S regulates Se-induce phytotoxicity remains unclear. In this work, a self-developed specific fluorescent probe (WSP-1) was applied to track endogenous H2S in situ in the roots of Brassica rapa under Se(IV) stress. Se(IV)-induced root growth stunt was closely correlated with the inhibition of endogenous H2S generation in root tips. Se(IV) stress dampened the expression of most LCD and DCD homologues in the roots of B. rapa. By using various specific fluorescent probes for bio-imaging root tips in situ, we found that the increase in endogenous H2S by the application of H2S donor NaHS could significantly alleviate Se(IV)-induced reactive oxygen species (ROS) over-accumulation, oxidative impairment, and cell death in root tips, which further resulted in the recovery of root growth under Se(IV) stress. However, dampening the endogenous H2S could block the alleviated effect of NaHS on Se(IV)-induced phytotoxicity. Finally, the increase in endogenous H2S resulted in the enhancement of glutathione (GSH) in Se(IV)-treated roots, which may share the similar molecular mechanism for the dominant role of H2S in removing ROS by activating GSH biosynthesis in mammals. Altogether, these data provide the first direct evidences confirming the pivotal role of endogenous H2S in modulating Se(IV)-induced phytotoxicity in roots.

  12. Selenium Inhibits Root Elongation by Repressing the Generation of Endogenous Hydrogen Sulfide in Brassica rapa

    PubMed Central

    Zheng, Mei-Yu; Xian, Ming; Qi, Zhong-Qiang; Li, You-Qin; Hu, Liang-Bin; Chen, Jian; Yang, Li-Fei

    2014-01-01

    Selenium (Se) has been becoming an emerging pollutant causing severe phytotoxicity, which the biochemical mechanism is rarely known. Although hydrogen sulfide (H2S) has been suggested as an important exogenous regulator modulating plant physiological adaptions in response to heavy metal stress, whether and how the endogenous H2S regulates Se-induce phytotoxicity remains unclear. In this work, a self-developed specific fluorescent probe (WSP-1) was applied to track endogenous H2S in situ in the roots of Brassica rapa under Se(IV) stress. Se(IV)-induced root growth stunt was closely correlated with the inhibition of endogenous H2S generation in root tips. Se(IV) stress dampened the expression of most LCD and DCD homologues in the roots of B. rapa. By using various specific fluorescent probes for bio-imaging root tips in situ, we found that the increase in endogenous H2S by the application of H2S donor NaHS could significantly alleviate Se(IV)-induced reactive oxygen species (ROS) over-accumulation, oxidative impairment, and cell death in root tips, which further resulted in the recovery of root growth under Se(IV) stress. However, dampening the endogenous H2S could block the alleviated effect of NaHS on Se(IV)-induced phytotoxicity. Finally, the increase in endogenous H2S resulted in the enhancement of glutathione (GSH) in Se(IV)-treated roots, which may share the similar molecular mechanism for the dominant role of H2S in removing ROS by activating GSH biosynthesis in mammals. Altogether, these data provide the first direct evidences confirming the pivotal role of endogenous H2S in modulating Se(IV)-induced phytotoxicity in roots. PMID:25333279

  13. Endogenous progesterone and its cellular binding sites in wheat exposed to drought stress.

    PubMed

    Janeczko, Anna; Oklešťková, Jana; Siwek, Agata; Dziurka, Michał; Pociecha, Ewa; Kocurek, Maciej; Novák, Ondřej

    2013-11-01

    Progesterone is a basic hormone that regulates the metabolism in mammals. The presence of this compound has also been found in certain plants. It is believed that progesterone can regulate growth processes and resistance to stress, however, its precise role in plants remains unknown. The research conducted in this study was aimed at analyzing the content of endogenous progesterone and its cellular binding sites in the leaves of spring wheat exposed to drought. Changes were studied in two cultivars of wheat - a cultivar sensitive to drought (Katoda) and tolerant cultivar (Monsun). Plants had undergone periodic droughts during the seedling stage or in the phase of heading. The occurrence of free progesterone as well as its conjugated forms was observed in wheat studied. The amount of progesterone ranged from 0.2 to 5.8pmolgFW(-1) and was dependent on the cultivar, age of the plants, stage of development and fluctuated as a result of the exposure to drought. Cv. Katoda responded to a water deficit by lowering the amount of progesterone and cv. Monsun by increasing its level. Progesterone in plants grown in limited water conditions occurred primarily in a free form. While in the optimal watering conditions, some of its pool was found in the form of conjugates. In the spring wheat the occurrence of binding sites for progesterone was detected in cell membranes, cytoplasm and nuclei in the range of 10-36fmol/mg of protein. The wheat cultivars tested, Monsun and Katoda, differ in their concentration of cellular binding sites for progesterone. This number varied in the individual fractions during different stages of plant development and due to the effect of drought stress. The number of binding sites for progesterone located in the membrane fraction of seedlings and flag leaves increased significantly under drought in the cv. Katoda (35-46%), but did not change in the cv. Monsun. Whereas the number of cytoplasmic progesterone binding sites increased during the drought in

  14. Endogenous progesterone and its cellular binding sites in wheat exposed to drought stress.

    PubMed

    Janeczko, Anna; Oklešťková, Jana; Siwek, Agata; Dziurka, Michał; Pociecha, Ewa; Kocurek, Maciej; Novák, Ondřej

    2013-11-01

    Progesterone is a basic hormone that regulates the metabolism in mammals. The presence of this compound has also been found in certain plants. It is believed that progesterone can regulate growth processes and resistance to stress, however, its precise role in plants remains unknown. The research conducted in this study was aimed at analyzing the content of endogenous progesterone and its cellular binding sites in the leaves of spring wheat exposed to drought. Changes were studied in two cultivars of wheat - a cultivar sensitive to drought (Katoda) and tolerant cultivar (Monsun). Plants had undergone periodic droughts during the seedling stage or in the phase of heading. The occurrence of free progesterone as well as its conjugated forms was observed in wheat studied. The amount of progesterone ranged from 0.2 to 5.8pmolgFW(-1) and was dependent on the cultivar, age of the plants, stage of development and fluctuated as a result of the exposure to drought. Cv. Katoda responded to a water deficit by lowering the amount of progesterone and cv. Monsun by increasing its level. Progesterone in plants grown in limited water conditions occurred primarily in a free form. While in the optimal watering conditions, some of its pool was found in the form of conjugates. In the spring wheat the occurrence of binding sites for progesterone was detected in cell membranes, cytoplasm and nuclei in the range of 10-36fmol/mg of protein. The wheat cultivars tested, Monsun and Katoda, differ in their concentration of cellular binding sites for progesterone. This number varied in the individual fractions during different stages of plant development and due to the effect of drought stress. The number of binding sites for progesterone located in the membrane fraction of seedlings and flag leaves increased significantly under drought in the cv. Katoda (35-46%), but did not change in the cv. Monsun. Whereas the number of cytoplasmic progesterone binding sites increased during the drought in

  15. Organic compounds in meteorites

    NASA Technical Reports Server (NTRS)

    Lawless, J. G.

    1980-01-01

    Recent studies of carbonaceous chondrites provide evidence that certain organic compounds are indigenous and the result of an abiotic, chemical synthesis. The results of several investigators have established the presence of amino acids and precursors, mono- and dicarboxylic acids, N-heterocycles, and hydrocarbons as well as other compounds. For example, studies of the Murchison and Murray meteorites have revealed the presence of at least 40 amino acids with nearly equal abundances of D and L isomers. The population consists of both protein and nonprotein amino acids including a wide variety of linear, cyclic, and polyfunctional types. Results show a trend of decreasing concentration with increasing carbon number, with the most abundant being glycine (41 n Moles/g). These and other results to be reviewed provide persuasive support for the theory of chemical evolution and provide the only natural evidence for the protobiological subset of molecules from which life on earth may have arisen.

  16. Development of an HPLC assay to study the effect of endogenous and exogenous substances on heat-induced aggregation of human serum albumin.

    PubMed

    Saso, L; Casini, M L; Valentini, G; Mattei, E; Panzironi, C; Silvestrini, B

    1998-03-01

    The mechanism of action of non-steroidal anti-inflammatory drugs which are used in high doses in chronic inflammatory conditions is not clearly understood. Their known protein-stabilizing properties could play a significant role. The inhibition of cyclooxygenase may not be essential for their anti-rheumatic activity, since compounds with strong anti-denaturant properties and devoid of anti-inflammatory activity were shown to be effective in an experimental model of rheumatoid arthritis. Hence, to develop new anti-rheumatic drugs it is essential that a simple in vitro method to evaluate the anti-denaturant activity of endogenous and exogenous compounds is available. We developed a new assay, using gel permeation high performance liquid chromatography, to study the effect of endogenous and exogenous compounds on heat-induced aggregation of human serum albumin in conditions in which protein precipitation does not occur. Non-steroidal anti-inflammatory drugs like diclofenac, ibuprofen and naproxen inhibited the aggregation of albumin at low concentrations (EC50 10(-4)-10(-5) mol/l) comparable to those active in a classical turbidimetric method, whereas the effect of weak stabilizers, like sodium cloride and formic, fumaric, maleic, malonic, and succinic acid (EC50 10(-1)-10(-2) mol/l in the Mizushima test) was not detectable. Furthermore, the HPLC assay allowed the examination of a number of coloured substances, including bilirubin, which appeared to be a strong stabilizer of its physiological carrier, albumin. These data could be clinically relevant, since the drugs examined are used at very high doses in rheumatoid arthritis and related conditions, with plasma levels that could cause significant stabilization of serum albumin and perhaps other proteins.

  17. Compound cycle engine program

    NASA Technical Reports Server (NTRS)

    Bobula, G. A.; Wintucky, W. T.; Castor, J. G.

    1987-01-01

    The Compound Cycle Engine (CCE) is a highly turbocharged, power compounded power plant which combines the lightweight pressure rise capability of a gas turbine with the high efficiency of a diesel. When optimized for a rotorcraft, the CCE will reduce fuel burn for a typical 2 hr (plus 30 min reserve) mission by 30 to 40 percent when compared to a conventional advanced technology gas turbine. The CCE can provide a 50 percent increase in range-payload product on this mission. A program to establish the technology base for a Compound Cycle Engine is presented. The goal of this program is to research and develop those technologies which are barriers to demonstrating a multicylinder diesel core in the early 1990's. The major activity underway is a three-phased contract with the Garrett Turbine Engine Company to perform: (1) a light helicopter feasibility study, (2) component technology development, and (3) lubricant and material research and development. Other related activities are also presented.

  18. Antifungal compounds from cyanobacteria.

    PubMed

    Shishido, Tânia K; Humisto, Anu; Jokela, Jouni; Liu, Liwei; Wahlsten, Matti; Tamrakar, Anisha; Fewer, David P; Permi, Perttu; Andreote, Ana P D; Fiore, Marli F; Sivonen, Kaarina

    2015-04-13

    Cyanobacteria are photosynthetic prokaryotes found in a range of environments. They are infamous for the production of toxins, as well as bioactive compounds, which exhibit anticancer, antimicrobial and protease inhibition activities. Cyanobacteria produce a broad range of antifungals belonging to structural classes, such as peptides, polyketides and alkaloids. Here, we tested cyanobacteria from a wide variety of environments for antifungal activity. The potent antifungal macrolide scytophycin was detected in Anabaena sp. HAN21/1, Anabaena cf. cylindrica PH133, Nostoc sp. HAN11/1 and Scytonema sp. HAN3/2. To our knowledge, this is the first description of Anabaena strains that produce scytophycins. We detected antifungal glycolipopeptide hassallidin production in Anabaena spp. BIR JV1 and HAN7/1 and in Nostoc spp. 6sf Calc and CENA 219. These strains were isolated from brackish and freshwater samples collected in Brazil, the Czech Republic and Finland. In addition, three cyanobacterial strains, Fischerella sp. CENA 298, Scytonema hofmanni PCC 7110 and Nostoc sp. N107.3, produced unidentified antifungal compounds that warrant further characterization. Interestingly, all of the strains shown to produce antifungal compounds in this study belong to Nostocales or Stigonematales cyanobacterial orders.

  19. Compound chondrules fused cold

    NASA Astrophysics Data System (ADS)

    Hubbard, Alexander

    2015-07-01

    About 4-5% of chondrules are compound: two separate chondrules stuck together. This is commonly believed to be the result of the two component chondrules having collided shortly after forming, while still molten. This allows high velocity impacts to result in sticking. However, at T ∼ 1100 K, the temperature below which chondrules collide as solids (and hence usually bounce), coalescence times for droplets of appropriate composition are measured in tens of seconds. Even at 1025 K, at which temperature theory predicts that the chondrules must have collided extremely slowly to have stuck together, the coalescence time scale is still less than an hour. These coalescence time scales are too short for the collision of molten chondrules to explain the observed frequency of compound chondrules. We suggest instead a scenario where chondrules stuck together in slow collisions while fully solid; and the resulting chondrule pair was subsequently briefly heated to a temperature in the range of 900-1025 K. In that temperature window the coalescence time is finite but long, covering a span of hours to a decade. This is particularly interesting because those temperatures are precisely the critical window for thermally ionized MRI activity, so compound chondrules provide a possible probe into that vital regime.

  20. Compound cycle engine program

    NASA Technical Reports Server (NTRS)

    Bobula, G. A.; Wintucky, W. T.; Castor, J. G.

    1986-01-01

    The Compound Cycle Engine (CCE) is a highly turbocharged, power compounded power plant which combines the lightweight pressure rise capability of a gas turbine with the high efficiency of a diesel. When optimized for a rotorcraft, the CCE will reduce fuel burned for a typical 2 hr (plus 30 min reserve) mission by 30 to 40 percent when compared to a conventional advanced technology gas turbine. The CCE can provide a 50 percent increase in range-payload product on this mission. A program to establish the technology base for a Compound Cycle Engine is presented. The goal of this program is to research and develop those technologies which are barriers to demonstrating a multicylinder diesel core in the early 1990's. The major activity underway is a three-phased contract with the Garrett Turbine Engine Company to perform: (1) a light helicopter feasibility study, (2) component technology development, and (3) lubricant and material research and development. Other related activities are also presented.