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Sample records for channel agonist bay

  1. Characteristics of the binding of [3H]nitrendipine to rabbit ventricular membranes: modification by other Ca++ channel antagonists and by the Ca++ channel agonist Bay K 8644

    International Nuclear Information System (INIS)

    Janis, R.A.; Sarmiento, J.G.; Maurer, S.C.; Bolger, G.T.; Triggle, D.J.

    1984-01-01

    This study was carried out to characterize [ 3 H]nitrendipine binding to cardiac membranes and to test the hypothesis that high affinity binding of Ca++ channel antagonists and agonists is to Ca++ channels. Binding was specific, rapid, reversible and stereoselective. The relative order of potency of nifedipine analogs for inhibition of binding was the same as that for inhibition of smooth and cardiac muscle contraction. Results with diltiazem, verapamil and lidoflazine were consistent with the hypothesis that nondihydropyridine Ca++ channel antagonists act at one or more sites allosterically linked to the 1,4-dihydropyridine site in cardiac cells. The Ca++ channel agonist Bay K 8644 [methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine- 5-carboxylate] displaced specifically bound [ 3 H]nitrendipine in an apparently competitive manner with an IC50 value of 5 nM. The results suggest that organic antagonists do not act by physically blocking the Ca++ channel. The data also support the hypothesis that the high affinity binding sites for [ 3 H]nitrendipine in isolated cardiac membranes are associated with Ca++ channels that are inactivated or are otherwise unavailable for opening

  2. Characteristics of the binding of (/sup 3/H)nitrendipine to rabbit ventricular membranes: modification by other Ca++ channel antagonists and by the Ca++ channel agonist Bay K 8644

    Energy Technology Data Exchange (ETDEWEB)

    Janis, R.A.; Sarmiento, J.G.; Maurer, S.C.; Bolger, G.T.; Triggle, D.J.

    1984-10-01

    This study was carried out to characterize (/sup 3/H)nitrendipine binding to cardiac membranes and to test the hypothesis that high affinity binding of Ca++ channel antagonists and agonists is to Ca++ channels. Binding was specific, rapid, reversible and stereoselective. The relative order of potency of nifedipine analogs for inhibition of binding was the same as that for inhibition of smooth and cardiac muscle contraction. Results with diltiazem, verapamil and lidoflazine were consistent with the hypothesis that nondihydropyridine Ca++ channel antagonists act at one or more sites allosterically linked to the 1,4-dihydropyridine site in cardiac cells. The Ca++ channel agonist Bay K 8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine- 5-carboxylate) displaced specifically bound (/sup 3/H)nitrendipine in an apparently competitive manner with an IC50 value of 5 nM. The results suggest that organic antagonists do not act by physically blocking the Ca++ channel. The data also support the hypothesis that the high affinity binding sites for (/sup 3/H)nitrendipine in isolated cardiac membranes are associated with Ca++ channels that are inactivated or are otherwise unavailable for opening.

  3. Calcium channel agonists and antagonists regulate protein phosphorylation in intact synaptosomes

    International Nuclear Information System (INIS)

    Robinson, P.J.; Lovenberg, Walter

    1986-01-01

    Protein phosphorylation in intact synaptosomes is highly sensitive to alterations in calcium fluxes and was used to probe the possible mechanism of action of the calcium channel agonist BAY K 8644 and antagonists verapamil and nifedipine. These agents (at 1μM) all increased the basal phosphorylation of a specific set of 4 synaptosomal phosphoproteins termed P139, P124, P96 and P60, but did not alter depolarization-dependent protein phosphorylation. The increases could not be explained by a direct stimulation of protein kinases and appears unrelated to the known effects of these + drugs on K + -stimulated neuro-transmitter release. This finding may reveal a possible new mechanism of action for drugs which interact with calcium channels. (Author)

  4. Study on origin and sedimentary environment of marine sediments from Kii Channel, Hiroshima Bay and Tosa Bay

    International Nuclear Information System (INIS)

    Suzuki, Misaki

    2008-01-01

    The trace amounts of elements in the sediments of sea bottom in Kii Channel, Hiroshima Bay and Tosa Bay were determined quantitatively by the neutron activation analysis. The following facts were illustrated particularly from the quantitative analysis of scandium, rare earths, thorium and uranium: 1) It was known from Ce/La ratio that the geological feature in the west part of Japan is reflected in Kii Channel, Hiroshima Bay and Tosa Bay; 2) The rare-earth element pattern and La/Lu ratio suggest the fact that Kii Channel, Hiroshima Bay and Tosa Bay are essentially composed of the materials of which origin is land; 3) From the fact that Ce/La ratio in these sites are slightly under 1.0, these sites are considered to be affected mainly by the materials of which origin is land; 4) The sedimentary environment in the marine bottom of the Japanese coasts has been found to be mostly under a reductive state. (M.H.)

  5. 33 CFR 117.753 - Ship Channel, Great Egg Harbor Bay.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Ship Channel, Great Egg Harbor Bay. 117.753 Section 117.753 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements New Jersey § 117.753 Ship Channel, Great Egg Harbor Bay. The draw of the S52 (Ship...

  6. Sigma-1 receptor agonists directly inhibit Nav1.2/1.4 channels.

    Directory of Open Access Journals (Sweden)

    Xiao-Fei Gao

    Full Text Available (+-SKF 10047 (N-allyl-normetazocine is a prototypic and specific sigma-1 receptor agonist that has been used extensively to study the function of sigma-1 receptors. (+-SKF 10047 inhibits K(+, Na(+ and Ca2+ channels via sigma-1 receptor activation. We found that (+-SKF 10047 inhibited Na(V1.2 and Na(V1.4 channels independently of sigma-1 receptor activation. (+-SKF 10047 equally inhibited Na(V1.2/1.4 channel currents in HEK293T cells with abundant sigma-1 receptor expression and in COS-7 cells, which barely express sigma-1 receptors. The sigma-1 receptor antagonists BD 1063,BD 1047 and NE-100 did not block the inhibitory effects of (+-SKF-10047. Blocking of the PKA, PKC and G-protein pathways did not affect (+-SKF 10047 inhibition of Na(V1.2 channel currents. The sigma-1 receptor agonists Dextromethorphan (DM and 1,3-di-o-tolyl-guanidine (DTG also inhibited Na(V1.2 currents through a sigma-1 receptor-independent pathway. The (+-SKF 10047 inhibition of Na(V1.2 currents was use- and frequency-dependent. Point mutations demonstrated the importance of Phe(1764 and Tyr(1771 in the IV-segment 6 domain of the Na(V1.2 channel and Phe(1579 in the Na(V1.4 channel for (+-SKF 10047 inhibition. In conclusion, our results suggest that sigma-1 receptor agonists directly inhibit Na(V1.2/1.4 channels and that these interactions should be given special attention for future sigma-1 receptor function studies.

  7. 33 CFR 165.1195 - Regulated Navigation Area; Humboldt Bay Bar Channel and Humboldt Bay Entrance Channel, Humboldt...

    Science.gov (United States)

    2010-07-01

    ... Entrance Channel, Humboldt Bay, California. (b) Definitions. As used in this section— COTP means the... person in charge of a vessel to which this notice applies shall obtain permission to cross within four... place during daylight hours, the vessel has only a single tow or no tow, the visibility at the bar is...

  8. G-protein mediates voltage regulation of agonist binding to muscarinic receptors: effects on receptor-Na+ channel interaction

    International Nuclear Information System (INIS)

    Cohen-Armon, M.; Garty, H.; Sokolovsky, M.

    1988-01-01

    The authors previous experiments in membranes prepared from rat heart and brain led them to suggest that the binding of agonist to the muscarinic receptors and to the Na + channels is a coupled event mediated by guanine nucleotide binding protein(s) [G-protein(s)]. These in vitro findings prompted us to employ synaptoneurosomes from brain stem tissue to examine (i) the binding properties of [ 3 H] acetylcholine at resting potential and under depolarization conditions in the absence and presence of pertussis toxin; (ii) the binding of [ 3 H]batrachotoxin to Na + channel(s) in the presence of the muscarinic agonists; and (iii) muscarinically induced 22 Na + uptake in the presence and absence of tetrodotoxin, which blocks Na + channels. The findings indicate that agonist binding to muscarinic receptors is voltage dependent, that this process is mediated by G-protein(s), and that muscarinic agonists induce opening of Na + channels. The latter process persists even after pertussis toxin treatment, indicating that it is not likely to be mediated by pertussis toxin sensitive G-protein(s). The system with its three interacting components-receptor, G-protein, and Na + channel-is such that at resting potential the muscarinic receptor induces opening of Na + channels; this property may provide a possible physiological mechanism for the depolarization stimulus necessary for autoexcitation or repetitive firing in heart or brain tissues

  9. Does centennial morphodynamic evolution lead to higher channel efficiency in San Pablo Bay, California?

    Science.gov (United States)

    van der Wegen, M.; Jaffe, B.E.; Barnard, P.L.; Jaffee, B.E.; Schoellhamer, D.H.

    2013-01-01

    Measured bathymetries on 30 year interval over the past 150 years show that San Pablo Bay experienced periods of considerable deposition followed by periods of net erosion. However, the main channel in San Pablo Bay has continuously narrowed. The underlying mechanisms and consequences of this tidal channel evolution are not well understood. The central question of this study is whether tidal channels evolve towards a geometry that leads to more efficient hydraulic conveyance and sediment throughput. We applied a hydrodynamic process-based, numerical model (Delft3D), which was run on 5 San Pablo Bay bathymetries measured between 1856 and 1983. Model results shows increasing energy dissipation levels for lower water flows leading to an approximately 15% lower efficiency in 1983 compared to 1856. During the same period the relative seaward sediment throughput through the San Pablo Bay main channel increased by 10%. A probable explanation is that San Pablo Bay is still affected by the excessive historic sediment supply. Sea level rise and Delta surface water area variations over 150 years have limited effect on the model results. With expected lower sediment concentrations in the watershed and less impact of wind waves due to erosion of the shallow flats, it is possible that energy dissipations levels will decrease again in future decades. Our study suggests that the morphodynamic adaptation time scale to excessive variations in sediment supply to estuaries may be on the order of centuries.

  10. Agonist of inward rectifier K+ channels enhances the protection of ischemic postconditioning in isolated rat hearts.

    Science.gov (United States)

    Liao, Z; Feng, Z; Long, C

    2014-07-01

    Selective inhibition of inward rectifier K + channels could abolish the protection mediated by ischemic preconditioning, but the roles of these channels in ischemic postconditioning have not been well characterized. Our study aims to evaluate the effect of inward rectifier K + channels on the protection induced by ischemic postconditioning. Langendorff-perfused rat hearts (n=8 per group) were split into four groups: postconditioning hearts (IPO group); ischemic postconditioning with BaCl 2 hearts (PB group); ischemic postconditioning with zacopride hearts (PZ group); and without ischemic postconditioning (CON group). After suffering 30 minutes of global ischemia, groups IPO, PB and PZ went through 10 seconds of ischemic postconditioning with three different perfusates: respectively, Krebs-Henseleit buffer (IPO group); 20 μmol/L BaCl 2 (antagonist of the channel, PB group); 1 μmol/L zacopride (agonist of the channel, PZ group). At the end of reperfusion, the myocardial performance was better preserved in the PZ group than the other three groups. The PB group showed no significant differences from the CON group. Our study has shown that the I K1 channel agonist zacopride is associated with the enhancement of ischemic postconditioning. © The Author(s) 2014.

  11. Endogenous Isoquinoline Alkaloids Agonists of Acid-Sensing Ion Channel Type 3

    Directory of Open Access Journals (Sweden)

    Dmitry I. Osmakov

    2017-09-01

    Full Text Available Acid-sensing ion channels (ASICs ASIC3 expressed mainly in peripheral sensory neurons play an important role in pain perception and inflammation development. In response to acidic stimuli, they can generate a unique biphasic current. At physiological pH 7.4, human ASIC3 isoform (hASIC3 is desensitized and able to generate only a sustained current. We found endogenous isoquinoline alkaloids (EIAs, which restore hASIC3 from desensitization and recover the transient component of the current. Similarly, rat ASIC3 isoform (rASIC3 can also be restored from desensitization (at pH < 7.0 by EIAs with the same potency. At physiological pH and above, EIAs at high concentrations were able to effectively activate hASIC3 and rASIC3. Thus, we found first endogenous agonists of ASIC3 channels that could both activate and prevent or reverse desensitization of the channel. The decrease of EIA levels could be suggested as a novel therapeutic strategy for treatment of pain and inflammation.

  12. Inverse agonist-like action of cadmium on G-protein-gated inward-rectifier K+ channels

    International Nuclear Information System (INIS)

    Inanobe, Atsushi; Matsuura, Takanori; Nakagawa, Atsushi; Kurachi, Yoshihisa

    2011-01-01

    Highlights: → We examined allosteric control of K + channel gating. → We identified a high-affinity site for Cd 2+ to inhibit Kir3.2 activity. → The 6-coordination geometry supports the binding. → Cd 2+ inhibits Kir3.2 by trapping the conformation in the closed state. -- Abstract: The gate at the pore-forming domain of potassium channels is allosterically controlled by a stimulus-sensing domain. Using Cd 2+ as a probe, we examined the structural elements responsible for gating in an inward-rectifier K + channel (Kir3.2). One of four endogenous cysteines facing the cytoplasm contributes to a high-affinity site for inhibition by internal Cd 2+ . Crystal structure of its cytoplasmic domain in complex with Cd 2+ reveals that octahedral coordination geometry supports the high-affinity binding. This mode of action causes the tethering of the N-terminus to CD loop in the stimulus-sensing domain, suggesting that their conformational changes participate in gating and Cd 2+ inhibits Kir3.2 by trapping the conformation in the closed state like 'inverse agonist'.

  13. Mesozooplankton assemblages in two bays in the Beagle Channel (Argentina during January, 2001

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    Melisa Daiana Fernández-Severini

    2005-12-01

    Full Text Available This paper describes the composition and abundance of mesozooplankton of Bahía Ushuaia and Bahía Golondrina. These small bays are located in the northern Beagle Channel. Sampling was carried out from January 20 to 23, 2001 and samples were collected from the upper layer at nine stations. This study is the first research on mesozooplankton in this part of the Beagle Channel. Due to their dominance in the mesozooplankton community, we compared our Copepoda data with those reported by other authors from Antarctic coastal environments. By applying cluster analysis, we found two station groups in both bays: one in slightly polluted zones and the other in undisturbed external zones. Four assemblages in Bahía Ushuaia and two in Bahía Golondrina were determined by using non-metric multidimensional scaling (MDS and cluster analysis. Mesozooplanktonic assemblages showed a certain resemblance in zones with and without anthropogenic influence. Most of the copepod species in our samples are typical of the sub-Antarctic region. Oithona similis (=O. helgolandica sensu Ramírez, 1966, Oncaea curvata, and Ctenocalanus citer show either similar or higher abundances at Antarctic coastal sites, including the upper layer in oceanic areas, in comparison with sub-Antarctic coastal localities. This suggests that, in agreement with other findings, the Polar Front is probably not a major geographic boundary for the distribution of these species.

  14. Inverse agonist-like action of cadmium on G-protein-gated inward-rectifier K{sup +} channels

    Energy Technology Data Exchange (ETDEWEB)

    Inanobe, Atsushi, E-mail: inanobe@pharma2.med.osaka-u.ac.jp [Department of Pharmacology, Graduate School of Medicine, Osaka University, Osaka (Japan); Center for Advanced Medical Engineering and Informatics, Osaka University, Osaka (Japan); Matsuura, Takanori [Laboratory of Protein Informatics, Institute for Protein Research, Osaka University, Osaka (Japan); Nakagawa, Atsushi [Laboratory of Supramolecular Crystallography, Institute for Protein Research, Osaka University, Osaka (Japan); Kurachi, Yoshihisa, E-mail: ykurachi@pharma2.med.osaka-u.ac.jp [Department of Pharmacology, Graduate School of Medicine, Osaka University, Osaka (Japan); Center for Advanced Medical Engineering and Informatics, Osaka University, Osaka (Japan)

    2011-04-08

    Highlights: {yields} We examined allosteric control of K{sup +} channel gating. {yields} We identified a high-affinity site for Cd{sup 2+} to inhibit Kir3.2 activity. {yields} The 6-coordination geometry supports the binding. {yields} Cd{sup 2+} inhibits Kir3.2 by trapping the conformation in the closed state. -- Abstract: The gate at the pore-forming domain of potassium channels is allosterically controlled by a stimulus-sensing domain. Using Cd{sup 2+} as a probe, we examined the structural elements responsible for gating in an inward-rectifier K{sup +} channel (Kir3.2). One of four endogenous cysteines facing the cytoplasm contributes to a high-affinity site for inhibition by internal Cd{sup 2+}. Crystal structure of its cytoplasmic domain in complex with Cd{sup 2+} reveals that octahedral coordination geometry supports the high-affinity binding. This mode of action causes the tethering of the N-terminus to CD loop in the stimulus-sensing domain, suggesting that their conformational changes participate in gating and Cd{sup 2+} inhibits Kir3.2 by trapping the conformation in the closed state like 'inverse agonist'.

  15. PPARα-Independent Arterial Smooth Muscle Relaxant Effects of PPARα Agonists

    Directory of Open Access Journals (Sweden)

    Neerupma Silswal

    2012-01-01

    Full Text Available We sought to determine direct vascular effects of peroxisome proliferator-activated receptor alpha (PPARα agonists using isolated mouse aortas and middle cerebral arteries (MCAs. The PPARα agonists GW7647, WY14643, and gemfibrozil acutely relaxed aortas held under isometric tension and dilated pressurized MCAs with the following order of potency: GW7647≫WY14643>gemfibrozil. Responses were endothelium-independent, and the use of PPARα deficient mice demonstrated that responses were also PPARα-independent. Pretreating arteries with high extracellular K+ attenuated PPARα agonist-mediated relaxations in the aorta, but not in the MCA. In the aorta, the ATP sensitive potassium (KATP channel blocker glibenclamide also impaired relaxations whereas the other K+ channel inhibitors, 4-aminopyridine and Iberiotoxin, had no effect. In aortas, GW7647 and WY14643 elevated cGMP levels by stimulating soluble guanylyl cyclase (sGC, and inhibition of sGC with ODQ blunted relaxations to PPARα agonists. In the MCA, dilations were inhibited by the protein kinase C (PKC activator, phorbol 12,13-dibutyrate, and also by ODQ. Our results demonstrated acute, nonreceptor-mediated relaxant effects of PPARα agonists on smooth muscle of mouse arteries. Responses to PPARα agonists in the aorta involved KATP channels and sGC, whereas in the MCA the PKC and sGC pathways also appeared to contribute to the response.

  16. Analysis of multi-channel seismic reflection and magnetic data along 13 degrees N latitude across the Bay of Bengal

    Digital Repository Service at National Institute of Oceanography (India)

    Rao, D.G.; Bhattacharya, G.C.; Ramana, M.V.; Subrahmanyam, V.; Ramprasad, T.; Krishna, K.S.; Chaubey, A.K.; Murty, G.P.S.; Srinivas, K.; Desa, M.; Reddy, S.I.; Ashalata, B.; Subrahmanyam, C.; Mital, G.S.; Drolia, R.K.; rai, S.N.; Ghosh, S.K.; Singh, R.N.; Majumdar, M.

    Analysis of the multi-channel seismic reflection, magnetic and bathymetric data collected along a transect, 1110 km long parallel to 13 degrees N lat. across the Bay of Bengal was made. The transect is from the continental shelf off Madras...

  17. Inotropic effect, binding properties, and calcium flux effects of the calcium channel agonist CGP 28392 in intact cultured embryonic chick ventricular cells

    International Nuclear Information System (INIS)

    Laurent, S.; Kim, D.; Smith, T.W.; Marsh, J.D.

    1985-01-01

    CGP 28392 is a recently described dihydropyridine derivative with positive inotropic properties. To study the mechanism of action of this putative calcium channel agonist, we have related the effects of CGP 28392 on contraction (measured with an optical video system) and radioactive calcium uptake to ligand-binding studies in cultured, spontaneously beating chick embryo ventricular cells. CGP 28392 produced a concentration-dependent increase in amplitude and velocity of contraction (EC 50 = 2 x 10(-7) M; maximum contractile effect = 85% of the calcium 3.6 mM response). Nifedipine produced a shift to the right of the concentration-effect curve for CGP 28392 without decreasing the maximum contractile response, suggesting competitive antagonism (pA2 = 8.3). Computer analysis of displacement of [ 3 H]nitrendipine binding to intact heart cells by unlabeled CGP 28392 indicated a K /sub D/ = 2.2 +/- 0.95 x 10(-7) M, in good agreement with the EC 50 for the inotropic effect. CGP 28392 increased the rate of radioactive calcium influx (+39% at 10 seconds) without altering beating rate, while nifedipine decreased radioactive calcium influx and antagonized the CGP 28392-induced increase in calcium influx. Our results indicate that, in intact cultured myocytes, CGP 28392 acts as a calcium channel agonist and competes for the dihydropyridine-binding site of the slow calcium channel. In contrast to calcium channel blockers, CGP 28392 increases calcium influx and enhances the contractile state

  18. Subaqueous hot springs in Köyceğiz Lake, Dalyan Channel and Fethiye-Göcek Bay (SW Turkey): Locations, chemistry and origins

    KAUST Repository

    Avşar, Ö zgü r; Avsar, Ulas; Arslan, Şebnem; Kurtuluş, Bedri; Niedermann, Samuel; Gü leç , Nilgü n

    2017-01-01

    In this study, horizontal temperature measurements along organized grids have been used to detect subaqueous hot springs. The study area, located in the southwest of Turkey and comprised of Köyceğiz Lake, Dalyan Channel and Fethiye-Göcek Bay

  19. Description of gravity cores from San Pablo Bay and Carquinez Strait, San Francisco Bay, California

    Science.gov (United States)

    Woodrow, Donald L.; John L. Chin,; Wong, Florence L.; Fregoso, Theresa A.; Jaffe, Bruce E.

    2017-06-27

    Seventy-two gravity cores were collected by the U.S. Geological Survey in 1990, 1991, and 2000 from San Pablo Bay and Carquinez Strait, California. The gravity cores collected within San Pablo Bay contain bioturbated laminated silts and sandy clays, whole and broken bivalve shells (mostly mussels), fossil tube structures, and fine-grained plant or wood fragments. Gravity cores from the channel wall of Carquinez Strait east of San Pablo Bay consist of sand and clay layers, whole and broken bivalve shells (less than in San Pablo Bay), trace fossil tubes, and minute fragments of plant material.

  20. Studies of movement of sediments in Santos bay

    International Nuclear Information System (INIS)

    Bandeira, J.V.; Aun, P.E.; Bomtempo, V.L.; Salim, L.H.; Minardi, P.S.P.; Santos, J.A.

    1990-01-01

    In the years of 1973, 74, 80, 81 and 85 several studies were performed at Santos bay, using radioactive tracers, with the following main objectives: to evaluate the behaviour (on the bottom and in suspension) of the mixture of silt and clay which is dredged from the estuary and from its access channel and dumped at pre-determined sites, in the bay and surrounding regions, with the objective of optimizing dredging disposal operations; to quantify the movement of sandy sediments on the bottom, in 3 areas of the bay, in summer and winter conditions, to obtain pertinent information related to the siltation of the access channel. As results of these studies, it was found that: the ancient dumping site, near Itaipu Point, in the western limit of the bay, was inadequate, since the material could return to the bay and to the estuary. The dumping site was moved to a region at the south of Moela Island, located eastwards relative to the bay, which brought substantial economies in dredging works; the bottom sediment transport was quantified, following clouds of tagged materials for about 8 months, thus obtaining important conclusions about transport rates in different regions of the bay. An analysis of the intervening hydrodynamic agents is also presented. (author) (L.J.C.)

  1. Recent research on the hydrodynamics of the Sacramento - San Joaquin River Delta and north San Francisco Bay

    Science.gov (United States)

    Burau, J.R.; Monismith, S.G.; Stacey, M.T.; Oltmann, R.N.; Lacy, J.R.; Schoellhamer, D.H.

    1999-01-01

    This article presents an overview of recent findings from hydrodynamic research on circulation and mixing in the Sacramento-San Joaquin Delta (Delta) (Figure 1) and North San Francisco Bay (North Bay) (Figure 2). For the purposes of this article, North Bay includes San Pablo Bay, Carquinez Strait, and Suisun Bay. The findings presented are those gained from field studies carried out by the U.S. Geological Survey (USGS), as part of the Interagency Ecological Program (IEP), and Stanford University beginning about 1993. The premise behind these studies was that a basic understanding of circulation and mixing patterns in the Bay and Delta is an essential part of understanding how biota and water quality are affected by natural hydrologic variability, water appropriation, and development activities. Data collected for the field studies described in this article have significantly improved our understanding of Bay and Delta hydrodynamics. Measured flows ,in the Delta have provided valuable information on how water moves through the Delta's network of channels and how export pumping affects flows. Studies of the shallows and shallow-channel exchange processes conducted in Honker Bay have shown that the water residence time in Honker Bay is much shorter than previously reported (on the order of hours to several tidal cycles instead ofweeks). Suisun Bay studies have provided data on hydrodynamic transport and accumulation mechanisms that operate primarily in the channels. The Suisun Bay studies have caused us to revise our understanding of residual circulation in the channels of North Bay and of "entrapment" mechanisms in the low salinity zone. Finally, detailed tidal and residual (tidally averaged) time-scale studies of the mechanisms that control gravitational circulation in the estuary show that density-driven transport in the channels is governed by turbulence time-scale (seconds) interactions between the mean flow and stratification. The hydrodynamic research

  2. Predicting seasonal variations in coastal seabird habitats in the English Channel and the Bay of Biscay

    Science.gov (United States)

    Virgili, A.; Lambert, C.; Pettex, E.; Dorémus, G.; Van Canneyt, O.; Ridoux, V.

    2017-07-01

    Seabirds, like all animals, have to live in suitable habitats to fulfil their energetic needs for both somatic and reproductive growth and maintenance. Apart from migration trips, all coastal seabirds are linked to the coast, because they need to return daily to land for resting or breeding. Their use of marine habitats strongly depends on their biology, but also on environmental conditions, and can be described using habitat models. This study aimed to: (1) identify the processes that mostly influence seabird distributions along the coasts of the English Channel and the Bay of Biscay; (2) determine seasonal variations of these processes, (3) provide prediction maps that describe the species distributions. We collected data of coastal seabird sightings from aerial surveys carried out in the English Channel and the eastern North Atlantic in the winter 2011-2012 and summer 2012. We classified seabirds into morphological groups and described their habitats using physiographic and oceanographic variables in Generalised Additive Models (GAMs). Finally, we produced maps of predicted distributions by season for each group. The distributions of coastal seabirds were essentially determined by the distance to the nearest coast, with a weaker influence of oceanographic variables. The nature of the substrate, sand or rock, combined with the timing of reproduction, also contributed to determine seasonal at-sea distributions for some species. The highest densities were predicted near the coast, particularly in bays and estuaries for strictly coastal species with possible variations depending on the season. From this study, we were able to predict the seasonal distribution of the studied species according to varying environmental parameters that changed over time, allowing us to understand better their behaviour and ecology.

  3. Chloride ions in the pore of glycine and GABA channels shape the time course and voltage dependence of agonist currents

    Science.gov (United States)

    Moroni, Mirko; Biro, Istvan; Giugliano, Michele; Vijayan, Ranjit; Biggin, Philip C.; Beato, Marco; Sivilotti, Lucia G.

    2011-01-01

    In the vertebrate CNS, fast synaptic inhibition is mediated by GABA and glycine receptors. We recently reported that the time course of these synaptic currents is slower when intracellular chloride is high. Here we extend these findings to measure the effects of both extracellular and intracellular chloride on the deactivation of glycine and GABA currents at both negative and positive holding potentials. Currents were elicited by fast agonist application to outside-out patches from HEK293 cells expressing rat glycine or GABA receptors. The slowing effect of high extracellular chloride on current decay was detectable only in low intracellular chloride (4 mM). Our main finding is that glycine and GABA receptors “sense” chloride concentrations because of interactions between the M2 pore-lining domain and the permeating ions. This hypothesis is supported by the observation that the sensitivity of channel gating to intracellular chloride is abolished if the channel is engineered to become cation-selective, or if positive charges in the external pore vestibule are eliminated by mutagenesis. The appropriate interaction between permeating ions and channel pore is also necessary to maintain the channel voltage sensitivity of gating, which prolongs current decay at depolarized potentials. Voltage-dependence is abolished by the same mutations that suppress the effect of intracellular chloride and also by replacing chloride with another permeant ion, thiocyanate. These observations suggest that permeant chloride affects gating by a foot-in-the-door effect, binding to a channel site with asymmetrical access from the intracellular and extracellular sides of the membrane. PMID:21976494

  4. Modern sedimentary environments in a large tidal estuary, Delaware Bay

    Science.gov (United States)

    Knebel, H.J.

    1989-01-01

    Data from an extensive grid of sidescan-sonar records reveal the distribution of sedimentary environments in the large, tidally dominated Delaware Bay estuary. Bathymetric features of the estuary include large tidal channels under the relatively deep (> 10 m water depth) central part of the bay, linear sand shoals (2-8 m relief) that parallel the sides of the tidal channels, and broad, low-relief plains that form the shallow bay margins. The two sedimentary environments that were identified are characterized by either (1) bedload transport and/or erosion or (2) sediment reworking and/or deposition. Sand waves and sand ribbons, composed of medium to coarse sands, define sites of active bedload transport within the tidal channels and in gaps between the linear shoals. The sand waves have spacings that vary from 1 to 70 m, amplitudes of 2 m or less, and crestlines that are usually straight. The orientations of the sand waves and ribbons indicate that bottom sediment movement may be toward either the northwest or southeast along the trends of the tidal channels, although sand-wave asymmetry indicates that the net bottom transport is directed northwestward toward the head of the bay. Gravelly, coarse-grained sediments, which appear as strongly reflective patterns on the sonographs, are also present along the axes and flanks of the tidal channels. These coarse sediments are lag deposits that have developed primarily where older strata were eroded at the bay floor. Conversely, fine sands that compose the linear shoals and muddy sands that cover the shallow bay margins appear mainly on the sonographs either as smooth featureless beds that have uniform light to moderate shading or as mosaics of light and dark patches produced by variations in grain size. These acoustic and textural characteristics are the result of sediment deposition and reworking. Data from this study (1) support the hypothesis that bed configurations under deep tidal flows are functions of current

  5. Modulation of Tidal Channel Signatures on SAR Images Over Gyeonggi Bay in Relation to Environmental Factors

    Directory of Open Access Journals (Sweden)

    Tae-Sung Kim

    2018-04-01

    Full Text Available In this study, variations of radar backscatter features of the tidal channel in Gyeonggi Bay in the Eastern Yellow Sea were investigated using spaceborne synthetic aperture radar (SAR images. Consistent quasi-linear bright features appeared on the SAR images. Examining the detailed local bathymetry chart, we found that the features were co-located with the major axis of the tidal channel in the region. It was also shown that modulation of the radar backscatter features changed according to the environmental conditions at the time of imaging. For the statistical analysis, the bathymetric features over the tidal channel were extracted by an objective method. In terms of shape, the extracted features had higher variability in width than in length. The analysis of the variation in intensity with the coinciding bathymetric distribution confirmed that the quasi-linear bright features on the SAR images are fundamentally imprinted due to the surface current convergence and divergence caused by the bathymetry-induced tidal current variation. Furthermore, the contribution of environmental factors to the intensity modulation was quantitatively analyzed. A comparison of the variation in normalized radar cross section (NRCS with tidal current showed a positive correlation only with the perpendicular component of tidal current (r= 0.47. This implies that the modulation in intensity of the tidal channel signatures is mainly affected by the interaction with cross-current flow. On the other hand, the modulation of the NRCS over the tidal channel tended to be degraded as wind speed increased (r= −0.65. Considering the environmental circumstances in the study area, it can be inferred that the imaging capability of SAR for the detection of tidal channel signatures mainly relies on wind speed.

  6. Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve

    Energy Technology Data Exchange (ETDEWEB)

    Matsushita, Akitomo; Ohtsubo, Sena; Fujita, Tsugumi; Kumamoto, Eiichi, E-mail: kumamote@cc.saga-u.ac.jp

    2013-04-26

    Highlights: •TRPA1 agonists inhibited compound action potentials in frog sciatic nerves. •This inhibition was not mediated by TRPA1 channels. •This efficacy was comparable to those of lidocaine and cocaine. •We found for the first time an ability of TRPA1 agonists to inhibit nerve conduction. -- Abstract: Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively) at high concentrations inhibit action potential conduction, it remains to be unknown whether TRPA1 agonists have a similar action. The present study examined the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC), which differ in chemical structure from each other, on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. CA and AITC concentration-dependently reduced the peak amplitude of the CAP with the IC{sub 50} values of 1.2 and 1.5 mM, respectively; these activities were resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1 antagonist HC-030031. The CA and AITC actions were distinct in property; the latter but not former action was delayed in onset and partially reversible, and CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by hydroxy-α-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1 channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC{sub 50} = 0.38 mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have an ability to inhibit nerve conduction without TRP activation, although their agonists are quite different in chemical structure from each other.

  7. Principles of agonist recognition in Cys-loop receptors

    Directory of Open Access Journals (Sweden)

    Timothy eLynagh

    2014-04-01

    Full Text Available Cys-loop receptors are ligand-gated ion channels that are activated by a structurally diverse array of neurotransmitters, including acetylcholine, serotonin, glycine and GABA. After the term chemoreceptor emerged over 100 years ago, there was some wait until affinity labeling, molecular cloning, functional studies and X-ray crystallography experiments identified the extracellular interface of adjacent subunits as the principal site of agonist binding. The question of how subtle differences at and around agonist-binding sites of different Cys-loop receptors can accommodate transmitters as chemically diverse as glycine and serotonin has been subject to intense research over the last three decades. This review outlines the functional diversity and current structural understanding of agonist-binding sites, including those of invertebrate Cys-loop receptors. Together, this provides a framework to understand the atomic determinants involved in how these valuable therapeutic targets recognize and bind their ligands.

  8. Physical processes in a coupled bay-estuary coastal system: Whitsand Bay and Plymouth Sound

    Science.gov (United States)

    Uncles, R. J.; Stephens, J. A.; Harris, C.

    2015-09-01

    Whitsand Bay and Plymouth Sound are located in the southwest of England. The Bay and Sound are separated by the ∼2-3 km-wide Rame Peninsula and connected by ∼10-20 m-deep English Channel waters. Results are presented from measurements of waves and currents, drogue tracking, surveys of salinity, temperature and turbidity during stratified and unstratified conditions, and bed sediment surveys. 2D and 3D hydrodynamic models are used to explore the generation of tidally- and wind-driven residual currents, flow separation and the formation of the Rame eddy, and the coupling between the Bay and the Sound. Tidal currents flow around the Rame Peninsula from the Sound to the Bay between approximately 3 h before to 2 h after low water and form a transport path between them that conveys lower salinity, higher turbidity waters from the Sound to the Bay. These waters are then transported into the Bay as part of the Bay-mouth limb of the Rame eddy and subsequently conveyed to the near-shore, east-going limb and re-circulated back towards Rame Head. The Simpson-Hunter stratification parameter indicates that much of the Sound and Bay are likely to stratify thermally during summer months. Temperature stratification in both is pronounced during summer and is largely determined by coastal, deeper-water stratification offshore. Small tidal stresses in the Bay are unable to move bed sediment of the observed sizes. However, the Bay and Sound are subjected to large waves that are capable of driving a substantial bed-load sediment transport. Measurements show relatively low levels of turbidity, but these respond rapidly to, and have a strong correlation with, wave height.

  9. Latest results from Daya Bay

    Science.gov (United States)

    Vorobel, Vit; Daya Bay Collaboration

    2017-07-01

    The Daya Bay Reactor Neutrino Experiment was designed to measure θ 13, the smallest mixing angle in the three-neutrino mixing framework, with unprecedented precision. The experiment consists of eight functionally identical detectors placed underground at different baselines from three pairs of nuclear reactors in South China. Since Dec. 2011, the experiment has been running stably for more than 4 years, and has collected the largest reactor anti-neutrino sample to date. Daya Bay is able to greatly improve the precision on θ 13 and to make an independent measurement of the effective mass splitting in the electron antineutrino disappearance channel. Daya Bay can also perform a number of other precise measurements, such as a high-statistics determination of the absolute reactor antineutrino flux and spectrum, as well as a search for sterile neutrino mixing, among others. The most recent results from Daya Bay are discussed in this paper, as well as the current status and future prospects of the experiment.

  10. Matagorda Ship Channel, Texas: Jetty Stability Study

    National Research Council Canada - National Science Library

    Kraus, Nicholas C; Lin, Lihwa; Batten, Brian K; Brown, Gary L

    2006-01-01

    .... The current has produced a large area of scour on the bay side of the inlet adjacent to the west jetty, and vessels encountering a strong along-channel and cross-channel current at the entrance...

  11. Properties of glutamate-gated ion channels in horizontal cells of the perch retina.

    Science.gov (United States)

    Schmidt, K F

    1997-08-01

    The effect of two different concentrations of L-glutamate and kainate on the gating kinetics of amino acid-sensitive non-NMDA channels were studied in cultured teleost retinal horizontal cells by single-channel recording and by noise analysis of whole-cell currents. When the glutamate agonist kainate was applied clearly parabolic mean-variance relations of whole-cell membrane currents (up to 3000 pA) indicated that this agonist was acting on one type of channels with a conductance of 5-10 pS. The cells were less sensitive when L-glutamate was used as the agonist and in most cases whole-cell currents amounted to less than 200 pA. The mean-variance relation of glutamate induced currents was complex, indicating that more than one type of channel opening could be involved. Power spectra of whole-cell currents were fitted with two Lorentzians with time constants of approx. 1 and 5-20 msec. Effects on amplitudes and time constants of agonist concentrations are demonstrated. Two categories of unitary events with mean open times of approx. 1 and 7 msec and conductances of approx. 7 and 12 pS, respectively, were obtained in single-channel recordings from cell-attached patches at different concentrations of glutamate in the pipette.

  12. Seasonal distribution and abundance of cetaceans within French waters- Part II: The Bay of Biscay and the English Channel

    Science.gov (United States)

    Laran, Sophie; Authier, Matthieu; Blanck, Aurélie; Doremus, Ghislain; Falchetto, Hélène; Monestiez, Pascal; Pettex, Emeline; Stephan, Eric; Van Canneyt, Olivier; Ridoux, Vincent

    2017-07-01

    From the Habitat Directive to the recent Marine Strategy Framework Directive, the conservation status of cetaceans in European water has been of concern for over two decades. In this study, a seasonal comparison of the abundance and distribution of cetaceans was carried out in two contrasted regions of the Eastern North Atlantic, the Bay of Biscay and the English Channel. Estimates were obtained in the two sub-regions (375,000 km²) from large aerial surveys conducted in the winter (November 2011 to February 2012) and in the summer (May to August 2012). The most abundant species encountered in the Channel, the harbour porpoise, displayed strong seasonal variations in its distribution but a stable abundance (18,000 individuals, CV=30%). In the Bay of Biscay, abundance and distribution patterns of common / striped dolphins varied from 285,000 individuals (95% CI: 174,000-481,000) in the winter, preferentially distributed close to the shelf break, to 494,000 individuals (95% CI: 342,000-719,000) distributed beyond the shelf break in summer. Baleen whales also exhibited an increase of their density in summer. Seasonal abundances of bottlenose dolphins were quite stable, with a large number of 'pelagic' encounters offshore in winter. No significant seasonal difference was estimated for pilot whales and sperm whale. These surveys provided baseline estimates to inform policies to be developed, or for existing conservation instruments such as the Habitats Directive. In addition, our results supported the hypothesis of a shift in the summer distributions of some species such as harbour porpoise and minke whale in European waters.

  13. PARTIAL AGONISTS, FULL AGONISTS, ANTAGONISTS - DILEMMAS OF DEFINITION

    NARCIS (Netherlands)

    HOYER, D; BODDEKE, HWGM

    The absence of selective antagonists makes receptor characterization difficult, and largely dependent on the use of agonists. However, there has been considerable debate as to whether certain drugs acting at G protein-coupled receptors are better described as agonists, partial agonists or

  14. Monitoring Water Quality at Lake Merritt, Oakland, CA Following Improvements to the Tidal Channel to the San Francisco Bay

    Science.gov (United States)

    Bracho, H.; Martinez, J.; Johnson, M.; Turrey, A.; Avila, M.; Medina, S.; Rubio, E.; Ahumada, E.; Nguyen, S.; Guzman, Y.

    2014-12-01

    Elliot Ahumada, Esosa Oghogho, Samantha Nguyen, Humberto Bracho, Diego Quintero, Ashanti Johnson and Kevin Cuff Lake Merritt is a tidal lagoon in the center of Oakland, California, just east of Downtown. Water quality at Lake Merritt has been a major concern for community members and researchers for many years (Pham 200X). Results of past research lead to recommendations to lengthen a channel that connects Lake Merritt with the San Francisco Bay to improve water flow and quality. In 2012 the City of Oakland responded to these recommendations by initiating the creation of a 230-meter long channel. In conducting our research we use a water quality index that takes into account measurements of pH, temperature, water hardness (dissolved solids), ammonia, salinity, dissolved oxygen, and nitrate. Newly collected data is then compared with that collected by Pham using comparable parameters to assess the impact of recent changes at the Lake on its overall water quality. In addition, we measured the abundance of aquatic species at four different sites within the Lake. Preliminary results suggest that an increase in the abundance of fish and improved overall water quality have resulted from channel extension at Lake Merritt.

  15. Mechanical stress activates NMDA receptors in the absence of agonists

    OpenAIRE

    Maneshi, Mohammad Mehdi; Maki, Bruce; Gnanasambandam, Radhakrishnan; Belin, Sophie; Popescu, Gabriela K.; Sachs, Frederick; Hua, Susan Z.

    2017-01-01

    While studying the physiological response of primary rat astrocytes to fluid shear stress in a model of traumatic brain injury (TBI), we found that shear stress induced Ca2+ entry. The influx was inhibited by MK-801, a specific pore blocker of N-Methyl-D-aspartic acid receptor (NMDAR) channels, and this occurred in the absence of agonists. Other NMDA open channel blockers ketamine and memantine showed a similar effect. The competitive glutamate antagonists AP5 and GluN2B-selective inhibitor i...

  16. A Unified Model of the GABA(A) Receptor Comprising Agonist and Benzodiazepine Binding Sites

    DEFF Research Database (Denmark)

    Kongsbak, Kristine Grønning; Bergmann, Rikke; Sørensen, Pernille Louise

    2013-01-01

    We present a full-length a1b2c2 GABA receptor model optimized for agonists and benzodiazepine (BZD) allosteric modulators. We propose binding hypotheses for the agonists GABA, muscimol and THIP and for the allosteric modulator diazepam (DZP). The receptor model is primarily based on the glutamate......-gated chloride channel (GluCl) from C. elegans and includes additional structural information from the prokaryotic ligand-gated ion channel ELIC in a few regions. Available mutational data of the binding sites are well explained by the model and the proposed ligand binding poses. We suggest a GABA binding mode...... of the agonists in the orthosteric site. The carbonyl group of DZP is predicted to interact with two threonines a1T206 and c2T142, similar to the acidic moiety of GABA. The chlorine atom of DZP is placed near the important a1H101 and the N-methyl group near a1Y159, a1T206, and a1Y209. We present a binding mode...

  17. Evacuation by sedimentary processes of fluvioglaciais glacier meltwater channels in Wanda, King George Island, Antarctica

    International Nuclear Information System (INIS)

    Da Rosa, K.; Vieira, R.; Velho, L.; Hammes, D.; Marquetto, L.; Lopes Simões, F.; Cardia Simões, J.

    2010-01-01

    Full text: Wanda Glacier is located on the western shore of Admiralty Bay, King George Island, Antarctic Peninsula . The glacier is characterized by the current land base and communicates with the Admiralty Bay through a proglacial lagoon, a result of the downturn in decades process. This generates glacier meltwater streams flowing through channels proglaciais falling on proglacial lagoon or directly on the bay, contributing suspended particulate matter into the bay .This paper presents preliminary results of field activities conducted in the glacier Wanda Operantar XXVIII, during the summer of 2009/10 . Investigates the influence of basal meltwater through fluvioglaciais channels and variability in suspended sediment evacuation by means of these, relating to the concentration of suspended particulate matter in the Bay, particularly in the cove Martel . Data were obtained through measurements of desgarga and the concentration of suspended material in the proglaciais defrost from the baseline flow of glacier water channels . Additionally, meteorological data such as rainfall, were associated with variations in the concentration of suspended sediment during the period . Was also made ​​in support of field mapping of meltwater channels

  18. 33 CFR 110.95 - Newport Bay Harbor, Calif.

    Science.gov (United States)

    2010-07-01

    ... 268° from Lido Isle East Light 2, this line being the northwest line of the main fairway; west of the... of a line bearing 268° from Newport Bay Channel Light 11, this line being the south line of the main... Channel Light 11, this line being the southerly line of the main fairway. Note: This area is reserved for...

  19. BAY K 8644-induced oscillations in rabbit gall-bladder transepithelial potential difference

    DEFF Research Database (Denmark)

    Hansen, C P; Holstein-Rathlou, N H; Frederiksen, O

    1986-01-01

    The effects of the Ca2+-channel activator BAY K 8644 (a novel dihydropyridine) on transepithelial potential difference (Pd), electrical resistance (Rt), and unidirectional Na+-fluxes were studied in the rabbit gall-bladder. It was observed that BAY K 8644 at concentrations between 10(-7) and 10...

  20. Low complexity variational bayes iterative reviver for MIMO-OFDM systems

    DEFF Research Database (Denmark)

    Xiong, Chunlin; Wang, Hua; Zhang, Xiaoying

    2009-01-01

    A low complexity iterative receiver is proposed in this paper for MIMO-OFDM systems in time-varying multi-path channel based on the variational Bayes (VB) method. According to the VB method, the estimation algorithms of the signal distribution and the channel distribution are derived for the rece...

  1. Seafloor geomorphology of western Antarctic Peninsula bays: a signature of ice flow behaviour

    Science.gov (United States)

    Munoz, Yuribia P.; Wellner, Julia S.

    2018-01-01

    Glacial geomorphology is used in Antarctica to reconstruct ice advance during the Last Glacial Maximum and subsequent retreat across the continental shelf. Analogous geomorphic assemblages are found in glaciated fjords and are used to interpret the glacial history and glacial dynamics in those areas. In addition, understanding the distribution of submarine landforms in bays and the local controls exerted on ice flow can help improve numerical models by providing constraints through these drainage areas. We present multibeam swath bathymetry from several bays in the South Shetland Islands and the western Antarctic Peninsula. The submarine landforms are described and interpreted in detail. A schematic model was developed showing the features found in the bays: from glacial lineations and moraines in the inner bay to grounding zone wedges and drumlinoid features in the middle bay and streamlined features and meltwater channels in the outer bay areas. In addition, we analysed local variables in the bays and observed the following: (1) the number of landforms found in the bays scales to the size of the bay, but the geometry of the bays dictates the types of features that form; specifically, we observe a correlation between the bay width and the number of transverse features present in the bays. (2) The smaller seafloor features are present only in the smaller glacial systems, indicating that short-lived atmospheric and oceanographic fluctuations, responsible for the formation of these landforms, are only recorded in these smaller systems. (3) Meltwater channels are abundant on the seafloor, but some are subglacial, carved in bedrock, and some are modern erosional features, carved on soft sediment. Lastly, based on geomorphological evidence, we propose the features found in some of the proximal bay areas were formed during a recent glacial advance, likely the Little Ice Age.

  2. Over 100 years of environmental change recorded by foraminifers and sediments in Mobile Bay, Alabama, Gulf of Mexico, USA

    Science.gov (United States)

    Osterman, Lisa E.; Smith, Christopher G.

    2012-12-01

    The marine microfauna of Mobile Bay has been profoundly influenced by the development and expansion of the primary shipping channel over the last ˜100 years. Foraminifers and sediments from seven box cores with excess lead-210 chronology document that channel dredging and spoil disposal have altered circulation, reduced estuarine mixing, changed sedimentation patterns, and caused a faunal turnover within the bay. Beginning in the late 1800s, changes in estuarine mixing allowed for greater low-pH freshwater influence in the bay, and ultimately began environmental changes that resulted in the loss of calcareous foraminifers. By the early 1900s, box cores throughout Mobile Bay record a ˜100-year trend of increasing calcareous test dissolution that continues to the present. Since the completion of the current shipping channel in the 1950s, restricted tidal flushing and increased terrestrial organic matter, documented by carbon-to-nitrogen ratios, stimulated an increase in agglutinated foraminiferal densities. However, in deeper areas of the bay, hypoxic water has negatively impacted the marine microfauna. Comparisons of the present-day foraminiferal assemblage with foraminifers collected in the early 1970s indicate that the continued biologic loss of calcareous foraminifers in the bay has allowed the introduction of a new agglutinated foraminiferal species into the bay.

  3. Functional TRP and ASIC-like channels in cultured urothelial cells from the rat.

    Science.gov (United States)

    Kullmann, F Aura; Shah, M A; Birder, L A; de Groat, W C

    2009-04-01

    Transient receptor potential (TRP) and acid-sensing ion channels (ASIC) are molecular detectors of chemical, mechanical, thermal, and nociceptive stimuli in sensory neurons. They have been identified in the urothelium, a tissue considered part of bladder sensory pathways, where they might play a role in bladder function. This study investigated functional properties of TRP and ASIC channels in cultured urothelial cells from the rat using patch-clamp and fura 2 Ca(2+) imaging techniques. The TRPV4 agonist 4alpha-phorbol-12,13 didecanoate (4alpha-PDD; 1-5 microM) and the TRPA1/TRPM8 agonist icilin (50-100 microM) elicited transient currents in a high percentage of cells (>70%). 4alpha-PDD responses were suppressed by the TRPV4 antagonist HC-010961 (10 microM). The TRPV1 agonist capsaicin (1-100 microM) and the TRPA1/TRPM8 agonist menthol (5-200 microM) elicited transient currents in a moderate percentage of cells ( approximately 25%). All of these agonists increased intracellular calcium concentration ([Ca(2+)](i)). Most cells responded to more than one TRP agonist (e.g., capsaicin and 4alpha-PDD), indicating coexpression of different TRP channels. In the presence of the TRPV1 antagonist capsazepine (10 microM), changes in pH induced by HCl elicited ionic currents (pH 5.5) and increased [Ca(2+)](i) (pH 6.5) in approximately 50% of cells. Changes in pH using acetic acid (pH 5.5) elicited biphasic-like currents. Responses induced by acid were sensitive to amiloride (10 microM). In summary, urothelial cells express multiple TRP and ASIC channels, whose activation elicits ionic currents and Ca(2+) influx. These "neuron-like" properties might be involved in transmitter release, such as ATP, that can act on afferent nerves or smooth muscle to modulate their responses to different stimuli.

  4. Seafloor geomorphology of western Antarctic Peninsula bays: a signature of ice flow behaviour

    Directory of Open Access Journals (Sweden)

    Y. P. Munoz

    2018-01-01

    Full Text Available Glacial geomorphology is used in Antarctica to reconstruct ice advance during the Last Glacial Maximum and subsequent retreat across the continental shelf. Analogous geomorphic assemblages are found in glaciated fjords and are used to interpret the glacial history and glacial dynamics in those areas. In addition, understanding the distribution of submarine landforms in bays and the local controls exerted on ice flow can help improve numerical models by providing constraints through these drainage areas. We present multibeam swath bathymetry from several bays in the South Shetland Islands and the western Antarctic Peninsula. The submarine landforms are described and interpreted in detail. A schematic model was developed showing the features found in the bays: from glacial lineations and moraines in the inner bay to grounding zone wedges and drumlinoid features in the middle bay and streamlined features and meltwater channels in the outer bay areas. In addition, we analysed local variables in the bays and observed the following: (1 the number of landforms found in the bays scales to the size of the bay, but the geometry of the bays dictates the types of features that form; specifically, we observe a correlation between the bay width and the number of transverse features present in the bays. (2 The smaller seafloor features are present only in the smaller glacial systems, indicating that short-lived atmospheric and oceanographic fluctuations, responsible for the formation of these landforms, are only recorded in these smaller systems. (3 Meltwater channels are abundant on the seafloor, but some are subglacial, carved in bedrock, and some are modern erosional features, carved on soft sediment. Lastly, based on geomorphological evidence, we propose the features found in some of the proximal bay areas were formed during a recent glacial advance, likely the Little Ice Age.

  5. Glutamate receptor agonists

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  6. Procaine rapidly inactivates acetylcholine receptors from Torpedo and competes with agonist for inhibition sites

    International Nuclear Information System (INIS)

    Forman, S.A.; Miller, K.W.

    1989-01-01

    The relationship between the high-affinity procaine channel inhibition site and the agonist self-inhibition site on acetylcholine receptors (AChRs) from Torpedo electroplaque was investigated by using rapid 86 Rb + quenched-flux assays at 4 degree C in native AChR-rich vesicles on which 50-60% of ACh activation sites were blocked with α-bungarotoxin (α-BTX). In the presence of channel-activating acetylcholine (ACh) concentrations alone, AChR undergoes one phase of inactivation in under a second. Addition of procaine produces two-phase inactivation similar to that seen with self-inhibiting ACh concentrations rapid inactivation complete in 30-75 ms is followed by fast desensitization at the same k d observed without procaine. The dependence of k r on [procaine] is consistent with a bimolecular association between procaine and its AChR site. Inhibition of AChR function by mixtures of procaine plus self-inhibiting concentrations of ACh or suberyldicholine was studied by reducing the level of α-BTX block in vesicles. The data support a mechanism where procaine binds preferentially to the open-channel AChR state, since no procaine-induced inactivation is observed without agonist and k r 's dependence on [ACh] in channel-activating range closely parallels that of 86 Rb + flux response to ACh

  7. Role of TRP Channels in Dinoflagellate Mechanotransduction.

    Science.gov (United States)

    Lindström, J B; Pierce, N T; Latz, M I

    2017-10-01

    Transient receptor potential (TRP) ion channels are common components of mechanosensing pathways, mainly described in mammals and other multicellular organisms. To gain insight into the evolutionary origins of eukaryotic mechanosensory proteins, we investigated the involvement of TRP channels in mechanosensing in a unicellular eukaryotic protist, the dinoflagellate Lingulodinium polyedra. BLASTP analysis of the protein sequences predicted from the L. polyedra transcriptome revealed six sequences with high similarity to human TRPM2, TRPM8, TRPML2, TRPP1, and TRPP2; and characteristic TRP domains were identified in all sequences. In a phylogenetic tree including all mammalian TRP subfamilies and TRP channel sequences from unicellular and multicellular organisms, the L. polyedra sequences grouped with the TRPM, TPPML, and TRPP clades. In pharmacological experiments, we used the intrinsic bioluminescence of L. polyedra as a reporter of mechanoresponsivity. Capsaicin and RN1734, agonists of mammalian TRPV, and arachidonic acid, an agonist of mammalian TRPV, TRPA, TRPM, and Drosophila TRP, all stimulated bioluminescence in L. polyedra. Mechanical stimulation of bioluminescence, but not capsaicin-stimulated bioluminescence, was inhibited by gadolinium (Gd 3+ ), a general inhibitor of mechanosensitive ion channels, and the phospholipase C (PLC) inhibitor U73122. These pharmacological results are consistent with the involvement of TRP-like channels in mechanosensing by L. polyedra. The TRP channels do not appear to be mechanoreceptors but rather are components of the mechanotransduction signaling pathway and may be activated via a PLC-dependent mechanism. The presence and function of TRP channels in a dinoflagellate emphasize the evolutionary conservation of both the channel structures and their functions.

  8. BAY 41-2272 activates host defence against local and disseminated Candida albicans infections

    Directory of Open Access Journals (Sweden)

    Paulo Vítor Soeiro-Pereira

    2015-02-01

    Full Text Available In our previous study, we have found that 5-cyclopropyl-2-[1-(2-fluoro-benzyl-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine (BAY 41-2272, a guanylate cyclase agonist, activates human monocytes and the THP-1 cell line to produce the superoxide anion, increasing in vitro microbicidal activity, suggesting that this drug can be used to modulate immune functioning in primary immunodeficiency patients. In the present work, we investigated the potential of the in vivo administration of BAY 41-2272 for the treatment of Candida albicans and Staphylococcus aureus infections introduced via intraperitoneal and subcutaneous inoculation. We found that intraperitoneal treatment with BAY 41-2272 markedly increased macrophage-dependent cell influx to the peritoneum in addition to macrophage functions, such as spreading, zymosan particle phagocytosis and nitric oxide and phorbol myristate acetate-stimulated hydrogen peroxide production. Treatment with BAY 41-2272 was highly effective in reducing the death rate due to intraperitoneal inoculation of C. albicans, but not S. aureus. However, we found that in vitro stimulation of peritoneal macrophages with BAY 41-2272 markedly increased microbicidal activities against both pathogens. Our results show that the prevention of death by the treatment of C. albicans-infected mice with BAY 41-2272 might occur primarily by the modulation of the host immune response through macrophage activation.

  9. Quantum-correlation breaking channels, quantum conditional probability and Perron-Frobenius theory

    Science.gov (United States)

    Chruściński, Dariusz

    2013-03-01

    Using the quantum analog of conditional probability and classical Bayes theorem we discuss some aspects of particular entanglement breaking channels: quantum-classical and classical-classical channels. Applying the quantum analog of Perron-Frobenius theorem we generalize the recent result of Korbicz et al. (2012) [8] on full and spectrum broadcasting from quantum-classical channels to arbitrary quantum channels.

  10. Quantum-correlation breaking channels, quantum conditional probability and Perron–Frobenius theory

    International Nuclear Information System (INIS)

    Chruściński, Dariusz

    2013-01-01

    Using the quantum analog of conditional probability and classical Bayes theorem we discuss some aspects of particular entanglement breaking channels: quantum–classical and classical–classical channels. Applying the quantum analog of Perron–Frobenius theorem we generalize the recent result of Korbicz et al. (2012) [8] on full and spectrum broadcasting from quantum–classical channels to arbitrary quantum channels.

  11. Over 100 years of environmental change recorded by foraminifers and sediments in a large Gulf of Mexico estuary, Mobile Bay, AL, USA

    Science.gov (United States)

    Osterman, Lisa E.; Smith, Christopher G.

    2012-01-01

    The marine microfauna of Mobile Bay has been profoundly influenced by the development and expansion of the primary shipping channel over the last ˜100 years. Foraminifers and sediments from seven box cores with excess lead-210 chronology document that channel dredging and spoil disposal have altered circulation, reduced estuarine mixing, changed sedimentation patterns, and caused a faunal turnover within the bay. Beginning in the late 1800s, changes in estuarine mixing allowed for greater low-pH freshwater influence in the bay, and ultimately began environmental changes that resulted in the loss of calcareous foraminifers. By the early 1900s, box cores throughout Mobile Bay record a ˜ 100-year trend of increasing calcareous test dissolution that continues to the present. Since the completion of the current shipping channel in the 1950s, restricted tidal flushing and increased terrestrial organic matter, documented by carbon-to-nitrogen ratios, stimulated an increase in agglutinated foraminiferal densities. However, in deeper areas of the bay, hypoxic water has negatively impacted the marine microfauna. Comparisons of the present-day foraminiferal assemblage with foraminifers collected in the early 1970s indicate that the continued biologic loss of calcareous foraminifers in the bay has allowed the introduction of a new agglutinated foraminiferal species into the bay.

  12. Immunolocalization and distribution of functional temperature-sensitive TRP channels in salivary glands.

    Science.gov (United States)

    Sobhan, Ubaidus; Sato, Masaki; Shinomiya, Takashi; Okubo, Migiwa; Tsumura, Maki; Muramatsu, Takashi; Kawaguchi, Mitsuru; Tazaki, Masakazu; Shibukawa, Yoshiyuki

    2013-11-01

    Transient receptor potential (TRP) cation channels are unique cellular sensors involved in multiple cellular functions. Their role in salivary secretion remains to be elucidated. The expression and localization of temperature-sensitive TRP channels in salivary (submandibular, sublingual and parotid) glands were analyzed by immunohistochemistry and quantitative real-time reverse transcription plus the polymerase chain reaction (RT-PCR). The effects of various TRP channel agonists on carbachol (CCh)-induced salivary secretion in the submandibular gland and on the intracellular Ca(2+) concentration ([Ca(2+)]i) in a submandibular epithelial cell line were also investigated. Immunohistochemistry revealed the expression of TRP-melastatin subfamily member 8 (TRPM8) and TRP-ankyrin subfamily member 1 (TRPA1) in myoepithelial, acinar and ductal cells in the sublingual, submandibular and parotid glands. In addition, TRP-vanilloid subfamily member 1 (TRPV1), TRPV3 and TRPV4 were also expressed in myoepithelial, acinar and ductal cells in all three types of gland. Quantitative real-time RT-PCR results demonstrated the mRNA expression of TRPV1, TRPV3, TRPV4, TRPM8 and TRPA1 in acinar and ductal cells in these salivary glands. Perfusion of the entire submandibular gland with the TRPV1 agonist capsaicin (1 μM) via the submandibular artery significantly increased CCh-induced salivation, whereas perfusion with TRPM8 and TRPA1 agonists (0.5 μM WS12 and 100 μM allyl isothiocyanate) decreased it. Application of agonists for each of the thermosensitive TRP channels increased [Ca(2+)]i in a submandibular epithelial cell line. These results indicate that temperature-sensitive TRP channels are localized and distributed in acinar, ductal and myoepithelial cells in salivary glands and that they play a functional role in the regulation and/or modulation of salivary secretion.

  13. Asymmetric fluxes of water and sediments in a mesotidal mudflat channel

    Science.gov (United States)

    Mariotti, G.; Fagherazzi, S.

    2011-01-01

    The hydrodynamics of a small tributary channel and its adjacent mudflat is studied in Willapa Bay, Washington State, USA. Velocity profiles and water levels are simultaneously measured at different locations in the channel and on the mudflat for two weeks. The above tidal flat and channel hydrodynamics differ remarkably during the tidal cycle. When the water surface level is above the tidal flat elevation, the channel is inactive. At this stage, the above tidal flat flow is predominantly aligned along the Bay axis, oscillating with the tide as a standing wave with peak velocities up to 0.3 m/s. When the mudflat becomes emergent, the flow concentrates in the channel. During this stage, current velocities up to 1 m/s are measured during ebb; and up to 0.6 m/s during flood. Standard equations for open-channel flow are utilized to study the channel hydrodynamics. From the continuity equation, a lateral inflow is predicted during ebb, which likely originates from the drainage of the mudflat through the lateral runnels. Both advective acceleration and lateral discharge terms, estimated directly from the velocity profiles, play a significant role in the momentum equation. The computed drag coefficient for bottom friction is small, due to an absence of vegetation and bottom bedforms in the channel. Sediment fluxes are calculated by combining flow and suspended sediment concentration estimated using the acoustic backscatter signal of the instruments. A net export of the sediment from the channel is found during ebb, which is not balanced by the sediment import during flood. When the mudflat is submerged, ebb-flood asymmetries in suspended sediment concentration are present, leading to a net sediment flux toward the inner part of the Willapa Bay. Finally, a residual flow is detected inside the channel at high slack water, probably associated with the thermohaline circulation.

  14. Single Channel Analysis of Isoflurane and Ethanol Enhancement of Taurine-Activated Glycine Receptors.

    Science.gov (United States)

    Kirson, Dean; Todorovic, Jelena; Mihic, S John

    2018-01-01

    The amino acid taurine is an endogenous ligand acting on glycine receptors (GlyRs), which is released by astrocytes in many brain regions, such as the nucleus accumbens and prefrontal cortex. Taurine is a partial agonist with an efficacy significantly lower than that of glycine. Allosteric modulators such as ethanol and isoflurane produce leftward shifts of glycine concentration-response curves but have no effects at saturating glycine concentrations. In contrast, in whole-cell electrophysiology studies these modulators increase the effects of saturating taurine concentrations. A number of possible mechanisms may explain these enhancing effects, including modulator effects on conductance, channel open times, or channel closed times. We used outside-out patch-clamp single channel electrophysiology to investigate the mechanism of action of 200 mM ethanol and 0.55 mM isoflurane in enhancing the effects of a saturating concentration of taurine. Neither modulator enhanced taurine-mediated conductance. Isoflurane increased the probability of channel opening. Isoflurane also increased the lifetimes of the two shortest open dwell times while both agents decreased the likelihood of occurrence of the longest-lived intracluster channel-closing events. The mechanism of enhancement of GlyR functioning by these modulators is dependent on the efficacy of the agonist activating the receptor and the concentration of agonist tested. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  15. Post-Translational Modifications of TRP Channels

    Directory of Open Access Journals (Sweden)

    Olaf Voolstra

    2014-04-01

    Full Text Available Transient receptor potential (TRP channels constitute an ancient family of cation channels that have been found in many eukaryotic organisms from yeast to human. TRP channels exert a multitude of physiological functions ranging from Ca2+ homeostasis in the kidney to pain reception and vision. These channels are activated by a wide range of stimuli and undergo covalent post-translational modifications that affect and modulate their subcellular targeting, their biophysical properties, or channel gating. These modifications include N-linked glycosylation, protein phosphorylation, and covalent attachment of chemicals that reversibly bind to specific cysteine residues. The latter modification represents an unusual activation mechanism of ligand-gated ion channels that is in contrast to the lock-and-key paradigm of receptor activation by its agonists. In this review, we summarize the post-translational modifications identified on TRP channels and, when available, explain their physiological role.

  16. Canonical sound speed profile for the central Bay of Bengal

    Digital Repository Service at National Institute of Oceanography (India)

    Murty, T.V.R.; PrasannaKumar, S.; Somayajulu, Y.K.; Sastry, J.S.; De Figueiredo, R.J.P.

    Following Munk's canonical theory, an algorithm has been presented for computing sound channel parameters in the western and southern Bay of Bengal. The estimated canonical sound speed profile using these parameters has been compared with computed...

  17. A study of the degree of Pollution in Nakivubo Channel, Kampala ...

    African Journals Online (AJOL)

    Nakivubo channel traverses highly populated Kampala slums, markets, industrial areas and a wetland. It discharges its water at Murchison bay in Lake Victoria. The degree of pollution in the channel has a direct effect on the aquatic life in the lake, the health of communities along the channel, and the cost of water treatment ...

  18. Responses of water environment to tidal flat reduction in Xiangshan Bay: Part I hydrodynamics

    Science.gov (United States)

    Li, Li; Guan, Weibing; Hu, Jianyu; Cheng, Peng; Wang, Xiao Hua

    2018-06-01

    Xiangshan Bay consists of a deep tidal channel and three shallow inlets. A large-scale tidal flat has been utilized through coastal construction. To ascertain the accumulate influences of these engineering projects upon the tidal dynamics of the channel-inlets system, this study uses FVCOM to investigate the tides and flow asymmetries of the bay, and numerically simulate the long-term variations of tidal dynamics caused by the loss of tidal flats. It was found that the reduction of tidal flat areas from 1963 to 2010 slightly dampened M2 tidal amplitudes (0.1 m, ∼6%) and advanced its phases by reducing shoaling effects, while amplified M4 tidal amplitudes (0.09 m, ∼27%) and advanced its phases by reducing bottom friction, in the inner bay. Consequently, the ebb dominance was dampened indicated by reduced absolute value of elevation skewness (∼20%) in the bay. The tides and tidal asymmetry were impacted by the locations, areas and slopes of the tidal flats through changing tidal prism, shoaling effect and bottom friction, and consequently impacted tidal duration asymmetry in the bay. Tides and tidal asymmetry were more sensitive to the tidal flat at the head of the bay than the side bank. Reduced/increased tidal flat slopes around the Tie inlet dampened the ebb dominance. Tidal flat had a role in dissipating the M4 tide rather than generating it, while the advection only play a secondary role in generating the M4 tide. The full-length tidal flats reclamation would trigger the reverse of ebb to flood dominance in the bay. This study would be applicable for similar narrow bays worldwide.

  19. Persistent organochlorine pollutants in eggs of colonial waterbirds from Galveston Bay and East Texas, USA

    Science.gov (United States)

    Frank, D.S.; Mora, M.A.; Sericano, J.L.; Blankenship, Alan L.; Kannan, K.; Giesy, J.P.

    2001-01-01

    Eggs of neotropic cormorants (Phalacrocorax brasilianus), black-crowned night herons (Nycticorax nycticorax), and great egrets (Ardea alba) nesting on several locations in Galveston Bay (TX, USA) and at two control sites outside the bay were collected during April–May 1996 and analyzed for chlorinated pesticides, PCBs, polychlorinated dibenzo-p-dioxins, and polychlor-inated dibenzofurans. Additionally, concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TCDD-EQs) were determined by use of relative potency factors (TEQs) or the H4IIE-luc bioassay TCDD-EQs. Concentrations of 1,1,-dichloro-2,2-bis(p-chlo-rophenyl)ethylene (DDE) were greater in eggs of neotropic cormorants from Alexander Island (mean = 1,040 ng/g wet wt) in the Houston Ship Channel (Houston, TX, USA) and in those from Telfair Island (mean = 1,460 ng/g wet wt), a reference location outside the bay, than in most locations inside the bay (mean range = 119–453 ng/g wet wt). Mean PCB concentrations were greater in eggs of neotropic cormorants from Alexander Island (mean = 5,720 ng/g wet wt) than in eggs of cormorants from areas farther away from the ship channel, including two reference sites outside the bay (mean range = 404–3,140 ng/g wet wt). The TCDD was the main dioxin congener detected in eggs from all locations within Galveston Bay. Instrumental TEQs in eggs ranged from 67 pg/g wet weight at control sites to 452 pg/g wet weight at Alexander Island. Concentrations of TCDD-EQs determined in the H4IIE assay were correlated with instrumental TEQs and were greater in eggs of cormorants from islands within the bay, although these were farther away from the ship channel. Overall, concentrations of DDE, PCBs, TCDD, and TCDD-EQs were less than the threshold levels known to affect reproduction. However, some eggs contained concentrations of total PCBs or DDE greater than what would elicit adverse effects on birds. No identifiable deformities or abnormalities were detected in embryos

  20. Benthic foraminiferal census data from Mobile Bay, Alabama--counts of surface samples and box cores

    Science.gov (United States)

    Richwine, Kathryn A.; Osterman, Lisa E.

    2012-01-01

    A study was undertaken in order to understand recent environmental change in Mobile Bay, Alabama. For this study a series of surface sediment and box core samples was collected. The surface benthic foraminiferal data provide the modern baseline conditions of the bay and can be used as a reference for changing paleoenvironmental parameters recorded in the box cores. The 14 sampling locations were chosen in the bay to cover the wide diversity of fluvial and marine-influenced environments on both sides of the shipping channel.

  1. Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders.

    Science.gov (United States)

    Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; De Maeyer, J H; Stanghellini, V

    2012-04-01

    The nonselective 5-HT(4) receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT(4) agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006-2008 and DDW 2008-2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT(4) agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT(4) agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT(1) receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT(4) agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT(4) agonists with no hERG or 5-HT(1) affinity (renzapride, clebopride, mosapride). 5-HT(4) agonists for GI disorders differ in chemical structure and selectivity for 5-HT(4) receptors. Selectivity for 5-HT(4) over non-5-HT(4) receptors may influence the agent's safety and overall risk-benefit profile. Based on available evidence, highly selective 5-HT(4) agonists may offer improved safety to treat patients with impaired GI motility. © 2012 Blackwell Publishing Ltd.

  2. Systematic review: cardiovascular safety profile of 5-HT4 agonists developed for gastrointestinal disorders

    Science.gov (United States)

    Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; Maeyer, J H; Stanghellini, V

    2012-01-01

    Summary Background The nonselective 5-HT4 receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). Aim To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT4 agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Methods Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006–2008 and DDW 2008–2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Results Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT4 agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT4 agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT1 receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT4 agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT4 agonists with no hERG or 5-HT1 affinity (renzapride, clebopride, mosapride). Conclusions 5-HT4 agonists for GI disorders differ in chemical structure and selectivity for 5-HT4 receptors. Selectivity for 5-HT4 over non-5-HT4 receptors may influence the agent's safety and overall risk–benefit profile. Based on available evidence, highly selective 5-HT4 agonists may offer improved safety to treat patients with impaired GI motility. PMID:22356640

  3. Acid Volatile Sulfides (avs) and the Bioavailability of Trace Metals in the Channel of the SÃO Francisco River, Sepetiba Bay - de Janeiro-Brazil

    Science.gov (United States)

    Monte, Christiane; Rodrigues, Ana Paula; Marinho, Matheus; Quaresma, Tássia; Machado, Wilson

    2014-05-01

    Sepetiba Bay has 430 Km2 of internal and 2,500 Km2 area of the drainage basin (Lacerda et al., 2007), located 60 km west of the city of Rio de Janeiro. Sepetiba Bay has 430 Km2 of internal and 2,500 Km2 area of the drainage basin (Lacerda et al., 2007), located 60 km west of the city of Rio de Janeiro.The San Francisco channel comes from the Guandu River and empties into Sepetiba Bay and is the main contributor of freshwater to the estuarine system. The Guandu River system/channel of San Francisco receives contribution of domestic and industrial effluents, which go largely to Sepetiba Bay. This work aimed to evaluate the .This work aimed to evaluate the ratio SEM/AVS as a way of predicting bioavailability trace metals from industrial sewage, mainly, in the estuarine system of Sepetiba. This model is based on the property of some Divalent metal cations (Cd, Cu, Ni, Pb and Zn), by presenting a low solubility constant, are removed from the soluble fraction by precipitation, forming secondary metal sulfides. Were held four transects, made up of three points each, the coast line to the center of the Bay. The surface sediment was collected with a van Veen sampler type ,packed in glass jars and kept frozen until analysis.The determination of SEM/AVS followed the methodology described by Allen et al. (1991). The variation between sulfide 159.88 ± 0.05 µmol/g on 12 points. The metals that entered the sum of simultaneous extraction were: Cd, Cu, Ni, Pb and Zn ranging from: 6.47 ± 0.11 µmol/g on sum.The means (± standard deviation) ratio SEM/AVS per transect were: 1.04 ± 1.20 (transect 1); 0.48 ± 0.53 (transect 2); 1.26 ± 1.32 (transect 3) and 0.18 ± 0.14 (transect 4). Only transects 1 and 3 had higher results than 1 , meaning that there are more divalent metal sulfides in the environment. This means that only the sulfides would not be capable of complex and may reflect the potential bioavailability of these in the aquatic environment. There is no statistical

  4. Channel Shallowing as Mitigation of Coastal Flooding

    Directory of Open Access Journals (Sweden)

    Philip M. Orton

    2015-07-01

    Full Text Available Here, we demonstrate that reductions in the depth of inlets or estuary channels can be used to reduce or prevent coastal flooding. A validated hydrodynamic model of Jamaica Bay, New York City (NYC, is used to test nature-based adaptation measures in ameliorating flooding for NYC's two largest historical coastal flood events. In addition to control runs with modern bathymetry, three altered landscape scenarios are tested: (1 increasing the area of wetlands to their 1879 footprint and bathymetry, but leaving deep shipping channels unaltered; (2 shallowing all areas deeper than 2 m in the bay to be 2 m below Mean Low Water; (3 shallowing only the narrowest part of the inlet to the bay. These three scenarios are deliberately extreme and designed to evaluate the leverage each approach exerts on water levels. They result in peak water level reductions of 0.3%, 15%, and 6.8% for Hurricane Sandy, and 2.4%, 46% and 30% for the Category-3 hurricane of 1821, respectively (bay-wide averages. These results suggest that shallowing can provide greater flood protection than wetland restoration, and it is particularly effective at reducing "fast-pulse" storm surges that rise and fall quickly over several hours, like that of the 1821 storm. Nonetheless, the goal of flood mitigation must be weighed against economic, navigation, and ecological needs, and practical concerns such as the availability of sediment.

  5. Water quality of Tampa Bay, Florida, June 1972-May 1976

    Science.gov (United States)

    Goetz, Carole L.; Goodwin, Carl R.

    1980-01-01

    A comprehensive assessment of the water quality of Tampa Bay, Florida, was initiated in 1970 to provide background information to evaluate the effects of widening and deepening the ship channel to the port of Tampa. This report provides results of water-quality sampling in the bay from 1972 to 1976, prior to dredging. Measurements of temperature, dissolved oxygen, pH, turbidity, specific conductance, biochemical oxygen demand, and total organic carbon were made as well as measurements for several nutrient, metal, and pesticide parameters. Many parameters were measured at as many as three points in the vertical. These data indicate that Tampa Bay is well-mixed vertically with little density stratification. Time histories of average temperature, dissolved oxygen, pH, turbidity, specific conductance and nutrient values within four subareas of Tampa Bay are given to reveal seasonal or other trends during the period of record. Temperature, dissolved oxygen, pH, turbidity, specific conductance, nutrient, biochemical oxygen demand, total organic carbon, and metal data are also presented as areal distributions. Nutrient concentrations were generally higher in Hillsborough Bay than in other sub-areas of Tampa Bay. Biochemical oxygen demand, total organic carbon, and total organic nitrogen distribution patterns show regions of highest concentrations to be along bay shorelines near population centers. Of the metals analyzed, all were present in concentrations of less than 1 milligram per liter. (USGS)

  6. Sedimentary gravity flows from subaerial fan-deltas in Loreto Bay, Baja California Sur, Mexico

    Science.gov (United States)

    Navarro-Lozano, José O.; Nava-Sánchez, Enrique H.; Godínez-Orta, Lucio

    2010-05-01

    Fan-deltas from Loreto Bay show recent evidences of sedimentary gravity flows as a result from catastrophic events during hurricane rainfalls. The knowledge of hydrological characteristics of these flows is important for understanding the effects of storms on fan-deltas geomorphology in this region, as well as for the urban developing planning of the city of Loreto in order to avoid hazardous zones. The analysis of precipitation and hurricane tracks data for the period 1945 to 2009 indicates that hurricanes have caused catastrophic floods every 20 years. Stratigraphy from the channel incision shows a sequence of stream flow and debris flow controlled by changes in the competence and capacity of the stream, which are associated to the gentle slope (<2 °) of the fan-deltas. However fans from the north of the bay (Arce and Gúa) show deposits of debris flows associated to catastrophic floods, which have caused the incision channel to drift towards the southern part of the fans, while flows from Las Parras fan-delta, from the middle of the bay, are dominated by stream flows. These differences in the type of the flows are controlled by lithology, shape and size of the drainage basin, and slope of the transit zone in the feeder channel.

  7. Literature Review of Unconsolidated Sediment in San Francisco Bay and Nearby Pacific Ocean Coast

    Directory of Open Access Journals (Sweden)

    Barry R. Keller

    2009-09-01

    Full Text Available A review of the geologic literature regarding sedimentation in the San Francisco Bay estuarine system shows that the main part of the bay occupies a structural tectonic depression that developed in Pleistocene time. Eastern parts, including San Pablo Bay and Suisun Bay, have had sedimentation throughout late Mesozoic and Tertiary. Carquinez Strait and the Golden Gate may represent antecedent stream erosion. Sedimentation has included estuarine, alluvial, and eolian deposition. The ages of estuarine deposition includes the modern high sea level stand and earlier Pleistocene interglacial periods. Sediment sources can be generally divided into the Coast Ranges, particularly the Franciscan Complex, and “Sierran.” Much of the estuarine system is floored by very fine sediment, with local areas of sand floor. Near the Golden Gate, sediment size decreases in both directions away from the deep channel. Bedforms include sand waves (submarine dunes, flat beds, and rock and boulders. These are interpreted in terms of dominant transport directions. Near the Golden Gate is an ebb-tidal delta on the outside (including San Francisco bar and a flood-tidal delta on the inside (parts of Central Bay. The large tidal prism causes strong tidal currents, which in the upper part of the estuary are normally much stronger than river currents, except during large floods. Cultural influences have altered conditions, including hydraulic mining debris, blasting of rocks, dredging of navigation channels, filling of the bay, and commercial sand mining. Many of these have served to decrease the tidal prism, correspondingly decreasing the strength of tidal currents.

  8. Multi-channel phase-equivalent transformation and supersymmetry

    OpenAIRE

    Shirokov, A. M.; Sidorenko, V. N.

    2000-01-01

    Phase-equivalent transformation of local interaction is generalized to the multi-channel case. Generally, the transformation does not change the number of the bound states in the system and their energies. However, with a special choice of the parameters, the transformation removes one of the bound states and is equivalent to the multi-channel supersymmetry transformation recently suggested by Sparenberg and Baye. Using the transformation, it is also possible to add a bound state to the discr...

  9. Sigma-1 receptor agonist increases axon outgrowth of hippocampal neurons via voltage-gated calcium ions channels.

    Science.gov (United States)

    Li, Dong; Zhang, Shu-Zhuo; Yao, Yu-Hong; Xiang, Yun; Ma, Xiao-Yun; Wei, Xiao-Li; Yan, Hai-Tao; Liu, Xiao-Yan

    2017-12-01

    Sigma-1 receptors (Sig-1Rs) are unique endoplasmic reticulum proteins that have been implicated in both neurodegenerative and ischemic diseases, such as Alzheimer's disease and stroke. Accumulating evidence has suggested that Sig-1R plays a role in neuroprotection and axon outgrowth. The underlying mechanisms of Sig-1R-mediated neuroprotection have been well elucidated. However, the mechanisms underlying the effects of Sig-1R on axon outgrowth are not fully understood. To clarify this issue, we utilized immunofluorescence to compare the axon lengths of cultured naïve hippocampal neurons before and after the application of the Sig-1R agonist, SA4503. Then, electrophysiology and immunofluorescence were used to examine voltage-gated calcium ion channel (VGCCs) currents in the cell membranes and growth cones. We found that Sig-1R activation dramatically enhanced the axonal length of the naïve hippocampal neurons. Application of the Sig-1R antagonist NE100 and gene knockdown techniques both demonstrated the effects of Sig-1R. The growth-promoting effect of SA4503 was accompanied by the inhibition of voltage-gated Ca 2+ influx and was recapitulated by incubating the neurons with the L-type, N-type, and P/Q-type VGCC blockers, nimodipine, MVIIA and ω-agatoxin IVA, respectively. This effect was unrelated to glial cells. The application of SA4503 transformed the growth cone morphologies from complicated to simple, which favored axon outgrowth. Sig-1R activation can enhance axon outgrowth and may have a substantial influence on neurogenesis and neurodegenerative diseases. © 2017 John Wiley & Sons Ltd.

  10. Negative cooperativity in binding of muscarinic receptor agonists and GDP as a measure of agonist efficacy.

    Science.gov (United States)

    Jakubík, J; Janíčková, H; El-Fakahany, E E; Doležal, V

    2011-03-01

    Conventional determination of agonist efficacy at G-protein coupled receptors is measured by stimulation of guanosine-5'-γ-thiotriphosphate (GTPγS) binding. We analysed the role of guanosine diphosphate (GDP) in the process of activation of the M₂ muscarinic acetylcholine receptor and provide evidence that negative cooperativity between agonist and GDP binding is an alternative measure of agonist efficacy. Filtration and scintillation proximity assays measured equilibrium binding as well as binding kinetics of [³⁵S]GTPγS and [³H]GDP to a mixture of G-proteins as well as individual classes of G-proteins upon binding of structurally different agonists to the M₂ muscarinic acetylcholine receptor. Agonists displayed biphasic competition curves with the antagonist [³H]-N-methylscopolamine. GTPγS (1 µM) changed the competition curves to monophasic with low affinity and 50 µM GDP produced a similar effect. Depletion of membrane-bound GDP increased the proportion of agonist high-affinity sites. Carbachol accelerated the dissociation of [³H]GDP from membranes. The inverse agonist N-methylscopolamine slowed GDP dissociation and GTPγS binding without changing affinity for GDP. Carbachol affected both GDP association with and dissociation from G(i/o) G-proteins but only its dissociation from G(s/olf) G-proteins. These findings suggest the existence of a low-affinity agonist-receptor conformation complexed with GDP-liganded G-protein. Also the negative cooperativity between GDP and agonist binding at the receptor/G-protein complex determines agonist efficacy. GDP binding reveals differences in action of agonists versus inverse agonists as well as differences in activation of G(i/o) versus G(s/olf) G-proteins that are not identified by conventional GTPγS binding. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  11. Modified cytoplasmic Ca2+ sequestration contributes to spinal cord injury-induced augmentation of nerve-evoked contractions in the rat tail artery.

    Directory of Open Access Journals (Sweden)

    Hussain Al Dera

    Full Text Available In rat tail artery (RTA, spinal cord injury (SCI increases nerve-evoked contractions and the contribution of L-type Ca2+ channels to these responses. In RTAs from unoperated rats, these channels play a minor role in contractions and Bay K8644 (L-type channel agonist mimics the effects of SCI. Here we investigated the mechanisms underlying the facilitatory actions of SCI and Bay K8644 on nerve-evoked contractions of RTAs and the hypothesis that Ca2+ entering via L-type Ca2+ channels is rapidly sequestered by the sarcoplasmic reticulum (SR limiting its role in contraction. In situ electrochemical detection of noradrenaline was used to assess if Bay K8644 increased noradrenaline release. Perforated patch recordings were used to assess if SCI changed the Ca2+ current recorded in RTA myocytes. Wire myography was used to assess if SCI modified the effects of Bay K8644 and of interrupting SR Ca2+ uptake on nerve-evoked contractions. Bay K8644 did not change noradrenaline-induced oxidation currents. Neither the size nor gating of Ca2+ currents differed between myocytes from sham-operated (control and SCI rats. Bay K8644 increased nerve-evoked contractions in RTAs from both control and SCI rats, but the magnitude of this effect was reduced by SCI. By contrast, depleting SR Ca2+ stores with ryanodine or cyclopiazonic acid selectively increased nerve-evoked contractions in control RTAs. Cyclopiazonic acid also selectively increased the blockade of these responses by nifedipine (L-type channel blocker in control RTAs, whereas ryanodine increased the blockade produced by nifedipine in both groups of RTAs. These findings suggest that Ca2+ entering via L-type channels is normally rapidly sequestered limiting its access to the contractile mechanism. Furthermore, the findings suggest SCI reduces the role of this mechanism.

  12. Morphology of channels and channel-sand bodies in the Glauconitic sandstone member (Upper Mannville), Little Bow area, Alberta

    Energy Technology Data Exchange (ETDEWEB)

    Hopkins, J.C.; Hermanson, S.W.; Lawton, D.C.

    1982-12-01

    Large channels in the Glauconitic sandstone member of southern Alberta have proved to be difficult exploration targets because of an irregular distribution of reservoir sands within the channels. In the Little Bow area, two channels are present in the lower part of the Glauconitic member and have cut into the underlying Calcareous member. The channels can be recognized where they truncate regional markers of the Calcareous member -- the Bantry shale and Ostracod limestone, and where channel-fill deposits exhibit uniform geophysical log characters, indicating sandstone- or mudstone-filled reaches. Sediments of the Glauconitic member adjacent to the channels comprise a series of splay sandstones and mudstones that prograded into interdistributary bays of the lower delta plain. The two channels associated with these deposits are interpreted as distributary channels. Sand bodies within the channels formed as lateral bars and are isolated by mudstones which mark the abandoned stream course. Geological exploration for these discontinuous channel sandstones is difficult, and high-resolutio seismic data integrated with sound geologic modelling are critical for successful prospect delineation.

  13. Identification of Natural Compound Carnosol as a Novel TRPA1 Receptor Agonist

    Directory of Open Access Journals (Sweden)

    Chenxi Zhai

    2014-11-01

    Full Text Available The transient receptor potential ankyrin 1 (TRPA1 cation channel is one of the well-known targets for pain therapy. Herbal medicine is a rich source for new drugs and potentially useful therapeutic agents. To discover novel natural TRPA1 agonists, compounds isolated from Chinese herbs were screened using a cell-based calcium mobilization assay. Out of the 158 natural compounds derived from traditional Chinese herbal medicines, carnosol was identified as a novel agonist of TRPA1 with an EC50 value of 12.46 µM. And the agonistic effect of carnosol on TRPA1 could be blocked by A-967079, a selective TRPA1 antagonist. Furthermore, the specificity of carnosol was verified as it showed no significant effects on two other typical targets of TRP family member: TRPM8 and TRPV3. Carnosol exhibited anti-inflammatory and anti-nociceptive properties; the activation of TRPA1 might be responsible for the modulation of inflammatory nociceptive transmission. Collectively, our findings indicate that carnosol is a new anti-nociceptive agent targeting TRPA1 that can be used to explore further biological role in pain therapy.

  14. Flavonoid Regulation of HCN2 Channels*

    Science.gov (United States)

    Carlson, Anne E.; Rosenbaum, Joel C.; Brelidze, Tinatin I.; Klevit, Rachel E.; Zagotta, William N.

    2013-01-01

    The hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels are pacemaker channels whose currents contribute to rhythmic activity in the heart and brain. HCN channels open in response to hyperpolarizing voltages, and the binding of cAMP to their cyclic nucleotide-binding domain (CNBD) facilitates channel opening. Here, we report that, like cAMP, the flavonoid fisetin potentiates HCN2 channel gating. Fisetin sped HCN2 activation and shifted the conductance-voltage relationship to more depolarizing potentials with a half-maximal effective concentration (EC50) of 1.8 μm. When applied together, fisetin and cAMP regulated HCN2 gating in a nonadditive fashion. Fisetin did not potentiate HCN2 channels lacking their CNBD, and two independent fluorescence-based binding assays reported that fisetin bound to the purified CNBD. These data suggest that the CNBD mediates the fisetin potentiation of HCN2 channels. Moreover, binding assays suggest that fisetin and cAMP partially compete for binding to the CNBD. NMR experiments demonstrated that fisetin binds within the cAMP-binding pocket, interacting with some of the same residues as cAMP. Together, these data indicate that fisetin is a partial agonist for HCN2 channels. PMID:24085296

  15. Essential oils of culinary herbs and spices display agonist and antagonist activities at human aryl hydrocarbon receptor AhR.

    Science.gov (United States)

    Bartoňková, Iveta; Dvořák, Zdeněk

    2018-01-01

    Essential oils (EOs) of culinary herbs and spices are used to flavor, color and preserve foods and drinks. Dietary intake of EOs is significant, deserving an attention of toxicologists. We examined the effects of 31 EOs of culinary herbs and spices on the transcriptional activity of human aryl hydrocarbon receptor (AhR), which is a pivotal xenobiotic sensor, having also multiple roles in human physiology. Tested EOs were sorted out into AhR-inactive ones (14 EOs) and AhR-active ones, including full agonists (cumin, jasmine, vanilla, bay leaf), partial agonists (cloves, dill, thyme, nutmeg, oregano) and antagonists (tarragon, caraway, turmeric, lovage, fennel, spearmint, star anise, anise). Major constituents (>10%) of AhR-active EOs were studied in more detail. We identified AhR partial agonists (carvacrol, ligustilide, eugenol, eugenyl acetate, thymol, ar-turmerone) and antagonists (trans-anethole, butylidine phtalide, R/S-carvones, p-cymene), which account for AhR-mediated activities of EOs of fennel, anise, star anise, caraway, spearmint, tarragon, cloves, dill, turmeric, lovage, thyme and oregano. We also show that AhR-mediated effects of some individual constituents of EOs differ from those manifested in mixtures. In conclusion, EOs of culinary herbs and spices are agonists and antagonists of human AhR, implying a potential for food-drug interactions and interference with endocrine pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. A DFT approach to discriminate the antagonist and partial agonist activity of ligands binding to the NMDA receptor

    Science.gov (United States)

    Haslak, Zeynep Pinar; Bozkurt, Esra; Dutagaci, Bercem; De Proft, Frank; Aviyente, Viktorya; De Vleeschouwer, Freija

    2018-02-01

    The activation of N-methyl-D-aspartate receptors is found to be intimately associated with neurodegenerative diseases which make them promising therapeutic targets. Despite the significantly increasing multidisciplinary interests centred on this ionotropic channel, design of new ligands with intended functional activity remains a great challenge. In this article, a computational study based on density functional theory is presented to understand the structural factors of ligands determining their function as antagonists and partial agonists. With this aim, the GluN1 subunit is chosen as being one of the essential components in the activation mechanism, and quantum chemical calculations are implemented for 30 antagonists and 30 partial agonists known to bind to this subunit with different binding affinities. Several quantum chemical descriptors are investigated which might unlock the difference between antagonists and partial agonists.

  17. Expression of inwardly rectifying potassium channels (GIRKs) and beta-adrenergic regulation of breast cancer cell lines

    International Nuclear Information System (INIS)

    Plummer, Howard K III; Yu, Qiang; Cakir, Yavuz; Schuller, Hildegard M

    2004-01-01

    Previous research has indicated that at various organ sites there is a subset of adenocarcinomas that is regulated by beta-adrenergic and arachidonic acid-mediated signal transduction pathways. We wished to determine if this regulation exists in breast adenocarcinomas. Expression of mRNA that encodes a G-protein coupled inwardly rectifying potassium channel (GIRK1) has been shown in tissue samples from approximately 40% of primary human breast cancers. Previously, GIRK channels have been associated with beta-adrenergic signaling. Breast cancer cell lines were screened for GIRK channels by RT-PCR. Cell cultures of breast cancer cells were treated with beta-adrenergic agonists and antagonists, and changes in gene expression were determined by both relative competitive and real time PCR. Potassium flux was determined by flow cytometry and cell signaling was determined by western blotting. Breast cancer cell lines MCF-7, MDA-MB-361 MDA-MB 453, and ZR-75-1 expressed mRNA for the GIRK1 channel, while MDA-MB-468 and MDA-MB-435S did not. GIRK4 was expressed in all six breast cancer cell lines, and GIRK2 was expressed in all but ZR-75-1 and MDA-MB-435. Exposure of MDA-MB-453 cells for 6 days to the beta-blocker propranolol (1 μM) increased the GIRK1 mRNA levels and decreased beta 2 -adrenergic mRNA levels, while treatment for 30 minutes daily for 7 days had no effect. Exposure to a beta-adrenergic agonist and antagonist for 24 hours had no effect on gene expression. The beta adrenergic agonist, formoterol hemifumarate, led to increases in K + flux into MDA-MB-453 cells, and this increase was inhibited by the GIRK channel inhibitor clozapine. The tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a high affinity agonist for beta-adrenergic receptors stimulated activation of Erk 1/2 in MDA-MB-453 cells. Our data suggests β-adrenergic receptors and GIRK channels may play a role in breast cancer

  18. The mechanism of action of endothelin-1 as compared with other agonists in vascular smooth muscle

    International Nuclear Information System (INIS)

    Wallnoefer, A.W.; Weir, S.; Rueegg, U.C.; Cauvin, C.

    1989-01-01

    The effects of endothelin-1 (ET-1) on tension and membrane potential in rat isolated mesenteric resistance vessels (MRVs) and on 45Ca influx, 45Ca efflux, inositol-1,4,5-triphosphate (IP3) production, and cytoplasmic Ca2+ concentration ([Ca2+]1) in cultured aortic smooth muscle cells were compared with those of other agonists. ET-1 induced contractions of the MRVs, which were slow in onset, but reached a similar maximum amplitude (at 10 nM ET-1) as that seen with norepinephrine (NE, 10 microM) or [arg8]vasopressin (AVP, 0.1 microM). The EC50 for ET-1 was 1.3 +/- 0.1 nM. Removal of extracellular Ca2+ reduced ET-1-induced contractions to 11 +/- 3% of those in Ca2+-containing medium. With NE, the same procedure reduced contractions to 47 +/- 7% of those in Ca2+-containing medium, while with AVP, the reduction was similar in magnitude to that induced by ET-1 (11 +/- 5% of those in Ca2+-containing medium). Relaxation of ET-1-induced and NE-induced contractions by diltiazem was not complete (maximal at 58 +/- 6% with 10 microM diltiazem after 6 nM ET-1, and at 70 +/- 3% after 0.1 microM NE), in contrast to that of 80 mM K+-induced contractions, which were potently (IC50 = 0.2 microM) and completely reversed (100% relaxation at 10 microM diltiazem). ET-1 (6 nM) caused a small but significant depolarization of the MRVs (approximately 7 mV), the magnitude of which was only about one-third of that induced by equieffective contractile concentrations of NE and AVP. The voltage-sensitive Ca2+ channel agonist Bay K 8644 (1 microM), in contrast to ET-1, NE, and AVP, produced a small contraction (30 +/- 2% of the maximum response to NE), but no further depolarization when added in the presence of 15 mM K+ (which elicited approximately 12 mV depolarization but no contraction)

  19. Ion Channels of Pituitary Gonadotrophs and Their Roles in Signaling and Secretion

    Directory of Open Access Journals (Sweden)

    Stanko S. Stojilkovic

    2017-06-01

    Full Text Available Gonadotrophs are basophilic cells of the anterior pituitary gland specialized to secrete gonadotropins in response to elevation in intracellular calcium concentration. These cells fire action potentials (APs spontaneously, coupled with voltage-gated calcium influx of insufficient amplitude to trigger gonadotropin release. The spontaneous excitability of gonadotrophs reflects the expression of voltage-gated sodium, calcium, potassium, non-selective cation-conducting, and chloride channels at their plasma membrane (PM. These cells also express the hyperpolarization-activated and cyclic nucleotide-gated cation channels at the PM, as well as GABAA, nicotinic, and purinergic P2X channels gated by γ-aminobutyric acid (GABA, acetylcholine (ACh, and ATP, respectively. Activation of these channels leads to initiation or amplification of the pacemaking activity, facilitation of calcium influx, and activation of the exocytic pathway. Gonadotrophs also express calcium-conducting channels at the endoplasmic reticulum membranes gated by inositol trisphosphate and intracellular calcium. These channels are activated potently by hypothalamic gonadotropin-releasing hormone (GnRH and less potently by several paracrine calcium-mobilizing agonists, including pituitary adenylate cyclase-activating peptides, endothelins, ACh, vasopressin, and oxytocin. Activation of these channels causes oscillatory calcium release and a rapid gonadotropin release, accompanied with a shift from tonic firing of single APs to periodic bursting type of electrical activity, which accounts for a sustained calcium signaling and gonadotropin secretion. This review summarizes our current understanding of ion channels as signaling molecules in gonadotrophs, the role of GnRH and paracrine agonists in their gating, and the cross talk among channels.

  20. Interaction between Ca++-channel antagonists and α2-adrenergic receptors in rabbit ileal cell membrane

    International Nuclear Information System (INIS)

    Homeidan, F.R.; Wicks, J.; Cusolito, S.; El-Sabban, M.E.; Sharp, G.W.G.; Donowitz, M.

    1986-01-01

    An interaction between Ca ++ -channel antagonists and the α 2 -adrenergic receptor on active electrolyte transport was demonstrated in rabbit ileum. Clonidine, an α 2 -agonist, stimulated NaCl absorption apparently by Ca ++ -channel antagonism since it inhibited 45 Ca ++ uptake across the basolateral membrane and decreased total ileal calcium content. This stimulation was inhibited by the Ca ++ -channel antagonists dl- and l-verapamil and cadmium but not by nifedipine. The binding of 3 H-yohimbine, a specific α 2 -adrenergic antagonist, was studied on purified ileal cell membranes using a rapid filtration technique. dl-Verapamil and Cd ++ inhibited the specific binding of 3 H-yohimbine over the same concentration range in which they affected transport. In contrast, nifedipine had no effect on binding, just as it had no effect on clonidine-stimulated NaCl absorption. These data demonstrate that there is an interaction between Ca ++ -channels and α 2 -adrenergic receptors in ileal basolateral membranes. Some Ca ++ -channel antagonists alter α 2 -adrenergic binding to the receptor and α 2 -agonist binding leads to changes in Ca ++ entry. A close spatial relationship between the Ca ++ -channel and the α 2 -receptor could explain the data

  1. Oceanographic characteristics of an impacted coastal bay: Baía de Guanabara, Rio de Janeiro, Brazil

    Science.gov (United States)

    Kjerfve, Björn; Ribeiro, Cesar H. A.; Dias, Gilberto T. M.; Filippo, Alessandro M.; Da Silva Quaresma, Valéria

    1997-11-01

    Baía de Guanabara is a 384 km 2 eutrophic coastal bay in Brazil, impacted by the polluted discharge from the Rio de Janeiro metropolitan area. The structurally controlled bay has a central channel with a depth of 30 m and a sandy bottom near the entrance, reflecting wave and tidal forcing. In contrast, the bay-averaged water depth is 5.7 m and the bottom sediments are mostly muds as a result of the Holocene transgression and rapid fluvial sedimentation, accelerated by channelization of rivers and deforestation. An extensive sand bank is located seaward of the bay entrance and a flood-oriented sand wave system indicates sand transport into the bay. The mean freshwater discharge measures 100±59 m 3 s -1 and is greatest in the rainy austral summer in December and January. Tides are mixed mainly semidiurnal with a range of 0.7 m, and peak spring tidal currents reach 0.5 m s -1 inside the bay and 1.6 m s -1 near the bay entrance. The passage of northward propagating polar fronts results in regular strong southwesterly winds and heavy wave forcing. The bay has mean salinities from 21.0 to 34.5‰ with an average of 29.5±4.8‰. The vertical salinity stratification, Δs/s, varies from 0.06 to 0.21 and is relatively weak and inversely proportional to rms tidal currents. The residual circulation is characterized by both gravitational circulation and transverse residual tidal circulation, measuring 800 and 400 m 3 s -1 respectively. The renewal time of 50% of the bay water volume is 11.4 days. Untreated sewage runoff enters the bay from the west, resulting in locally poor water quality, where the near-bottom mean dissolved oxygen measures only 3.1 mg 1 -1 and results in anoxic bottom muds. The worst water quality is indicated by average fecal coliform of 1140 counts ml -1 and excessive ammonia and phosphate loading. The average chlorophyll concentration in this region responds to the nutrient loading and exceeds 130 μg 1 -1 although 57 μg 1 -1 is the overall mean for

  2. Ice Penetrating Radar Reveals Spatially Variable Features in Basal Channel under the Nansen Ice Shelf, Terra Nova Bay, Antarctica

    Science.gov (United States)

    Wray, P. L.; Dow, C. F.; Mueller, D.; Lee, W. S.; Lindzey, L.; Greenbaum, J. S.; Blankenship, D. D.

    2017-12-01

    The stability of Antarctic ice shelves is of great concern as their current thinning and future collapse will contribute to sea-level rise via the acceleration of grounded tributary glaciers into the ocean. The study of the sub-ice-shelf environment is essential for understanding ice-ocean interaction, where warming ocean temperatures have already begun to threaten the long-term viability of Antarctic ice shelves. Obtaining direct measurements of the sub-ice-shelf cavity remains challenging. Here, we demonstrate that ground-based geophysical methods can deliver high resolution monitoring and mapping of the spatial and temporal changes in features, melt rates, and ice mass transport of this environment. In November 2016, 84 km of ground-based, low frequency, Ice Penetrating Radar (IPR) surveys were completed on three sites over the Nansen Ice Shelf in Terra Nova Bay, Antarctica. The surveys examined an ocean-sourced basal channel incised into the bottom of the shelf, originally detected from a large surface depression. Results reveal high resolution features of a several kilometre-wide, 100 m high channel, with 40 m high sub-channels, zones of significant marine ice accumulation, and basal crevasses penetrating large fractions of the ice shelf thickness. Data from multiple airborne geophysical surveys were compared to the November 2016 IPR data to calculate mass change both spatially and temporally. Many of the smaller scale features we detected are not represented through hydrostatic equilibrium as calculated from ice thicknesses, due to bridging stresses, and as such can not be detected with satellite based remote sensing methods. Our in-field geophysical methods produced high-resolution information of these features, which underscores the need for similar surveys over vulnerable ice shelves to better understand ice-ocean processes.

  3. A Tidally Averaged Sediment-Transport Model for San Francisco Bay, California

    Science.gov (United States)

    Lionberger, Megan A.; Schoellhamer, David H.

    2009-01-01

    A tidally averaged sediment-transport model of San Francisco Bay was incorporated into a tidally averaged salinity box model previously developed and calibrated using salinity, a conservative tracer (Uncles and Peterson, 1995; Knowles, 1996). The Bay is represented in the model by 50 segments composed of two layers: one representing the channel (>5-meter depth) and the other the shallows (0- to 5-meter depth). Calculations are made using a daily time step and simulations can be made on the decadal time scale. The sediment-transport model includes an erosion-deposition algorithm, a bed-sediment algorithm, and sediment boundary conditions. Erosion and deposition of bed sediments are calculated explicitly, and suspended sediment is transported by implicitly solving the advection-dispersion equation. The bed-sediment model simulates the increase in bed strength with depth, owing to consolidation of fine sediments that make up San Francisco Bay mud. The model is calibrated to either net sedimentation calculated from bathymetric-change data or measured suspended-sediment concentration. Specified boundary conditions are the tributary fluxes of suspended sediment and suspended-sediment concentration in the Pacific Ocean. Results of model calibration and validation show that the model simulates the trends in suspended-sediment concentration associated with tidal fluctuations, residual velocity, and wind stress well, although the spring neap tidal suspended-sediment concentration variability was consistently underestimated. Model validation also showed poor simulation of seasonal sediment pulses from the Sacramento-San Joaquin River Delta at Point San Pablo because the pulses enter the Bay over only a few days and the fate of the pulses is determined by intra-tidal deposition and resuspension that are not included in this tidally averaged model. The model was calibrated to net-basin sedimentation to calculate budgets of sediment and sediment-associated contaminants. While

  4. Long-term morphologic evolution of the Hangzhou Bay, China

    Science.gov (United States)

    Wen, W.; Zhijun, D.; Hualiang, X.

    2013-12-01

    Estuaries are the most productive ecosystems of coastal zones in the world, which are significant to mankind as places of navigation, recreation and commerce as well as extensive and diverse habitats for wildlife. However, most estuary environments in the world had occurred greatly changes in recent decades. These estuaries have suffered from impacts of forcing factors including wave climate, mean sea level change and storm surge, especial to the intensive human activities such as training wall construction, channel dredging, sand mining and dam constructions. Thus, there have been increasing concerns about estuary environment changes under effects of different factors. Riverine loads into the Changjiang Estuary have declined dramatically with the construction of Three Gorges Dam (TGD) in 2003. The morphological evolution of the Hangzhou bay that located the southern proximity of the Yangtze estuary starts to attract increasing attentions due to most material of the Hangzhou bay received from Yangtze estuary. In this paper, historical bathymetric charts were digitized and analyzed within a GIS to provide quantitative estimate of changes in volumes in different regions below 0 m elevation. The results show that Hangzhou bay has experienced a major loss in estuarine volume of about 15% with annual mean sediment deposition rate of 80 million m3/a during the last 75 years. However, there is a large-scale spatial adjustment in Hangzhou bay: Bathymetric changes of the Hangzhou bay can be rapidly shifted within the range of 8-10 classes. Volume of the Jinshanzui upstream of the Hangzhou bay has obviously decreased in the last 75 years, especially during 2003-2008. However, Volume of the southern Hangzhou bay has experienced slowly decrease with minor deposition. The northern Hangzhou bay had largely volume changes with rapidly decrease during 1931-1981, and drastically increase since 2003. Further analysis of the bathymetric data relating to possible factors indicates

  5. Binding of [125I]iodipine to parathyroid cell membranes: Evidence of a dihydropyridine-sensitive calcium channel

    International Nuclear Information System (INIS)

    Jones, J.I.; Fitzpatrick, L.A.

    1990-01-01

    The parathyroid cell is unusual, in that an increase in extracellular calcium concentrations inhibits PTH release. Calcium channels are glycoproteins that span cell membranes and allow entry of extracellular calcium into cells. We have demonstrated that the calcium channel agonist (+)202-791, which opens calcium channels, inhibits PTH release and that the antagonist (-)202-791, which closes calcium channels, stimulates PTH release. To identify the calcium channels responsible for these effects, we used a radioligand that specifically binds to calcium channels. Bovine parathyroid cell membranes were prepared and incubated under reduced lighting with [125I] iodipine (SA, 2000 Ci/mmol), which recognizes 1,4-dihydropyridine-sensitive calcium channels. Bound ligand was separated from free ligand by rapid filtration through Whatman GF/B filters. Nonspecific binding was measured by the inclusion of nifedipine at 10 microM. Specific binding represented approximately 40% of the total binding. The optimal temperature for [125I] iodipine binding was 4 C, and binding reached equilibrium by 30 min. The equilibrium dissociation constant (Kd) was approximately 550 pM, and the maximum number of binding sites was 780 fmol/mg protein. Both the calcium channel agonist (+)202-791 and antagonist (-)202-791 competitively inhibited [125I] iodipine binding, with 50% inhibition concentrations of 20 and 300 nM, respectively. These data indicate the presence of dihydropyridine-sensitive calcium channels on parathyroid cell membranes

  6. Characterizing ligand-gated ion channel receptors with genetically encoded Ca2++ sensors.

    Directory of Open Access Journals (Sweden)

    John G Yamauchi

    2011-01-01

    Full Text Available We present a cell based system and experimental approach to characterize agonist and antagonist selectivity for ligand-gated ion channels (LGIC by developing sensor cells stably expressing a Ca(2+ permeable LGIC and a genetically encoded Förster (or fluorescence resonance energy transfer (FRET-based calcium sensor. In particular, we describe separate lines with human α7 and human α4β2 nicotinic acetylcholine receptors, mouse 5-HT(3A serotonin receptors and a chimera of human α7/mouse 5-HT(3A receptors. Complete concentration-response curves for agonists and Schild plots of antagonists were generated from these sensors and the results validate known pharmacology of the receptors tested. Concentration-response relations can be generated from either the initial rate or maximal amplitudes of FRET-signal. Although assaying at a medium throughput level, this pharmacological fluorescence detection technique employs a clonal line for stability and has versatility for screening laboratory generated congeners as agonists or antagonists on multiple subtypes of ligand-gated ion channels. The clonal sensor lines are also compatible with in vivo usage to measure indirectly receptor activation by endogenous neurotransmitters.

  7. 33 CFR 100.124 - Maggie Fischer Memorial Great South Bay Cross Bay Swim, Great South Bay, New York.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Maggie Fischer Memorial Great South Bay Cross Bay Swim, Great South Bay, New York. 100.124 Section 100.124 Navigation and Navigable... NAVIGABLE WATERS § 100.124 Maggie Fischer Memorial Great South Bay Cross Bay Swim, Great South Bay, New York...

  8. Acoustic tag detections of green sturgeon in the Columbia River and Coos Bay estuaries, Washington and Oregon, 2010–11

    Science.gov (United States)

    Hansel, Hal C.; Romine, Jason G.; Perry, Russell W.

    2017-11-08

    The Columbia River, in Washington and Oregon, and Coos Bay, in Oregon, are economically important shipping channels that are inhabited by several fishes protected under the Endangered Species Act (ESA). Maintenance of shipping channels involves dredge operations to maintain sufficient in-channel depths to allow large ships to navigate the waterways safely. Fishes entrained by dredge equipment often die or experience delayed mortality. Other potential negative effects of dredging include increased turbidity, reductions in prey resources, and the release of harmful contaminants from the dredged sediments. One species of concern is the ESA-listed green sturgeon (Acipenser medirostris; Southern Distinct Population Segment). In this study, we used acoustic telemetry to identify habitat use, arrival and departure timing, and the extent of upstream migration of green sturgeon in the Columbia River and Coos Bay to help inform dredge operations to minimize potential take of green sturgeon. Autonomous acoustic receivers were deployed in Coos Bay from the mouth to river kilometer (rkm) 21.6 from October 2009 through October 2010. In the Columbia River Estuary, receivers were deployed between the mouth and rkm 37.8 from April to November in 2010 and 2011. A total of 29 subadult and adult green sturgeon were tagged with temperature and pressure sensor tags and released during the study, primarily in Willapa Bay and Grays Harbor, Washington, and the Klamath River, Oregon. Green sturgeon detected during the study but released by other researchers also were included in the study.The number of tagged green sturgeon detected in the two estuaries differed markedly. In Coos Bay, only one green sturgeon was detected for about 2 hours near the estuary mouth. In the Columbia River Estuary, 9 green sturgeon were detected in 2010 and 10 fish were detected in 2011. Green sturgeon entered the Columbia River from May through October during both years, with the greatest numbers of fish being

  9. Partial pressure (or fugacity) of carbon dioxide, salinity and other variables collected from Surface underway observations using Carbon dioxide (CO2) gas analyzer and other instruments from POLARSTERN in the Bay of Biscay, English Channel and others from 2010-01-31 to 2010-11-25 (NCEI Accession 0157388)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0157388 includes Surface underway, chemical, meteorological and physical data collected from POLARSTERN in the Bay of Biscay, English Channel, North...

  10. Cold suppresses agonist-induced activation of TRPV1.

    Science.gov (United States)

    Chung, M-K; Wang, S

    2011-09-01

    Cold therapy is frequently used to reduce pain and edema following acute injury or surgery such as tooth extraction. However, the neurobiological mechanisms of cold therapy are not completely understood. Transient receptor potential vanilloid 1 (TRPV1) is a capsaicin- and heat-gated nociceptive ion channel implicated in thermosensation and pathological pain under conditions of inflammation or injury. Although capsaicin-induced nociception, neuropeptide release, and ionic currents are suppressed by cold, it is not known if cold suppresses agonist-induced activation of recombinant TRPV1. We demonstrate that cold strongly suppressed the activation of recombinant TRPV1 by multiple agonists and capsaicin-evoked currents in trigeminal ganglia neurons under normal and phosphorylated conditions. Cold-induced suppression was partially impaired in a TRPV1 mutant that lacked heat-mediated activation and potentiation. These results suggest that cold-induced suppression of TRPV1 may share a common molecular basis with heat-induced potentiation, and that allosteric inhibition may contribute, in part, to the cold-induced suppression. We also show that combination of cold and a specific antagonist of TRPV1 can produce an additive suppression. Our results provide a mechanistic basis for cold therapy and may enhance anti-nociceptive approaches that target TRPV1 for managing pain under inflammation and tissue injury, including that from tooth extraction.

  11. Mangrove root communities in Jobos Bay

    International Nuclear Information System (INIS)

    Yoshioka, P.M.

    1975-01-01

    Based on the presence and absence of species, at least two major types of mangrove root communities exist in Jobos Bay. One community, occurring mainly along the Aguirre Ship Channel, is composed of species characteristic of coastal waters. Another occurring in Jobos Bay and in mangrove channels in the vinicity of Mar Negro Lagoon is characterized by embayment species. Water mass is the best single parameter which correlates with the different communities. In general, subtidal species are more susceptible to elevated temperatures than intertidal species and consequently will be the first affected. Because most of the predators and competitors are subtidal, the predation and competition which limit populations may be cut back. The effect will first be seen in increased populations of barnacles, because they are severely limited by predation and competition but are physiologically quite tolerant. The intertidal species should flourish (on a relative basis) and their vertical distributions should be extended downward. These effects are only primary. Many species which would do best in thermally altered situations are colonizing or fugitive species. It is unknown whether such an assemblage could persist with continued recruitment and growth of new individuals. The dominance of these colonizing or fugitive species may be only temporary, however, because blue-green algae are tolerant of elevated temperatures and have a negative effect on barnacle recruitment and growth. Consequently, blue-green algae may eventually dominate thermally affected mangrove roots

  12. The epileptogenic spectrum of opiate agonists.

    Science.gov (United States)

    Snead, O C; Bearden, L J

    1982-11-01

    The present authors gave mu, delta, kappa, epsilon and sigma opiate receptor agonists intracerebroventricularly to rats both singly and in combination while monitoring the electroencephalogram from cortical and depth electrodes. Dose-response curves were plotted with naloxone against the changes produced by each agonist, and the effect of a number of anticonvulsant drugs on agonist-induced seizures was ascertained. Each opiate agonist produced a different seizure pattern with a different naloxone dose-response curve and anticonvulsant profile. The order of convulsive potency was epsilon greater than delta greater than mu greater than sigma much greater than kappa. Petit mal-like seizure activity was unique to the delta agonist, leucine-enkephalin, while only the mu agonist, morphine produced generalized convulsive seizures. These experiments raise the possibility that opiate systems in the brain may be involved in the pathogenesis of a wide spectrum of seizure disorders.

  13. Sustainable development in the Hudson Bay/James Bay bioregion

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    An overview is presented of projects planned for the James Bay/Hudson Bay region, and the expected environmental impacts of these projects. The watershed of James Bay and Hudson Bay covers well over one third of Canada, from southern Alberta to central Ontario to Baffin Island, as well as parts of north Dakota and Minnesota in the U.S.A. Hydroelectric power developments that change the timing and rate of flow of fresh water may cause changes in the nature and duration of ice cover, habitats of marine mammals, fish and migratory birds, currents into and out of Hudson Bay/James Bay, seasonal and annual loads of sediments and nutrients to marine ecosystems, and anadromous fish populations. Hydroelectric projects are proposed for the region by Quebec, Ontario and Manitoba. In January 1992, the Canadian Arctic Resources Committee (CARC), the Environmental Committee of Sanikuluaq, and the Rawson Academy of Arctic Science will launch the Hudson Bay/James Bay Bioregion Program, an independent initiative to apply an ecosystem approach to the region. Two main objectives are to provide a comprehensive assessment of the cumulative impacts of human activities on the marine and freshwater ecosystems of the Hudson Bay/James Bay bioregion, and to foster sustainable development by examining and proposing cooperative processes for decision making among governments, developers, aboriginal peoples and other stakeholders. 1 fig

  14. Cav1.2 channel current block by the PKA inhibitor H-89 in rat tail artery myocytes via a PKA-independent mechanism: Electrophysiological, functional, and molecular docking studies.

    Science.gov (United States)

    Fusi, Fabio; Trezza, Alfonso; Spiga, Ottavia; Sgaragli, Giampietro; Bova, Sergio

    2017-09-15

    To characterize the role of cAMP-dependent protein kinase (PKA) in regulating vascular Ca 2+ current through Ca v 1.2 channels [I Ca1.2 ], we have documented a marked capacity of the isoquinoline H-89, widely used as a PKA inhibitor, to reduce current amplitude. We hypothesized that the I Ca1.2 inhibitory activity of H-89 was mediated by mechanisms unrelated to PKA inhibition. To support this, an in-depth analysis of H-89 vascular effects on both I Ca1.2 and contractility was undertaken by performing whole-cell patch-clamp recordings and functional experiments in rat tail main artery single myocytes and rings, respectively. H-89 inhibited I Ca1.2 with a pIC 50 (M) value of about 5.5, even under conditions where PKA activity was either abolished by both the PKA antagonists KT5720 and protein kinase inhibitor fragment 6-22 amide or enhanced by the PKA stimulators 6-Bnz-cAMP and 8-Br-cAMP. Inhibition of I Ca1.2 by H-89 appeared almost irreversible upon washout, was charge carrier- and voltage-dependent, and antagonised by the Ca v 1.2 channel agonist (S)-(-)-Bay K 8644. H-89 did not alter both potency and efficacy of verapamil, did not affect current kinetics or voltage-dependent activation, while shifting to the left the 50% voltage of inactivation in a concentration-dependent manner. H-89 docked at the α 1C subunit in a pocket region close to that of (S)-(-)-Bay K 8644 docking, forming a hydrogen bond with the same, key amino acid residue Tyr-1489. Finally, both high K + - and (S)-(-)-Bay K 8644-induced contractions of rings were fully reverted by H-89. In conclusion, these results indicate that H-89 inhibited vascular I Ca1.2 and, consequently, the contractile function through a PKA-independent mechanism. Therefore, caution is recommended when interpreting experiments where H-89 is used to inhibit vascular smooth muscle PKA. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Triazolophostins: a library of novel and potent agonists of IP3 receptors

    OpenAIRE

    Vibhute, Amol M; Konieczny, Vera; Taylor, Colin William; Sureshan, Kana M

    2015-01-01

    IP3 receptors are channels that mediate the release of Ca2+ from the intracellular stores of cells stimulated by hormones or neurotransmitters. Adenophostin A (AdA) is the most potent agonist of IP3 receptors, with the β-anomeric adenine contributing to the increased potency. The potency of AdA and its stability towards the enzymes that degrade IP3 have aroused interest in AdA analogs for biological studies. The complex structure of AdA poses problems that have necessitated optimization of sy...

  16. Evaluation of partial beta-adrenoceptor agonist activity.

    Science.gov (United States)

    Lipworth, B J; Grove, A

    1997-01-01

    A partial beta-adrenoceptor (beta-AR) agonist will exhibit opposite agonist and antagonist activity depending on the prevailing degree of adrenergic tone or the presence of a beta-AR agonist with higher intrinsic activity. In vivo partial beta-AR agonist activity will be evident at rest with low endogenous adrenergic tone, as for example with chronotropicity (beta 1/beta 2), inotropicity (beta 1) or peripheral vasodilatation and finger tremor (beta 2). beta-AR blocking drugs which have partial agonist activity may exhibit a better therapeutic profile when used for hypertension because of maintained cardiac output without increased systemic vascular resistance, along with an improved lipid profile. In the presence of raised endogenous adrenergic tone such as exercise or an exogenous full agonist, beta-AR subtype antagonist activity will become evident in terms of effects on exercise induced heart rate (beta 1) and potassium (beta 2) responses. Reduction of exercise heart rate will occur to a lesser degree in the case of a beta-adrenoceptor blocker with partial beta 1-AR agonist activity compared with a beta-adrenoceptor blocker devoid of partial agonist activity. This may result in reduced therapeutic efficacy in the treatment of angina on effort when using beta-AR blocking drugs with partial beta 1-AR agonist activity. Effects on exercise hyperkalaemia are determined by the balance between beta 2-AR partial agonist activity and endogenous adrenergic activity. For predominantly beta 2-AR agonist such as salmeterol and salbutamol, potentiation of exercise hyperkalaemia occurs. For predominantly beta 2-AR antagonists such as carteolol, either potentiation or attenuation of exercise hyperkalaemia occurs at low and high doses respectively. beta 2-AR partial agonist activity may also be expressed as antagonism in the presence of an exogenous full agonist, as for example attenuation of fenoterol induced responses by salmeterol. Studies are required to investigate whether

  17. Omega-conotoxin- and nifedipine-insensitive voltage-operated calcium channels mediate K(+)-induced release of pro-thyrotropin-releasing hormone-connecting peptides Ps4 and Ps5 from perifused rat hypothalamic slices.

    Science.gov (United States)

    Valentijn, K; Tranchand Bunel, D; Vaudry, H

    1992-07-01

    The rat thyrotropin-releasing hormone (TRH) precursor (prepro-TRH) contains five copies of the TRH progenitor sequence linked together by intervening sequences. Recently, we have shown that the connecting peptides prepro-TRH-(160-169) (Ps4) and prepro-TRH-(178-199) (Ps5) are released from rat hypothalamic neurones in response to elevated potassium concentrations, in a calcium-dependent manner. In the present study, the role of voltage-operated calcium channels in potassium-induced release of Ps4 and Ps5 was investigated, using a perifusion system for rat hypothalamic slices. The release of Ps4 and Ps5 stimulated by potassium (70 mM) was blocked by the inorganic ions Co2+ (2.6 mM) and Ni2+ (5 mM). In contrast, the stimulatory effect of KCl was insensitive to Cd2+ (100 microM). The dihydropyridine antagonist nifedipine (10 microM) had no effect on K(+)-evoked release of Ps4 and Ps5. Furthermore, the response to KCl was not affected by nifedipine (10 microM) in combination with diltiazem (1 microM), a benzothiazepine which increases the affinity of dihydropyridine antagonists for their receptor. The dihydropyridine agonist BAY K 8644, at concentrations as high as 1 mM, did not stimulate the basal secretion of Ps4 and Ps5. In addition, BAY K 8644 had no potentiating effect on K(+)-induced release of Ps4 and Ps5. The marine cone snail toxin omega-conotoxin, a blocker of both L- and N-type calcium channels had no effect on the release of Ps4 and Ps5 stimulated by potassium. Similarly, the omega-conopeptide SNX-111, a selective blocker of N-type calcium channels, did not inhibit the stimulatory effect of potassium. The release of Ps4 and Ps5 evoked by high K+ was insensitive to the non-selective calcium channel blocker verapamil (20 microM). Amiloride (1 microM), a putative blocker of T-type calcium channels, did not affect KCl-induced secretion of the two connecting peptides. Taken together, these results indicate that two connecting peptides derived from the pro-TRH, Ps

  18. Mechanical stress activates NMDA receptors in the absence of agonists.

    Science.gov (United States)

    Maneshi, Mohammad Mehdi; Maki, Bruce; Gnanasambandam, Radhakrishnan; Belin, Sophie; Popescu, Gabriela K; Sachs, Frederick; Hua, Susan Z

    2017-01-03

    While studying the physiological response of primary rat astrocytes to fluid shear stress in a model of traumatic brain injury (TBI), we found that shear stress induced Ca 2+ entry. The influx was inhibited by MK-801, a specific pore blocker of N-Methyl-D-aspartic acid receptor (NMDAR) channels, and this occurred in the absence of agonists. Other NMDA open channel blockers ketamine and memantine showed a similar effect. The competitive glutamate antagonists AP5 and GluN2B-selective inhibitor ifenprodil reduced NMDA-activated currents, but had no effect on the mechanically induced Ca 2+ influx. Extracellular Mg 2+ at 2 mM did not significantly affect the shear induced Ca 2+ influx, but at 10 mM it produced significant inhibition. Patch clamp experiments showed mechanical activation of NMDAR and inhibition by MK-801. The mechanical sensitivity of NMDARs may play a role in the normal physiology of fluid flow in the glymphatic system and it has obvious relevance to TBI.

  19. Borneol Is a TRPM8 Agonist that Increases Ocular Surface Wetness.

    Directory of Open Access Journals (Sweden)

    Gui-Lan Chen

    Full Text Available Borneol is a compound widely used in ophthalmic preparations in China. Little is known about its exact role in treating eye diseases. Here we report that transient receptor potential melastatin 8 (TRPM8 channel is a pharmacological target of borneol and mediates its therapeutic effect in the eyes. Ca2+ measurement and electrophysiological recordings revealed that borneol activated TRPM8 channel in a temperature- and dose-dependent manner, which was similar to but less effective than the action of menthol, an established TRPM8 agonist. Borneol significantly increased tear production in guinea pigs without evoking nociceptive responses at 25°C, but failed to induce tear secretion at 35°C. In contrast, menthol evoked tearing response at both 25 and 35°C. TRPM8 channel blockers N-(3-Aminopropyl-2-[(3-methylphenylmethoxy]-N-(2-thienylmethylbenzamide hydrochloride (AMTB and N-(4-tert-butylphenyl-4-(3-chloropyridin-2-ylpiperazine-1-carboxamide (BCTC abolished borneol- and menthol-induced tear secretion. Borneol at micromolar concentrations did not affect the viability of human corneal epithelial cells. We conclude that borneol can activate the cold-sensing TRPM8 channel and modestly increase ocular surface wetness, which suggests it is an active compound in ophthalmic preparations and particularly useful in treating dry eye syndrome.

  20. Distribution and behavior of major and trace elements in Tokyo Bay, Mutsu Bay and Funka Bay marine sediments

    International Nuclear Information System (INIS)

    Honda, Teruyuki; Kimura, Ken-ichiro

    2003-01-01

    Fourteen major and trace elements in marine sediment core samples collected from the coasts along eastern Japan, i.e. Tokyo Bay (II) (the recess), Tokyo Bay (IV) (the mouth), Mutsu Bay and Funka Bay and the Northwest Pacific basin as a comparative subject were determined by the instrumental neutron activation analysis (INAA). The sedimentation rates and sedimentary ages were calculated for the coastal sediment cores by the 210 Pb method. The results obtained in this study are summarized as follows: (1) Lanthanoid abundance patterns suggested that the major origin of the sediments was terrigenous material. La*/Lu* and Ce*/La* ratios revealed that the sediments from Tokyo Bay (II) and Mutsu Bay more directly reflected the contribution from river than those of other regions. In addition, the Th/Sc ratio indicated that the coastal sediments mainly originated in the materials from the volcanic island-arcs, Japanese islands, whereas those from the Northwest Pacific mainly from the continent. (2) The correlation between the Ce/U and Th/U ratios with high correlation coefficients of 0.920 to 0.991 indicated that all the sediments from Tokyo Bay (II) and Funka Bay were in reducing conditions while at least the upper sediments from Tokyo Bay (IV) and Mutsu Bay were in oxidizing conditions. (3) It became quite obvious that the sedimentation mechanism and the sedimentation environment at Tokyo Bay (II) was different from those at Tokyo Bay (IV), since the sedimentation rate at Tokyo Bay (II) was approximately twice as large as that at Tokyo Bay (IV). The sedimentary age of the 5th layer (8∼10 cm in depth) from Funka Bay was calculated at approximately 1940∼50, which agreed with the time, 1943∼45 when Showa-shinzan was formed by the eruption of the Usu volcano. (author)

  1. New and Improved Results from Daya Bay

    CERN Multimedia

    CERN. Geneva

    2017-01-01

    Despite the great progress achieved in the last decades, neutrinos remain among the least understood fundamental particles to have been experimentally observed. The Daya Bay Reactor Neutrino Experiment consists of eight identically designed detectors placed underground at different baselines from three groups of nuclear reactors in China, a configuration that is ideally suited for studying the properties of these elusive particles. In this talk I will review the improved results released last summer by the Daya Bay collaboration. These results include (i) a precision measurement of the θ13 mixing angle and the effective mass splitting in the electron antineutrino disappearance channel with a dataset comprising more than 2.5 million antineutrino interactions, (ii) a high-statistics measurement of the absolute flux and spectrum of reactor-produced electron antineutrinos, and (iii) a search for light sterile neutrino mixing performed with more than three times the statistics of the previous result. I w...

  2. Exploitation of tidal power in the Bay of Cadiz: ancient tidal mills

    Directory of Open Access Journals (Sweden)

    José J. Alonso del Rosario

    2006-03-01

    Full Text Available Tidal mills were the main industrial activity in the Bay of Cadiz for centuries. They were the last step in the production of salt and flour made by grinding grains. They were installed along the shallow channels, called “caños”, around the Bay, where the frictional and geometrical effects are very strong. The authors have analyzed the propagation of the semidiurnal tidal waves along the Caño de Sancti Petri and the available tidal power in the area. The ancient tidal mills were located where the available tidal potential energy is highest, which ensured productivity for grinding salt and wheat in ancient times. Some considerations about the possibility of installing tidal power plants in the Bay of Cadiz now are given, which show that it could be a real and renewal alternative source of energy for the area.

  3. Sediment transport in the San Francisco Bay Coastal System: An overview

    Science.gov (United States)

    Barnard, Patrick L.; Schoellhamer, David H.; Jaffe, Bruce E.; Lester J. McKee,

    2013-01-01

    The papers in this special issue feature state-of-the-art approaches to understanding the physical processes related to sediment transport and geomorphology of complex coastal-estuarine systems. Here we focus on the San Francisco Bay Coastal System, extending from the lower San Joaquin-Sacramento Delta, through the Bay, and along the adjacent outer Pacific Coast. San Francisco Bay is an urbanized estuary that is impacted by numerous anthropogenic activities common to many large estuaries, including a mining legacy, channel dredging, aggregate mining, reservoirs, freshwater diversion, watershed modifications, urban run-off, ship traffic, exotic species introductions, land reclamation, and wetland restoration. The Golden Gate strait is the sole inlet connecting the Bay to the Pacific Ocean, and serves as the conduit for a tidal flow of ~ 8 x 109 m3/day, in addition to the transport of mud, sand, biogenic material, nutrients, and pollutants. Despite this physical, biological and chemical connection, resource management and prior research have often treated the Delta, Bay and adjacent ocean as separate entities, compartmentalized by artificial geographic or political boundaries. The body of work herein presents a comprehensive analysis of system-wide behavior, extending a rich heritage of sediment transport research that dates back to the groundbreaking hydraulic mining-impact research of G.K. Gilbert in the early 20th century.

  4. Hydrodynamic Aspects at Vitória Bay Mouth, ES

    Directory of Open Access Journals (Sweden)

    FLÁVIA A.A. GARONCE

    2014-06-01

    Full Text Available Understading the hydrodynamic behavior and suspended particulated matter (SPM transport are of great importance in port regions such as Vitória Harbor, which is located at Vitória Bay, Vitória – ES, Brazil. Vitória Bay is an estuary that has not been systematically assessed through a temporal analysis in order to identify its hydrodynamics characteristics and SPM exchange. This study aims to investigate salt and suspended particulate matter flux at the estuarine mouth of Vitória Bay by understanding the temporal variation of salinity, temperature and tidal currents within the water column and at the channel crosssection. Results showed that the estuarine mouth tended to present partial stratification periods during neap tides and little stratification in spring tides. The circulation pattern was mainly influenced by the tide, with little influence from river discharge. With regard to the SPM, the mouth of the estuary tended to show low concentrations, with the highest values occurring during the dry season. A close relationship between momentary discharge, SPM and salt fluxes was observed. Despite all the data was collected at the mouth of the estuary, the system showed an importation trend of salt in all cycles and SPM importation for three of the four studied tidal cycles. Thus, Vitoria Bay is not exporting SPM to the adjacent inner shelf.

  5. First Investigation of Microbial Community Composition in the Bridge (Gadeok Channel) between the Jinhae-Masan Bay and the South Sea of Korea

    Science.gov (United States)

    Lee, Jiyoung; Lim, Jae-Hyun; Park, Junhyung; Youn, Seok-Hyun; Oh, Hyun-Ju; Kim, Ju-Hyoung; Kim, Myung Kyum; Cho, Hyeyoun; Yoon, Joo-Eun; Kim, Soyeon; Markkandan, Kesavan; Park, Ki-Tae; Kim, Il-Nam

    2018-02-01

    Microbial community composition varies based on seasonal dynamics (summer: strongly stratified water column; autumn: weakly stratified water column; winter: vertically homogeneous water column) and vertical distributions (surface, middle, and bottom depths) in the Gadeok Channel, which is the primary passage to exchange waters and materials between the Jinhae-Masan Bay and the South Sea waters. The microbial community composition was analyzed from June to December 2016 using 16S rRNA gene sequencing. The community was dominated by the phyla Proteobacteria (45%), Bacteroidetes (18%), Cyanobacteria (15%), Verrucomicrobia (6%), and Actinobacteria (6%). Alphaproteobacteria (29%) was the most abundant microbial class, followed by Flavobacteria (15%) and Gammaproteobacteria (15%) in all samples. The composition of the microbial communities was found to vary vertically and seasonally. The orders Flavobacteriales and Stramenopiles showed opposing seasonal patterns; Flavobacteriales was more abundant in August and December while Stramenopiles showed high abundance in June and October at all depths. The genus Synechococcus reached extremely high abundance (14%) in the June surface water column, but was much less abundant in December water columns. Clustering analysis showed that there was a difference in the microbial community composition pattern between the strongly stratified season and well-mixed season. These results indicate that the seasonal dynamics of physicochemical and hydrologic conditions throughout the water column are important parameters in shaping the microbial community composition in the Gadeok Channel.

  6. Application of individual foraminifera Mg/Ca and δ18O analyses for paleoceanographic reconstructions in the Bay of Bengal and other active depositional environments

    Science.gov (United States)

    Fritz-Endres, T.; Dekens, P.; Fehrenbacher, J. S.; Spero, H. J.; Stine, A.

    2017-12-01

    Paleoceanographic research traditionally focuses on regions where sediment deposition is minimally affected by transport. However, sediment fans near tectonically active regions provide an opportunity to link oceanographic climate to terrestrial processes. Sediment cores recovered during IODP Expedition 354 in the Bay of Bengal include hemipelagic sections that record the history of tectonic uplift and the development of the Indian Monsoon through the last 10 Ma. Although these cores provide a unique opportunity to link marine and terrestrial climate, the complex depositional environment requires that the source of foraminifera is carefully considered before using these proxies to reconstruct oceanographic conditions. Foraminifera in Bengal Fan sediments may have been transported via turbidity currents from the northern Bay of Bengal, where the seasonal variability of SST and SSS is larger compared to the southern Bay of Bengal. We measured single Globigerinoides sacculifer Mg/Ca and δ18O from mudline samples of IODP Site U1454 (8.4°N, 85.5°E, 3721 m water depth) near the modern active channel and Site U1449 (8.4°N, 88.7°E, 3653 m water depth) far from channel activity. We compare these sites to single G. sacculifer from the core-top sample of Site 342KL (20.6°N, 90.1°E, 1256 m water depth) located on the continental shelf. Each foraminifera lives 2-4 weeks and the distribution of 60 to 80 data points reflects the seasonal range of SST and SSS at the location where the foraminifera calcified. Measurements in foraminifera from Site U1449 (away from active channel) are statistically different from the site in the northern Bay of Bengal and more consistent with local conditions. Conversely, foraminifera from the site near the active channel reflect a combined signal of local conditions recorded from the site far from channel activity and those recorded from the continental shelf. This suggests a portion of foraminifera from the active channel site have been

  7. Dissolved inorganic carbon, alkalinity, temperature, salinity and other variables collected from discrete sample and profile observations using Alkalinity titrator, CTD and other instruments from the PRIDE OF BILBAO in the Bay of Biscay, English Channel and North Atlantic Ocean from 2005-09-26 to 2010-09-16 (NODC Accession 0108092)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NODC Accession 0108092 includes chemical, discrete sample, physical and profile data collected from PRIDE OF BILBAO in the Bay of Biscay, English Channel and North...

  8. Humic Substances from Manila Bay and Bolinao Bay Sediments

    Directory of Open Access Journals (Sweden)

    Elma Llaguno

    1997-12-01

    Full Text Available The C,H,N composition of sedimentary humic acids (HA extracted from three sites in Manila Bay and six sites in Bolinao Bay yielded H/C atomic ratios of 1.1-1.4 and N/C atomic ratios of 0.09 - 0.16. The Manila Bay HA's had lower H/C and N/C ratios compared to those from Bolinao Bay. The IR spectra showed prominent aliphatic C-H and amide I and II bands. Manila Bay HA's also had less diverse molecular composition based on the GC-MS analysis of the CuO and alkaline permanganate oxidation products of the humic acids.

  9. Effects of local anesthetics on cholinergic agonist binding affinity of central nervous system. cap alpha. -bungarotoxin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Lukas, R.L.; Bennett, E.L.

    1979-12-01

    In general, pharmacological effects of local anesthetics may be attributed to their ability to reversibly block the propagation of nerve and muscle action potentials. At physiologically potent concentrations, local anesthetics (LA) also act as noncompetitive antagonists of the physiological response of post-synaptic nicotinic acetylcholine receptors (nAChR) to cholinergic agonists, and increase agonist binding affinities of nAChR from electric organ. It is postulated that the primary site of LA action on nAChR function is at the receptor-coupled ionophore. Furthermore, LA-nAChR ionophore interactions are thought to accelerate physiological desensitization of nAChR, manifest biochemically as increased affinity of nAChR for agonist. Specific receptors for ..cap alpha..-bungarotoxin (..cap alpha..-Bgt), a potent competitive antagonist at nAChR sites in the periphery, have been detected in rat central nervous system membrane preparations. The affinity of these central ..cap alpha..-Bgt receptors (..cap alpha..-BgtR) for cholinergic agonists is found to increase on exposure to agonist. Nevertheless, on the basis of inconsistent pharmacological and physiological results, uncertainty remains regarding the relationship between ..cap alpha..-BgtR and authentic nAChR in the CNS, despite a wide body of biochemical and histological evidence consistent with their identity. Reasoning that if CNS ..cap alpha..-BgtR are true in nAChR, coupled to functional ion channels, LA might be expected to cause biochemically measurable increases in ..cap alpha..-BgtR affinity for cholinergic agonists, we have undertaken a study of the effects of LA on the ability of acetylcholine (ACh) to inhibit interaction of ..cap alpha..-BgtR with /sup 3/H-labeled ..cap alpha..-Bgt.

  10. Characterization of Dredged Oyster Shell Deposits at Mobile Bay, Alabama Using Geophysical Methods

    Directory of Open Access Journals (Sweden)

    Stanley C. Nwokebuihe

    2016-12-01

    Full Text Available The need for disposing materials dredged from ship channels is a common problem in bays and lagoons. This study is aimed at investigating the suitability of scour features produced by dredging oyster shell deposits in Mobile Bay, Alabama, to dispose excavated channel material. A study area approximately 740 by 280 m lying about 5 km east of Gaillard Island was surveyed using underwater electrical resistivity tomography (UWERT and continuous electrical resistivity profiling (CERP tools. The geophysical survey was conducted with the intent to map scour features created by oyster shell dredging activities in the bay between 1947 and 1982. The geoelectrical surveys show that oyster beds are characterized by high resistivity values greater than 1.1 ohm.m while infilled dredge cuts show lower resistivity, generally from 0.6 to 1.1 ohm.m. The difference in resistivity mainly reflects the lithology and the consolidation of the shallow sediments: consolidated silty clay and sandy sediments rich in oyster shell deposits (with less clay content overlying unconsolidated clayey materials infilling the scours. Results show that most of the infilled dredge cuts are mostly distributed in the north-south direction. Considering that the scours are generally up to 6 m deep across the survey location, it is estimated that about 0.8 million cubic meters of oyster shells and overlying strata were dredged from the survey location.

  11. Ecological evaluation of proposed dredged material from Winyah Bay, South Carolina

    International Nuclear Information System (INIS)

    Ward, J.A.; Gardiner, W.W.; Pinza, M.R.; Word, J.Q.

    1993-10-01

    The navigational channels of Winyah Bay, Georgetown Harbor, South Carolina require dredging to enable normal shipping traffic to use these areas. Before dredging, environmental assessments must be conducted to determine the suitability of this dredged sediment for unconfined, open-water disposal. The Charleston, South Carolina District Office of the US Army Corps of Engineers (USACE) requested that the Battelle/Marine Science Laboratory (MSL) collect sediment samples and conduct the required physical/chemical, toxicological, and bioaccumulation evaluations as required in the 1991 Implementation Manual. This report is intended to provide information required to address potential ecological effects of the Entrance Channel and Inner Harbor sediments proposed disposal in the ocean

  12. Retigabine diminishes the effects of acetylcholine, adrenaline and adrenergic agonists on the spontaneous activity of guinea pig smooth muscle strips in vitro.

    Science.gov (United States)

    Apostolova, Elisaveta; Zagorchev, Plamen; Kokova, Vesela; Peychev, Lyudmil

    2017-03-01

    The aim of this study is to evaluate the effect of retigabine on the smooth muscle response to acetylcholine, adrenaline, α-and β-adrenoceptor agonists. We studied the change in the spontaneous smooth muscle contraction of guinea pig gastric corpus strips before and after 20-min treatment with 2μM retigabine. We also evaluated the effect of retigabine on the smooth muscle response to 10μM acetylcholine, 1 and 10μM adrenaline, 1μM methoxamine, 0.1μM p-iodoclonidine and 10μM isoproterenol. We observed a significant reduction in the effects of all studied mediators and agonists when they were added to organ baths in the presence of retigabine. Retigabine diminished the effect of acetylcholine on the spontaneous smooth muscle activity. The effect was fully antagonized by XE-991 (Kv7 channel blocker), which supports our hypothesis about the role of KCNQ channels in the registered changes. The increase in the contraction force after adding of 1μM adrenaline, methoxamine, and 0.1μM p-iodoclonidine was also significantly smaller in presence of retigabine. However, comparing the effect of 10μM adrenaline on the contractility before and after treatment with retigabine, we observed increased contractility when retigabine was present in the organ baths. A possible explanation for the observed diminished effects of mediators and receptor agonists is that the effect of retigabine on smooth muscle contractility is complex. The membrane hyperpolarization, the interaction between Kv7 channels and adrenoceptors, and the influence on signaling pathways may contribute to the summary smooth muscle response. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Asymptotic behavior of Bayes estimators for hidden Markov models with application to ion channels

    NARCIS (Netherlands)

    de Gunst, M.C.M.; Shcherbakova, O.V.

    2008-01-01

    In this paper we study the asymptotic behavior of Bayes estimators for hidden Markov models as the number of observations goes to infinity. The theorem that we prove is similar to the Bernstein-von Mises theorem on the asymptotic behavior of the posterior distribution for the case of independent

  14. Phytochemicals from Ruta graveolens Activate TAS2R Bitter Taste Receptors and TRP Channels Involved in Gustation and Nociception.

    Science.gov (United States)

    Mancuso, Giuseppe; Borgonovo, Gigliola; Scaglioni, Leonardo; Bassoli, Angela

    2015-10-16

    Ruta graveolens (rue) is a spontaneous plant in the Mediterranean area with a strong aroma and a very intense bitter taste, used in gastronomy and in folk medicine. From the leaves, stems and fruits of rue, we isolated rutin, rutamarin, three furanocoumarins, two quinolinic alkaloids, a dicoumarin and two long chain ketones. Bitter taste and chemesthetic properties have been evaluated by in vitro assays with twenty receptors of the TAS2R family and four TRP ion channels involved in gustation and nociception. Among the alkaloids, skimmianine was active as a specific agonist of T2R14, whereas kokusaginin did not activate any of the tested receptors. The furanocoumarins activates TAS2R10, 14, and 49 with different degrees of selectivity, as well as the TRPA1 somatosensory ion channel. Rutamarin is an agonist of TRPM5 and TRPV1 and a strong antagonist of TRPM8 ion channels.

  15. The Challenge of Interpreting Glutamate-Receptor Ion-Channel Structures.

    Science.gov (United States)

    Mayer, Mark L

    2017-11-21

    Ion channels activated by glutamate mediate excitatory synaptic transmission in the central nervous system. Similar to other ligand-gated ion channels, their gating cycle begins with transitions from a ligand-free closed state to glutamate-bound active and desensitized states. In an attempt to reveal the molecular mechanisms underlying gating, numerous structures for glutamate receptors have been solved in complexes with agonists, antagonists, allosteric modulators, and auxiliary proteins. The embarrassingly rich library of structures emerging from this work reveals very dynamic molecules with a more complex conformational spectrum than anticipated from functional studies. Unanticipated conformations solved for complexes with competitive antagonists and a lack of understanding of the structural basis for ion channel subconductance states further highlight challenges that have yet to be addressed. Published by Elsevier Inc.

  16. Dopaminergic agonists for hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Gluud, L L; Gluud, C

    2004-01-01

    Hepatic encephalopathy may be associated with an impairment of the dopaminergic neurotransmission. Dopaminergic agonists may therefore have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be associated with an impairment of the dopaminergic neurotransmission. Dopaminergic agonists may therefore have a beneficial effect on patients with hepatic encephalopathy....

  17. Noise control of subsonic cavity flows using plasma actuated receptive channels

    International Nuclear Information System (INIS)

    Gupta, Arnob Das; Roy, Subrata

    2014-01-01

    We introduce a passive receptive rectangular channel at the trailing edge of an open rectangular cavity to reduce the acoustic tones generated due to coherent shear layer impingement. The channel is numerically tested at Mach 0.3 using an unsteady three-dimensional large eddy simulation. Results show reduction in pressure fluctuations in the cavity due to which sound pressure levels are suppressed. Two linear dielectric barrier discharge plasma actuators are placed inside the channel to enhance the flow through it. Specifically, acoustic suppression of 7 dB was obtained for Mach 0.3 flow with the plasma actuated channel. Also, the drag coefficient for the cavity reduced by over three folds for the channel and over eight folds for the plasma actuated channel. Such a channel can be useful in noise and drag reduction for various applications, including weapons bay, landing gear and branched piping systems. (fast track communication)

  18. Beta-agonists and animal welfare

    Science.gov (United States)

    The use of beta-agonists in animal feed is a high profile topic within the U.S. as consumers and activist groups continue to question its safety. The only beta-agonist currently available for use in swine is ractopamine hydrochloride (RAC). This is available as Paylean™ (Elanco Animal Health – FDA a...

  19. Heterologous Expression in Remodeled C. elegans: A Platform for Monoaminergic Agonist Identification and Anthelmintic Screening.

    Science.gov (United States)

    Law, Wenjing; Wuescher, Leah M; Ortega, Amanda; Hapiak, Vera M; Komuniecki, Patricia R; Komuniecki, Richard

    2015-04-01

    Monoamines, such as 5-HT and tyramine (TA), paralyze both free-living and parasitic nematodes when applied exogenously and serotonergic agonists have been used to clear Haemonchus contortus infections in vivo. Since nematode cell lines are not available and animal screening options are limited, we have developed a screening platform to identify monoamine receptor agonists. Key receptors were expressed heterologously in chimeric, genetically-engineered Caenorhabditis elegans, at sites likely to yield robust phenotypes upon agonist stimulation. This approach potentially preserves the unique pharmacologies of the receptors, while including nematode-specific accessory proteins and the nematode cuticle. Importantly, the sensitivity of monoamine-dependent paralysis could be increased dramatically by hypotonic incubation or the use of bus mutants with increased cuticular permeabilities. We have demonstrated that the monoamine-dependent inhibition of key interneurons, cholinergic motor neurons or body wall muscle inhibited locomotion and caused paralysis. Specifically, 5-HT paralyzed C. elegans 5-HT receptor null animals expressing either nematode, insect or human orthologues of a key Gαo-coupled 5-HT1-like receptor in the cholinergic motor neurons. Importantly, 8-OH-DPAT and PAPP, 5-HT receptor agonists, differentially paralyzed the transgenic animals, with 8-OH-DPAT paralyzing mutant animals expressing the human receptor at concentrations well below those affecting its C. elegans or insect orthologues. Similarly, 5-HT and TA paralyzed C. elegans 5-HT or TA receptor null animals, respectively, expressing either C. elegans or H. contortus 5-HT or TA-gated Cl- channels in either C. elegans cholinergic motor neurons or body wall muscles. Together, these data suggest that this heterologous, ectopic expression screening approach will be useful for the identification of agonists for key monoamine receptors from parasites and could have broad application for the identification

  20. Heterologous Expression in Remodeled C. elegans: A Platform for Monoaminergic Agonist Identification and Anthelmintic Screening.

    Directory of Open Access Journals (Sweden)

    Wenjing Law

    2015-04-01

    Full Text Available Monoamines, such as 5-HT and tyramine (TA, paralyze both free-living and parasitic nematodes when applied exogenously and serotonergic agonists have been used to clear Haemonchus contortus infections in vivo. Since nematode cell lines are not available and animal screening options are limited, we have developed a screening platform to identify monoamine receptor agonists. Key receptors were expressed heterologously in chimeric, genetically-engineered Caenorhabditis elegans, at sites likely to yield robust phenotypes upon agonist stimulation. This approach potentially preserves the unique pharmacologies of the receptors, while including nematode-specific accessory proteins and the nematode cuticle. Importantly, the sensitivity of monoamine-dependent paralysis could be increased dramatically by hypotonic incubation or the use of bus mutants with increased cuticular permeabilities. We have demonstrated that the monoamine-dependent inhibition of key interneurons, cholinergic motor neurons or body wall muscle inhibited locomotion and caused paralysis. Specifically, 5-HT paralyzed C. elegans 5-HT receptor null animals expressing either nematode, insect or human orthologues of a key Gαo-coupled 5-HT1-like receptor in the cholinergic motor neurons. Importantly, 8-OH-DPAT and PAPP, 5-HT receptor agonists, differentially paralyzed the transgenic animals, with 8-OH-DPAT paralyzing mutant animals expressing the human receptor at concentrations well below those affecting its C. elegans or insect orthologues. Similarly, 5-HT and TA paralyzed C. elegans 5-HT or TA receptor null animals, respectively, expressing either C. elegans or H. contortus 5-HT or TA-gated Cl- channels in either C. elegans cholinergic motor neurons or body wall muscles. Together, these data suggest that this heterologous, ectopic expression screening approach will be useful for the identification of agonists for key monoamine receptors from parasites and could have broad application for

  1. Organic carbon balance and net ecosystem metabolism in Chesapeake Bay

    Science.gov (United States)

    Kemp, W.M.; Smith, E.M.; Marvin-DiPasquale, M.; Boynton, W.R.

    1997-01-01

    The major fluxes of organic carbon associated with physical transport and biological metabolism were compiled, analyzed and compared for the mainstem portion of Chesapeake Bay (USA). In addition, 5 independent methods were used to calculate the annual mean net ecosystem metabolism (NEM = production - respiration) for the integrated Bay. These methods, which employed biogeochemical models, nutrient mass-balances anti summation of individual organic carbon fluxes, yielded remarkably similar estimates, with a mean NEM of +50 g C m-2 yr-1 (?? SE = 751, which is approximately 8% of the estimated annual average gross primary production. These calculations suggest a strong cross-sectional pattern in NEM throughout the Bay, wherein net heterotrophic metabolism prevails in the pelagic zones of the main channel, while net autotrophy occurs in the littoral zones which flank the deeper central area. For computational purposes, the estuary was separated into 3 regions along the land-sea gradient: (1) the oligohaline Upper Bay (11% of total area); (2) the mesohaline Mid Bay (36% of area); and (3) the polyhaline Lower Bay (53% of area). A distinct regional trend in NEM was observed along this salinity gradient, with net here(atrophy (NEM = 87 g C m-2 yr-1) in the Upper Bay, balanced metabolism in the Mid Bay and net autotrophy (NEM = +92 g C m-2 yr-1) in the Lower Bay. As a consequence of overall net autotrophy, the ratio of dissolved inorganic nitrogen (DIN) to total organic nitrogen (TON) changed from DIN:TON = 5.1 for riverine inputs to DIN:TON = 0.04 for water exported to the ocean. A striking feature of this organic C mass-balance was the relative dominance of biologically mediated metabolic fluxes compared to physical transport fluxes. The overall ratio of physical TOC inputs (1) to biotic primary production (P) was 0.08 for the whole estuary, but varied dramatically from 2.3 in the Upper Bay to 0.03 in the Mid and Lower Bay regions. Similarly, ecosystem respiration was

  2. Continuous resistivity profiling data from Great South Bay, Long Island, New York

    Science.gov (United States)

    Cross, V.A.; Bratton, J.F.; Kroeger, K.D.; Crusius, John; Worley, C.R.

    2013-01-01

    An investigation of submarine aquifers adjacent to the Fire Island National Seashore and Long Island, New York was conducted to assess the importance of submarine groundwater discharge as a potential nonpoint source of nitrogen delivery to Great South Bay. Over 200 kilometers of continuous resistivity profiling data were collected to image the fresh-saline groundwater interface in sediments beneath the bay. In addition, groundwater sampling was performed at sites (1) along the north shore of Great South Bay, particularly in Patchogue Bay, that were representative of the developed Long Island shoreline, and (2) at sites on and adjacent to Fire Island, a 50-kilometer-long barrier island on the south side of Great South Bay. Other field activities included sediment coring, stationary electrical resistivity profiling, and surveys of in situ pore water conductivity. Results of continuous resistivity profiling surveys are described in this report. The onshore and offshore shallow hydrostratigraphy of the Great South Bay shorelines, particularly the presence and nature of submarine confining units, appears to exert primary control on the dimensions and chemistry of the submarine groundwater flow and discharge zones. Sediment coring has shown that the confining units commonly consist of drowned and buried peat layers likely deposited in salt marshes. Low-salinity groundwater extends from 10 to 100 meters offshore along much of the north and south shores of Great South Bay based on continuous resistivity profiling data, especially off the mouths of tidal creeks and beneath shallow flats to the north of Fire Island adjacent to modern salt marshes. Human modifications of much of the shoreline and nearshore areas along the north shore of the bay, including filling of salt marshes, construction of bulkheads and piers, and dredging of navigation channels, has substantially altered the natural hydrogeology of the bay's shorelines by truncating confining units and increasing

  3. Holocene depositional history of a large glaciated estuary, Penobscot Bay, Maine

    Science.gov (United States)

    Knebel, H.J.

    1986-01-01

    redistributed Holocene sediments: (1) atop the shallow margins; (2) within constricted channels; (3) around topographic highs; and (4) over the shallow bedrock sill at the bay mouth. The variable distribution, characteristics, and thickness (0 to more than 30 m) of Holocene deposits in Penobscot Bay primarily reflect: (1) the irregular glacially eroded bedrock topography beneath the bay; (2) the paleogeography of the bay during the sea-level lowstand; (3) the postglacial location of the ancestral Penobscot River; and (4) the wave and current regime during and since the Holocene sea-level transgression. ?? 1986.

  4. Molecular Basis for Allosteric Inhibition of Acid-Sensing Ion Channel 1a by Ibuprofen

    DEFF Research Database (Denmark)

    Lynagh, Timothy; Romero-Rojo, José Luis; Lund, Camilla

    2017-01-01

    -clamp fluorometry. Our results show that ibuprofen is an allosteric inhibitor of ASIC1a, which binds to a crucial site in the agonist transduction pathway and causes conformational changes that oppose channel activation. Ibuprofen inhibits several ASIC subtypes, but certain ibuprofen derivatives show some...

  5. The transient receptor potential, TRP4, cation channel is a novel member of the family of calmodulin binding proteins.

    OpenAIRE

    Trost, C; Bergs, C; Himmerkus, N; Flockerzi, V

    2001-01-01

    The mammalian gene products, transient receptor potential (trp)1 to trp7, are related to the Drosophila TRP and TRP-like ion channels, and are candidate proteins underlying agonist-activated Ca(2+)-permeable ion channels. Recently, the TRP4 protein has been shown to be part of native store-operated Ca(2+)-permeable channels. These channels, most likely, are composed of other proteins in addition to TRP4. In the present paper we report the direct interaction of TRP4 and calmodulin (CaM) by: (1...

  6. Subaqueous hot springs in Köyceğiz Lake, Dalyan Channel and Fethiye-Göcek Bay (SW Turkey): Locations, chemistry and origins

    KAUST Repository

    Avşar, Özgür

    2017-08-07

    In this study, horizontal temperature measurements along organized grids have been used to detect subaqueous hot springs. The study area, located in the southwest of Turkey and comprised of Köyceğiz Lake, Dalyan Channel and Fethiye-Göcek Bay, was scanned by measuring temperatures horizontally, 2–3m above the bottom of the lake or sea. After analyzing the temperature data along the grids, the locations with anomalous temperature values were detected, and divers headed here for further verification. Accordingly, among these anomalies, the divers confirmed seven of them as subaqueous hot springs. Three of these hot springs are located in the Köyceğiz Lake, three of them are located in the Dalyan Channel and one hot spring is located in the Fethiye-Göcek Bay. At the locations where temperature anomalies were detected, the divers collected samples directly from the subaqueous hot spring using a syringe-type sampler. We evaluated these water samples together with samples collected from hot and cold springs on land and from local rivers, lakes and the sea, with an aim to generate a conceptual hydrogeochemical model of the geothermal system in the study area. This model predicts that rainwater precipitating in the highlands percolates through fractures and faults into the deeper parts of the Earth\\'s crust, here it is heated and ascends through the sea bottom via buried faults. Pervious carbonate nappes that are underlain and overlain by impervious rocks create a confined aquifer. The southern boundary of the Carbonate-Marmaris nappes is buried under alluvium and/or sea/lake water bodies and this phenomenon determines whether hot springs occur on land or subaqueous. The chemical and isotopic properties of the hot springs point to seawater mixing at deep levels. Thus, the mixing most probably occurs while the water is ascending through the faults and fractures. The gas geochemistry results reveal that the lowest mantle He contributions occur in the samples from K

  7. Subaqueous hot springs in Köyceğiz Lake, Dalyan Channel and Fethiye-Göcek Bay (SW Turkey): Locations, chemistry and origins

    Science.gov (United States)

    Avşar, Özgür; Avşar, Ulaş; Arslan, Şebnem; Kurtuluş, Bedri; Niedermann, Samuel; Güleç, Nilgün

    2017-10-01

    In this study, horizontal temperature measurements along organized grids have been used to detect subaqueous hot springs. The study area, located in the southwest of Turkey and comprised of Köyceğiz Lake, Dalyan Channel and Fethiye-Göcek Bay, was scanned by measuring temperatures horizontally, 2-3 m above the bottom of the lake or sea. After analyzing the temperature data along the grids, the locations with anomalous temperature values were detected, and divers headed here for further verification. Accordingly, among these anomalies, the divers confirmed seven of them as subaqueous hot springs. Three of these hot springs are located in the Köyceğiz Lake, three of them are located in the Dalyan Channel and one hot spring is located in the Fethiye-Göcek Bay. At the locations where temperature anomalies were detected, the divers collected samples directly from the subaqueous hot spring using a syringe-type sampler. We evaluated these water samples together with samples collected from hot and cold springs on land and from local rivers, lakes and the sea, with an aim to generate a conceptual hydrogeochemical model of the geothermal system in the study area. This model predicts that rainwater precipitating in the highlands percolates through fractures and faults into the deeper parts of the Earth's crust, here it is heated and ascends through the sea bottom via buried faults. Pervious carbonate nappes that are underlain and overlain by impervious rocks create a confined aquifer. The southern boundary of the Carbonate-Marmaris nappes is buried under alluvium and/or sea/lake water bodies and this phenomenon determines whether hot springs occur on land or subaqueous. The chemical and isotopic properties of the hot springs point to seawater mixing at deep levels. Thus, the mixing most probably occurs while the water is ascending through the faults and fractures. The gas geochemistry results reveal that the lowest mantle He contributions occur in the samples from K

  8. Oceanographic data collected from Cathlamet Bay North Channel (USCG day mark green 3) by Center for Coastal Margin Observation and Prediction (CMOP) and assembled by Northwest Association of Networked Ocean Observation Systems (NANOOS) in the Columbia River Estuary and North East Pacific Ocean from 2000-07-02 to 2016-11-09 (NCEI Accession 0161822)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0161822 contains navigational and physical data collected at Cathlamet Bay North Channel (USCG day mark green 3), a fixed station in the Columbia...

  9. Understanding and analyzing the hydro-sedimentary processes in the Bay of Toulon. Contribution for modelling the dispersion of radionuclides

    International Nuclear Information System (INIS)

    Dufresne, Christiane

    2014-01-01

    This doctoral research aims to enhance knowledge of the hydro-sedimentary processes in the Bay of Toulon and to represent these processes through a post accidental managing tool, developed to simulate the dispersion of radionuclides. This work is based on a multidisciplinary strategy, using numerical modelling and in situ measurements to study the complex problem of contaminants in the marine environment. Hydrodynamic of the Bay and water mass exchanges through the channel have been studied. Results are highly linked to the atmospheric conditions and the water exchange times of the Little Bay range from two to six days, depending on wind conditions. Recorded data in the Las and Eygoutier Rivers led to the description and the estimation of the catchment yields to the Bay, poorly studied before. With one ton of particulate matter annually discharged by the Las River, the Little Bay seems to be a sedimentation area. In case of accidental release of radionuclides, this area appears to be a trapping zone. (author)

  10. Conceptual Design Studies of the KSTAR Bay-Nm Cassette and Thomson Scattering Optics

    International Nuclear Information System (INIS)

    Feder, R.; Ellis, R.; Johnson, D.; Park, H.; Lee, H.G.

    2005-01-01

    A Multi-Channel Thomson Scattering System viewing the edge and core of the KSTAR plasma will be installed at the mid-plane port Bay-N. An engineering design study was undertaken at PPPL in collaboration with the Korea Basic Science Institute (KBSI) to determine the optimal optics and cassette design. Design criteria included environmental, mechanical and optical factors. All of the optical design options have common design features; the Thomson Scattering laser, an in-vacuum shutter, a quartz heat shield and primary vacuum window, a set of optical elements and a fiber optic bundle. Neutron radiation damage was a major factor in the choice of competing lens-based and mirror-based optical designs. Both the mirror based design and the lens design are constrained by physical limits of the Bay-N cassette and interference with the Bay-N micro-wave launcher. The cassette will contain the optics and a rail system for maintenance of the optics

  11. Does calcium influx regulate melatonin production through the circadian pacemaker in chick pineal cells? Effects of nitrendipine, Bay K 8644, Co2+, Mn2+, and low external Ca2+.

    Science.gov (United States)

    Zatz, M; Mullen, D A

    1988-11-01

    We have recently described a system, using dispersed chick pineal cells in static culture, which displays a persistent, photosensitive, circadian rhythm of melatonin production and release. Here, we describe the effects of nitrendipine (NTR) (a dihydropyridine 'antagonist' of L-type calcium channels), Bay K 8644 (BK) (a dihydropyridine calcium channel 'agonist'), cobalt and manganese ions (both inorganic calcium channel blockers), and low external calcium concentrations, on the melatonin rhythm. NTR inhibited and BK stimulated melatonin output; they were potent and effective. Co2+, Mn2+, and low external Ca2+ markedly inhibited melatonin output. These results support a role for calcium influx through voltage-dependent calcium channels (L-type) in the regulation of melatonin production. Four or 8 h pulses of white light or darkness, in otherwise constant red light, cause, in addition to acute effects, phase-dependent phase shifts of the melatonin rhythm in subsequent cycles. Such phase shifts indicate an effect on (proximal to) the pacemaker generating the rhythm. Four or 8 h pulses of NTR, BK, Co2+, or low Ca2+, however, did not appreciably alter the phase of subsequent melatonin cycles. Neither did BK interfere with phase shifts induced by light pulses. Mn2+ pulses did induce phase-dependent phase shifts, but, unlike those evoked by light or dark pulses, these were all delays. Such effects of Mn2+ in other systems have been attributed to, and are characteristic of, 'metabolic inhibitors'. On balance, the results fail to support a prominent role for calcium influx in regulating the pacemaker underlying the circadian rhythm in chick pineal cells. Rather, calcium influx appears to regulate melatonin production primarily by acting on the melatonin-synthesizing apparatus, distal to the pacemaker.

  12. Phytochemicals from Ruta graveolens Activate TAS2R Bitter Taste Receptors and TRP Channels Involved in Gustation and Nociception

    Directory of Open Access Journals (Sweden)

    Giuseppe Mancuso

    2015-10-01

    Full Text Available Ruta graveolens (rue is a spontaneous plant in the Mediterranean area with a strong aroma and a very intense bitter taste, used in gastronomy and in folk medicine. From the leaves, stems and fruits of rue, we isolated rutin, rutamarin, three furanocoumarins, two quinolinic alkaloids, a dicoumarin and two long chain ketones. Bitter taste and chemesthetic properties have been evaluated by in vitro assays with twenty receptors of the TAS2R family and four TRP ion channels involved in gustation and nociception. Among the alkaloids, skimmianine was active as a specific agonist of T2R14, whereas kokusaginin did not activate any of the tested receptors. The furanocoumarins activates TAS2R10, 14, and 49 with different degrees of selectivity, as well as the TRPA1 somatosensory ion channel. Rutamarin is an agonist of TRPM5 and TRPV1 and a strong antagonist of TRPM8 ion channels.

  13. In vivo effects of the IKr agonist NS3623 on cardiac electrophysiology of the guinea pig

    DEFF Research Database (Denmark)

    Hansen, Rie Schultz; Olesen, Søren-Peter; Rønn, Lars Christian B

    2008-01-01

    to examining the in vivo effects of NS3623. Injection of 30 mg/kg NS3623 shortened the corrected QT interval by 25 +/- 4% in anaesthetized guinea pigs. Accordingly, 50 mg/kg of NS3623 shortened the QT interval by 30 +/- 6% in conscious guinea pigs. Finally, pharmacologically induced QT prolongation by a h......ERG channel antagonist (0.15 mg/kg E-4031) could be reverted by injection of NS3623 (50 mg/kg) in conscious guinea pigs. In conclusion, the present in vivo study demonstrates that injection of the hERG channel agonist NS3623 results in shortening of the QTc interval as well as reversal of a pharmacologically...... induced QT prolongation in both anaesthetized and conscious guinea pigs....

  14. Modification of kindled amygdaloid seizures by opiate agonists and antagonists.

    Science.gov (United States)

    Albertson, T E; Joy, R M; Stark, L G

    1984-03-01

    The effects of 19 opiate agonists and antagonists on kindled amygdaloid seizures in the rat were studied. The mu agonists tended to reduce the length of elicited afterdischarges and behavioral ranks, while markedly increasing postictal electroencephalogram spikes and behavioral arrest time. These effects were reversed by naloxone. The kappa agonists reduced behavioral rank and variably reduced afterdischarge length with a concomitant lengthening of postictal behavioral arrest time and number of electroencephalogram spikes. The putative sigma agonist, SKF 10,047, reduced afterdischarge durations only at the higher doses tested. The decreases found after the sigma agonists in postictal electroencephalogram spiking and time of behavioral arrest were not reversed by naloxone. Only the lower doses of normeperidine were found to decrease seizure thresholds. The mixed agonist/antagonists (MAA) cyclazocine and cyclorphan markedly increased seizure threshold and reduced afterdischarge duration and behavioral rank. Only the MAA pentazocine tended to increase threshold but not suprathreshold afterdischarge durations. The order of ability to modify the ictal events was MAA (selected) greater than kappa agonists greater than mu agonists greater than sigma agonists. The increase in postictal events (behavior arrest and spikes) was caused most effectively by pretreatment with mu agonist greater than kappa agonist greater than selected MAA greater than sigma agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Top-down control of phytoplankton by oysters in Chesapeake Bay, USA: Comment on Pomeroy et al. (2006)

    Science.gov (United States)

    Pomeroy et al. (2006) proposed that temporal and spatial mismatches between eastern oyster filtration and phytoplankton abundance will preclude restored stocks of eastern oysters from reducing the severity of hypoxia in the deep channel of central Chesapeake Bay. We refute this c...

  16. Inhomogeneity of optical turbulence over False Bay (South Africa)

    Science.gov (United States)

    Ullwer, Carmen; Sprung, Detlev; van Eijk, Alexander M. J.; Gunter, Willi; Stein, Karin

    2017-09-01

    Atmospheric turbulence impacts on the propagation of electro-optical radiation. Typical manifestations of optical turbulence are scintillation (intensity fluctuations), beam wander and (for laser systems) reduction of beam quality. For longer propagation channels, it is important to characterize the vertical and horizontal distribution (inhomogeneity) of the optical turbulence. In the framework of the First European South African Transmission ExpeRiment (FESTER) optical turbulence was measured between June 2015 and February 2016 on a 2 km over-water link over False Bay. The link ran from the Institute of Maritime Technology (IMT) in Simons Town to the lighthouse at Roman Rock Island. Three Boundary layer scintillometers (BLS900) allowed assessing the vertical distribution of optical turbulence at three different heights between 5 and 12 m above the water surface. The expected decrease of Cn2 with height is not always found. These results are analyzed in terms of the meteorological scenarios, and a comparison is made with a fourth optical link providing optical turbulence data over a 8.7 km path from IMT to Kalk Bay, roughly 36° to the north of the three 2 km paths. The results are related to the inhomogeneous meteorological conditions over the Bay as assessed with the numerical weather prediction tool, the Weather Forecast and Research model WRF.

  17. 33 CFR 100.919 - International Bay City River Roar, Bay City, MI.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false International Bay City River Roar, Bay City, MI. 100.919 Section 100.919 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... Bay City River Roar, Bay City, MI. (a) Regulated Area. A regulated area is established to include all...

  18. Bank-derived material dominates fluvial sediment in a suburban Chesapeake Bay watershed

    Science.gov (United States)

    Cashman, M. J.; Gellis, A.; Gorman-Sanisaca, L.; Noe, G. B.; Cogliandro, V.; Baker, A.

    2017-12-01

    Excess fine sediment is a leading cause of ecological degradation within the Chesapeake Bay watershed. The Piedmont physiographic province, which includes parts of the Washington, D.C. metro area, has the highest sediment yields in the Chesapeake Bay. In order to effectively employ sediment mitigation measures, it is necessary to identify and quantify the contributions of sediments sources within rapidly urbanizing areas in the Piedmont. This sediment fingerprinting study examines the inputs of various sediment sources to Upper Difficult Run (14.2 km2; 22.6% impervious surface), an urbanized watershed in Fairfax County, Virginia. A source sediment library was constructed from collections of stream bank material, forest soils, and road dust from across the watershed. Target fluvial sediments were collected from fine channel margin deposits and from suspended sediment using an autosampler during 16 storm events from 2008 - 2012. Apportionment of the target samples to the source sediments was performed using Sed_SAT, a publically available toolkit for sediment fingerprinting. Bed sediment was found to be dominated by stream bank sources (mean: 96%), with minor contributions from forest (4%) and no detectable contribution from roads (0%). Suspended fine sediments were also found to predominantly originate from stream bank sources (SSC-weighted mean: 91%), with minor contributions from roads (8%), and negligible contributions from forests (1%). Stream bank sources dominated at all discharges, with the greatest contributions from overland sources found only at low discharges. On the rising limb of the hydrograph and at peak flow, sediment concentrations increased due to increasing contributions of bank material rather than surface erosion caused by overland flow. Results demonstrate that stream bank erosion is responsible for the vast majority of fine sediment occurring in this suburban basin of the Chesapeake Bay watershed. This is likely a consequence of storm

  19. Resource utilisation by deep-sea megabenthos in the Canadian High Arctic (Baffin Bay and Parry Channel)

    Science.gov (United States)

    Bourgeois, Solveig; Witte, Ursula; Harrison, Ailish M.; Makela, Anni; Kazanidis, Georgios; Archambault, Philippe

    2016-04-01

    Ongoing climate change in the Arctic is causing drastic alteration of the Arctic marine ecosystem functioning, such as shifts in patterns of primary production, and modifying the present tight pelagic-benthic coupling. Subsequently benthic communities, which rely upon organic matter produced in the top layers of the Ocean, will also be affected by these changes. The benthic megafaunal communities play a significant role in ecological processes and ecosystem functioning (i.e. organic matter recycling, bioturbation, food source for the higher trophic levels…). Yet, information is scarce regarding the main food sources for dominant benthic organisms, and therefore the impact of the ongoing changes is difficult to assess. The goal of this study is to investigate the preferential feeding of different carbon sources by megabenthic organisms in the Canadian High Arctic and to identify environmental drivers which explain the observed trends. In summer 2013, benthic megafauna was collected at 9 stations spread along latitudinal (58 to 81°N) and longitudinal (62 to 114°W) transects in the Baffin Bay and Parry Channel, respectively. Carbon and nitrogen bulk stable isotope analyses (δ13C and δ15N) were performed on several species divided into groups according to their feeding type. This study highlights distinct trends in δ13C values of benthic organisms suggesting the importance of both phytoplankton and ice algae as carbon sources for megafauna in the Canadian High Arctic. The importance of physical and biological parameters as drivers of food web structure will be furthermore discussed.

  20. Sigma-1 Receptor Plays a Negative Modulation on N-type Calcium Channel

    Directory of Open Access Journals (Sweden)

    Kang Zhang

    2017-05-01

    Full Text Available The sigma-1 receptor is a 223 amino acids molecular chaperone with a single transmembrane domain. It is resident to eukaryotic mitochondrial-associated endoplasmic reticulum and plasma membranes. By chaperone-mediated interactions with ion channels, G-protein coupled receptors and cell-signaling molecules, the sigma-1 receptor performs broad physiological and pharmacological functions. Despite sigma-1 receptors have been confirmed to regulate various types of ion channels, the relationship between the sigma-1 receptor and N-type Ca2+ channel is still unclear. Considering both sigma-1 receptors and N-type Ca2+ channels are involved in intracellular calcium homeostasis and neurotransmission, we undertake studies to explore the possible interaction between these two proteins. In the experiment, we confirmed the expression of the sigma-1 receptors and the N-type calcium channels in the cholinergic interneurons (ChIs in rat striatum by using single-cell reverse transcription-polymerase chain reaction (scRT-PCR and immunofluorescence staining. N-type Ca2+ currents recorded from ChIs in the brain slice of rat striatum was depressed when sigma-1 receptor agonists (SKF-10047 and Pre-084 were administrated. The inhibition was completely abolished by sigma-1 receptor antagonist (BD-1063. Co-expression of the sigma-1 receptors and the N-type calcium channels in Xenopus oocytes presented a decrease of N-type Ca2+ current amplitude with an increase of sigma-1 receptor expression. SKF-10047 could further depress N-type Ca2+ currents recorded from oocytes. The fluorescence resonance energy transfer (FRET assays and co-immunoprecipitation (Co-IP demonstrated that sigma-1 receptors and N-type Ca2+ channels formed a protein complex when they were co-expressed in HEK-293T (Human Embryonic Kidney -293T cells. Our results revealed that the sigma-1 receptors played a negative modulation on N-type Ca2+ channels. The mechanism for the inhibition of sigma-1 receptors on

  1. Ventricular action potential adaptation to regular exercise: role of β-adrenergic and KATP channel function.

    Science.gov (United States)

    Wang, Xinrui; Fitts, Robert H

    2017-08-01

    Regular exercise training is known to affect the action potential duration (APD) and improve heart function, but involvement of β-adrenergic receptor (β-AR) subtypes and/or the ATP-sensitive K + (K ATP ) channel is unknown. To address this, female and male Sprague-Dawley rats were randomly assigned to voluntary wheel-running or control groups; they were anesthetized after 6-8 wk of training, and myocytes were isolated. Exercise training significantly increased APD of apex and base myocytes at 1 Hz and decreased APD at 10 Hz. Ca 2+ transient durations reflected the changes in APD, while Ca 2+ transient amplitudes were unaffected by wheel running. The nonselective β-AR agonist isoproterenol shortened the myocyte APD, an effect reduced by wheel running. The isoproterenol-induced shortening of APD was largely reversed by the selective β 1 -AR blocker atenolol, but not the β 2 -AR blocker ICI 118,551, providing evidence that wheel running reduced the sensitivity of the β 1 -AR. At 10 Hz, the K ATP channel inhibitor glibenclamide prolonged the myocyte APD more in exercise-trained than control rats, implicating a role for this channel in the exercise-induced APD shortening at 10 Hz. A novel finding of this work was the dual importance of altered β 1 -AR responsiveness and K ATP channel function in the training-induced regulation of APD. Of physiological importance to the beating heart, the reduced response to adrenergic agonists would enhance cardiac contractility at resting rates, where sympathetic drive is low, by prolonging APD and Ca 2+ influx; during exercise, an increase in K ATP channel activity would shorten APD and, thus, protect the heart against Ca 2+ overload or inadequate filling. NEW & NOTEWORTHY Our data demonstrated that regular exercise prolonged the action potential and Ca 2+ transient durations in myocytes isolated from apex and base regions at 1-Hz and shortened both at 10-Hz stimulation. Novel findings were that wheel running shifted the

  2. Detection of TRPV4 channel current-like activity in Fawn Hooded hypertensive (FHH rat cerebral arterial muscle cells.

    Directory of Open Access Journals (Sweden)

    Debebe Gebremedhin

    Full Text Available The transient receptor potential vallinoid type 4 (TRPV4 is a calcium entry channel known to modulate vascular function by mediating endothelium-dependent vasodilation. The present study investigated if isolated cerebral arterial myocytes of the Fawn Hooded hypertensive (FHH rat, known to display exaggerated KCa channel current activity and impaired myogenic tone, express TRPV4 channels at the transcript and protein level and exhibit TRPV4-like single-channel cationic current activity. Reverse transcription polymerase chain reaction (RT-PCR, Western blot, and immunostaining analysis detected the expression of mRNA transcript and translated protein of TRPV4 channel in FHH rat cerebral arterial myocytes. Patch clamp recording of single-channel current activity identified the presence of a single-channel cationic current with unitary conductance of ~85 pS and ~96 pS at hyperpolarizing and depolarizing potentials, respectively, that was inhibited by the TRPV4 channel antagonist RN 1734 or HC 067074 and activated by the potent TRPV4 channel agonist GSK1016790A. Application of negative pressure via the interior of the patch pipette increased the NPo of the TRPV4-like single-channel cationic current recorded in cell-attached patches at a patch potential of 60 mV that was inhibited by prior application of the TRPV4 channel antagonist RN 1734 or HC 067047. Treatment with the TRPV4 channel agonist GSK1016790A caused concentration-dependent increase in the NPo of KCa single-channel current recorded in cell-attached patches of cerebral arterial myocytes at a patch potential of 40 mV, which was not influenced by pretreatment with the voltage-gated L-type Ca2+ channel blocker nifedipine or the T-type Ca2+ channel blocker Ni2+. These findings demonstrate that FHH rat cerebral arterial myocytes express mRNA transcript and translated protein for TRPV4 channel and display TRPV4-like single-channel cationic current activity that was stretch-sensitive and

  3. Dopamine agonist withdrawal syndrome: implications for patient care.

    Science.gov (United States)

    Nirenberg, Melissa J

    2013-08-01

    Dopamine agonists are effective treatments for a variety of indications, including Parkinson's disease and restless legs syndrome, but may have serious side effects, such as orthostatic hypotension, hallucinations, and impulse control disorders (including pathological gambling, compulsive eating, compulsive shopping/buying, and hypersexuality). The most effective way to alleviate these side effects is to taper or discontinue dopamine agonist therapy. A subset of patients who taper a dopamine agonist, however, develop dopamine agonist withdrawal syndrome (DAWS), which has been defined as a severe, stereotyped cluster of physical and psychological symptoms that correlate with dopamine agonist withdrawal in a dose-dependent manner, cause clinically significant distress or social/occupational dysfunction, are refractory to levodopa and other dopaminergic medications, and cannot be accounted for by other clinical factors. The symptoms of DAWS include anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalized pain, and drug cravings. The severity and prognosis of DAWS is highly variable. While some patients have transient symptoms and make a full recovery, others have a protracted withdrawal syndrome lasting for months to years, and therefore may be unwilling or unable to discontinue DA therapy. Impulse control disorders appear to be a major risk factor for DAWS, and are present in virtually all affected patients. Thus, patients who are unable to discontinue dopamine agonist therapy may experience chronic impulse control disorders. At the current time, there are no known effective treatments for DAWS. For this reason, providers are urged to use dopamine agonists judiciously, warn patients about the risks of DAWS prior to the initiation of dopamine agonist therapy, and follow patients closely for withdrawal symptoms during dopamine agonist taper.

  4. 77 FR 2972 - Thunder Bay Power Company, Thunder Bay Power, LLC, et al.

    Science.gov (United States)

    2012-01-20

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Thunder Bay Power Company, Thunder Bay Power, LLC, et al.; Notice of Application for Transfer of Licenses, and Soliciting Comments and Motions To Intervene Thunder Bay Power Company Project No. 2404-095 Thunder Bay Power, LLC Midwest Hydro, Inc...

  5. Detection of turbidity dynamics in Tampa Bay, Florida using multispectral imagery from ERTS-1

    Science.gov (United States)

    Coker, A. E.; Higer, A. L.; Goodwin, C. R.

    1973-01-01

    In 1970, Congress authorized the deepening of the Tampa Bay channel (Rivers and Harbors Act of 1970) from 34 to 44 feet. In order to determine the effects of this deepening on circulation, water quality, and biota, during and after the construction, the U.S. Geological Survey, in cooperation with the Tampa Port Authority, has collected data and developed a digital simulation model of the bay. In addition to data collected using conventional tools, use is being made of data collected from ERTS-1. Return beam vidicon (RBV) multispectral data were collected, while a shell dredging barge was operating in the bay, and used for turbidity recognition and unique spectral signatures representative of type and amount of material in suspension. A three-dimensional concept of the dynamics of the plume was achieved by superimposing the parts of the plume recognized in each RBV band. This provides a background for automatic computer processing of ERTS data and three-dimensional modeling of turbidity plumes.

  6. Involvement of TRPV3 and TRPM8 ion channel proteins in induction of mammalian cold-inducible proteins.

    Science.gov (United States)

    Fujita, Takanori; Liu, Yu; Higashitsuji, Hiroaki; Itoh, Katsuhiko; Shibasaki, Koji; Fujita, Jun; Nishiyama, Hiroyuki

    2018-01-01

    Cold-inducible RNA-binding protein (CIRP), RNA-binding motif protein 3 (RBM3) and serine and arginine rich splicing factor 5 (SRSF5) are RNA-binding proteins that are transcriptionally upregulated in response to moderately low temperatures and a variety of cellular stresses in mammalian cells. Induction of these cold-inducible proteins (CIPs) is dependent on transient receptor potential (TRP) V4 channel protein, but seems independent of its ion channel activity. We herein report that in addition to TRPV4, TRPV3 and TRPM8 are necessary for the induction of CIPs. We established cell lines from the lung of TRPV4-knockout (KO) mouse, and observed induction of CIPs in them by western blot analysis. A TRPV4 antagonist RN1734 suppressed the induction in wild-type mouse cells, but not in TRPV4-KO cells. A TRPV3 channel blocker S408271 and a TRPM8 channel blocker AMTB as well as siRNAs against TRPV3 and TRPM8 suppressed the CIP induction in mouse TRPV4-KO cells and human U-2 OS cells. A TRPV3 channel agonist 2-APB induced CIP expression, but camphor did not. Neither did a TRPM8 channel agonist WS-12. These results suggest that TRPV4, TRPV3 and TRPM8 proteins, but not their ion channel activities are necessary for the induction of CIPs at 32 °C. Identification of proteins that differentially interact with these TRP channels at 37 °C and 32 °C would help elucidate the underlying mechanisms of CIP induction by hypothermia. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Geomorphic change in Dingzi Bay, East China since the 1950s: impacts of human activity and fluvial input

    Science.gov (United States)

    Tian, Qing; Wang, Qing; Liu, Yalong

    2017-06-01

    This study examines the geomorphic evolution of Dingzi Bay, East China in response to human activity and variations in fluvial input since the 1950s. The analysis is based on data from multiple mathematical methods, along with information obtained from Remote Sensing, Geographic Information System and Global Position System technology. The results show that the annual runoff and sediment load discharged into Dingzi Bay display significant decreasing trends overall, and marked downward steps were observed in 1966 and 1980. Around 60%-80% of the decline is attributed to decreasing precipitation in the Wulong River Basin. The landform types in Dingzi Bay have changed significantly since the 1950s, especially over the period between 1981 and 1995. Large areas of tidal flats, swamp, salt fields, and paddy fields have been reclaimed, and aquaculture ponds have been constructed. Consequently, the patterns of erosion and deposition in the bay have changed substantially. Despite a reduction in sediment input of 65.68% after 1966, low rates of sediment deposition continued in the bay. However, deposition rates changed significantly after 1981 owing to large-scale development in the bay, with a net depositional area approximately 10 times larger than that during 1961-1981. This geomorphic evolution stabilized following the termination of large-scale human activity in the bay after 1995. Overall, Dingzi Bay has shown a tendency towards silting-up during 1952-2010, with the bay head migrating seaward, the number of channels in the tidal creek system decreasing, and the tidal inlet becoming narrower and shorter. In conclusion, largescale development and human activity in Dingzi Bay have controlled the geomorphic evolution of the bay since the 1950s.

  8. Spatial distribution of sound channel and its parameters in north Indian ocean

    Digital Repository Service at National Institute of Oceanography (India)

    Ashalatha, K.; Murty, T.V.R.; Prasad, K.V.S.R.

    of Bengal and 10-30 m in the Arabian Sea. The Bay of Bengal and the Arabian Sea have depth limited nature of the profile, i.e. surface sound speed exceeds the near bottom values. This has an important implication in the sound propagation in the SOFAR channel...

  9. Aqueous leaf extract of Averrhoa carambola L. (Oxalidaceae reduces both the inotropic effect of BAY K 8644 on the guinea pig atrium and the calcium current on GH3cells

    Directory of Open Access Journals (Sweden)

    Carla M. L. Vasconcelos

    Full Text Available It was previously showed that aqueous leaf extract (AqEx of Averrhoa carambola depresses the guinea pig atrial inotropism. Therefore, experiments were carried out on guinea pig left atrium and on pituitary GH3 cells in order to evaluate the effect of AqEx on the cellular calcium influx. The atrium was mounted in an organ chamber (5 mL, Tyrode, 27 ± 0.1 ºC, 95 % O2, 5 % CO2, stretched to 10 mN, and paced at 2 Hz (0.5 ms, 400 V and GH3 cells were submitted to a whole cell voltage clamp configuration. In the atrium, the AqEx (1500 µg/mL shifted to the right the concentration-effect curve of the positive inotropic effect produced by (± BAY K 8644, an L-type calcium channel agonist. The AqEx increased EC50 (concentration required to promote 50% of the maximum effect of the inotropic effect of BAY K 8644 from 7.8 ± 0.38 to 115.1 ± 0.44 nM (N = 3; p < 0.05. In GH3 cells assayed with 500 µg/mL of AqEx, the L-type calcium inward current declined 30 % (from 282 to 190 pA. Nevertheless, the extract did not change the voltage correspondent to the peak current. These data suggest that, at least in part, the negative inotropic effect of AqEx on the guinea pig atrium is due to a reduction of the L-type calcium current.

  10. A Soluble Fluorescent Binding Assay Reveals PIP2 Antagonism of TREK-1 Channels

    Directory of Open Access Journals (Sweden)

    Cerrone Cabanos

    2017-08-01

    Full Text Available Lipid regulation of ion channels by low-abundance signaling lipids phosphatidylinositol 4,5-bisphosphate (PIP2 and phosphatidic acid (PA has emerged as a central cellular mechanism for controlling ion channels and the excitability of nerves. A lack of robust assays suitable for facile detection of a lipid bound to a channel has hampered the probing of the lipid binding sites and measuring the pharmacology of putative lipid agonists for ion channels. Here, we show a fluorescent PIP2 competition assay for detergent-purified potassium channels, including TWIK-1-related K+-channel (TREK-1. Anionic lipids PA and phosphatidylglycerol (PG bind dose dependently (9.1 and 96 μM, respectively and agonize the channel. Our assay shows PIP2 binds with high affinity (0.87 μM but surprisingly can directly antagonize TREK-1 in liposomes. We propose a model for TREK-1 lipid regulation where PIP2 can compete with PA and PG agonism based on the affinity of the lipid for a site within the channel.

  11. Population structure and maturity stages of Fritillaria borealis (Appendicularia, Tunicata: seasonal cycle in Ushuaia Bay (Beagle Channel

    Directory of Open Access Journals (Sweden)

    María Laura Presta

    2015-09-01

    Full Text Available AbstractFritillaria borealis is a cosmopolitan species, very frequent in sub-antarctic and antarctic waters. The objective of this paper was to analyze its size structure and maturity stages at two sites in Ushuaia Bay: a coastal site exposed to anthropogenic pressure (E1 and a reference site (E2 located in the external zone of the bay. Zooplankton was collected during the 2012 seasonal cycle. The sampling method involved the use of a 67 µm-mesh net. Appendicularians were classified in four maturity stages: I undifferentiated gonads, II testis and ovary differentiated, III expanded testis, IV discharged testis, expanded ovary. Our results showed that the highest densities of F. borealisoccurred in spring and summer at both sites; coinciding with high values of chlorophyll-a. The percentage of juveniles (I and II exhibited a spatial and temporal pattern similar to that observed for chlorophyll-a values. During spring-summer, juveniles and mature specimens (III and IV showed a greater gonadal development than those individuals found in autumn-winter. In conclusion, the mismatching in the population structure and the pattern of densities of F. borealis between coastal and external zones would suggest the existence of two sub-populations susceptible to the influence of the anthropogenic impact in the bay.

  12. Ecological evaluation of proposed dredged material from the John F. Baldwin Ship Channel: Phase 3 -- biological testing

    Energy Technology Data Exchange (ETDEWEB)

    Kohn, N.P.; Karle, L.M.; Pinza, M.R.; Mayhew, H.L.; White, P.J.; Gruendell, B.D.; Word, J.Q. [Battelle/Marine Sciences Lab., Sequim, WA (United States)

    1993-10-01

    The John F. Baldwin Ship Channel is a 28-mile-long portion of the San Francisco Bay to Stockton Ship Channel, the primary shipping lane through San Francisco Bay and Delta. The San Francisco District of the US Army Corps of Engineers (USACE) is responsible for construction of the John F. Baldwin Ship Channel, which is authorized to be deepened to a project depth of {minus}45 ft relative to mean lower low water (MLLW). Approximately 8.5 million cubic yards (mcy) of sediment will be removed from the channel to reach this project depth. The USACE requested Battelle/Marine Sciences Laboratory (MSL) to conduct testing for ocean disposal under the guidelines in Evaluation of Dredged Material Proposed for Ocean Disposal-Testing Manual (EPA/USACE 1991). This testing manual contains a tiered evaluation approach developed specifically for ocean disposal of dredged material at a selected site. In this study, John F. Baldwin Ship Channel sediments were evaluated under the Tier III (biological) testing guidance, which is considered to be highly stringent and protective of the environment. The Tier III guidance for ocean disposal testing requires tests of water column effects, (following dredged material disposal), deposited sediment toxicity, and bioaccumulation of contaminants from deposited sediment (dredged material).

  13. TRPA1 expression levels and excitability brake by KV channels influence cold sensitivity of TRPA1-expressing neurons.

    Science.gov (United States)

    Memon, Tosifa; Chase, Kevin; Leavitt, Lee S; Olivera, Baldomero M; Teichert, Russell W

    2017-06-14

    The molecular sensor of innocuous (painless) cold sensation is well-established to be transient receptor potential cation channel, subfamily M, member 8 (TRPM8). However, the role of transient receptor potential cation channel, subfamily A, member 1 (TRPA1) in noxious (painful) cold sensation has been controversial. We find that TRPA1 channels contribute to the noxious cold sensitivity of mouse somatosensory neurons, independent of TRPM8 channels, and that TRPA1-expressing neurons are largely non-overlapping with TRPM8-expressing neurons in mouse dorsal-root ganglia (DRG). However, relatively few TRPA1-expressing neurons (e.g., responsive to allyl isothiocyanate or AITC, a selective TRPA1 agonist) respond overtly to cold temperature in vitro, unlike TRPM8-expressing neurons, which almost all respond to cold. Using somatosensory neurons from TRPM8-/- mice and subtype-selective blockers of TRPM8 and TRPA1 channels, we demonstrate that responses to cold temperatures from TRPA1-expressing neurons are mediated by TRPA1 channels. We also identify two factors that affect the cold-sensitivity of TRPA1-expressing neurons: (1) cold-sensitive AITC-sensitive neurons express relatively more TRPA1 transcripts than cold-insensitive AITC-sensitive neurons and (2) voltage-gated potassium (K V ) channels attenuate the cold-sensitivity of some TRPA1-expressing neurons. The combination of these two factors, combined with the relatively weak agonist-like activity of cold temperature on TRPA1 channels, partially explains why few TRPA1-expressing neurons respond to cold. Blocking K V channels also reveals another subclass of noxious cold-sensitive DRG neurons that do not express TRPM8 or TRPA1 channels. Altogether, the results of this study provide novel insights into the cold-sensitivity of different subclasses of somatosensory neurons. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. A stratigraphic model to support remediation of groundwater contamination in the southern San Francisco Bay area

    International Nuclear Information System (INIS)

    Steinpress, M.G.

    1993-01-01

    Some early regional studies in the southern San Francisco Bay Area applied the term 'older bay mud' to Wisconsin and older deposits thought to be estuarine in origin. This outdated interpretation has apparently contributed to an expectation of laterally-continuous aquifers and aquitards. In fact, heterogeneous alluvial deposits often create complex hydrogeologic settings that defy simple remedial approaches. A more useful stratigraphic model provides a foundation for conducting site investigations and assessing the feasibility of remediation. A synthesis of recent regional studies and drilling results at one site on the southwest margin of the Bay indicate that the upper quaternary stratigraphy consists of four primary units in the upper 200 feet of sediments (oldest to youngest): (1) Illinoian glacial-age alluvium (an important groundwater source); (2) Sangamon interglacial-age deposits, which include fine-grained alluvial deposits and estuarine deposits equivalent to the Yerba Buena Mud (a regional confining layer); (3) Wisconsin glacial-age alluvial fan and floodplain deposits; and (4) Holocene interglacial-age sediments, which include fine-grained alluvial and estuarine deposits equivalent to the 'younger bay mud'. Remedial investigations generally focus on groundwater contamination in the Wisconsin and Holocene alluvial deposits. Detailed drilling results indicate that narrow sand and gravel channels occur in anastomosing patterns within a Wisconsin to Holocene floodplain sequence dominated by interchannel silts and clays. The identification of these small-scale high-permeability conduits is critical to understanding and predicting contaminant transport on a local scale. Discontinuous site-specific aquitards do not provide competent separation where stacked channels occur and the correlation of aquitards over even small distance is often tenuous at best

  15. Sports doping: emerging designer and therapeutic β2-agonists.

    Science.gov (United States)

    Fragkaki, A G; Georgakopoulos, C; Sterk, S; Nielen, M W F

    2013-10-21

    Beta2-adrenergic agonists, or β2-agonists, are considered essential bronchodilator drugs in the treatment of bronchial asthma, both as symptom-relievers and, in combination with inhaled corticosteroids, as disease-controllers. The use of β2-agonists is prohibited in sports by the World Anti-Doping Agency (WADA) due to claimed anabolic effects, and also, is prohibited as growth promoters in cattle fattening in the European Union. This paper reviews the last seven-year (2006-2012) literature concerning the development of novel β2-agonists molecules either by modifying the molecule of known β2-agonists or by introducing moieties producing indole-, adamantyl- or phenyl urea derivatives. New emerging β2-agonists molecules for future therapeutic use are also presented, intending to emphasize their potential use for doping purposes or as growth promoters in the near future. © 2013.

  16. FMRFamide-gated sodium channel and ASIC channels: a new class of ionotropic receptors for FMRFamide and related peptides.

    Science.gov (United States)

    Lingueglia, Eric; Deval, Emmanuel; Lazdunski, Michel

    2006-05-01

    FMRFamide and related peptides typically exert their action through G-protein coupled receptors. However, two ionotropic receptors for these peptides have recently been identified. They are both members of the epithelial amiloride-sensitive Na+ channel and degenerin (ENaC/DEG) family of ion channels. The invertebrate FMRFamide-gated Na+ channel (FaNaC) is a neuronal Na+-selective channel which is directly gated by micromolar concentrations of FMRFamide and related tetrapeptides. Its response is fast and partially desensitizing, and FaNaC has been proposed to participate in peptidergic neurotransmission. On the other hand, mammalian acid-sensing ion channels (ASICs) are not gated but are directly modulated by FMRFamide and related mammalian peptides like NPFF and NPSF. ASICs are activated by external protons and are therefore extracellular pH sensors. They are expressed both in the central and peripheral nervous system and appear to be involved in many physiological and pathophysiological processes such as hippocampal long-term potentiation and defects in learning and memory, acquired fear-related behavior, retinal function, brain ischemia, pain sensation in ischemia and inflammation, taste perception, hearing functions, and mechanoperception. The potentiation of ASIC activity by endogenous RFamide neuropeptides probably participates in the response to noxious acidosis in sensory and central neurons. Available data also raises the possibility of the existence of still unknown FMRFamide related endogenous peptides acting as direct agonists for ASICs.

  17. 33 CFR 162.125 - Sturgeon Bay and the Sturgeon Bay Ship Canal, Wisc.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Sturgeon Bay and the Sturgeon Bay Ship Canal, Wisc. 162.125 Section 162.125 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY INLAND WATERWAYS NAVIGATION REGULATIONS § 162.125 Sturgeon Bay and the Sturgeon Bay Ship...

  18. TRPV1 channels in human skeletal muscle feed arteries: implications for vascular function.

    Science.gov (United States)

    Ives, Stephen J; Park, Song Young; Kwon, Oh Sung; Gifford, Jayson R; Andtbacka, Robert H I; Hyngstrom, John R; Richardson, Russell S

    2017-09-01

    What is the central question of this study? We sought to determine whether human skeletal muscle feed arteries (SFMAs) express TRPV 1 channels and what role they play in modulating vascular function. What is the main finding and its importance? Human SMFAs do express functional TRPV 1 channels that modulate vascular function, specifically opposing α-adrenergic receptor-mediated vasocontraction and potentiating vasorelaxation, in an endothelium-dependent manner, as evidenced by the α 1 -receptor-mediated responses. Thus, the vasodilatory role of TRPV 1 channels, and their ligand capsaicin, could be a potential therapeutic target for improving vascular function. Additionally, given the 'sympatholytic' effect of TRPV 1 activation and known endogenous activators (anandamide, reactive oxygen species, H + , etc.), TRPV 1 channels might contribute to functional sympatholysis during exercise. To examine the role of the transient receptor potential vanilloid type 1 (TRPV 1 ) ion channel in the vascular function of human skeletal muscle feed arteries (SMFAs) and whether activation of this heat-sensitive receptor could be involved in modulating vascular function, SMFAs from 16 humans (63 ± 5 years old, range 41-89 years) were studied using wire myography with capsaicin (TRPV 1 agonist) and without (control). Specifically, phenylephrine (α 1 -adrenergic receptor agonist), dexmedetomidine (α 2 -adrenergic receptor agonist), ACh and sodium nitroprusside concentration-response curves were established to assess the role of TRPV 1 channels in α-receptor-mediated vasocontraction as well as endothelium-dependent and -independent vasorelaxation, respectively. Compared with control conditions, capsaicin significantly attenuated maximal vasocontraction in response to phenylephrine [control, 52 ± 8% length-tension max (LT max ) and capsaicin, 21 ± 5%LT max ] and dexmedetomidine (control, 29 ± 12%LT max and capsaicin, 2 ± 3%LT max ), while robustly enhancing maximal

  19. Sodium channels as targets for volatile anesthetics

    Directory of Open Access Journals (Sweden)

    Karl F. Herold

    2012-03-01

    Full Text Available The molecular mechanisms of modern inhaled anesthetics although widely used in clinical settings are still poorly understood. Considerable evidence supports effects on membrane proteins such as ligand- and voltage-gated ion channels of excitable cells. Na+ channels are crucial to action potential initiation and propagation, and represent potential targets for volatile anesthetics. Inhibition of presynaptic Na+ channels leads to reduced neurotransmitter release at the synapse and could therefore contribute to the mechanisms by which volatile anesthetics produce their characteristic effects: amnesia, unconsciousness, and immobility. Early studies on crayfish and squid giant axon showed inhibition of Na+ currents by volatile anesthetics. Subsequent studies using native neuronal preparations and heterologous expression systems with various mammalian Na+ channel isoforms implicated inhibition of presynaptic Na+ channels in anesthetic actions. Volatile anesthetics reduce peak Na+ current and shift the voltage of half-maximal steady-state inactivation towards more negative potentials, thus stabilizing the fast-inactivated state. Furthermore recovery from fast-inactivation is slowed together with an enhanced use-dependent block during pulse train protocols. These effects can reduce neurotransmitter release by depressing presynaptic excitability, depolarization and Ca entry, and ultimately transmitter release. This reduction in transmitter release is more portent for glutamatergic vs. GABAergic terminals. Involvement of Na+ channel inhibition in mediating the immobility caused by volatile anesthetics has been demonstrated in animal studies, in which intrathecal infusion of the Na+ channel blocker tetrodotoxin increases volatile anesthetic potency, whereas infusion of the Na+ channels agonist veratridine reduces anesthetic potency. These studies indicate that inhibition of presynaptic Na+ channels by volatile anesthetics is involved in mediating some of

  20. Seasonal variability in the surface sediments of Mobile Bay, Alabama, recorded by geochemistry and foraminifera, 2009–2010

    Science.gov (United States)

    Umberger, D.K.; Osterman, L.E.; Smith, C.G.; Frazier, J.; Richwine, K.A.

    2012-01-01

    A study was undertaken in order to document and quantify recent environmental change in Mobile Bay, Alabama. The study was part of the Northern Gulf of Mexico (NGOM) Ecosystem Change and Hazard Susceptibility project, a regional project funded by the Coastal and Marine Geology Program to understand how natural forcings and anthropogenic modifications influence coastal ecosystems and their susceptibility to coastal hazards. Mobile Bay is a large drowned-river estuary that has been modified significantly by humans to accommodate the Port of Mobile. Examples include repeated dredging of a large shipping channel down the central axis of the bay and construction of a causeway across the head of the bay and at the foot of the bayhead delta. In addition to modifications, the bay is also known to have episodic periods of low oxygen (hypoxia) that result in significant mortality to fish and benthic organisms (May, 1973). For this study a series of surface sediment samples were collected. Surface benthic foraminiferal and bulk geochemical data provide the modern baseline conditions of the bay and can be used as a reference to changing environmental parameters in the past (Osterman and Smith, in press) and into the future. This report archives data collected as part of the Mobile Bay Study that may be used in future environmental change studies.

  1. Bird surveys at McKinley Bay and Hutchison Bay, Northwest Territories, in 1991

    Energy Technology Data Exchange (ETDEWEB)

    Cornish, B J; Dickson, D L; Dickson, H L

    1992-03-01

    McKinley Bay is a shallow protected bay along the eastern Beaufort Sea coast which provides an important habitat for diving ducks. Since 1979, the bay has been the site of a winter harbor and support base for oil and gas exploraton in the Beaufort Sea. Aerial surveys for bird abundance and distribution were conducted in August 1991 as a continuation of long-term monitoring of birds in McKinley Bay and Hutchison Bay, a nearby area used as a control. The main objectives of the 1991 surveys were to expand the set of baseline data on natural annual fluctuations in diving duck numbers, and to determine if numbers of diving ducks had changed since the initial 1981-85 surveys. On the day with the best survey conditions, the population of diving ducks at McKinley bay was estimated at ca 32,000, significantly more than 1981-85. At Hutchison Bay, there were an estimated 11,000 ducks. As in previous years, large numbers of diving ducks were observed off Atkinson Point at the northwest corner of McKinley Bay, at the south end of the bay, and in the northeast corner near a long spit. Most divers in Hutchison Bay were at the west side. Diving ducks, primarily Oldsquaw and scoter, were the most abundant bird group in the study area. Observed distribution patterns of birds are discussed with reference to habitat preferences. 16 refs., 7 figs., 30 tabs.

  2. Pb’s high sedimentation inside the bay mouth of Jiaozhou Bay

    Science.gov (United States)

    Yang, Dongfang; Miao, Zhenqing; Huang, Xinmin; Wei, Linzhen; Feng, Ming

    2017-12-01

    Sedimentation is one of the key environmental behaviors of pollutants in the ocean. This paper analyzed the seasonal and temporal variations of Pb’s sedimentation process in Jiaozhou Bay in 1987. Results showed that Pb contents in bottom waters in Jiaozhou Bay in May, July and November 1987 were 1.87-2.60 μg L-1, 15.11-19.68 μg L-1 and 11.08-15.18 μg L-1, and the pollution levels of Pb in May, July and November 1987 were slight, heavy and heavy, respectively. In May 1987, there was low sedimentation process in waters in the outside of the bay mouth, yet were high sedimentation process in waters in the middle and inside of the bay mouth. In July and November 1987, there was low sedimentation process in waters in the outside of the bay mouth, yet were high sedimentation process in waters in the inside of the bay mouth. The seasonal-temporal variation of sedimentation processes of Pb were determined by the variations of sources input and the vertical water’s effect.

  3. Renovascular BK(Ca) channels are not activated in vivo under resting conditions and during agonist stimulation

    DEFF Research Database (Denmark)

    Magnusson, Linda; Sørensen, Charlotte Mehlin; Braunstein, Thomas Hartig

    2006-01-01

    We investigated the role of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels for the basal renal vascular tone in vivo. Furthermore, the possible buffering by BK(Ca) of the vasoconstriction elicited by angiotensin II (ANG II) or norepinephrine (NE) was investigated. The possible activation.......3 nmol/min) did not have any effect. Renal injection of ANG II (1-4 ng) or NE (10-40 ng) produced a transient decrease in RBF. These responses were not affected by preinfusion of TEA or IBT. Renal infusion of the BK(Ca) opener NS-1619 (90.0 nmol/min) did not affect basal RBF or the response to NE......, there is no indication for a major role for BK(Ca) channels in the control of basal renal tone in vivo. Furthermore, BK(Ca) channels do not have a buffering effect on the rat renal vascular responses to ANG II and NE. The fact that NS-1619 attenuates the ANG II response indicates that the renal vascular BK(Ca) channels...

  4. Early Holocene estuary development of the Hesselø Bay area, southern Kattegat, Denmark and its implication for Ancylus Lake drainage

    DEFF Research Database (Denmark)

    Bendixen, Carina; Boldreel, Lars Ole; Jensen, Jørn Bo

    2017-01-01

    environment and a description of coastal processes associated with a river outlet into the bay are presented. Weichselian glacial deposits form the lowermost interpreted unit, covered by late glacial (LG) and postglacial (PG, Holocene) sediments. A funnel-shaped estuary existed at the mouth of channels......High-resolution shallow seismic data, sediment core information, radiocarbon dating and sequence stratigraphy have been used to interpret the late glacial to early Holocene geological evolution of Hesselø Bay in the southern Kattegat, Denmark. A reconstruction of the early Holocene coastal...... in the period 10.3–9.2 cal. ka BP; the channels drained water from south to north. The early PG is characterised by estuarine and coastal deposits. The early Holocene bars that developed in the estuary are preserved as morphological features on the present-day seabed, possibly as a result of rapid relative sea...

  5. Overlapping binding site for the endogenous agonist, small-molecule agonists, and ago-allosteric modulators on the ghrelin receptor

    DEFF Research Database (Denmark)

    Holst, Birgitte; Frimurer, Thomas M; Mokrosinski, Jacek

    2008-01-01

    A library of robust ghrelin receptor mutants with single substitutions at 22 positions in the main ligand-binding pocket was employed to map binding sites for six different agonists: two peptides (the 28-amino-acid octanoylated endogenous ligand ghrelin and the hexapeptide growth hormone......, and PheVI:23 on the opposing face of transmembrane domain (TM) VI. Each of the agonists was also affected selectively by specific mutations. The mutational map of the ability of L-692,429 and GHRP-6 to act as allosteric modulators by increasing ghrelin's maximal efficacy overlapped with the common....... It is concluded that although each of the ligands in addition exploits other parts of the receptor, a large, common binding site for both small-molecule agonists--including ago-allosteric modulators--and the endogenous agonist is found on the opposing faces of TM-III and -VI of the ghrelin receptor....

  6. Exploring the binding energy profiles of full agonists, partial agonists, and antagonists of the α7 nicotinic acetylcholine receptor.

    Science.gov (United States)

    Tabassum, Nargis; Ma, Qianyun; Wu, Guanzhao; Jiang, Tao; Yu, Rilei

    2017-09-01

    Nicotinic acetylcholine receptors (nAChRs) belong to the Cys-loop receptor family and are important drug targets for the treatment of neurological diseases. However, the precise determinants of the binding efficacies of ligands for these receptors are unclear. Therefore, in this study, the binding energy profiles of various ligands (full agonists, partial agonists, and antagonists) were quantified by docking those ligands with structural ensembles of the α7 nAChR exhibiting different degrees of C-loop closure. This approximate treatment of interactions suggested that full agonists, partial agonists, and antagonists of the α7 nAChR possess distinctive binding energy profiles. Results from docking revealed that ligand binding efficacy may be related to the capacity of the ligand to stabilize conformational states with a closed C loop.

  7. Gonadotropin releasing hormone agonists: Expanding vistas

    Directory of Open Access Journals (Sweden)

    Navneet Magon

    2011-01-01

    Full Text Available Gonadotropin-releasing hormone (GnRH agonists are derived from native GnRH by amino acid substitution which yields the agonist resistant to degradation and increases its half-life. The hypogonadotropic hypogonadal state produced by GnRH agonists has been often dubbed as "pseudomenopause" or "medical oophorectomy," which are both misnomers. GnRH analogues (GnRH-a work by temporarily "switching off" the ovaries. Ovaries can be "switched off" for the therapy and therapeutic trial of many conditions which include but are not limited to subfertility, endometriosis, adenomyosis, uterine leiomyomas, precocious puberty, premenstrual dysphoric disorder, chronic pelvic pain, or the prevention of menstrual bleeding in special clinical situations. Rapidly expanding vistas of usage of GnRH agonists encompass use in sex reassignment of male to female transsexuals, management of final height in cases of congenital adrenal hyperplasia, and preserving ovarian function in women undergoing cytotoxic chemotherapy. Hypogonadic side effects caused by the use of GnRH agonists can be tackled with use of "add-back" therapy. Goserelin, leuprolide, and nafarelin are commonly used in clinical practice. GnRH-a have provided us a powerful therapeutic approach to the treatment of numerous conditions in reproductive medicine. Recent synthesis of GnRH antagonists with a better tolerability profile may open new avenues for both research and clinical applications. All stakeholders who are partners in women′s healthcare need to join hands to spread awareness so that these drugs can be used to realize their full potential.

  8. Sports doping: Emerging designer and therapeutic B2-agonists

    NARCIS (Netherlands)

    Fragkaki, A.G.; Georgakopoulos, C.; Sterk, S.S.; Nielen, M.W.F.

    2013-01-01

    Beta2-adrenergic agonists, or ß2-agonists, are considered essential bronchodilator drugs in the treatment of bronchial asthma, both as symptom-relievers and, in combination with inhaled corticosteroids, as disease-controllers. The use of ß2-agonists is prohibited in sports by the World Anti-Doping

  9. A functional assay to measure postsynaptic gamma-aminobutyric acidB responses in cultured spinal cord neurons: Heterologous regulation of the same K+ channel

    Energy Technology Data Exchange (ETDEWEB)

    Kamatchi, G.L.; Ticku, M.K. (Univ. of Texas Health Science Center, San Antonio (USA))

    1991-02-01

    The stimulation of postsynaptic gamma-aminobutyric acid (GABA)B receptors leads to slow inhibitory postsynaptic potentials due to the influx of K(+)-ions. This was studied biochemically, in vitro in mammalian cultured spinal cord neurons by using 86Rb as a substitute for K+. (-)-Baclofen, a GABAB receptor agonist, produced a concentration-dependent increase in the 86Rb-influx. This effect was stereospecific and blocked by GABAB receptor antagonists like CGP 35 348 (3-aminopropyl-diethoxymethyl-phosphonic acid) and phaclofen. Apart from the GABAB receptors, both adenosine via adenosine1 receptors and 5-hydroxytryptamine (5-HT) via 5-HT1 alpha agonists also increased the 86Rb-influx. These agonists failed to show any additivity between them when they were combined in their maximal concentration. In addition, their effect was antagonized specifically by their respective antagonists without influencing the others. These findings suggest the presence of GABAB, adenosine1 and 5-HT1 alpha receptors in the cultured spinal cord neurons, which exhibit a heterologous regulation of the same K(+)-channel. The effect of these agonists were antagonized by phorbol 12,13-didecanoate, an activator of protein kinase C, and pretreatment with pertussis toxin. This suggests that these agonists by acting on their own receptors converge on the same K(+)-channel through the Gi/Go proteins. In summary, we have developed a biochemical functional assay for studying and characterizing GABAB synaptic pharmacology in vitro, using spinal cord neurons.

  10. Nereistoxin and cartap neurotoxicity attributable to direct block of the insect nicotinic receptor/channel.

    Science.gov (United States)

    Lee, Seog-Jong; Tomizawa, Motohiro; Casida, John E

    2003-04-23

    Nereistoxin (NTX) (4-dimethylamino-1,2-dithiolane) is the naturally occurring prototype for cartap [the bis(thiocarbamate) derivative of the NTX dithiol], which is generally regarded as a proinsecticide reverting to NTX. The aim of this study is to define the target site(s) for dithiolanes and dithiol esters. The affinity of [(3)H]NTX was not suitable for binding assays with honeybee (Apis mellifera) head membranes. However, NTX and cartap are equally potent, direct-acting, and competitive displacers of [(3)H]thienylcyclohexylpiperidine binding at the noncompetitive blocker (NCB) site of the Apis nicotinic acetylcholine receptor (nAChR)/channel. NTX also binds at the Apis [(3)H]imidacloprid agonist site, but cartap does not. As candidate metabolic pathways, sequential N-desmethylation and S-oxidation of NTX progressively reduce its potency at the NCB site and toxicity to houseflies. A P450 inhibitor reduces the toxicity of NTX and enhances it with cartap. Surprisingly, cartap is not just a pro-NTX but instead directly induces inhibitory neurotoxicity by blocking the nAChR/channel, whereas NTX may have dual NCB and agonist targets.

  11. Development of a Rapid Throughput Assay for Identification of hNav1.7 Antagonist Using Unique Efficacious Sodium Channel Agonist, Antillatoxin

    Directory of Open Access Journals (Sweden)

    Fang Zhao

    2016-02-01

    Full Text Available Voltage-gated sodium channels (VGSCs are responsible for the generation of the action potential. Among nine classified VGSC subtypes (Nav1.1–Nav1.9, Nav1.7 is primarily expressed in the sensory neurons, contributing to the nociception transmission. Therefore Nav1.7 becomes a promising target for analgesic drug development. In this study, we compared the influence of an array of VGSC agonists including veratridine, BmK NT1, brevetoxin-2, deltamethrin and antillatoxin (ATX on membrane depolarization which was detected by Fluorescence Imaging Plate Reader (FLIPR membrane potential (FMP blue dye. In HEK-293 cells heterologously expressing hNav1.7 α-subunit, ATX produced a robust membrane depolarization with an EC50 value of 7.8 ± 2.9 nM whereas veratridine, BmK NT1, and deltamethrin produced marginal response. Brevetoxin-2 was without effect on membrane potential change. The ATX response was completely inhibited by tetrodotoxin suggesting that the ATX response was solely derived from hNav1.7 activation, which was consistent with the results where ATX produced a negligible response in null HEK-293 cells. Six VGSC antagonists including lidocaine, lamotrigine, phenytoin, carbamazepine, riluzole, and 2-amino-6-trifluoromethylthiobenzothiazole all concentration-dependently inhibited ATX response with IC50 values comparable to that reported from patch-clamp experiments. Considered together, we demonstrate that ATX is a unique efficacious hNav1.7 activator which offers a useful probe to develop a rapid throughput screening assay to identify hNav1.7 antagonists.

  12. Development of a Rapid Throughput Assay for Identification of hNav1.7 Antagonist Using Unique Efficacious Sodium Channel Agonist, Antillatoxin.

    Science.gov (United States)

    Zhao, Fang; Li, Xichun; Jin, Liang; Zhang, Fan; Inoue, Masayuki; Yu, Boyang; Cao, Zhengyu

    2016-02-16

    Voltage-gated sodium channels (VGSCs) are responsible for the generation of the action potential. Among nine classified VGSC subtypes (Nav1.1-Nav1.9), Nav1.7 is primarily expressed in the sensory neurons, contributing to the nociception transmission. Therefore Nav1.7 becomes a promising target for analgesic drug development. In this study, we compared the influence of an array of VGSC agonists including veratridine, BmK NT1, brevetoxin-2, deltamethrin and antillatoxin (ATX) on membrane depolarization which was detected by Fluorescence Imaging Plate Reader (FLIPR) membrane potential (FMP) blue dye. In HEK-293 cells heterologously expressing hNav1.7 α-subunit, ATX produced a robust membrane depolarization with an EC50 value of 7.8 ± 2.9 nM whereas veratridine, BmK NT1, and deltamethrin produced marginal response. Brevetoxin-2 was without effect on membrane potential change. The ATX response was completely inhibited by tetrodotoxin suggesting that the ATX response was solely derived from hNav1.7 activation, which was consistent with the results where ATX produced a negligible response in null HEK-293 cells. Six VGSC antagonists including lidocaine, lamotrigine, phenytoin, carbamazepine, riluzole, and 2-amino-6-trifluoromethylthiobenzothiazole all concentration-dependently inhibited ATX response with IC50 values comparable to that reported from patch-clamp experiments. Considered together, we demonstrate that ATX is a unique efficacious hNav1.7 activator which offers a useful probe to develop a rapid throughput screening assay to identify hNav1.7 antagonists.

  13. Conformational variability of the glycine receptor M2 domain in response to activation by different agonists

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Dibas, Mohammed I; Lester, Henry A

    2007-01-01

    change. Although taurine and beta-alanine were weak partial agonists at the alpha1R19'C glycine receptor, they induced large fluorescence changes. Propofol, which drastically enhanced these currents, did not induce a glycine-like blue shift in the spectral emission peak. The inhibitors strychnine...... and picrotoxin elicited fluorescence and current changes as expected for a competitive antagonist and an open channel blocker, respectively. Glycine and taurine (or beta-alanine) also produced an increase and a decrease, respectively, in the fluorescence of a label attached to the nearby L22'C residue. Thus...

  14. The onset of deglaciation of Cumberland Bay and Stromness Bay, South Georgia

    NARCIS (Netherlands)

    Van Der Putten, N.; Verbruggen, C.

    Carbon dating of basal peat deposits in Cumberland Bay and Stromness Bay and sediments from a lake in Stromness Bay, South Georgia indicates deglaciation at the very beginning of the Holocene before c. 9500 14C yr BP. This post-dates the deglaciation of one local lake which has been ice-free since

  15. Do cold, low salinity waters pass through the Indo-Sri Lanka Channel during winter?

    Digital Repository Service at National Institute of Oceanography (India)

    Rao, R.R.; Girishkumar, M.S.; Ravichandran, M.; Gopalakrishna, V.V.; Pankajakshan, T.

    cooler, low-salinity waters from the head Bay of Bengal (BoB) into the south-eastern AS. But due to a lack of any direct in situ measurements, it is not clear whether any part of this current that flows through the Indo-Sri Lanka Channel (ISLC...

  16. Nearshore circulation and water-column properties in the Skagit River Delta, northern Puget Sound, Washington: juvenile Chinook Salmon habitat availability in the Swinomish Channel

    Science.gov (United States)

    Grossman, Eric E.; Stevens, Andrew W.; Gelfenbaum, Guy; Curran, Christopher

    2007-01-01

    Time-series and spatial measurements of nearshore hydrodynamic processes and water properties were made in the Swinomish Channel to quantify the net direction and rates of surface water transport that influence habitat for juvenile Chinook salmon along their primary migratory corridor between the Skagit River and Padilla Bay in northern Puget Sound, Washington. During the spring outmigration of Skagit River Chinook between March and June 2007, currents measured with fixed acoustic doppler current profilers (ADCP) at the south and north end of the Swinomish Channel and with roving ADCP revealed that the currents are highly asymmetric with a dominant flow to the north (toward Padilla Bay). Maximum surface current velocities reached 1.5 m/s and were generally uniform across the channel near McGlinn Island Causeway. Transport times for surface water to travel the 11 km from the southern end of Swinomish Channel at McGlinn Island to Padilla Bay ranged from 2.1 hours to 5.5 days. The mean travel time was ~1 day, while 17 percent of the time, transport of water and passive particles occurred within 3.75 hours. Surface water in the Swinomish Channel during this time was generally very saline 20-27 psu, except south of the Rainbow Bridge in the town of La Conner where it ranged 0-15 psu depending on tide and Skagit River discharge. This salinity regime restricts suitable low salinity (

  17. Large-conductance Ca2+-activated K+ channel β1-subunit knockout mice are not hypertensive

    Science.gov (United States)

    Garver, Hannah; Galligan, James J.; Fink, Gregory D.

    2011-01-01

    Large-conductance Ca2+-activated K+ (BK) channels are composed of pore-forming α-subunits and accessory β1-subunits that modulate Ca2+ sensitivity. BK channels regulate arterial myogenic tone and renal Na+ clearance/K+ reabsorption. Previous studies using indirect or short-term blood pressure measurements found that BK channel β1-subunit knockout (BK β1-KO) mice were hypertensive. We evaluated 24-h mean arterial pressure (MAP) and heart rate in BK β1-KO mice using radiotelemetry. BK β1-KO mice did not have a higher 24-h average MAP when compared with wild-type (WT) mice, although MAP was ∼10 mmHg higher at night. The dose-dependent peak declines in MAP by nifedipine were only slightly larger in BK β1-KO mice. In BK β1-KO mice, giving 1% NaCl to mice to drink for 7 days caused a transient (5 days) elevation of MAP (∼5 mmHg); MAP returned to pre-saline levels by day 6. BK β1-KO mesenteric arteries in vitro demonstrated diminished contractile responses to paxilline, increased reactivity to Bay K 8644 and norepinephrine (NE), and maintained relaxation to isoproterenol. Paxilline and Bay K 8644 did not constrict WT or BK β1-KO mesenteric veins (MV). BK β1-subunits are not expressed in MV. The results indicate that BK β1-KO mice are not hypertensive on normal or high-salt intake. BK channel deficiency increases arterial reactivity to NE and L-type Ca2+ channel function in vitro, but the L-type Ca2+ channel modulation of MAP is not altered in BK β1-KO mice. BK and L-type Ca2+ channels do not modulate murine venous tone. It appears that selective loss of BK channel function in arteries only is not sufficient to cause sustained hypertension. PMID:21131476

  18. Solubilization, partial purification, and reconstitution of glutamate- and N-methyl-D-aspartate-activated cation channels from brain synaptic membranes

    International Nuclear Information System (INIS)

    Ly, A.M.; Michaelis, E.K.

    1991-01-01

    L-Glutamate-activated cation channel proteins from rat brain synaptic membranes were solubilized, partially purified, and reconstituted into liposomes. Optimal conditions for solubilization and reconstitution included treatment of the membranes with nonionic detergents in the presence of neutral phospholipids plus glycerol. Quench-flow procedures were developed to characterize the rapid kinetics of ion flux induced by receptor agonists. [ 14 C]Methylamine, a cation that permeates through the open channel of both vertebrate and invertebrate glutamate receptors, was used to measure the activity of glutamate receptor-ion channel complexes in reconstituted liposomes. L-Glutamate caused an increase in the rate of [ 14 C]methylamine influx into liposomes reconstituted with either solubilized membrane proteins or partially purified glutamate-binding proteins. Of the major glutamate receptor agonists, only N-methyl-D-aspartate activated cation fluxes in liposomes reconstituted with glutamate-binding proteins. In liposomes reconstituted with glutamate-binding proteins, N-methyl-D-aspartate- or glutamate-induced influx of NA + led to a transient increase in the influx of the lipid-permeable anion probe S 14 CN - . These results indicate the functional reconstitution of N-methyl-D-aspartate-sensitive glutamate receptors and the role of the ∼69-kDa protein in the function of these ion channels

  19. Pharmacological profile of DA-6886, a novel 5-HT4 receptor agonist to accelerate colonic motor activity in mice.

    Science.gov (United States)

    Lee, Min Jung; Cho, Kang Hun; Park, Hyun Min; Sung, Hyun Jung; Choi, Sunghak; Im, Weonbin

    2014-07-15

    DA-6886, the gastrointestinal prokinetic benzamide derivative is a novel 5-HT4 receptor agonist being developed for the treatment of constipation-predominant irritable bowel syndrome (IBS-C). The purpose of this study was to characterize in vitro and in vivo pharmacological profile of DA-6886. We used various receptor binding assay, cAMP accumulation assay, organ bath experiment and colonic transit assay in normal and chemically constipated mice. DA-6886 exhibited high affinity and selectivity to human 5-HT4 receptor splice variants, with mean pKi of 7.1, 7.5, 7.9 for the human 5-HT4a, 5-HT4b and 5-HT4d, respectively. By contrast, DA-6886 did not show significant affinity for several receptors including dopamine D2 receptor, other 5-HT receptors except for 5-HT2B receptor (pKi value of 6.2). The affinity for 5-HT4 receptor was translated into functional agonist activity in Cos-7 cells expressing 5-HT4 receptor splice variants. Furthermore, DA-6886 induced relaxation of the rat oesophagus preparation (pEC50 value of 7.4) in a 5-HT4 receptor antagonist-sensitive manner. The evaluation of DA-6886 in CHO cells expressing hERG channels revealed that it inhibited hERG channel current with an pIC50 value of 4.3, indicating that the compound was 1000-fold more selective for the 5-HT4 receptor over hERG channels. In the normal ICR mice, oral administration of DA-6886 (0.4 and 2mg/kg) resulted in marked stimulation of colonic transit. Furthermore, in the loperamide-induced constipation mouse model, 2mg/kg of DA-6886 significantly improved the delay of colonic transit, similar to 10mg/kg of tegaserod. Taken together, DA-6886 is a highly potent and selective 5-HT4 receptor agonist to accelerate colonic transit in mice, which might be therapeutic agent having a favorable safety profile in the treatment of gastrointestinal motor disorders such as IBS-C and chronic constipation. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Lignin phenols used to infer organic matter sources to Sepetiba Bay - RJ, Brasil

    Science.gov (United States)

    Rezende, C. E.; Pfeiffer, W. C.; Martinelli, L. A.; Tsamakis, E.; Hedges, J. I.; Keil, R. G.

    2010-04-01

    Lignin phenols were measured in the sediments of Sepitiba Bay, Rio de Janeiro, Brazil and in bedload sediments and suspended sediments of the four major fluvial inputs to the bay; São Francisco and Guandu Channels and the Guarda and Cação Rivers. Fluvial suspended lignin yields (Σ8 3.5-14.6 mgC 10 g dw -1) vary little between the wet and dry seasons and are poorly correlated with fluvial chlorophyll concentrations (0.8-50.2 μgC L -1). Despite current land use practices that favor grassland agriculture or industrial uses, fluvial lignin compositions are dominated by a degraded leaf-sourced material. The exception is the Guarda River, which has a slight influence from grasses. The Lignin Phenol Vegetation Index, coupled with acid/aldehyde and 3.5 Db/V ratios, indicate that degraded leaf-derived phenols are also the primary preserved lignin component in the bay. The presence of fringe Typha sp. and Spartina sp. grass beds surrounding portions of the Bay are not reflected in the lignin signature. Instead, lignin entering the bay appears to reflect the erosion of soils containing a degraded signature from the former Atlantic rain forest that once dominated the watershed, instead of containing a significant signature derived from current agricultural uses. A three-component mixing model using the LPVI, atomic N:C ratios, and stable carbon isotopes (which range between -26.8 and -21.8‰) supports the hypothesis that fluvial inputs to the bay are dominated by planktonic matter (78% of the input), with lignin dominated by leaf (14% of the input) over grass (6%). Sediments are composed of a roughly 50-50 mixture of autochthonous material and terrigenous material, with lignin being primarily sourced from leaf.

  1. Modification of opiate agonist binding by pertussis toxin

    Energy Technology Data Exchange (ETDEWEB)

    Abood, M.E.; Lee, N.M.; Loh, H.H.

    1986-03-05

    Opiate agonist binding is decreased by GTP, suggesting the possible involvement of GTP binding proteins in regulation of opiate receptor binding. This possibility was addressed by asking whether pertussis toxin treatment, which results in ADP-ribosylation and modification of G proteins, would alter opiate agonist binding. The striatum was chosen for the initial brain area to be studied, since regulation of opiate action in this area had been shown to be modified by pertussis toxin. Treatment of striatal membranes with pertussis toxin results in up to a 55% decrease in /sup 3/(H)-DADLE binding as compared with membranes treated identically without toxin. This corresponds to a near complete ADP-ribosylation of both G proteins in the striatal membrane. The decrease in agonist binding appears to be due to an altered affinity of the receptor for agonist as opposed to a decrease in the number of sites. This effect of pertussis toxin on opiate agonist binding demonstrates the actual involvement of G proteins in regulation of opiate receptor binding.

  2. Modification of opiate agonist binding by pertussis toxin

    International Nuclear Information System (INIS)

    Abood, M.E.; Lee, N.M.; Loh, H.H.

    1986-01-01

    Opiate agonist binding is decreased by GTP, suggesting the possible involvement of GTP binding proteins in regulation of opiate receptor binding. This possibility was addressed by asking whether pertussis toxin treatment, which results in ADP-ribosylation and modification of G proteins, would alter opiate agonist binding. The striatum was chosen for the initial brain area to be studied, since regulation of opiate action in this area had been shown to be modified by pertussis toxin. Treatment of striatal membranes with pertussis toxin results in up to a 55% decrease in 3 (H)-DADLE binding as compared with membranes treated identically without toxin. This corresponds to a near complete ADP-ribosylation of both G proteins in the striatal membrane. The decrease in agonist binding appears to be due to an altered affinity of the receptor for agonist as opposed to a decrease in the number of sites. This effect of pertussis toxin on opiate agonist binding demonstrates the actual involvement of G proteins in regulation of opiate receptor binding

  3. cAMP control of HCN2 channel Mg2+ block reveals loose coupling between the cyclic nucleotide-gating ring and the pore.

    Directory of Open Access Journals (Sweden)

    Alex K Lyashchenko

    Full Text Available Hyperpolarization-activated cyclic nucleotide-regulated HCN channels underlie the Na+-K+ permeable IH pacemaker current. As with other voltage-gated members of the 6-transmembrane KV channel superfamily, opening of HCN channels involves dilation of a helical bundle formed by the intracellular ends of S6 albeit this is promoted by inward, not outward, displacement of S4. Direct agonist binding to a ring of cyclic nucleotide-binding sites, one of which lies immediately distal to each S6 helix, imparts cAMP sensitivity to HCN channel opening. At depolarized potentials, HCN channels are further modulated by intracellular Mg2+ which blocks the open channel pore and blunts the inhibitory effect of outward K+ flux. Here, we show that cAMP binding to the gating ring enhances not only channel opening but also the kinetics of Mg2+ block. A combination of experimental and simulation studies demonstrates that agonist acceleration of block is mediated via acceleration of the blocking reaction itself rather than as a secondary consequence of the cAMP enhancement of channel opening. These results suggest that the activation status of the gating ring and the open state of the pore are not coupled in an obligate manner (as required by the often invoked Monod-Wyman-Changeux allosteric model but couple more loosely (as envisioned in a modular model of protein activation. Importantly, the emergence of second messenger sensitivity of open channel rectification suggests that loose coupling may have an unexpected consequence: it may endow these erstwhile "slow" channels with an ability to exert voltage and ligand-modulated control over cellular excitability on the fastest of physiologically relevant time scales.

  4. Molecular mechanisms of Cys-loop ion channel receptor modulation by ivermectin

    DEFF Research Database (Denmark)

    Lynagh, Timothy; Lynch, Joseph W.

    2012-01-01

    Ivermectin is an anthelmintic drug that works by inhibiting neuronal activity and muscular contractility in arthropods and nematodes. It works by activating glutamate-gated chloride channels (GluClRs) at nanomolar concentrations. These receptors, found exclusively in invertebrates, belong to the ...... to the neurotransmitter binding site, thus suggesting a mechanism by which ivermectin potentiates neurotransmitter-gated currents. Together, this information provides new insights into the mechanisms of action of this important drug.......) to its site. Several lines of evidence suggest that ivermectin opens the channel pore via a structural change distinct from that induced by the neurotransmitter agonist. Conformational changes occurring at locations distant from the pore can be probed using voltage-clamp fluorometry (VCF), a technique...

  5. 75 FR 8297 - Tongass National Forest, Thorne Bay Ranger District, Thorne Bay, AK

    Science.gov (United States)

    2010-02-24

    ..., Thorne Bay, AK AGENCY: Forest Service, USDA. ACTION: Cancellation of Notice of intent to prepare an... Roberts, Zone Planner, Thorne Bay Ranger District, Tongass National Forest, P.O. Box 19001, Thorne Bay, AK 99919, telephone: 907-828-3250. SUPPLEMENTARY INFORMATION: The 47,007-acre Kosciusko Project Area is...

  6. 77 FR 44140 - Drawbridge Operation Regulation; Sturgeon Bay Ship Canal, Sturgeon Bay, WI

    Science.gov (United States)

    2012-07-27

    ... Maple-Oregon Bridges so vehicular traffic congestion would not develop on downtown Sturgeon Bay streets... movement of vehicular traffic in Sturgeon Bay. The Sturgeon Bay Ship Canal is approximately 8.6 miles long... significant increase in vehicular and vessel traffic during the peak tourist and navigation season between...

  7. Reciprocity of agonistic support in ravens.

    Science.gov (United States)

    Fraser, Orlaith N; Bugnyar, Thomas

    2012-01-01

    Cooperative behaviour through reciprocation or interchange of valuable services in primates has received considerable attention, especially regarding the timeframe of reciprocation and its ensuing cognitive implications. Much less, however, is known about reciprocity in other animals, particularly birds. We investigated patterns of agonistic support (defined as a third party intervening in an ongoing conflict to attack one of the conflict participants, thus supporting the other) in a group of 13 captive ravens, Corvus corax. We found support for long-term, but not short-term, reciprocation of agonistic support. Ravens were more likely to support individuals who preened them, kin and dominant group members. These results suggest that ravens do not reciprocate on a calculated tit-for-tat basis, but aid individuals from whom reciprocated support would be most useful and those with whom they share a good relationship. Additionally, dyadic levels of agonistic support and consolation (postconflict affiliation from a bystander to the victim) correlated strongly with each other, but we found no evidence to suggest that receiving agonistic support influences the victim's likelihood of receiving support (consolation) after the conflict ends. Our findings are consistent with an emotionally mediated form of reciprocity in ravens and provide additional support for convergent cognitive evolution in birds and mammals.

  8. Enhanced land subsidence in Galveston Bay, Texas: Interaction between sediment accumulation rates and relative sea level rise

    Science.gov (United States)

    Al Mukaimi, Mohammad E.; Dellapenna, Timothy M.; Williams, Joshua R.

    2018-07-01

    Galveston Bay is the second largest estuary along the northern Gulf of Mexico coast, with a watershed containing one of largest concentrations of petroleum and chemical industries globally, as well as Houston, the fifth largest metropolitan area in the USA. Throughout the last century, extensive groundwater extraction to support these industries and an expanding population has resulted in significantly enhanced land subsidence (0.6-3.0 cm yr-1). The highest subsidence rates observed in the bay are within the lower 15 km of the San Jacinto River/Houston Ship Channel region (SJR/HSC), with distal areas in East and West Galveston Bays having subsidence rates on the order of 0.2 cm yr-1. In order to investigate the impacts of subsidence on sedimentation, a series of 22 vibracores were collected throughout the bay, and 210Pb and 137Cs radioisotope geochronologies and grain size distributions were determined. Sediment accumulation rates are highest (1.9 ± 0.5 cm yr-1) in the SJR/HSC, and decrease (sedimentation rates are significantly (p sedimentation rates are lower (as much as 50%) than estimated RSLR, indicating a sediment accretionary deficit. In areas (e.g., Scott Bay) within the SJR/HSC, the bay has deepened by more than 1.5 m, suggesting that sediment accumulation cannot keep pace with RSLR. Ultimately, this has resulted in a loss of coastal wetlands and a conversion of marine habitats from relatively shallow to deeper water settings.

  9. 78 FR 46813 - Safety Zone; Evening on the Bay Fireworks; Sturgeon Bay, WI

    Science.gov (United States)

    2013-08-02

    ...-AA00 Safety Zone; Evening on the Bay Fireworks; Sturgeon Bay, WI AGENCY: Coast Guard, DHS. ACTION.... This temporary safety zone will restrict vessels from a portion of Sturgeon Bay due to a fireworks... hazards associated with the fireworks display. DATES: This rule is effective from 8 p.m. until 10 p.m. on...

  10. PRIMARILY RESULTS OF PHYTOPLANKTON DNA AND VARIATION TO ENVIRONMENTAL FACTORS IN DURRES`S BAY COASTAL WATERS (ALBANIA

    Directory of Open Access Journals (Sweden)

    Laura Gjyli

    2013-10-01

    Full Text Available After isolation of phytoplankton DNA in coastal waters of Durres Bay, Albania, quantification and analysis of quality were investigated with spectrophotometric analysis. Analysis of UV absorption by the nucleotides provides a simple and accurate estimation of the concentration of nucleic acids in a sample. This method is however limited by the quantity of DNA and the purity of the preparation. Also biotic environment factors as Chlorophyll a and abiotic environment factors as temperature, salinity, pH, dissolved oxygen, turbidity, nitrate, phosphate were investigated to assess DNA quantities in different environment conditions. The Chlorophyll a was studied also to access the level of trophy. The sample stations were: Golem Beach (GB, Channel of Plepa (ChP, Hekurudha Beach (HB, Ex-Fuel Quay in Marine Durres Harbour (EFQ, Water Channel of Durres City (WChDC and Currila Beach (CB. Samples are taken in one meter depth from the water surface. Water samples were collected monthly from April to October 2011. The most abundant stations with phytoplankton DNA are Channel of Plepa and Water Channel of Durres City. This confirms that there are spills of fresh waters, sewage or agricultural water spills, often discharge in coastal waters. Referring Mutliple Regression Analysis and single regression analysis, the association between phytoplankton DNA and environment factors was strong (R2 = 0.75. Basing in single correlation and statistically significance (p-value ≤ 0.05, the enviroment factors that correlated to phytoplankton DNA were pH, salinity and phosphate; explaining thus the variation of total phytoplankton in Durres Bay coastal waters.

  11. Contribution to investigations on trace elements transport in the Channel: spatial distribution of industrial tracers in mytilus edulis and fucus serratus

    International Nuclear Information System (INIS)

    Germain, P.; Masson, M.; Baron, Y.

    1990-01-01

    The distribution of artificial tracers - gamma emitters - has been studied in biological indicator species, mussels and fucus, along the french and english Channel shores in order to gain a better knowledge of trace elements transports in the Channel coastal areas. The main conclusions are supplied by 106 Ru-Rh and 60 Co. Extension of species labelling is larger eastwards than westwards, and the differences recorded between french and english shores show weak exchanges between south and north Channel; in the norman-breton gulf and in the Seine river bay, the distribution of radioactive tracers demonstrates complex current processes. The results are compared to the hydrodynamical studies carried out through models and follow-up of radioactive tracers in sea-water. Particular processes have been observed, corresponding to areas where the decay gradient from the source term is not respected (western Cotentin shore, western Seine Bay, Caux aerea). They are discussed in relation with fresh - sea water mixing, current and physico-chemical problems [fr

  12. 77 FR 38488 - Safety Zone; Alexandria Bay Chamber of Commerce, St. Lawrence River, Alexandria Bay, NY

    Science.gov (United States)

    2012-06-28

    ... 1625-AA00 Safety Zone; Alexandria Bay Chamber of Commerce, St. Lawrence River, Alexandria Bay, NY... restrict vessels from a portion of the St. Lawrence River during the Alexandria Bay Chamber of Commerce... of proposed rulemaking (NPRM) entitled Safety Zone; Alexandria Bay Chamber of Commerce, St. Lawrence...

  13. Evaluation of dredged material proposed for ocean disposal from Red Hook/Bay Ridge project areas, New York

    Energy Technology Data Exchange (ETDEWEB)

    Pinza, M.R.; Barrows, E.S.; Borde, A.B. [Battelle/Marine Sciences Lab., Sequim, WA (United States)

    1996-09-01

    The objective of the Red HookIBay Ridge project was to evaluate proposed dredged material from these two areas to determine its suitability for unconfined ocean disposal at the Mud Dump Site. Sediment samples were collected from the Red Hook/Bay Ridge project areas. Tests and analyses were conducted. The evaluation of proposed dredged material from the Red Hook/Bay Ridge project areas consisted of bulk sediment chemical analyses, chemical analyses of dredging site water and elutriate, water-column and benthic acute toxicity tests. Twenty-four individual sediment core samples were collected from these two areas and analyzed for grain size, moisture content, and total organic carbon (TOC). Three composite sediment samples, representing Red Hook Channel and the two Bay Ridge Reaches to be dredged, were analyzed for bulk density, specific gravity, metals, chlorinated pesticides, polychlorinated biphenyl (PCB) congeners, polynuclear aromatic hydrocarbons (PAH), and 1,4-dichlorobenzene. Dredging site water and elutriate water, which is prepared from the suspended-particulate phase (SPP) of the three Red Hook Bay Ridge sediment composites, were analyzed for metals, pesticides, and PCBS. Benthic acute toxicity tests were performed. Water-column or SPP toxicity tests were performed. Bioaccumulation tests were also conducted.

  14. Roselle Polyphenols Exert Potent Negative Inotropic Effects via Modulation of Intracellular Calcium Regulatory Channels in Isolated Rat Heart.

    Science.gov (United States)

    Lim, Yi-Cheng; Budin, Siti Balkis; Othman, Faizah; Latip, Jalifah; Zainalabidin, Satirah

    2017-07-01

    Roselle (Hibiscus sabdariffa Linn.) calyces have demonstrated propitious cardioprotective effects in animal and clinical studies; however, little is known about its action on cardiac mechanical function. This study was undertaken to investigate direct action of roselle polyphenols (RP) on cardiac function in Langendorff-perfused rat hearts. We utilized RP extract which consists of 12 flavonoids and seven phenolic acids (as shown by HPLC profiling) and has a safe concentration range between 125 and 500 μg/ml in this study. Direct perfusion of RP in concentration-dependent manner lowered systolic function of the heart as shown by lowered LVDP and dP/dt max , suggesting a negative inotropic effect. RP also reduced heart rate (negative chronotropic action) while simultaneously increasing maximal velocity of relaxation (positive lusitropic action). Conversely, RP perfusion increased coronary pressure, an indicator for improvement in coronary blood flow. Inotropic responses elicited by pharmacological agonists for L-type Ca 2+ channel [(±)-Bay K 8644], ryanodine receptor (4-chloro-m-cresol), β-adrenergic receptor (isoproterenol) and SERCA blocker (thapsigargin) were all abolished by RP. In conclusion, RP elicits negative inotropic, negative chronotropic and positive lusitropic responses by possibly modulating calcium entry, release and reuptake in the heart. Our findings have shown the potential use of RP as a therapeutic agent to treat conditions like arrhythmia.

  15. Ligand induced change of β2 adrenergic receptor from active to inactive conformation and its implication for the closed/open state of the water channel: insight from molecular dynamics simulation, free energy calculation and Markov state model analysis.

    Science.gov (United States)

    Bai, Qifeng; Pérez-Sánchez, Horacio; Zhang, Yang; Shao, Yonghua; Shi, Danfeng; Liu, Huanxiang; Yao, Xiaojun

    2014-08-14

    The reported crystal structures of β2 adrenergic receptor (β2AR) reveal that the open and closed states of the water channel are correlated with the inactive and active conformations of β2AR. However, more details about the process by which the water channel states are affected by the active to inactive conformational change of β2AR remain illusive. In this work, molecular dynamics simulations are performed to study the dynamical inactive and active conformational change of β2AR induced by inverse agonist ICI 118,551. Markov state model analysis and free energy calculation are employed to explore the open and close states of the water channel. The simulation results show that inverse agonist ICI 118,551 can induce water channel opening during the conformational transition of β2AR. Markov state model (MSM) analysis proves that the energy contour can be divided into seven states. States S1, S2 and S5, which represent the active conformation of β2AR, show that the water channel is in the closed state, while states S4 and S6, which correspond to the intermediate state conformation of β2AR, indicate the water channel opens gradually. State S7, which represents the inactive structure of β2AR, corresponds to the full open state of the water channel. The opening mechanism of the water channel is involved in the ligand-induced conformational change of β2AR. These results can provide useful information for understanding the opening mechanism of the water channel and will be useful for the rational design of potent inverse agonists of β2AR.

  16. Should We Use PPAR Agonists to Reduce Cardiovascular Risk?

    Directory of Open Access Journals (Sweden)

    Jennifer G. Robinson

    2008-01-01

    Full Text Available Trials of peroxisome proliferator-activated receptor (PPAR agonists have shown mixed results for cardiovascular prevention. Fibrates are PPAR- agonists that act primarily to improve dyslipidemia. Based on low- and high-density lipoprotein cholesterol (LDL and HDL effects, gemfibrozil may be of greater cardiovascular benefit than expected, fenofibrate performed about as expected, and bezafibrate performed worse than expected. Increases in both cardiovascular and noncardiovascular serious adverse events have been observed with some fibrates. Thiazolidinediones (TZDs are PPAR- agonists used to improve impaired glucose metabolism but also influence lipids. Pioglitazone reduces atherosclerotic events in diabetic subjects, but has no net cardiovascular benefit due to increased congestive heart failure risk. Rosiglitazone may increase the risk of atherosclerotic events, and has a net harmful effect on the cardiovascular system when congestive heart failure is included. The primary benefit of TZDs appears to be the prevention of diabetic microvascular complications. Dual PPAR-/ agonists have had unacceptable adverse effects but more selective agents are in development. PPAR- and pan-agonists are also in development. It will be imperative to prove that future PPAR agonists not only prevent atherosclerotic events but also result in a net reduction on total cardiovascular events without significant noncardiovascular adverse effects with long-term use.

  17. Inhibition of parathyroid hormone release by maitotoxin, a calcium channel activator

    International Nuclear Information System (INIS)

    Fitzpatrick, L.A.; Yasumoto, T.; Aurbach, G.D.

    1989-01-01

    Maitotoxin, a toxin derived from a marine dinoflagellate, is a potent activator of voltage-sensitive calcium channels. To further test the hypothesis that inhibition of PTH secretion by calcium is mediated via a calcium channel we studied the effect of maitotoxin on dispersed bovine parathyroid cells. Maitotoxin inhibited PTH release in a dose-dependent fashion, and inhibition was maximal at 1 ng/ml. Chelation of extracellular calcium by EGTA blocked the inhibition of PTH by maitotoxin. Maitotoxin enhanced the effects of the dihydropyridine calcium channel agonist (+)202-791 and increased the rate of radiocalcium uptake in parathyroid cells. Pertussis toxin, which ADP-ribosylates and inactivates a guanine nucleotide regulatory protein that interacts with calcium channels in the parathyroid cell, did not affect the inhibition of PTH secretion by maitotoxin. Maitotoxin, by its action on calcium channels allows entry of extracellular calcium and inhibits PTH release. Our results suggest that calcium channels are involved in the release of PTH. Inhibition of PTH release by maitotoxin is not sensitive to pertussis toxin, suggesting that maitotoxin may act distal to the site interacting with a guanine nucleotide regulatory protein, or maitotoxin could interact with other ions or second messengers to inhibit PTH release

  18. Principles of agonist recognition in Cys-loop receptors

    DEFF Research Database (Denmark)

    Lynagh, Timothy Peter; Pless, Stephan Alexander

    2014-01-01

    , functional studies, and X-ray crystallography experiments identified the extracellular interface of adjacent subunits as the principal site of agonist binding. The question of how subtle differences at and around agonist-binding sites of different Cys-loop receptors can accommodate transmitters as chemically...

  19. Positive Feedback Regulation of Agonist-Stimulated Endothelial Ca2+ Dynamics by KCa3.1 Channels in Mouse Mesenteric Arteries

    DEFF Research Database (Denmark)

    Qian, Xun; Francis, Michael; Köhler, Ralf

    2014-01-01

    Intermediate and small conductance KCa channels IK1 (KCa3.1) and SK3 (KCa2.3) are primary targets of endothelial Ca(2+) signals in the arterial vasculature, and their ablation results in increased arterial tone and hypertension. Activation of IK1 channels by local Ca(2+) transients from internal ...... stores or plasma membrane channels promotes arterial hyperpolarization and vasodilation. Here, we assess arteries from genetically altered IK1 knockout mice (IK1(-/-)) to determine whether IK1 channels exert a positive feedback influence on endothelial Ca(2+) dynamics....

  20. Long-acting β2-agonists in asthma

    DEFF Research Database (Denmark)

    Jacobson, Glenn A; Raidal, Sharanne; Hostrup, Morten

    2018-01-01

    Long-acting β2-agonists (LABAs) such as formoterol and salmeterol are used for prolonged bronchodilatation in asthma, usually in combination with inhaled corticosteroids (ICSs). Unexplained paradoxical asthma exacerbations and deaths have been associated with LABAs, particularly when used without...... and effects on BHR, particularly that (S)-enantiomers of β2-agonists may be deleterious to asthma control. LABAs display enantioselective pharmacokinetics and pharmacodynamics. Biological plausibility of the deleterious effects of β2-agonists (S)-enantiomers is provided by in vitro and in vivo studies from...... mechanism in rapid asthma deaths. More effort should therefore be applied to investigating potential enantiospecific effects of LABAs on safety, specifically bronchoprotection. Safety studies directly assessing the effects of LABA (S)-enantiomers on BHR are long overdue....

  1. Influence of Wind Strength and Duration on Relative Hypoxia Reductions by Opposite Wind Directions in an Estuary with an Asymmetric Channel

    Directory of Open Access Journals (Sweden)

    Ping Wang

    2016-09-01

    Full Text Available Computer model experiments are applied to analyze hypoxia reductions for opposing wind directions under various speeds and durations in the north–south oriented, two-layer-circulated Chesapeake estuary. Wind’s role in destratification is the main mechanism in short-term reduction of hypoxia. Hypoxia can also be reduced by wind-enhanced estuarine circulation associated with winds that have down-estuary straining components that promote bottom-returned oxygen-rich seawater intrusion. The up-bay-ward along-channel component of straining by the southerly or easterly wind induces greater destratification than the down-bay-ward straining by the opposite wind direction, i.e., northerly or westerly winds. While under the modulation of the west-skewed asymmetric cross-channel bathymetry in the Bay’s hypoxic zone, the westward cross-channel straining by easterly or northerly winds causes greater destratification than its opposite wind direction. The wind-induced cross-channel circulation can be completed much more rapidly than the wind-induced along-channel circulation, and the former is usually more effective than the latter in destratification and hypoxia reduction in an early wind period. The relative importance of cross-channel versus along-channel circulation for a particular wind direction can change with wind speed and duration. The existence of month-long prevailing unidirectional winds in the Chesapeake is explored, and the relative hypoxia reductions among different prevailing directions are analyzed. Scenarios of wind with intermittent calm or reversing directions on an hourly scale are also simulated and compared.

  2. Agonist-dependent modulation of G-protein coupling and transduction of 5-HT1A receptors in rat dorsal raphe nucleus.

    Science.gov (United States)

    Valdizán, Elsa Maria; Castro, Elena; Pazos, Angel

    2010-08-01

    5-HT1A receptors couple to different Go/Gi proteins in order to mediate a wide range of physiological actions. While activation of post-synaptic 5-HT1A receptors is mainly related to inhibition of adenylyl cyclase activity, functionality of autoreceptors located in raphe nuclei has been classically ascribed to modifications of the activity of potassium and calcium channels. In order to evaluate the possible existence of agonist-directed trafficking for 5-HT1A autoreceptors in the rat dorsal raphe nucleus, we studied their activation by two agonists with a different profile of efficacy [(+)8-OH-DPAT and buspirone], addressing simultaneously the identification of the specific Galpha subtypes ([35S]GTPgammaS labelling and immunoprecipitation) involved and the subsequent changes in cAMP formation. A significant increase (32%, plabelling of immunoprecipitates was obtained with anti-Galphai3 antibodies but not with anti-Galphao, anti-Galphai1, anti-Galphai2, anti-Galphaz or anti-Galphas antibodies. In contrast, in the presence of buspirone, significant [35S]GTPgammaS labelling of immunoprecipitates was obtained with anti-Galphai3 (50%, plabelling with anti-Galphai1, anti-Galphaz or anti-Galphas. The selective 5-HT1A antagonist WAY 100635 blocked the labelling induced by both agonists. Furthermore, (+)8-OH-DPAT failed to modify forskolin-stimulated cAMP accumulation, while buspirone induced a dose-dependent, WAY 100635-sensitive, inhibition of this response (Imax 30.8+/-4.9, pIC50 5.95+/-0.46). These results demonstrate the existence of an agonist-dependency pattern of G-protein coupling and transduction for 5-HT1A autoreceptors in native brain tissue. These data also open new perspectives for the understanding of the differential profiles of agonist efficacy in pre- vs. post-synaptic 5-HT1A receptor-associated responses.

  3. First direct electron microscopic visualization of a tight spatial coupling between GABAA-receptors and voltage-sensitive calcium channels

    DEFF Research Database (Denmark)

    Hansen, Gert Helge; Belhage, B; Schousboe, A

    1992-01-01

    Using cerebellar granule neurons in culture it was demonstrated that exposure of the cells to the GABAA receptor agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) leads to an increase in the number of voltage-gated calcium channels as revealed by quantitative preembedding indirect imm...

  4. Small-molecule AT2 receptor agonists

    DEFF Research Database (Denmark)

    Hallberg, Mathias; Sumners, Colin; Steckelings, U Muscha

    2018-01-01

    The discovery of the first selective, small-molecule ATR receptor (AT2R) agonist compound 21 (C21) (8) that is now extensively studied in a large variety of in vitro and in vivo models is described. The sulfonylcarbamate derivative 8, encompassing a phenylthiofen scaffold is the drug-like agonist...... with the highest affinity for the AT2R reported to date (Ki = 0.4 nM). Structure-activity relationships (SAR), regarding different biaryl scaffolds and functional groups attached to these scaffolds and with a particular focus on the impact of various para substituents displacing the methylene imidazole group of 8......, are discussed. Furthermore, the consequences of migration of the methylene imidazole group and presumed structural requirements for ligands that are aimed as AT2R agonists (e.g. 8) or AT2R antagonists (e.g. 9), respectively, are briefly addressed. A summary of the pharmacological actions of C21 (8) is also...

  5. Gradient Analysis and Classification of Carolina Bay Vegetation: A Framework for Bay Wetlands Conservation and Restoration

    Energy Technology Data Exchange (ETDEWEB)

    Diane De Steven,Ph.D.; Maureen Tone,PhD.

    1997-10-01

    This report address four project objectives: (1) Gradient model of Carolina bay vegetation on the SRS--The authors use ordination analyses to identify environmental and landscape factors that are correlated with vegetation composition. Significant factors can provide a framework for site-based conservation of existing diversity, and they may also be useful site predictors for potential vegetation in bay restorations. (2) Regional analysis of Carolina bay vegetation diversity--They expand the ordination analyses to assess the degree to which SRS bays encompass the range of vegetation diversity found in the regional landscape of South Carolina's western Upper Coastal Plain. Such comparisons can indicate floristic status relative to regional potentials and identify missing species or community elements that might be re-introduced or restored. (3) Classification of vegetation communities in Upper Coastal Plain bays--They use cluster analysis to identify plant community-types at the regional scale, and explore how this classification may be functional with respect to significant environmental and landscape factors. An environmentally-based classification at the whole-bay level can provide a system of templates for managing bays as individual units and for restoring bays to desired plant communities. (4) Qualitative model for bay vegetation dynamics--They analyze present-day vegetation in relation to historic land uses and disturbances. The distinctive history of SRS bays provides the possibility of assessing pathways of post-disturbance succession. They attempt to develop a coarse-scale model of vegetation shifts in response to changing site factors; such qualitative models can provide a basis for suggesting management interventions that may be needed to maintain desired vegetation in protected or restored bays.

  6. The sedimentary record of climatic and anthropogenic influence on the Patuxent estuary and Chesapeake Bay ecosystems

    Science.gov (United States)

    Cronin, T. M.; Vann, C.D.

    2003-01-01

    Ecological and paleoecological studies from the Patuxent River mouth reveal dynamic variations in benthic ostracode assemblages over the past 600 years due to climatic and anthropogenic factors. Prior to the late 20th century, centennial-scale changes in species dominance were influenced by climatic and hydrological factors that primarily affected salinity and at times led to oxygen depletion. Decadal-scale droughts also occurred resulting in higher salinities and migration of ostracode species from the deep channel (Loxoconcha sp., Cytheromorpha newportensis) into shallower water along the flanks of the bay. During the 19th century the abundance of Leptocythere nikraveshae and Perissocytheridea brachyforma suggest increased turbidity and decreased salinity. Unprecedented changes in benthic ostracodes at the Patuxent mouth and in the deep channel of the bay occurred after the 1960s when Cytheromorpha curta became the dominant species, reflecting seasonal anoxia. The change in benthic assemblages coincided with the appearance of deformities in foraminifers. A combination of increased nitrate loading due to greater fertilizer use and increased freshwater flow explains this shift. A review of the geochemical and paleoecological evidence for dissolved oxygen indicates that seasonal oxygen depletion in the main channel of Chesapeake Bay varies over centennial and decadal timescales. Prior to 1700 AD, a relatively wet climate and high freshwater runoff led to oxygen depletion but rarely anoxia. Between 1700 and 1900, progressive eutrophication occurred related to land dearance and increased sedimentation, but this was superimposed on the oscillatory pattern of oxygen depletion most likely driven by climatological and hydrological factors. It also seems probable that the four- to five-fold increase in sedimentation due to agricultural and timber activity could have contributed to an increased natural nutrient load, likely fueling the early periods (1700-1900) of hypoxla

  7. Agonist-dependent modulation of G-protein coupling and transduction of 5-HT1A receptors in rat dorsal raphe nucleus

    OpenAIRE

    Valdizán, Elsa M.; Castro, Elena; Pazos, Ángel

    2009-01-01

    5-HT1A receptors couple to different Go/Gi proteins in order to mediate a wide range of physiological actions. While activation of post-synaptic 5-HT1A receptors is mainly related to inhibition of adenylyl cyclase activity, functionality of autoreceptors located in raphe nuclei has been classically ascribed to modifications of the activity of potassium and calcium channels. In order to evaluate the possible existence of agonist-directed trafficking for 5-HT1A autoreceptors in the rat dorsal r...

  8. Long-acting beta(2)-agonists in management of childhood asthma

    DEFF Research Database (Denmark)

    Bisgaard, H

    2000-01-01

    This review assesses the evidence regarding the use of long-acting beta(2)-agonists in the management of pediatric asthma. Thirty double-blind, randomized, controlled trials on the effects of formoterol and salmeterol on lung function in asthmatic children were identified. Single doses of inhaled......, long-acting beta(2)-agonists provide effective bronchodilatation and bronchoprotection when used as intermittent, single-dose treatment of asthma in children, but not when used as regular treatment. Future studies should examine the positioning of long-acting beta(2)-agonists as an "as needed" rescue...... medication instead of short-acting beta(2)-agonists for pediatric asthma management....

  9. Trial Watch: Toll-like receptor agonists for cancer therapy.

    Science.gov (United States)

    Vacchelli, Erika; Eggermont, Alexander; Sautès-Fridman, Catherine; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-08-01

    Toll-like receptors (TLRs) have long been known for their ability to initiate innate immune responses upon exposure to conserved microbial components such as lipopolysaccharide (LPS) and double-stranded RNA. More recently, this family of pattern recognition receptors has been attributed a critical role in the elicitation of anticancer immune responses, raising interest in the development of immunochemotherapeutic regimens based on natural or synthetic TLR agonists. In spite of such an intense wave of preclinical and clinical investigation, only three TLR agonists are currently licensed by FDA for use in cancer patients: bacillus Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis that operates as a mixed TLR2/TLR4 agonist; monophosphoryl lipid A (MPL), a derivative of Salmonella minnesota that functions as a potent agonist of TLR4; and imiquimod, a synthetic imidazoquinoline that activates TLR7. One year ago, in the August and September issues of OncoImmunology , we described the main biological features of TLRs and discussed the progress of clinical studies evaluating the safety and therapeutic potential of TLR agonists in cancer patients. Here, we summarize the latest developments in this exciting area of research, focusing on preclinical studies that have been published during the last 13 mo and clinical trials launched in the same period to investigate the antineoplastic activity of TLR agonists.

  10. Ascorbic acid enables reversible dopamine receptor 3H-agonist binding

    International Nuclear Information System (INIS)

    Leff, S.; Sibley, D.R.; Hamblin, M.; Creese, I.

    1981-01-01

    The effects of ascorbic acid on dopaminergic 3 H-agonist receptor binding were studied in membrane homogenates of bovine anterior pituitary and caudate, and rat striatum. In all tissues virtually no stereospecific binding (defined using 1uM (+)butaclamol) of the 3 H-agonists N-propylnorapomorphine (NPA), apomorphine, or dopamine could be demonstrated in the absence of ascorbic acid. Although levels of total 3 H-agonist binding were three to five times greater in the absence than in the presence of 0.1% ascorbic acid, the increased binding was entirely non-stereospecific. Greater amounts of dopamine-inhibitable 3 H-NPA binding could be demonstrated in the absence of 0.1% ascorbic acid, but this measure of ''specific binding'' was demonstrated not to represent dopamine receptor binding since several other catecholamines and catechol were equipotent with dopamine and more potent than the dopamine agonist (+/-)amino-6,7-dihydroxy-1,2,3,4-tetrahydronapthalene (ADTN) in inhibiting this binding. High levels of dopamine-displaceable 3 H-agonist binding were detected in fresh and boiled homogenates of cerebellum, an area of brain which receives no dopaminergic innervation, further demonstrating the non-specific nature of 3 H-agonist binding in the absence of ascorbic acid. These studies emphasize that under typical assay conditions ascorbic acid is required in order to demonstrate reversible and specific 3 H-agonist binding to dopamine receptors

  11. Agonist-induced affinity alterations of a central nervous system. cap alpha. -bungarotoxin receptor

    Energy Technology Data Exchange (ETDEWEB)

    Lukas, R.J.; Bennett, E.L.

    1979-01-01

    The ability of cholinergic agonists to block the specific interaction of ..cap alpha..-bungarotoxin (..cap alpha..-Bgt) with membrane-bound sites derived from rat brain is enhanced when membranes are preincubated with agonist. Thus, pretreatment of ..cap alpha..-Bgt receptors with agonist (but not antagonist) causes transformation of sites to a high-affinity form toward agonist. This change in receptor state occurs with a half-time on the order of minutes, and is fully reversible on dilution of agonist. The results are consistent with the identity of ..cap alpha..-Bgt binding sites as true central nicotinic acetylcholine receptors. Furthermore, this agonist-induced alteration in receptor state may represent an in vitro correlate of physiological desensitization. As determined from the effects of agonist on toxin binding isotherms, and on the rate of toxin binding to specific sites, agonist inhibition of toxin binding to the high-affinity state is non-competitive. This result suggests that there may exist discrete toxin-binding and agonist-binding sites on central toxin receptors.

  12. Transport of bedload sediment and channel morphology of a southeast Alaska stream.

    Science.gov (United States)

    Margaret A. Estep; Robert L. Beschta

    1985-01-01

    During 1980-81, transport of bedload sediment and channel morphology were determined at Trap Bay Creek, a third-order stream that drains a 13.5-square kilometer watershed on Chichagof island in southeast Alaska. Bedload sediment was sampled for 10 storms: peak flows ranged from 0.6 to 19.0 cubic meters per second, and transport rates ranged from 4 to 4400 kilograms per...

  13. Discharge, water-quality characteristics, and nutrient loads from McKay Bay, Delaney Creek, and East Bay, Tampa, Florida, 1991-1993

    Science.gov (United States)

    Stoker, Y.E.; Levesque, V.A.; Fritz, E.M.

    1996-01-01

    Nutrient enrichment in Tampa Bay has caused a decline in water quality in the estuary. Efforts to reduce the nutrient loading to Tampa Bay have resulted in improvement in water quality from 1981 to 1991. However, Tampa Bay still is onsidered enriched with nutrients. Water quality in East Bay (located at the northeastern part of Hillsborough Bay, which is an embayment in Tampa Bay) is not improving at the same rate as the rest of the bay. East Bay is the center of shipping activity in Tampa Bay and the seventh largest port in the United States. One of the primary cargoes is phosphate ore and related products such as fertilizer. The potential for nutrient loading to East Bay from shipping activities is high and has not previously been measured. Nitrogen and phosphorus loads from East Bay to Hillsborough Bay were measured during selected time periods during June 1992 through May 1993; these data were used to estimate seasonal and annual loads. These loads were evaluated to determine whether the loss of fertilizer products from shipping activities resulted in increased nutrient loading to Hillsborough Bay. Discharge was measured, and water-quality samples were collected at the head of East Bay (exiting McKay Bay), and at the mouth of East Bay. Discharge and nitrogen and phosphorus concentrations for the period June 1992 through May 1993 were used to compute loads. Discharges from McKay Bay, Delaney Creek, and East Bay are highly variable because of the effect of tide. Flow patterns during discharge measurements generally were unidirectional in McKay Bay and Delaney Creek, but more complex, bidirectional patterns were observed at the mouth of East Bay. Tidally affected discharge data were digitally filtered with the Godin filter to remove the effects of tide so that residual, or net, discharge could be determined. Daily mean discharge from McKay Bay ranged from -1,900 to 2,420 cubic feet per second; from Delaney Creek, -3.8 to 162 cubic feet per second; and from East

  14. 46 CFR 7.20 - Nantucket Sound, Vineyard Sound, Buzzards Bay, Narragansett Bay, MA, Block Island Sound and...

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Nantucket Sound, Vineyard Sound, Buzzards Bay, Narragansett Bay, MA, Block Island Sound and easterly entrance to Long Island Sound, NY. 7.20 Section 7.20... Atlantic Coast § 7.20 Nantucket Sound, Vineyard Sound, Buzzards Bay, Narragansett Bay, MA, Block Island...

  15. Effect of α7 nicotinic acetylcholine receptor agonists and antagonists on motor function in mice

    International Nuclear Information System (INIS)

    Welch, Kevin D.; Pfister, James A.; Lima, Flavia G.; Green, Benedict T.; Gardner, Dale R.

    2013-01-01

    Nicotinic acetylcholine receptors (nAChRs) are ligand-gated cation channels found throughout the body, and serve to mediate diverse physiological functions. Muscle-type nAChRs located in the motor endplate region of muscle fibers play an integral role in muscle contraction and thus motor function. The toxicity and teratogenicity of many plants (which results in millions of dollars in losses annually to the livestock industry) are due to various toxins that bind to nAChRs including deltaline and methyllycaconitine (MLA) from larkspur (Delphinium) species, and nicotine and anabasine from tobacco (Nicotiana) species. The primary result of the actions of these alkaloids at nAChRs is neuromuscular paralysis and respiratory failure. The objective of this study was to further characterize the motor coordination deficiencies that occur upon exposure to a non-lethal dose of nAChR antagonists MLA and deltaline as well as nAChR agonists nicotine and anabasine. We evaluated the effect of nAChR agonists and antagonists on the motor function and coordination in mice using a balance beam, grip strength meter, rotarod, open field analysis and tremor monitor. These analyses demonstrated that within seconds after treatment the mice had significant loss of motor function and coordination that lasted up to 1 min, followed by a short period of quiescence. Recovery to normal muscle coordination was rapid, typically within approximately 10 min post-dosing. However, mice treated with the nAChR agonist nicotine and anabasine required a slightly longer time to recover some aspects of normal muscle function in comparison to mice treated with the nAChR antagonist MLA or deltaline. -- Highlights: ► Mice treated with nAChR agonists and antagonists have a loss in motor function. ► These deficits are temporary as near normal motor function returns within 10 min. ► There are compound-specific differences in the effects on motor function.

  16. 33 CFR 165.1182 - Safety/Security Zone: San Francisco Bay, San Pablo Bay, Carquinez Strait, and Suisun Bay, CA.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Safety/Security Zone: San... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY... Areas Eleventh Coast Guard District § 165.1182 Safety/Security Zone: San Francisco Bay, San Pablo Bay...

  17. Gating at the mouth of the acetylcholine receptor channel: energetic consequences of mutations in the alphaM2-cap.

    Directory of Open Access Journals (Sweden)

    Pallavi A Bafna

    2008-06-01

    Full Text Available Gating of nicotinic acetylcholine receptors from a C(losed to an O(pen conformation is the initial event in the postsynaptic signaling cascade at the vertebrate nerve-muscle junction. Studies of receptor structure and function show that many residues in this large, five-subunit membrane protein contribute to the energy difference between C and O. Of special interest are amino acids located at the two transmitter binding sites and in the narrow region of the channel, where CO gating motions generate a lowhigh change in the affinity for agonists and in the ionic conductance, respectively. We have measured the energy changes and relative timing of gating movements for residues that lie between these two locations, in the C-terminus of the pore-lining M2 helix of the alpha subunit ('alphaM2-cap'. This region contains a binding site for non-competitive inhibitors and a charged ring that influences the conductance of the open pore. alphaM2-cap mutations have large effects on gating but much smaller effects on agonist binding, channel conductance, channel block and desensitization. Three alphaM2-cap residues (alphaI260, alphaP265 and alphaS268 appear to move at the outset of channel-opening, about at the same time as those at the transmitter binding site. The results suggest that the alphaM2-cap changes its secondary structure to link gating motions in the extracellular domain with those in the channel that regulate ionic conductance.

  18. 78 FR 62293 - Safety Zone, Oyster Festival 30th Anniversary Fireworks Display, Oyster Bay; Oyster Bay, NY

    Science.gov (United States)

    2013-10-15

    ... Safety Zone, Oyster Festival 30th Anniversary Fireworks Display, Oyster Bay; Oyster Bay, NY AGENCY: Coast... zone on the navigable waters of Oyster Bay near Oyster Bay, NY for the Oyster Festival 30th Anniversary... Oyster Festival 30th Anniversary Fireworks Display is scheduled for October 19, 2013 and is one of...

  19. Development of a Hydrodynamic and Transport model of Bellingham Bay in Support of Nearshore Habitat Restoration

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Taiping; Yang, Zhaoqing; Khangaonkar, Tarang

    2010-04-22

    In this study, a hydrodynamic model based on the unstructured-grid finite volume coastal ocean model (FVCOM) was developed for Bellingham Bay, Washington. The model simulates water surface elevation, velocity, temperature, and salinity in a three-dimensional domain that covers the entire Bellingham Bay and adjacent water bodies, including Lummi Bay, Samish Bay, Padilla Bay, and Rosario Strait. The model was developed using Pacific Northwest National Laboratory’s high-resolution Puget Sound and Northwest Straits circulation and transport model. A sub-model grid for Bellingham Bay and adjacent coastal waters was extracted from the Puget Sound model and refined in Bellingham Bay using bathymetric light detection and ranging (LIDAR) and river channel cross-section data. The model uses tides, river inflows, and meteorological inputs to predict water surface elevations, currents, salinity, and temperature. A tidal open boundary condition was specified using standard National Oceanic and Atmospheric Administration (NOAA) predictions. Temperature and salinity open boundary conditions were specified based on observed data. Meteorological forcing (wind, solar radiation, and net surface heat flux) was obtained from NOAA real observations and National Center for Environmental Prediction North American Regional Analysis outputs. The model was run in parallel with 48 cores using a time step of 2.5 seconds. It took 18 hours of cpu time to complete 26 days of simulation. The model was calibrated with oceanographic field data for the period of 6/1/2009 to 6/26/2009. These data were collected specifically for the purpose of model development and calibration. They include time series of water-surface elevation, currents, temperature, and salinity as well as temperature and salinity profiles during instrument deployment and retrieval. Comparisons between model predictions and field observations show an overall reasonable agreement in both temporal and spatial scales. Comparisons of

  20. Hormones and β-Agonists

    NARCIS (Netherlands)

    Ginkel, van L.A.; Bovee, T.F.H.; Blokland, M.H.; Sterk, S.S.; Smits, N.G.E.; Pleadin, Jelka; Vulić, Ana

    2016-01-01

    This chapter provides some updated information on contemporary methods for hormone and β-agonist analyses. It deals with the classical approaches for the effective detection and identification of exogenous hormones. The chapter examines specific problems related to control strategies for natural

  1. eBay.com

    DEFF Research Database (Denmark)

    Engholm, Ida

    2014-01-01

    Celebrated as one of the leading and most valuable brands in the world, eBay has acquired iconic status on par with century-old brands such as Coca-Cola and Disney. The eBay logo is now synonymous with the world’s leading online auction website, and its design is associated with the company...

  2. Discharge between San Antonio Bay and Aransas Bay, southern Gulf Coast, Texas, May-September 1999

    Science.gov (United States)

    East, Jeffery W.

    2001-01-01

    Along the Gulf Coast of Texas, many estuaries and bays are important habitat and nurseries for aquatic life. San Antonio Bay and Aransas Bay, located about 50 and 30 miles northeast, respectively, of Corpus Christi, are two important estuarine nurseries on the southern Gulf Coast of Texas (fig. 1). According to the Texas Parks and Wildlife Department, “Almost 80 percent of the seagrasses [along the Texas Gulf Coast] are located in the Laguna Madre, an estuary that begins just south of Corpus Christi Bay and runs southward 140 miles to South Padre Island. Most of the remaining seagrasses, about 45,000 acres, are located in the heavily traveled San Antonio, Aransas and Corpus Christi Bay areas” (Shook, 2000).Population growth has led to greater demands on water supplies in Texas. The Texas Water Development Board, the Texas Parks and Wildlife Department, and the Texas Natural Resource Conservation Commission have the cooperative task of determining inflows required to maintain the ecological health of the State’s streams, rivers, bays, and estuaries. To determine these inflow requirements, the three agencies collect data and conduct studies on the need for instream flows and freshwater/ saline water inflows to Texas estuaries.To assist in the determination of freshwater inflow requirements, the U.S. Geological Survey (USGS), in cooperation with the Texas Water Development Board, conducted a hydrographic survey of discharge (flow) between San Antonio Bay and Aransas Bay during the period May–September 1999. Automated instrumentation and acoustic technology were used to maximize the amount and quality of data that were collected, while minimizing personnel requirements. This report documents the discharge measured at two sites between the bays during May–September 1999 and describes the influences of meteorologic (wind and tidal) and hydrologic (freshwater inflow) conditions on discharge between the two bays. The movement of water between the bays is

  3. Early Holocene estuary development of the Hesselø Bay area, southern Kattegat, Denmark and its implication for Ancylus Lake drainage

    Science.gov (United States)

    Bendixen, Carina; Boldreel, Lars Ole; Jensen, Jørn Bo; Bennike, Ole; Hübscher, Christian; Clausen, Ole Rønø

    2017-12-01

    High-resolution shallow seismic data, sediment core information, radiocarbon dating and sequence stratigraphy have been used to interpret the late glacial to early Holocene geological evolution of Hesselø Bay in the southern Kattegat, Denmark. A reconstruction of the early Holocene coastal environment and a description of coastal processes associated with a river outlet into the bay are presented. Weichselian glacial deposits form the lowermost interpreted unit, covered by late glacial (LG) and postglacial (PG, Holocene) sediments. A funnel-shaped estuary existed at the mouth of channels in the period 10.3-9.2 cal. ka BP; the channels drained water from south to north. The early PG is characterised by estuarine and coastal deposits. The early Holocene bars that developed in the estuary are preserved as morphological features on the present-day seabed, possibly as a result of rapid relative sea-level rise. The estuary existed simultaneously with the occurrence and drainage of the Ancylus Lake. The drainage of this lake occurred through the Dana River (palaeo-Great Belt channel) into the southern Kattegat and then into the study area. The level of the Ancylus Lake in the Baltic Sea region dropped significantly at about 10.2 cal. ka BP at the same time as the estuary developed in the Kattegat region. One outcome of the present study is an enhanced understanding of the Ancylus Lake drainage path. No evidence of major erosion is seen, which indicates non-catastrophic continuous water flow from the south without major drainage events of the Ancylus Lake to the southern Kattegat. During the Littorina transgression, coastal estuarine conditions characterized the Hesselø Bay area where elongated ridges formed a bar system. As the Littorina transgression continued, back-stepping of the bar system and coastline occurred. When the transgression breached the Great Belt threshold, flooding caused major erosion throughout the study area.

  4. Detection and mapping of the iron ore occurrence in the sea floor sediments in the coastal zone of the Sepetiba Bay. Rio de Janeiro. Brasil

    International Nuclear Information System (INIS)

    Vieira, P.

    2010-01-01

    This work is about the detection and mapping of the iron occurrence in the sea floor sediments in the coastal zone of the Sepetiba Bay. Rio de Janeiro. Brasil. The results of geochemical analysis revealed that the area around the mangrove forest located near the Itacuruca channel, the perpendicular direction to the Muriqui Yacht Club channel and the immediate vicinity of the the Guaiba Island Terminal were respectively the areas of highest iron ore concentration

  5. Unique interaction pattern for a functionally biased ghrelin receptor agonist

    DEFF Research Database (Denmark)

    Sivertsen, Bjørn Behrens; Lang, Manja; Frimurer, Thomas M.

    2011-01-01

    Based on the conformationally constrained D-Trp-Phe-D-Trp (wFw) core of the prototype inverse agonist [D-Arg(1),D-Phe(5),D-Trp(7,9),Leu(11)]substance P, a series of novel, small, peptide-mimetic agonists for the ghrelin receptor were generated. By using various simple, ring-constrained spacers...... connecting the D-Trp-Phe-D-Trp motif with the important C-terminal carboxyamide group, 40 nm agonism potency was obtained and also in one case (wFw-Isn-NH(2), where Isn is isonipecotic acid) ~80% efficacy. However, in contrast to all previously reported ghrelin receptor agonists, the piperidine-constrained w......Fw-Isn-NH(2) was found to be a functionally biased agonist. Thus, wFw-Isn-NH(2) mediated potent and efficacious signaling through the Ga(q) and ERK1/2 signaling pathways, but in contrast to all previous ghrelin receptor agonists it did not signal through the serum response element, conceivably the Ga(12...

  6. Stormwater impact in Guanabara Bay (Rio de Janeiro): Evidences of seasonal variability in the dynamic of the sediment heavy metals

    Science.gov (United States)

    Fonseca, E. M.; Baptista Neto, J. A.; Silva, C. G.; McAlister, J. J.; Smith, B. J.; Fernandez, M. A.

    2013-09-01

    Guanabara Bay is one of the most prominent coastal bays in Brazil. This environment is an estuary of 91 rivers and channels, surrounded by the metropolis of Rio de Janeiro. The bay receives considerable amounts of contaminants introduced from sewage effluents, industrial discharge, urban and agricultural runoff, atmospheric fallout, and the combined inputs from the rivers, making Guanabara Bay one of the most polluted coastal environments on the Brazilian coastline. The aim of this work is to study the concentration and fractionation of the heavy metals within the sediments of the bay. In order to understand the possible seasonal influence on the heavy metal fractionation, two campaigns were carried out in two different seasons of the year (rainy and dry). Twelve stations, in four different areas, with different oceanographic characteristics, where chosen. To assess the bioavailability of the metals a selective extraction procedure was used to study the geochemical fractionation and bioavailability of Zn, Cu, Cr, Ni and Pb. The rainy season was very important with respect to variation in the total concentrations of Cr, Ni and Pb and their fractionation within different "operational" phases present in Guanabara Bay sediments. The water-soluble phase showed little importance, with respect to metal adsorption and this would suggest very low mobility of metals in the water column. Nevertheless, the potentially available metals within these sediments showed a high probability for their release and therefore cause contamination of the water column, since different parts of the bay are constantly subjected to dredging projects promoted by the harbor authorities.

  7. Classification using Hierarchical Naive Bayes models

    DEFF Research Database (Denmark)

    Langseth, Helge; Dyhre Nielsen, Thomas

    2006-01-01

    Classification problems have a long history in the machine learning literature. One of the simplest, and yet most consistently well-performing set of classifiers is the Naïve Bayes models. However, an inherent problem with these classifiers is the assumption that all attributes used to describe......, termed Hierarchical Naïve Bayes models. Hierarchical Naïve Bayes models extend the modeling flexibility of Naïve Bayes models by introducing latent variables to relax some of the independence statements in these models. We propose a simple algorithm for learning Hierarchical Naïve Bayes models...

  8. 75 FR 11837 - Chesapeake Bay Watershed Initiative

    Science.gov (United States)

    2010-03-12

    ... DEPARTMENT OF AGRICULTURE Commodity Credit Corporation Chesapeake Bay Watershed Initiative AGENCY...: Notice of availability of program funds for the Chesapeake Bay Watershed Initiative. SUMMARY: The... through the Chesapeake Bay Watershed Initiative for agricultural producers in the Chesapeake Bay watershed...

  9. Urban Greening Bay Area

    Science.gov (United States)

    Information about the San Francisco Bay Water Quality Project (SFBWQP) Urban Greening Bay Area, a large-scale effort to re-envision urban landscapes to include green infrastructure (GI) making communities more livable and reducing stormwater runoff.

  10. USGS Tampa Bay Pilot Study

    Science.gov (United States)

    Yates, K.K.; Cronin, T. M.; Crane, M.; Hansen, M.; Nayeghandi, A.; Swarzenski, P.; Edgar, T.; Brooks, G.R.; Suthard, B.; Hine, A.; Locker, S.; Willard, D.A.; Hastings, D.; Flower, B.; Hollander, D.; Larson, R.A.; Smith, K.

    2007-01-01

    Many of the nation's estuaries have been environmentally stressed since the turn of the 20th century and will continue to be impacted in the future. Tampa Bay, one the Gulf of Mexico's largest estuaries, exemplifies the threats that our estuaries face (EPA Report 2001, Tampa Bay Estuary Program-Comprehensive Conservation and Management Plan (TBEP-CCMP)). More than 2 million people live in the Tampa Bay watershed, and the population constitutes to grow. Demand for freshwater resources, conversion of undeveloped areas to resident and industrial uses, increases in storm-water runoff, and increased air pollution from urban and industrial sources are some of the known human activities that impact Tampa Bay. Beginning on 2001, additional anthropogenic modifications began in Tampa Bat including construction of an underwater gas pipeline and a desalinization plant, expansion of existing ports, and increased freshwater withdrawal from three major tributaries to the bay. In January of 2001, the Tampa Bay Estuary Program (TBEP) and its partners identifies a critical need for participation from the U.S. Geological Survey (USGS) in providing multidisciplinary expertise and a regional-scale, integrated science approach to address complex scientific research issue and critical scientific information gaps that are necessary for continued restoration and preservation of Tampa Bay. Tampa Bay stakeholders identified several critical science gaps for which USGS expertise was needed (Yates et al. 2001). These critical science gaps fall under four topical categories (or system components): 1) water and sediment quality, 2) hydrodynamics, 3) geology and geomorphology, and 4) ecosystem structure and function. Scientists and resource managers participating in Tampa Bay studies recognize that it is no longer sufficient to simply examine each of these estuarine system components individually, Rather, the interrelation among system components must be understood to develop conceptual and

  11. Concentration of PSP (Paralytic Shellfish Poisoning) Toxin On Shellfish From Inner Ambon Bay and Kao Bay North Halmahera

    Science.gov (United States)

    Pello, F. S.; Haumahu, S.; Huliselan, N. V.; Tuapattinaja, M. A.

    2017-10-01

    The Inner Ambon Bay and Kao Bay have potential on fisheries resources which one of them is molluscs. Molluscs especially for class bivalve have economical values and are consumed by coastal community. The research had been done to analyze saxitoxin (STX) concentration on bivalves from Kao Bay and Inner Ambon Bay. The Saxitoxin Elisa Test Kit Protocol was used to determine saxitoxin concentration. The measurement showed that the highest concentration of saxitoxin (392.42 µg STXeq/100g shellfish meat) was Gafrarium tumidum from Ambon Bay, whereas concentration of saxitoxin (321.83 µg STXeq/100g shellfish meat) was Mactra mera from Kao Bay

  12. Marine littoral diatoms from the Gordon’s bay region of False Bay, Cape Province, South Africa

    CSIR Research Space (South Africa)

    Giffen, MH

    1971-01-01

    Full Text Available and Comic/i for Scientific and Industrial Research, Pretoria (Received: 5.2. 1970) The Gordon?s Bay region occupies the north western corner of False Bay, a large rectangular bay, bounded on the west by the Cape Peninsula ending at Cape Point...

  13. TRPV3, a thermosensitive channel is expressed in mouse distal colon epithelium

    International Nuclear Information System (INIS)

    Ueda, Takashi; Yamada, Takahiro; Ugawa, Shinya; Ishida, Yusuke; Shimada, Shoichi

    2009-01-01

    The thermo-transient receptor potential (thermoTRP) subfamily is composed of channels that are important in nociception and thermo-sensing. Here, we show a selective expression of TRPV3 channel in the distal colon throughout the gastrointestinal tract. Expression analyses clearly revealed that TRPV3 mRNA and proteins were expressed in the superficial epithelial cells of the distal colon, but not in those of the stomach, duodenum or proximal colon. In a subset of primary epithelial cells cultured from the distal colon, carvacrol, an agonist for TRPV3, elevated cytosolic Ca 2+ concentration in a concentration-dependent manner. This response was inhibited by ruthenium red, a TRPV channel antagonist. Organotypic culture supported that the carvacrol-responsive cells were present in superficial epithelial cells. Moreover, application of carvacrol evoked ATP release in primary colonic epithelial cells. We conclude that TRPV3 is present in absorptive cells in the distal colon and may be involved in a variety of cellular functions.

  14. Wave and Hydrodynamic Modeling for Engineering Design of Jetties at Tangier Island in Chesapeake Bay, USA

    Directory of Open Access Journals (Sweden)

    Lihwa Lin

    2015-12-01

    Full Text Available The protection of a boat canal at the western entrance of Tangier Island, Virginia, located in the lower Chesapeake Bay, is investigated using different structural alternatives. The existing entrance channel is oriented 45 deg with respect to the local shoreline, and exposed directly to the lower Bay without any protection. The adjacent shoreline has experienced progressive erosion in recent decades by flooding due to severe storms and waves. To protect the western entrance of the channel and shoreline, five different jetty and spur combinations were proposed to reduce wave energy in the lee of jetties. Environmental forces affecting the proposed jettied inlet system are quantified using the Coastal Modeling System, consisting of a spectral wave model and a depth-averaged circulation model with sediment transport calculations. Numerical simulations were conducted for design wave conditions and a 50-year return period tropical storm at the project site. Model results show a low crested jetty of 170-m length connecting to the north shore at a 45-deg angle, and a short south spur of 25-m long, provide adequate wave-reduction benefits among the five proposed alternatives. The model simulation indicates this alternative has the minimum impact on sedimentation around the structured inlet and boat canal.

  15. Nonlinear wave runup in long bays and firths: Samoa 2009 and Tohoku 2011 tsunamis

    Science.gov (United States)

    Didenkulova, I.; Pelinovsky, E.

    2012-04-01

    Last catastrophic tsunami events in Samoa on 29 September 2009 and in Japan on 11 March 2011 demonstrated that tsunami may experience abnormal amplification in long bays and firths and result in an unexpectedly high wave runup. The capital city Pago Pago, which is located at the toe of a narrow 4-km-long bay and represents the most characteristic example of a long and narrow bay, was considerably damaged during Samoa 2009 tsunami (destroyed infrastructures, boats and shipping containers carried inland into commercial areas, etc.) The runup height there reached 8 m over an inundation of 538 m at its toe, while the tsunami wave height measured by the tide-gauge at the entrance of the bay was at most 3 m. The same situation was observed during catastrophic Tohoku tsunami in Japan, which coast contains numerous long bays and firths, which experienced the highest wave runup and the strongest amplification. Such examples are villages: Ofunato, Ryori Bay, where the wave runup reached 30 m high, and Onagawa, where the wave amplified up to 17 m. Here we study the nonlinear dynamics of tsunami waves in an inclined U-shaped bay. Nonlinear shallow water equations can in this case be written in 1D form and solved analytically with the use of the hodograph transformation. This approach generalizes the well-known Carrier-Greenspan transformation for long wave runup on a plane beach. In the case of an inclined U-shaped bay it leads to the associated generalized wave equation for symmetrical wave in fractal space. In the special case of the channel of parabolic cross-section it is a spherical symmetrical linear wave equation. As a result, the solution of the Cauchy problem can be expressed in terms of elementary functions and has a simple form (with respect to analysis) for any kind of initial conditions. Wave regimes associated with various localized initial conditions, corresponding to problems of evolution and runup of tsunami, are considered and analyzed. Special attention is

  16. Radiocarbon dating, chronologic framework, and changes in accumulation rates of holocene estuarine sediments from Chesapeake Bay

    Science.gov (United States)

    Colman, Steven M.; Baucom, P.C.; Bratton, J.F.; Cronin, T. M.; McGeehin, J.P.; Willard, D.; Zimmerman, A.R.; Vogt, P.R.

    2002-01-01

    Rapidly accumulating Holocene sediments in estuaries commonly are difficult to sample and date. In Chesapeake Bay, we obtained sediment cores as much as 20 m in length and used numerous radiocarbon ages measured by accelarator mass spectrometry methods to provide the first detailed chronologies of Holocene sediment accumulation in the bay. Carbon in these sediments is a complex mixture of materials from a variety of sources. Analyses of different components of the sediments show that total organic carbon ages are largely unreliable, because much of the carbon (including coal) has been transported to the bay from upstream sources and is older than sediments in which it was deposited. Mollusk shells (clams, oysters) and foraminifera appear to give reliable results, although reworking and burrowing are potential problems. Analyses of museum specimens collected alive before atmospheric nuclear testing suggest that the standard reservoir correction for marine samples is appropriate for middle to lower Chesapeake Bay. The biogenic carbonate radiocarbon ages are compatible with 210 Pb and 137 Cs data and pollen stratigraphy from the same sites. Post-settlement changes in sediment transport and accumulation is an important environmental issue in many estuaries, including the Chesapeake. Our data show that large variations in sediment mass accumulation rates occur among sites. At shallow water sites, local factors seem to control changes in accumulation rates with time. Our two relatively deep-water sites in the axial channel of the bay have different long-term average accumulation rates, but the history of sediment accumulation at these sites appears to reflect overall conditions in the bay. Mass accumulation rates at the two deep-water sites rapidly increased by about fourfold coincident with widespread land clearance for agriculture in the Chesapeake watershed.

  17. Intracellular long-chain acyl CoAs activate TRPV1 channels.

    Directory of Open Access Journals (Sweden)

    Yi Yu

    Full Text Available TRPV1 channels are an important class of membrane proteins that play an integral role in the regulation of intracellular cations such as calcium in many different tissue types. The anionic phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2 is a known positive modulator of TRPV1 channels and the negatively charged phosphate groups interact with several basic amino acid residues in the proximal C-terminal TRP domain of the TRPV1 channel. We and other groups have shown that physiological sub-micromolar levels of long-chain acyl CoAs (LC-CoAs, another ubiquitous anionic lipid, can also act as positive modulators of ion channels and exchangers. Therefore, we investigated whether TRPV1 channel activity is similarly regulated by LC-CoAs. Our results show that LC-CoAs are potent activators of the TRPV1 channel and interact with the same PIP2-binding residues in TRPV1. In contrast to PIP2, LC-CoA modulation of TRPV1 is independent of Ca2+i, acting in an acyl side-chain saturation and chain-length dependent manner. Elevation of LC-CoAs in intact Jurkat T-cells leads to significant increases in agonist-induced Ca2+i levels. Our novel findings indicate that LC-CoAs represent a new fundamental mechanism for regulation of TRPV1 channel activity that may play a role in diverse cell types under physiological and pathophysiological conditions that alter fatty acid transport and metabolism such as obesity and diabetes.

  18. Understanding processes controlling sediment transports at the mouth of a highly energetic inlet system (San Francisco Bay, CA)

    Science.gov (United States)

    Elias, Edwin P.L.; Hansen, Jeff E.; Barnard, P.L.; Jaffee, B.E.; Schoellhamer, D.H.

    2013-01-01

    San Francisco Bay is one of the largest estuaries along the U.S. West Coast and is linked to the Pacific Ocean through the Golden Gate, a 100 m deep bedrock inlet. A coupled wave, flow and sediment transport model is used to quantify the sediment linkages between San Francisco Bay, the Golden Gate, and the adjacent open coast. Flow and sediment transport processes are investigated using an ensemble average of 24 climatologically derived wave cases and a 24.8 h representative tidal cycle. The model simulations show that within the inlet, flow and sediment transport is tidally dominated and driven by asymmetry of the ebb and flood tides. Peak ebb velocities exceed the peak flood velocities in the narrow Golden Gate channel as a result of flow convergence and acceleration. Persistent flow and sediment gyres at the headland tips are formed that limit sediment transfer from the ebb-tidal delta to the inlet and into the bay. The residual transport pattern in the inlet is dominated by a lateral segregation with a large ebb-dominant sediment transport (and flow) prevailing along the deeper north side of the Golden Gate channel, and smaller flood dominant transports along the shallow southern margin. The seaward edge of the ebb-tidal delta largely corresponds to the seaward extent of strong tidal flows. On the ebb-tidal delta, both waves and tidal forcing govern flow and sediment transport. Wave focusing by the ebb-tidal delta leads to strong patterns of sediment convergence and divergence along the adjacent Ocean Beach.

  19. Effect of α{sub 7} nicotinic acetylcholine receptor agonists and antagonists on motor function in mice

    Energy Technology Data Exchange (ETDEWEB)

    Welch, Kevin D., E-mail: kevin.welch@ars.usda.gov [USDA/ARS Poisonous Plant Research Laboratory, 1150 E. 1400N., Logan, UT 84341 (United States); Pfister, James A. [USDA/ARS Poisonous Plant Research Laboratory, 1150 E. 1400N., Logan, UT 84341 (United States); Lima, Flavia G. [Federal University of Goías, School of Veterinary Medicine, Goiânia, Goías (Brazil); Green, Benedict T.; Gardner, Dale R. [USDA/ARS Poisonous Plant Research Laboratory, 1150 E. 1400N., Logan, UT 84341 (United States)

    2013-02-01

    Nicotinic acetylcholine receptors (nAChRs) are ligand-gated cation channels found throughout the body, and serve to mediate diverse physiological functions. Muscle-type nAChRs located in the motor endplate region of muscle fibers play an integral role in muscle contraction and thus motor function. The toxicity and teratogenicity of many plants (which results in millions of dollars in losses annually to the livestock industry) are due to various toxins that bind to nAChRs including deltaline and methyllycaconitine (MLA) from larkspur (Delphinium) species, and nicotine and anabasine from tobacco (Nicotiana) species. The primary result of the actions of these alkaloids at nAChRs is neuromuscular paralysis and respiratory failure. The objective of this study was to further characterize the motor coordination deficiencies that occur upon exposure to a non-lethal dose of nAChR antagonists MLA and deltaline as well as nAChR agonists nicotine and anabasine. We evaluated the effect of nAChR agonists and antagonists on the motor function and coordination in mice using a balance beam, grip strength meter, rotarod, open field analysis and tremor monitor. These analyses demonstrated that within seconds after treatment the mice had significant loss of motor function and coordination that lasted up to 1 min, followed by a short period of quiescence. Recovery to normal muscle coordination was rapid, typically within approximately 10 min post-dosing. However, mice treated with the nAChR agonist nicotine and anabasine required a slightly longer time to recover some aspects of normal muscle function in comparison to mice treated with the nAChR antagonist MLA or deltaline. -- Highlights: ► Mice treated with nAChR agonists and antagonists have a loss in motor function. ► These deficits are temporary as near normal motor function returns within 10 min. ► There are compound-specific differences in the effects on motor function.

  20. Evaluating the Impact of Land Use Change on Submerged Aquatic Vegetation Stressors in Mobile Bay

    Science.gov (United States)

    Al-Hamdan, Mohammad; Estes, Maurice G., Jr.; Quattrochi, Dale; Thom, Ronald; Woodruff, Dana; Judd, Chaeli; Ellis, Jean; Watson, Brian; Rodriquez, Hugo; Johnson, Hoyt

    2009-01-01

    Alabama coastal systems have been subjected to increasing pressure from a variety of activities including urban and rural development, shoreline modifications, industrial activities, and dredging of shipping and navigation channels. The impacts on coastal ecosystems are often observed through the use of indicator species. One such indicator species for aquatic ecosystem health is submerged aquatic vegetation (SAV). Watershed and hydrodynamic modeling has been performed to evaluate the impact of land use change in Mobile and Baldwin counties on SAV stressors and controlling factors (temperature, salinity, and sediment) in Mobile Bay. Watershed modeling using the Loading Simulation Package in C++ (LSPC) was performed for all watersheds contiguous to Mobile Bay for land use scenarios in 1948, 1992, 2001, and 2030. Landsat-derived National Land Cover Data (NLCD) were used in the 1992 and 2001 simulations after having been reclassified to a common classification scheme. The Prescott Spatial Growth Model was used to project the 2030 land use scenario based on current trends. The LSPC model simulations provided output on changes in flow, temperature, and sediment for 22 discharge points into the Bay. Theses results were inputted in the Environmental Fluid Dynamics Computer Code (EFDC) hydrodynamic model to generate data on changes in temperature, salinity, and sediment on a grid with four vertical profiles throughout Mobile Bay. The changes in the aquatic ecosystem were used to perform an ecological analysis to evaluate the impact on SAV habitat suitability. This is the key product benefiting the Mobile Bay coastal environmental managers that integrates the influences of temperature, salinity, and sediment due to land use driven flow changes with the restoration potential of SAVs.

  1. Deactivation kinetics of acid-sensing ion channel 1a are strongly pH-sensitive.

    Science.gov (United States)

    MacLean, David M; Jayaraman, Vasanthi

    2017-03-21

    Acid-sensing ion channels (ASICs) are trimeric cation-selective ion channels activated by protons in the physiological range. Recent reports have revealed that postsynaptically localized ASICs contribute to the excitatory postsynaptic current by responding to the transient acidification of the synaptic cleft that accompanies neurotransmission. In response to such brief acidic transients, both recombinant and native ASICs show extremely rapid deactivation in outside-out patches when jumping from a pH 5 stimulus to a single resting pH of 8. Given that the resting pH of the synaptic cleft is highly dynamic and depends on recent synaptic activity, we explored the kinetics of ASIC1a and 1a/2a heteromers to such brief pH transients over a wider [H + ] range to approximate neuronal conditions better. Surprisingly, the deactivation of ASICs was steeply dependent on the pH, spanning nearly three orders of magnitude from extremely fast (pH 8 to very slow (>300 ms) at pH 7. This study provides an example of a ligand-gated ion channel whose deactivation is sensitive to agonist concentrations that do not directly activate the receptor. Kinetic simulations and further mutagenesis provide evidence that ASICs show such steeply agonist-dependent deactivation because of strong cooperativity in proton binding. This capacity to signal across such a large synaptically relevant bandwidth enhances the response to small-amplitude acidifications likely to occur at the cleft and may provide ASICs with the ability to shape activity in response to the recent history of the synapse.

  2. Aberrant modulation of a delayed rectifier potassium channel by glutamate in Alzheimer's disease.

    Science.gov (United States)

    Poulopoulou, Cornelia; Markakis, Ioannis; Davaki, Panagiota; Tsaltas, Eleftheria; Rombos, Antonis; Hatzimanolis, Alexandros; Vassilopoulos, Dimitrios

    2010-02-01

    In Alzheimer's disease (AD), potassium channel abnormalities have been reported in both neural and peripheral tissues. Herein, using whole-cell patch-clamp, we demonstrate an aberrant glutamate-dependent modulation of K(V)1.3 channels in T lymphocytes of AD patients. Although intrinsic K(V)1.3 properties in patients were similar to healthy individuals, glutamate (1-1000 microM) failed to yield the hyperpolarizing shift normally observed in K(V)1.3 steady-state inactivation (-4.4+/-2.7 mV in AD vs. -14.3+/-2.5 mV in controls, 10 microM glutamate), resulting in a 4-fold increase of resting channel activity. Specific agonist and antagonist data indicate that this abnormality is due to dysfunction of cognate group II mGluRs. Given that glutamate is present in plasma and that both mGluRs and K(V)1.3 channels regulate T-lymphocyte responsiveness, our finding may account for the presence of immune-associated alterations in AD. Furthermore, if this aberration reflects a corresponding one in neural tissue, it could provide a potential target in AD pathogenesis.

  3. 75 FR 15343 - Regulated Navigation Area: Narragansett Bay, RI and Mount Hope Bay, RI and MA, Including the...

    Science.gov (United States)

    2010-03-29

    ...: Narragansett Bay, RI and Mount Hope Bay, RI and MA, Including the Providence River and Taunton River AGENCY... River and Mount Hope Bay in the vicinity of the two Brightman Street bridges have not been adopted and... Island and Mt. Hope Bay, MA.'' The notice was prompted primarily by two events: (1) The U.S. Army Corps...

  4. Fine-scale relief related to late holocene channel shifting within the floor of the upper Redondo Fan, offshore Southern California

    Science.gov (United States)

    Normark, W.R.; Paull, C.K.; Caress, D.W.; Ussler, W.; Sliter, R.

    2009-01-01

    Erosional and depositional bedforms have been imaged at outcrop scale in the upper Redondo Fan, in the San Pedro Basin of offshore Southern California in ???600 m water depths, using an Autonomous Underwater Vehicle developed by the Monterey Bay Aquarium Research Institute. The Autonomous Underwater Vehicle is equipped with multibeam and chirp sub-bottom sonars. Sampling and photographic images using the Monterey Bay Aquarium Research Institute Remotely Operated Vehicle Tiburon provide groundtruth for the Autonomous Underwater Vehicle survey. The 0??3 m vertical and 1??5 m lateral bathymetric resolution and 0??1 m sub-bottom profile resolution provide unprecedented detail of bedform morphology and structure. Multiple channels within the Redondo Fan have been active at different times during the Late Holocene (0 to 3000 yr bp). The currently active channel extending from Redondo Canyon makes an abrupt 90?? turn at the canyon mouth before resuming a south-easterly course along the east side of the Redondo Fan. This channel is floored by sand and characterized by small steps generally <1 m in relief, spaced 10 to 80 m in the down-channel direction. A broader channel complex lies along the western side of the fan valley that was last active more than 850 years ago. Two distinct trains of large scours, with widths ranging from tens to a few hundred metres and depths of 20 m, occur on the floor of the western channel complex, which has a thin mud drape. If observed in cross-section only, these large scours would probably be misidentified as the thalweg of an active channel. ?? 2009 The Authors. Journal compilation ?? 2009 International Association of Sedimentologists.

  5. Metabolic effects of beta2-agonists in relation to exercise performance

    DEFF Research Database (Denmark)

    Kalsen, Anders

    2015-01-01

    athletes. The present PhD thesis is based on four manuscripts in which the acute effects of beta2-agonists on exercise performance were investigated. The aims were 1) to investigate whether supratherapeutic inhalation of beta2-agonists enhances muscle strength, anaerobic performance and aerobic performance......, 2) to uncover the mechanisms behind potential beta2-adrenergic improvements in anaerobic performance, 3) to investigate whether inhalation of beta2-agonists is ergogenic in elite athletes with or without airway hyperresponsiveness (AHR). Results from the studies of the thesis show...... administration of a certain dose, but a further increase in dose does not seem to elicit a greater performance-enhancing effect. Moreover, the effects of beta2-agonists on performance are unaffected by training status and AHR, but athletes with AHR who regularly use beta2-agonists get a reduced ergogenic...

  6. ASTER Images San Francisco Bay Area

    Science.gov (United States)

    2000-01-01

    These images of the San Francisco Bay region were acquired on March 3, 2000 by the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) on NASA's Terra satellite. Each covers an area 60 kilometers (37 miles) wide and 75 kilometers (47 miles) long. With its 14 spectral bands from the visible to the thermal infrared wavelength region, and its high spatial resolution of 15 to 90 meters (about 50 to 300 feet), ASTER will image the Earth for the next 6 years to map and monitor the changing surface of our planet.Upper Left: The color infrared composite uses bands in the visible and reflected infrared. Vegetation is red, urban areas are gray; sediment in the bays shows up as lighter shades of blue. Thanks to the 15 meter (50-foot) spatial resolution, shadows of the towers along the Bay Bridge can be seen.Upper right: A composite of bands in the short wave infrared displays differences in soils and rocks in the mountainous areas. Even though these regions appear entirely vegetated in the visible, enough surface shows through openings in the vegetation to allow the ground to be imaged.Lower left: This composite of multispectral thermal bands shows differences in urban materials in varying colors. Separation of materials is due to differences in thermal emission properties, analogous to colors in the visible.Lower right: This is a color coded temperature image of water temperature, derived from the thermal bands. Warm waters are in white and yellow, colder waters are blue. Suisun Bay in the upper right is fed directly from the cold Sacramento River. As the water flows through San Pablo and San Francisco Bays on the way to the Pacific, the waters warm up.Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) is one of five Earth-observing instruments launched December 18, 1999, on NASA's Terra satellite. The instrument was built by Japan's Ministry of International Trade and Industry. A joint U.S./Japan science team is responsible for

  7. NMDA receptors in mouse anterior piriform cortex initialize early odor preference learning and L-type calcium channels engage for long-term memory.

    Science.gov (United States)

    Mukherjee, Bandhan; Yuan, Qi

    2016-10-14

    The interactions of L-type calcium channels (LTCCs) and NMDA receptors (NMDARs) in memories are poorly understood. Here we investigated the specific roles of anterior piriform cortex (aPC) LTCCs and NMDARs in early odor preference memory in mice. Using calcium imaging in aPC slices, LTCC activation was shown to be dependent on NMDAR activation. Either D-APV (NMDAR antagonist) or nifedipine (LTCC antagonist) reduced somatic calcium transients in pyramidal cells evoked by lateral olfactory tract stimulation. However, nifedipine did not further reduce calcium in the presence of D-APV. In mice that underwent early odor preference training, blocking NMDARs in the aPC prevented short-term (3 hr) and long-term (24 hr) odor preference memory, and both memories were rescued when BayK-8644 (LTCC agonist) was co-infused. However, activating LTCCs in the absence of NMDARs resulted in loss of discrimination between the conditioned odor and a similar odor mixture at 3 hr. Elevated synaptic AMPAR expression at 3 hr was prevented by D-APV infusion but restored when LTCCs were directly activated, mirroring the behavioral outcomes. Blocking LTCCs prevented 24 hr memory and spared 3 hr memory. These results suggest that NMDARs mediate stimulus-specific encoding of odor memory while LTCCs mediate intracellular signaling leading to long-term memory.

  8. Bay breeze climatology at two sites along the Chesapeake bay from 1986-2010: Implications for surface ozone.

    Science.gov (United States)

    Stauffer, Ryan M; Thompson, Anne M

    Hourly surface meteorological measurements were coupled with surface ozone (O 3 ) mixing ratio measurements at Hampton, Virginia and Baltimore, Maryland, two sites along the Chesapeake Bay in the Mid-Atlantic United States, to examine the behavior of surface O 3 during bay breeze events and quantify the impact of the bay breeze on local O 3 pollution. Analyses were performed for the months of May through September for the years 1986 to 2010. The years were split into three groups to account for increasingly stringent environmental regulations that reduced regional emissions of nitrogen oxides (NO x ): 1986-1994, 1995-2002, and 2003-2010. Each day in the 25-year record was marked either as a bay breeze day, a non-bay breeze day, or a rainy/cloudy day based on the meteorological data. Mean eight hour (8-h) averaged surface O 3 values during bay breeze events were 3 to 5 parts per billion by volume (ppbv) higher at Hampton and Baltimore than on non-bay breeze days in all year periods. Anomalies from mean surface O 3 were highest in the afternoon at both sites during bay breeze days in the 2003-2010 study period. In conjunction with an overall lowering of baseline O 3 after the 1995-2002 period, the percentage of total exceedances of the Environmental Protection Agency (EPA) 75 ppbv 8-h O 3 standard that occurred on bay breeze days increased at Hampton for 2003-2010, while remaining steady at Baltimore. These results suggest that bay breeze circulations are becoming more important to causing exceedance events at particular sites in the region, and support the hypothesis of Martins et al. (2012) that highly localized meteorology increasingly drives air quality events at Hampton.

  9. Subtype selective kainic acid receptor agonists

    DEFF Research Database (Denmark)

    Bunch, Lennart; Krogsgaard-Larsen, Povl

    2009-01-01

    (S)-Glutamic acid (Glu) is the major excitatory neurotransmitter in the mammalian central nervous system, activating the plethora of glutamate receptors (GluRs). In broad lines, the GluRs are divided into two major classes: the ionotropic Glu receptors (iGluRs) and the metabotropic Glu receptors (m......GluRs). Within the iGluRs, five subtypes (KA1, KA2, iGluR5-7) show high affinity and express full agonist activity upon binding of the naturally occurring amino acid kainic acid (KA). Thus these receptors have been named the KA receptors. This review describes all-to our knowledge-published KA receptor agonists...

  10. Monitoring of bird abundance and distribution at McKinley Bay and Hutchison Bay, Northwest Territories, 1981 to 1993

    Energy Technology Data Exchange (ETDEWEB)

    Cornish, B J; Dickson, D L

    1994-04-01

    McKinley Bay has been identified as a preferred site for a harbor to support oil and gas production in the Beaufort Sea. As the bay is a molting area for several species of diving duck, a study was initiated to monitor the effect of harbor development on birds using the bay. Baseline information on the natural annual fluctuations in the number of birds were collected for nine years at McKinley Bay and eight years at neighboring Hutchinson Bay, an area chosen as the control. The final report of the predevelopment phase of the monitoring study is presented, including results of the 1993 surveys and a summary of results of all years of surveys. There were significantly more diving ducks in McKinley Bay in early August 1990 to 1993, on average, than from 1981 to 1985. No statistically significant change in total diving ducks was noted at Hutchinson Bay. Numbers of species of divers varied substantially between years at the two bays but not to the same degree. Significantly more Pacific loons, red-throated loons, and northern pintails were recorded in the 1990-1993 surveys at McKinley Bay than in earlier surveys. Potential explanations for the large between-year fluctuations in diving duck numbers are discussed. The variations may be due to bird responses to changes in the physical environment or related to the limitations of the aerial survey techniques used. Because of the large natural fluctuations in numbers of molting diving ducks using these bays in early August, it will be difficult to detect future impacts of industrial disturbance, even when sources of survey bias are minimized. It is concluded that aerial surveys of molting diving ducks in the two bays are unsuitable for monitoring the effects of industrial development. 41 refs., 7 figs., 23 tabs.

  11. Default Bayes factors for ANOVA designs

    NARCIS (Netherlands)

    Rouder, Jeffrey N.; Morey, Richard D.; Speckman, Paul L.; Province, Jordan M.

    2012-01-01

    Bayes factors have been advocated as superior to p-values for assessing statistical evidence in data. Despite the advantages of Bayes factors and the drawbacks of p-values, inference by p-values is still nearly ubiquitous. One impediment to the adoption of Bayes factors is a lack of practical

  12. 77 FR 21890 - Drawbridge Operation Regulation; Sturgeon Bay Ship Canal, Sturgeon Bay, WI

    Science.gov (United States)

    2012-04-12

    ... Street and Maple-Oregon Bridges so vehicular traffic congestion would not develop on downtown Sturgeon... the efficient movement of vehicular traffic in Sturgeon Bay. The Sturgeon Bay Ship Canal is... experiences a significant increase in vehicular and vessel traffic during the peak tourist and navigation...

  13. Ecdysone Agonist: New Insecticides with Novel Mode of Action

    Directory of Open Access Journals (Sweden)

    Y. Andi Trisyono

    2002-12-01

    Full Text Available Development of insect resistance to insecticide has been the major driving force for the development of new insecticides. Awareness and demand from public for more environmentally friendly insecticides have contributed in shifting the trend from using broad spectrum to selective insecticides. As a result, scientists have looked for new target sites beyond the nervous system. Insect growth regulators (IGRs are more selective insecticides than conventional insecticides, and ecdysone agonists are the newest IGRs being commercialized, e.g. tebufenozide, methoxyfenozide, and halofenozide. Ecdysone agonists bind to the ecdysteroid receptors, and they act similarly to the molting hormone 20-hydroxyecdysone. The binding provides larvae or nymphs with a signal to enter a premature and lethal molting cycle. In addition, the ecdysone agonists cause a reduction in the number of eggs laid by female insects. The ecdysone agonists are being developed as selective biorational insecticides. Tebufenozide and methoxyfenozide are used to control lepidopteran insect pests, whereas halofenozide is being used to control coleopteran insect pests. Their selectivity is due to differences in the binding affinity between these compounds to the receptors in insects from different orders. The selectivity of these compounds makes them candidates to be used in combinations with other control strategies to develop integrated pest management programs in agricultural ecosystems. Key words: new insecticides, selectivity, ecdysone agonists

  14. Oxytocin Modulates Nociception as an Agonist of Pain-Sensing TRPV1

    Directory of Open Access Journals (Sweden)

    Yelena Nersesyan

    2017-11-01

    Full Text Available Oxytocin is a hormone with various actions. Oxytocin-containing parvocellular neurons project to the brainstem and spinal cord. Oxytocin release from these neurons suppresses nociception of inflammatory pain, the molecular mechanism of which remains unclear. Here, we report that the noxious stimulus receptor TRPV1 is an ionotropic oxytocin receptor. Oxytocin elicits TRPV1 activity in native and heterologous expression systems, regardless of the presence of the classical oxytocin receptor. In TRPV1 knockout mice, DRG neurons exhibit reduced oxytocin sensitivity relative to controls, and oxytocin injections significantly attenuate capsaicin-induced nociception in in vivo experiments. Furthermore, oxytocin potentiates TRPV1 in planar lipid bilayers, supporting a direct agonistic action. Molecular modeling and simulation experiments provide insight into oxytocin-TRPV1 interactions, which resemble DkTx. Together, our findings suggest the existence of endogenous regulatory pathways that modulate nociception via direct action of oxytocin on TRPV1, implying its analgesic effect via channel desensitization.

  15. Hybrid sediment transport model for the “linguado” channel, state of Santa Catarina, Brazil

    Directory of Open Access Journals (Sweden)

    Edison Conde Perez dos Santos

    2017-12-01

    Full Text Available This study involves an assessment of various artificial intelligence-related techniques which aim to produce a more robust system for sediment transport modeling. The intelligent systems developed in this research are directly applicable to academic knowledge and use data from a report on "water circulation assessment in the “Linguado” Channel and Babitonga Bay ,”Santa Catarina”, Brazil, developed by  Military Engineering Institute (IME. The solution employed for sediment transport was built using an intelligent system from the conception of two hybrid models. The first was a Neuro-Fuzzy (ANFIS hybrid model for the study of hydrodynamic behavior, aiming to determine flow rate in the channel. The second was a fuzzy genetic model, able to assess sediment transport in the “Linguado” Channel. The study's conclusion compares the different effects involved in the dredging equilibrium in the “Linguado” Channel according to this hybrid model with the results obtained using a finite element model in the MIKE21® software.

  16. Reconstitution of high-affinity opioid agonist binding in brain membranes

    Energy Technology Data Exchange (ETDEWEB)

    Remmers, A.E.; Medzihradsky, F. (Univ. of Michigan Medical School, Ann Arbor (United States))

    1991-03-15

    In synaptosomal membranes from rat brain cortex, the {mu} selective agonist ({sup 3}H)dihydromorphine in the absence of sodium, and the nonselective antagonist ({sup 3}H)naltrexone in the presence of sodium, bound to two populations of opioid receptor sites with K{sub d} values of 0.69 and 8.7 nM for dihydromorphine, and 0.34 and 5.5 nM for naltrexone. The addition of 5 {mu}M guanosine 5{prime}-({gamma}-thio)triphosphate (GTP({gamma}S)) strongly reduced high-affinity agonist but not antagonist binding. Exposure of the membranes to high pH reduced the number of GTP({gamma}-{sup 35}S) binding sites by 90% and low K{sub m}, opioid-sensitive GTPase activity by 95%. In these membranes, high-affinity agonist binding was abolished and modulation of residual binding by GTP({gamma}S) was diminished. Alkali treatment of the glioma cell membranes prior to fusion inhibited most of the low K{sub m} GTPase activity and prevented the reconstitution of agonist binding. The results show that high-affinity opioid agonist binding reflects the ligand-occupied receptor - guanine nucleotide binding protein complex.

  17. 76 FR 28309 - Drawbridge Operation Regulation; Sturgeon Bay Ship Canal, Sturgeon Bay, WI

    Science.gov (United States)

    2011-05-17

    ... vehicular traffic congestion would not develop on downtown Sturgeon Bay streets due to unscheduled bridge... schedules during the peak tourist and navigation seasons to provide for the efficient movement of vehicular... between Lake Michigan and Green Bay. The area experiences a significant increase in vehicular and vessel...

  18. Continuous water-quality and suspended-sediment transport monitoring in the San Francisco Bay, California, water years 2014–15

    Science.gov (United States)

    Buchanan, Paul A.; Downing-Kunz, Maureen; Schoellhamer, David H.; Livsey, Daniel N.

    2018-03-08

    The U.S. Geological Survey (USGS) monitors water quality and suspended-sediment transport in the San Francisco Bay (bay) as part of a multi-agency effort to address management, water supply, and ecological concerns. The San Francisco Bay area is home to millions of people, and the bay teems both with resident and with migratory wildlife, plants, and fish. Freshwater mixes with salt water in the bay, which is subject both to riverine influences (floods, droughts, managed reservoir releases and freshwater diversions) and to marine influences (tides, waves, effects of salt water). To understand this environment, the USGS, along with its partners (see “Acknowledgements”), has been monitoring the bay’s waters continuously since 1988. Several water-quality variables are of particular importance to State and Federal resource managers and are monitored at key locations throughout the bay (fig. 1). Salinity, which indicates the relative mixing of fresh and ocean waters in the bay, is derived from specific conductance measurements. Water temperature, along with salinity, affects the density of water, which controls gravity-driven circulation patterns and stratification in the water column. Turbidity, a measure of light scattered from suspended particles in the water, is used to estimate suspended-sediment concentration (SSC). Suspended sediment affects the bay in multiple ways: attenuation of sunlight in the water column, affecting phytoplankton growth; deposition on tidal marsh and intertidal mudflats, which can help sustain these habitats as sea level rises; deposition in ports and shipping channels, which can necessitate dredging; and often, adsorption of contaminants, affecting their distribution and concentrations in the environment. Dissolved oxygen concentration, essential to a healthy ecosystem and a fundamental indicator of water quality, is affected by water temperature, salinity, ecosystem metabolism, tidal currents, and wind. Tidal currents in the bay

  19. Hypertrophic effect of inhaled beta -agonist with and without concurrent exercise training

    DEFF Research Database (Denmark)

    Jessen, Søren; Onslev, Johan; Lemminger, Anders

    2018-01-01

    INTRODUCTION: Due to a high prevalence of asthma and exercise-induced bronchoconstriction in elite athletes, there is a high use of beta2 -adrenoceptor agonists (beta2 -agonists) in the athletic population. While anabolic in rodents, no study has been able to detect hypertrophy in humans after...... chronic beta2 -agonist inhalation. METHODS: We investigated if inhaled beta2 -agonist, terbutaline, alters body composition and metabolic rate with and without concurrent exercise training in healthy young men. Sixty-seven participants completed a four-week intervention of daily terbutaline (8×0.5 mg...

  20. Estrogen receptor beta-selective agonists stimulate calcium oscillations in human and mouse embryonic stem cell-derived neurons.

    Directory of Open Access Journals (Sweden)

    Lili Zhang

    2010-07-01

    Full Text Available Estrogens are used extensively to treat hot flashes in menopausal women. Some of the beneficial effects of estrogens in hormone therapy on the brain might be due to nongenomic effects in neurons such as the rapid stimulation of calcium oscillations. Most studies have examined the nongenomic effects of estrogen receptors (ER in primary neurons or brain slices from the rodent brain. However, these cells can not be maintained continuously in culture because neurons are post-mitotic. Neurons derived from embryonic stem cells could be a potential continuous, cell-based model to study nongenomic actions of estrogens in neurons if they are responsive to estrogens after differentiation. In this study ER-subtype specific estrogens were used to examine the role of ERalpha and ERbeta on calcium oscillations in neurons derived from human (hES and mouse embryonic stem cells. Unlike the undifferentiated hES cells the differentiated cells expressed neuronal markers, ERbeta, but not ERalpha. The non-selective ER agonist 17beta-estradiol (E(2 rapidly increased [Ca2+]i oscillations and synchronizations within a few minutes. No change in calcium oscillations was observed with the selective ERalpha agonist 4,4',4''-(4-Propyl-[1H]-pyrazole-1,3,5-triyltrisphenol (PPT. In contrast, the selective ERbeta agonists, 2,3-bis(4-Hydroxyphenyl-propionitrile (DPN, MF101, and 2-(3-fluoro-4-hydroxyphenyl-7-vinyl-1,3 benzoxazol-5-ol (ERB-041; WAY-202041 stimulated calcium oscillations similar to E(2. The ERbeta agonists also increased calcium oscillations and phosphorylated PKC, AKT and ERK1/2 in neurons derived from mouse ES cells, which was inhibited by nifedipine demonstrating that ERbeta activates L-type voltage gated calcium channels to regulate neuronal activity. Our results demonstrate that ERbeta signaling regulates nongenomic pathways in neurons derived from ES cells, and suggest that these cells might be useful to study the nongenomic mechanisms of estrogenic compounds.

  1. In vitro desensitization of beta-adrenoceptors in guinea pig trachea: interactions between beta-adrenoceptor agonists and influence of adenosine and other drugs.

    Science.gov (United States)

    Matran, R; Naline, E; Advenier, C; Duroux, P

    1989-01-01

    The aim of this study was to investigate quantitatively the action of and the interaction between beta-adrenergic receptor agonists in desensitizing guinea pig isolated trachea. It was also to evaluate the influence of substances whose effects on desensitization are either disputed (theophylline, indomethacin, ketotifen, hydrocortisone) or unknown (nicardipine, Bay K 8644, fenspiride, adenosine). Tracheal strips were contracted with histamine (5 x 10(-5) M) or acetylcholine (5.10(-5) M) and concentration-response (C/R) curves for various beta-adrenoceptor agonists were determined before and after incubation (20 min to 4 h) with the same beta-adrenoceptor agonist (autodesensitization), with other beta-adrenoceptor agonists (cross-desensitization), or with a beta-adrenoceptor agonist and another substance. Our results show that the autodesensitization induced by isoprenaline is concentration dependent and that concentration dependence is more pronounced with salbutamol and fenoterol than with isoprenaline and adrenaline with respect to autodesensitization: shifts (log unit) of the C/R curves were 0.59 +/- 0.06 (N = 5) for salbutamol (10(-5) M), 0.78 +/- 0.09 (N = 5) for fenoterol (10(-6) M), 0.30 +/- 0.04 (N = 9) for isoprenaline (10(-5) M), and 0.33 +/- 0.05 (N = 5) for adrenaline (10(-5) M). Our studies of cross-desensitization (desensitization to isoprenaline, adrenaline, salbutamol, and fenoterol induced by incubation with isoprenaline 10(-5) M) showed a significantly greater shift in the C/R curves for fenoterol (0.56 +/- 0.08, N = 5) and salbutamol (0.62 +/- 0.05, N = 5) than for adrenaline (0.35 +/- 0.07, N = 5) and isoprenaline itself (0.30 +/- 0.05, N = 9). Of the substances we studied, none modified the desensitization induced by isoprenaline except hydrocortisone and adenosine. Hydrocortisone (10(-8) M) reduced it significantly, although to a negligible extent. Adenosine (3 x 10(-4) M) did not shift the C/R curve to isoprenaline by itself, but incubation

  2. 76 FR 22809 - Safety Zone; Bay Ferry II Maritime Security Exercise; San Francisco Bay, San Francisco, CA

    Science.gov (United States)

    2011-04-25

    ... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 165 [Docket No. USCG-2011-0196] RIN 1625-AA00 Safety Zone; Bay Ferry II Maritime Security Exercise; San Francisco Bay, San Francisco, CA AGENCY... Security Exercise; San Francisco Bay, San Francisco, CA. (a) Location. The limits of this safety zone...

  3. Regulation of ventilation and oxygen consumption by delta- and mu-opioid receptor agonists.

    Science.gov (United States)

    Schaeffer, J I; Haddad, G G

    1985-09-01

    To study the effect of endorphins on metabolic rate and on the relationship between O2 consumption (VO2) and ventilation, we administered enkephalin analogues (relatively selective delta-receptor agonists) and a morphiceptin analogue (a highly selective mu-receptor agonist) intracisternally in nine unanesthetized chronically instrumented adult dogs. Both delta- and mu-agonists decreased VO2 by 40-60%. delta-Agonists induced a dose-dependent decrease in mean instantaneous minute ventilation (VT/TT) associated with periodic breathing. The decrease in VT/TT started and resolved prior to the decrease and returned to baseline of VO2, respectively. In contrast, the mu-agonists induced an increase in VT/TT associated with rapid shallow breathing. Arterial PCO2 increased and arterial PO2 decreased after both delta- and mu-agonists. Low doses of intracisternal naloxone (0.002-2.0 micrograms/kg) reversed the opioid effect on VT/TT but not on VO2; higher doses of naloxone (5-25 micrograms/kg) reversed both. Naloxone administered alone had no effect on VT/TT or VO2. These data suggest that 1) both delta- and mu-agonists induce alveolar hypoventilation despite a decrease in VO2, 2) this hypoventilation results from a decrease in VT/TT after delta-agonists but an increase in dead space ventilation after mu-agonists, and 3) endorphins do not modulate ventilation and metabolic rate tonically, but we speculate that they may do so in response to stressful stimulation.

  4. FXR agonist activity of conformationally constrained analogs of GW 4064.

    Science.gov (United States)

    Akwabi-Ameyaw, Adwoa; Bass, Jonathan Y; Caldwell, Richard D; Caravella, Justin A; Chen, Lihong; Creech, Katrina L; Deaton, David N; Madauss, Kevin P; Marr, Harry B; McFadyen, Robert B; Miller, Aaron B; Navas, Frank; Parks, Derek J; Spearing, Paul K; Todd, Dan; Williams, Shawn P; Bruce Wisely, G

    2009-08-15

    Two series of conformationally constrained analogs of the FXR agonist GW 4064 1 were prepared. Replacement of the metabolically labile stilbene with either benzothiophene or naphthalene rings led to the identification of potent full agonists 2a and 2g.

  5. The Effect of Coastal Development on Storm Surge Flooding in Biscayne Bay, Florida, USA (Invited)

    Science.gov (United States)

    Zhang, K.; Liu, H.; Li, Y.

    2013-12-01

    Barrier islands and associated bays along the Atlantic and Gulf Coasts are a favorite place for both living and visiting. Many of them are vulnerable to storm surge flooding because of low elevations and constantly being subjected to the impacts of storms. The population increase and urban development along the barrier coast have altered the shoreline configuration, resulting in a dramatic change in the coastal flooding pattern in some areas. Here we present such a case based on numerical simulations of storm surge flooding caused by the1926 hurricane in the densely populated area surrounding Biscayne Bay in Miami, Florida. The construction of harbor and navigation channels, and the development of real estate and the roads connecting islands along Biscayne Bay have changed the geometry of Biscayne Bay since 1910s. Storm surge simulations show that the Port of Miami and Dodge Island constructed by human after 1950 play an important role in changing storm surge inundation pattern along Biscayne Bay. Dodge Island enhances storm surge and increases inundation in the area south of the island, especially at the mouth of Miami River (Downtown of Miami), and reduces storm surge flooding in the area north of the island, especially in Miami Beach. If the Hurricane Miami of 1926 happened today, the flooding area would be reduced by 55% and 20% in the Miami Beach and North Miami areas, respectively. Consequently, it would prevent 400 million of property and 10 thousand people from surge flooding according to 2010 U.S census and 2007 property tax data. Meanwhile, storm water would penetrate further inland south of Dodge Island and increase the flooding area by 25% in the Miami River and Downtown Miami areas. As a result, 200 million of property and five thousand people would be impacted by storm surge.

  6. Responses of upland herpetofauna to the restoration of Carolina Bays and thinning of forested Bay Margins.

    Energy Technology Data Exchange (ETDEWEB)

    Ledvina, Joseph A.

    2008-05-01

    Research on the effects of wetland restoration on reptiles and amphibians is becoming more common, but almost all of these studies have observed the colonization of recently disturbed habitats that were completely dry at the time of restoration. In a similar manner, investigations herpetofaunal responses to forest management have focused on clearcuts, and less intensive stand manipulations are not as well studied. To evaluate community and population responses of reptiles and amphibians to hydrology restoration and canopy removal in the interior of previously degraded Carolina bays, I monitored herpetofauna in the uplands adjacent to six historically degraded Carolina bays at the Savannah River Site (SRS) in South Carolina for four years after restoration. To evaluate the effects of forest thinning on upland herpetofauna, forests were thinned in the margins of three of these bays. I used repeated measures ANOVA to compare species richness and diversity and the abundance of selected species and guilds between these bays and with those at three reference bays that were not historically drained and three control bays that remained degraded. I also used Non-metric Multidimensional Scaling (NMDS) to look for community-level patterns based treatments.

  7. Preliminary assessment of channel stability and bed-material transport in the Tillamook Bay tributaries and Nehalem River basin, northwestern Oregon

    Science.gov (United States)

    Jones, Krista L.; Keith, Mackenzie K.; O'Connor, Jim E.; Mangano, Joseph F.; Wallick, J. Rose

    2012-01-01

    valley confinement. * Natural and human-caused disturbances such as mass movements, logging, fire, channel modifications for navigation and flood control, and gravel mining also have varying effects on channel condition, bed-material transport, and distribution and area of bars throughout the study areas and over time. * Existing datasets include at least 16 and 18 sets of aerial and orthophotographs that were taken of the study areas in the Tillamook Bay tributary basins and Nehalem River basin, respectively, from 1939 to 2011. These photographs are available for future assessments of long-term changes in channel condition, bar area, and vegetation establishment patterns. High resolution Light Detection And Ranging (LiDAR) surveys acquired in 2007-2009 could support future quantitative analyses of channel morphology and bed-material transport in all study areas. * A review of deposited and mined gravel volumes reported for instream gravel mining sites shows that bed-material deposition tends to rebuild mined bar surfaces in most years. Mean annual deposition volumes on individual bars exceeded 3,000 cubic meters (m3) on Donaldson Bar on the Wilson River, Dill Bar on the Kilchis River, and Plant and Winslow Bars on the Nehalem River. Cumulative reported volumes of bed-material deposition were greatest at Donaldson and Dill Bars, totaling over 25,000 m3 per site from 2004 to 2011. Within this period, reported cumulative mined volumes were greatest for the Donaldson, Plant, and Winslow Bars, ranging from 24,470 to 33,940 m3. * Analysis of historical stage-streamflow data collected by the U.S. Geological Survey on the Wilson River near Tillamook (14301500) and Nehalem River near Foss (14301000) shows that these rivers have episodically aggraded and incised, mostly following high flow events, but they do not exhibit systematic, long-term trends in bed elevation. * Multiple cross sections show that channels near bridge crossings in all six study areas are dynamic with many

  8. A Bayes linear Bayes method for estimation of correlated event rates.

    Science.gov (United States)

    Quigley, John; Wilson, Kevin J; Walls, Lesley; Bedford, Tim

    2013-12-01

    Typically, full Bayesian estimation of correlated event rates can be computationally challenging since estimators are intractable. When estimation of event rates represents one activity within a larger modeling process, there is an incentive to develop more efficient inference than provided by a full Bayesian model. We develop a new subjective inference method for correlated event rates based on a Bayes linear Bayes model under the assumption that events are generated from a homogeneous Poisson process. To reduce the elicitation burden we introduce homogenization factors to the model and, as an alternative to a subjective prior, an empirical method using the method of moments is developed. Inference under the new method is compared against estimates obtained under a full Bayesian model, which takes a multivariate gamma prior, where the predictive and posterior distributions are derived in terms of well-known functions. The mathematical properties of both models are presented. A simulation study shows that the Bayes linear Bayes inference method and the full Bayesian model provide equally reliable estimates. An illustrative example, motivated by a problem of estimating correlated event rates across different users in a simple supply chain, shows how ignoring the correlation leads to biased estimation of event rates. © 2013 Society for Risk Analysis.

  9. Appearance and water quality of turbidity plumes produced by dredging in Tampa Bay, Florida

    Science.gov (United States)

    Goodwin, Carl R.; Michaelis, D.M.

    1984-01-01

    Turbidity plumes in Tampa Bay, Florida, produced during ship-channel dredging operations from February 1977 to August 1978, were monitored in order to document plume appearance and water quality, evaluate plume influence on the characteristics of Tampa Bay water, and provide a data base for comparison with other areas that have similar sediment, dredge, placement, containment, and tide conditions. The plumes investigated originated from the operation of one hopper dredge and three cutterhead-pipeline dredges. Composition of bottom sediment was found to vary from 85 percent sand and shell fragments to 60 percent silt and clay. Placement methods for dredged sediment included beach nourishment, stationary submerged discharge, oscillating surface discharge, and construction of emergent dikes. Tidal currents ranged from slack water to flow velocities of 0.60 meter per second. Plumes were monitored simultaneously by (1) oblique and vertical 35-millimeter aerial photography and (2) water-quality sampling to determine water clarity and concentrations of nutrients, metals, pesticides, and industrial compounds. Forty-nine photographs depict plumes ranging in length from a few tens of meters to several kilometers and ranging in turbidity level from hopper-dredge unloading operations also produced plumes of low visibility. Primary turbidity plumes were produced directly by dredging and placement operations; secondary plumes were produced indirectly by resuspension of previously deposited material. Secondary plumes were formed both by erosion, in areas of high-velocity tidal currents, and by turbulence from vessels passing over fine material deposited in shallow areas. Where turbidity barriers were not used, turbidity plumes visible at the surface were good indicators of the location of turbid water at depth. Where turbidity barriers were used, turbid bottom water was found at locations having no visible surface plumes. A region of rapidly accelerating then decelerating flow

  10. The fine sand Abra alba community of the Bay of Morlaix twenty years after the Amoco Cadiz oil spill

    International Nuclear Information System (INIS)

    Dauvin, J.-C.

    1998-01-01

    The fine sand Abra alba community from the Bay of Morlaix (western English Channel) was strongly affected by the Amoco Cadiz oil spill of April 1978. The long term changes in the community (1977-1996) show that reconstitution of this community is slow (over 10 yr). A progressive recolonization by amphipod Ampelisca populations constituting the dominant species is observed. The results show that it is necessary to survey the affected communities for a long period of time (> 10 yr) after an event to identify the real ecological impact of an oil spill. The abiotic and biotic factor existing in the Bay of Morlaix are favorable to the establishment and the persistence of stable dominant Ampelisca populations in time. The 'climax' concept seems to be applicable to this type of stable environment. The soft-bottom Abra alba community of the Bay of Morlaix may only support a maximal carrying capacity of approximately 10-11 g m -2 (mean annual biomass in decalcified dry weight). The deficit of production during 11 annual cycles may have affected the fish biomass feeding on this community. (author)

  11. The fine sand Abra alba community of the Bay of Morlaix twenty years after the Amoco Cadiz oil spill

    Energy Technology Data Exchange (ETDEWEB)

    Dauvin, J.-C. [CNRS-UPRES-A Elico, Wimereux (France). Station Marine de Wimereux

    1998-09-01

    The fine sand Abra alba community from the Bay of Morlaix (western English Channel) was strongly affected by the Amoco Cadiz oil spill of April 1978. The long term changes in the community (1977-1996) show that reconstitution of this community is slow (over 10 yr). A progressive recolonization by amphipod Ampelisca populations constituting the dominant species is observed. The results show that it is necessary to survey the affected communities for a long period of time (> 10 yr) after an event to identify the real ecological impact of an oil spill. The abiotic and biotic factor existing in the Bay of Morlaix are favorable to the establishment and the persistence of stable dominant Ampelisca populations in time. The `climax` concept seems to be applicable to this type of stable environment. The soft-bottom Abra alba community of the Bay of Morlaix may only support a maximal carrying capacity of approximately 10-11 g m{sup -2} (mean annual biomass in decalcified dry weight). The deficit of production during 11 annual cycles may have affected the fish biomass feeding on this community. (author)

  12. Florida Bay: A history of recent ecological changes

    Science.gov (United States)

    Fourqurean, J.W.; Robblee, M.B.

    1999-01-01

    Florida Bay is a unique subtropical estuary at the southern tip of the Florida peninsula. Recent ecological changes (seagrass die-off, algal blooms, increased turbidity) to the Florida Bay ecosystem have focused the attention of the public, commercial interests, scientists, and resource managers on the factors influencing the structure and function of Florida Bay. Restoring Florida Bay to some historic condition is the goal of resource managers, but what is not clear is what an anthropogenically-unaltered Florida Bay would look like. While there is general consensus that human activities have contributed to the changes occurring in the Florida Bay ecosystem, a high degree of natural system variability has made elucidation of the links between human activity and Florida Bay dynamics difficult. Paleoecological analyses, examination of long-term datasets, and directed measurements of aspects of the ecology of Florida Bay all contribute to our understanding of the behavior of the bay, and allow quantification of the magnitude of the recent ecological changes with respect to historical variability of the system.

  13. Diel use of a saltwater creek by white-tip reef sharks Triaenodon obesus (Carcharhiniformes: Carcharhinidae) in Academy Bay, Galapagos Islands.

    Science.gov (United States)

    Peñiaherrera, César; Hearn, Alex R; Kuhn, Angela

    2012-06-01

    White-tip reef sharks are common inhabitants of the shallow waters surrounding the Galapagos Islands, where several known aggregation sites have become touristic attractions. With the aim to describe site fidelity and residency patterns of the white-tip reef sharks in a saltwater creek, we used the ultrasonic telemetry method. The study was undertaken in a saltwater channel South of Academy Bay, Santa Cruz Island, from May 2008-September 2009. A total of nine transmitters were attached to sharks and ultrasonic receivers were deployed at the inner and outside areas of the creek. From the total of fitted sharks, four lost their transmitters. The results obtained with the remaining sharks showed an elevated use of the inner area of the channel during the day, with more use of the external area during the night. However, none of the sharks were detected at the site every day, suggesting that they may have a number of preferred sites within their home range. More studies are needed to detail the home range and habitat use of this species, and to guide its protection level in the Academy Bay area.

  14. Continuous water-quality and suspended-sediment transport monitoring in the San Francisco Bay, California, water years 2011–13

    Science.gov (United States)

    Buchanan, Paul A.; Downing-Kunz, Maureen; Schoellhamer, David H.; Shellenbarger, Gregory; Weidich, Kurt

    2014-01-01

    The U.S. Geological Survey (USGS) monitors water quality and suspended-sediment transport in the San Francisco Bay. The San Francisco Bay area is home to millions of people, and the bay teems with both resident and migratory wildlife, plants, and fish. Fresh water mixes with salt water in the bay, which is subject both to riverine and marine (tides, waves, influx of salt water) influences. To understand this environment, the USGS, along with its partners, has been monitoring the bay’s waters continuously since 1988. Several water-quality variables are of particular importance to State and Federal resource managers and are monitored at key locations throughout the bay. Salinity, which indicates the relative mixing of fresh and ocean waters in the bay, is derived from specific conductance measurements. Water temperature, along with salinity, affects the density of water, which causes gravity driven circulation patterns and stratification in the water column. Turbidity is measured using light-scattering from suspended solids in water, and is used as a surrogate for suspended-sediment concentration (SSC). Suspended sediment often carries adsorbed contaminants; attenuates sunlight in the water column; deposits on tidal marsh and intertidal mudflats, which can help sustain these habitats as sea level rises; and deposits in ports and shipping channels, which can necessitate dredging. Dissolved oxygen, which is essential to a healthy ecosystem, is a fundamental indicator of water quality, and its concentration is affected by water temperature, salinity, ecosystem metabolism, tidal currents, and wind. Tidal currents in the bay reverse four times a day, and wind direction and intensity typically change on a daily cycle: consequently, salinity, water temperature, suspendedsediment concentration, and dissolvedoxygen concentration vary spatially and temporally throughout the bay, and continuous measurements are needed to observe these changes. The purpose of this fact sheet

  15. MELATONIN DAN MELATONIN RECEPTOR AGONIST SEBAGAI PENANGANAN INSOMNIA PRIMER KRONIS

    Directory of Open Access Journals (Sweden)

    Ni Luh Putu Ayu Maha Iswari

    2013-04-01

    Full Text Available Melatonin is a hormone that has an important role in the mechanism of sleep. Hypnotic effects of melatonin and melatonin receptor agonist are mediated via MT1 and MT2 receptors, especially in circadian rhythm pacemaker, suprachiasmatic nucleus, which is worked on the hypothalamic sleep switch. This mechanism is quite different with the GABAergic drugs such as benzodiazepine. Agonist melatonin triggers the initiation of sleep and normalize circadian rhythms so that makes it easier to maintain sleep. The main disadvantage of melatonin in helping sleep maintenance on primary insomnia is that the half life is very short. The solution to this problem is the use of prolonged-release melatonin and melatonin receptor agonist agents such as ramelteon. Melatoninergic agonist does not cause withdrawal effects, dependence, as well as cognitive and psychomotor disorders as often happens on the use of benzodiazepine.  

  16. Bird surveys at McKinley Bay and Hutchinson Bay, Northwest Territories, in 1990

    Energy Technology Data Exchange (ETDEWEB)

    Cornish, B J; Dickson, D L; Dickson, H L

    1991-03-01

    Monitoring surveys of bird abundance and distribution were conducted in 1990 at McKinley Bay in the Northwest Territories, the site of a winter harbour for drillships and the proposed location for a major year-round support base for oil and gas exploration. Primary objectives of the survey were to determine whether diving duck numbers had changed since the initial phase of the study from 1981-1985, and to provide additional baseline data on natural annual fluctuations in diving duck numbers. Three aerial surveys at each bay were carried out using techniques identical to those in previous years. On 5 August 1990, when survey conditions were considered best of the three surveys, more than twice as many diving ducks were found in McKinley Bay and Hutchinson Bay than on average during the five years of 1981-1985. Old squaw and scooters comprised ca 90% of the diving ducks observed, and both species showed significant increases in numbers. The increase in abundance of diving ducks was likely unrelated to industrial activity in the area since a similar increase occurred in the control area, Hutchinson Bay. Many factors, including both environmental factors such as those affecting nesting success and timing of the moult, and factors related to the survey methods, could be involved in causing the large fluctuations observed. 9 refs., 8 figs., 10 tabs.

  17. Bird surveys at McKinley Bay and Hutchinson Bay, Northwest Territories, in 1990

    International Nuclear Information System (INIS)

    Cornish, B.J.; Dickson, D.L.; Dickson, H.L.

    1991-01-01

    Monitoring surveys of bird abundance and distribution were conducted in 1990 at McKinley Bay in the Northwest Territories, the site of a winter harbour for drillships and the proposed location for a major year-round support base for oil and gas exploration. Primary objectives of the survey were to determine whether diving duck numbers had changed since the initial phase of the study from 1981-1985, and to provide additional baseline data on natural annual fluctuations in diving duck numbers. Three aerial surveys at each bay were carried out using techniques identical to those in previous years. On 5 August 1990, when survey conditions were considered best of the three surveys, more than twice as many diving ducks were found in McKinley Bay and Hutchinson Bay than on average during the five years of 1981-1985. Old squaw and scooters comprised ca 90% of the diving ducks observed, and both species showed significant increases in numbers. The increase in abundance of diving ducks was likely unrelated to industrial activity in the area since a similar increase occurred in the control area, Hutchinson Bay. Many factors, including both environmental factors such as those affecting nesting success and timing of the moult, and factors related to the survey methods, could be involved in causing the large fluctuations observed. 9 refs., 8 figs., 10 tabs

  18. Block of GABA(A) receptor ion channel by penicillin: electrophysiological and modeling insights toward the mechanism.

    Science.gov (United States)

    Rossokhin, Alexey V; Sharonova, Irina N; Bukanova, Julia V; Kolbaev, Sergey N; Skrebitsky, Vladimir G

    2014-11-01

    GABA(A) receptors (GABA(A)R) mainly mediate fast inhibitory neurotransmission in the central nervous system. Different classes of modulators target GABA(A)R properties. Penicillin G (PNG) belongs to the class of noncompetitive antagonists blocking the open GABA(A)R and is a prototype of β-lactam antibiotics. In this study, we combined electrophysiological and modeling approaches to investigate the peculiarities of PNG blockade of GABA-activated currents recorded from isolated rat Purkinje cells and to predict the PNG binding site. Whole-cell patch-сlamp recording and fast application system was used in the electrophysiological experiments. PNG block developed after channel activation and increased with membrane depolarization suggesting that the ligand binds within the open channel pore. PNG blocked stationary component of GABA-activated currents in a concentration-dependent manner with IC50 value of 1.12mM at -70mV. The termination of GABA and PNG co-application was followed by a transient tail current. Protection of the tail current from bicuculline block and dependence of its kinetic parameters on agonist affinity suggest that PNG acts as a sequential open channel blocker that prevents agonist dissociation while the channel remains blocked. We built the GABA(A)R models based on nAChR and GLIC structures and performed an unbiased systematic search of the PNG binding site. Monte-Carlo energy minimization was used to find the lowest energy binding modes. We have shown that PNG binds close to the intracellular vestibule. In both models the maximum contribution to the energy of ligand-receptor interactions revealed residues located on the level of 2', 6' and 9' rings formed by a bundle of M2 transmembrane segments, indicating that these residues most likely participate in PNG binding. The predicted structural models support the described mechanism of PNG block. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. 78 FR 27126 - East Bay, St. Andrews Bay and the Gulf of Mexico at Tyndall Air Force Base, Florida; Restricted...

    Science.gov (United States)

    2013-05-09

    ... DEPARTMENT OF DEFENSE Department of the Army, Corps of Engineers 33 CFR Part 334 East Bay, St. Andrews Bay and the Gulf of Mexico at Tyndall Air Force Base, Florida; Restricted Areas AGENCY: U.S. Army... read as follows: Sec. 334.665 East Bay, St. Andrews Bay and the Gulf of Mexico, Restricted Areas...

  20. Click-Chemistry-Mediated Synthesis of Selective Melanocortin Receptor 4 Agonists

    DEFF Research Database (Denmark)

    Palmer, Daniel; Gonçalves, Juliana P.L.; Hansen, Louise V.

    2017-01-01

    The melanocortin receptor 4 (MC4R) subtype of the melanocortin receptor family is a target for therapeutics to ameliorate metabolic dysfunction. Endogenous MC4R agonists possess a critical pharmacophore (HFRW), and cyclization of peptide agonists often enhances potency. Thus, 17 cyclized peptides...

  1. Spill management strategy for the Chesapeake Bay

    International Nuclear Information System (INIS)

    Butler, H.L.; Chapman, R.S.; Johnson, B.H.

    1990-01-01

    The Chesapeake Bay Program is a unique cooperative effort between state and Federal agencies to restore the health and productivity of America's largest estuary. To assist in addressing specific management issues, a comprehensive three-dimensional, time-varying hydrodynamic and water quality model has ben developed. The Bay modeling strategy will serve as an excellent framework for including submodules to predict the movement, dispersion, and weathering of accidental spills, such as for petroleum products or other chemicals. This paper presents sample results from the Bay application to illustrate the success of the model system in simulating Bay processes. Also, a review of model requirements for successful spill modeling in Chesapeake Bay is presented. Recommendations are given for implementing appropriate spill modules with the Bay model framework and establishing a strategy for model use in addressing management issues

  2. Rat Urinary Bladder Carcinogenesis by Dual-Acting PPARα+γ Agonists

    Directory of Open Access Journals (Sweden)

    Martin B. Oleksiewicz

    2008-01-01

    Full Text Available Despite clinical promise, dual-acting activators of PPARα and γ (here termed PPARα+γ agonists have experienced high attrition rates in preclinical and early clinical development, due to toxicity. In some cases, discontinuation was due to carcinogenic effect in the rat urothelium, the epithelial layer lining the urinary bladder, ureters, and kidney pelvis. Chronic pharmacological activation of PPARα is invariably associated with cancer in rats and mice. Chronic pharmacological activation of PPARγ can in some cases also cause cancer in rats and mice. Urothelial cells coexpress PPARα as well as PPARγ, making it plausible that the urothelial carcinogenicity of PPARα+γ agonists may be caused by receptor-mediated effects (exaggerated pharmacology. Based on previously published mode of action data for the PPARα+γ agonist ragaglitazar, and the available literature about the role of PPARα and γ in rodent carcinogenesis, we propose a mode of action hypothesis for the carcinogenic effect of PPARα+γ agonists in the rat urothelium, which combines receptor-mediated and off-target cytotoxic effects. The proposed mode of action hypothesis is being explored in our laboratories, towards understanding the human relevance of the rat cancer findings, and developing rapid in vitro or short-term in vivo screening approaches to faciliate development of new dual-acting PPAR agonist compounds.

  3. Identification of novel selective V2 receptor non-peptide agonists.

    Science.gov (United States)

    Del Tredici, Andria L; Vanover, Kim E; Knapp, Anne E; Bertozzi, Sine M; Nash, Norman R; Burstein, Ethan S; Lameh, Jelveh; Currier, Erika A; Davis, Robert E; Brann, Mark R; Mohell, Nina; Olsson, Roger; Piu, Fabrice

    2008-10-30

    Peptides with agonist activity at the vasopressin V(2) receptor are used clinically to treat fluid homeostasis disorders such as polyuria and central diabetes insipidus. Of these peptides, the most commonly used is desmopressin, which displays poor bioavailability as well as potent activity at the V(1b) receptor, with possible stress-related adverse effects. Thus, there is a strong need for the development of small molecule chemistries with selective V(2) receptor agonist activity. Using the functional cell-based assay Receptor Selection and Amplification Technology (R-SAT((R))), a screening effort identified three small molecule chemotypes (AC-94544, AC-88324, and AC-110484) with selective agonist activity at the V(2) receptor. One of these compounds, AC-94544, displayed over 180-fold selectivity at the V(2) receptor compared to related vasopressin and oxytocin receptors and no activity at 28 other G protein-coupled receptors (GPCRs). All three compounds also showed partial agonist activity at the V(2) receptor in a cAMP accumulation assay. In addition, in a rat model of central diabetes insipidus, AC-94544 was able to significantly reduce urine output in a dose-dependent manner. Thus, AC-94544, AC-88324, and AC-110484 represent novel opportunities for the treatment of disorders associated with V(2) receptor agonist deficiency.

  4. Crystal structure and dynamics of a lipid-induced potential desensitized-state of a pentameric ligand-gated channel

    Energy Technology Data Exchange (ETDEWEB)

    Basak, Sandip [Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, United States; Schmandt, Nicolaus [Department of Neuroscience, School of Medicine, Case Western Reserve University, Cleveland, United States; Gicheru, Yvonne [Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, United States; Chakrapani, Sudha [Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, United States

    2017-03-06

    Desensitization in pentameric ligand-gated ion channels plays an important role in regulating neuronal excitability. Here, we show that docosahexaenoic acid (DHA), a key ω-3 polyunsaturated fatty acid in synaptic membranes, enhances the agonist-induced transition to the desensitized state in the prokaryotic channel GLIC. We determined a 3.25 Å crystal structure of the GLIC-DHA complex in a potentially desensitized conformation. The DHA molecule is bound at the channel-periphery near the M4 helix and exerts a long-range allosteric effect on the pore across domain-interfaces. In this previously unobserved conformation, the extracellular-half of the pore-lining M2 is splayed open, reminiscent of the open conformation, while the intracellular-half is constricted, leading to a loss of both water and permeant ions. These findings, in combination with spin-labeling/EPR spectroscopic measurements in reconstituted-membranes, provide novel mechanistic details of desensitization in pentameric channels.

  5. CALCULATION AND ANALYSIS OF THE EXPECTED IMPACT OF THE HYDROTECHNICAL CONSTRUCTION ON THE ENVIRONMENTAL CONDITION IN THE WATER AREA AND BOTTOM TOPOGRAPHY IN CASE OF THE CONSTRUCTION OF THE APPROACH CHANNEL TO THE SABETTA PORT

    Directory of Open Access Journals (Sweden)

    Vvedensky Alexei Rostislavovich

    2017-05-01

    Full Text Available The estimation of changes in the ecological situation and bottom topography in the Ob Bay, which may be caused by the construction of the approach channel to the port of Sabetta, was carried out with the help of the developed complex of numerical models. Particular attention was paid to the study of the displacement of the boundaries of the saline water expansion and the sediment accumulation in the channel area. It is established that the possible influence of the approach channel on the hydrologic-hydrochemical characteristics is less than their natural interannual and seasonal variability in the investigated water area. The change in the bottom topography after the construction of the approach channel does not entail a significant change in the regime of hydrologic-hydrochemical parameters of the Ob Bay and, consequently, should not affect the biocenosis. The calculated changes in the bottom topography in the approach channel area will not exceed 2 % of the depth per year and will not become a significant obstacle to the reliable and uninterrupted operation of the Sabetta port.

  6. Structural mechanism underlying capsaicin binding and activation of TRPV1 ion channel

    Science.gov (United States)

    Cheng, Wei; Yang, Wei; Yu, Peilin; Song, Zhenzhen; Yarov-Yarovoy, Vladimir; Zheng, Jie

    2015-01-01

    Capsaicin bestows spiciness by activating TRPV1 channel with exquisite potency and selectivity. Capsaicin-bound channel structure was previously resolved by cryo-EM at 4.2-to-4.5 Å resolution, however important details required for mechanistic understandings are unavailable: capsaicin was registered as a small electron density, reflecting neither its chemical structure nor specific ligand-channel interactions. We obtained the missing atomic-level details by iterative computation, which were confirmed by systematic site-specific functional tests. We observed that the bound capsaicin takes “tail-up, head-down” configurations. The vanillyl and amide groups form specific interactions to anchor its bound position, while the aliphatic tail may sample a range of conformations, making it invisible in cryo-EM images. Capsaicin stabilizes the open state by “pull-and-contact” interactions between the vanillyl group and the S4-S5 linker. Our study provided a structural mechanism for the agonistic function of capsaicin and its analogs, and demonstrated an effective approach to obtain atomic level information from cryo-EM structures. PMID:26053297

  7. Strong activation of bile acid-sensitive ion channel (BASIC) by ursodeoxycholic acid

    Science.gov (United States)

    Wiemuth, Dominik; Sahin, Hacer; Lefèvre, Cathérine M.T.; Wasmuth, Hermann E.; Gründer, Stefan

    2013-01-01

    Bile acid-sensitive ion channel (BASIC) is a member of the DEG/ENaC gene family of unknown function. Rat BASIC (rBASIC) is inactive at rest. We have recently shown that cholangiocytes, the epithelial cells lining the bile ducts, are the main site of BASIC expression in the liver and identified bile acids, in particular hyo- and chenodeoxycholic acid, as agonists of rBASIC. Moreover, it seems that extracellular divalent cations stabilize the resting state of rBASIC, because removal of extracellular divalent cations opens the channel. In this addendum, we demonstrate that removal of extracellular divalent cations potentiates the activation of rBASIC by bile acids, suggesting an allosteric mechanism. Furthermore, we show that rBASIC is strongly activated by the anticholestatic bile acid ursodeoxycholic acid (UDCA), suggesting that BASIC might mediate part of the therapeutic effects of UDCA. PMID:23064163

  8. The RCK1 high-affinity Ca2+ sensor confers carbon monoxide sensitivity to Slo1 BK channels.

    Science.gov (United States)

    Hou, Shangwei; Xu, Rong; Heinemann, Stefan H; Hoshi, Toshinori

    2008-03-11

    Carbon monoxide (CO) is a lethal gas, but it is also increasingly recognized as a physiological signaling molecule capable of regulating a variety of proteins. Among them, large-conductance Ca(2+)- and voltage-gated K(+) (Slo1 BK) channels, important in vasodilation and neuronal firing, have been suggested to be directly stimulated by CO. However, the molecular mechanism of the stimulatory action of CO on the Slo1 BK channel has not been clearly elucidated. We report here that CO reliably and repeatedly activates Slo1 BK channels in excised membrane patches in the absence of Ca(2+) in a voltage-sensor-independent manner. The stimulatory action of CO on the Slo1 BK channel requires an aspartic acid and two histidine residues located in the cytoplasmic RCK1 domain, and the effect persists under the conditions known to inhibit the conventional interaction between CO and heme in other proteins. We propose that CO acts as a partial agonist for the high-affinity divalent cation sensor in the RCK1 domain of the Slo1 BK channel.

  9. Partial agonist therapy in schizophrenia: relevance to diminished criminal responsibility.

    Science.gov (United States)

    Gavaudan, Gilles; Magalon, David; Cohen, Julien; Lançon, Christophe; Léonetti, Georges; Pélissier-Alicot, Anne-Laure

    2010-11-01

    Pathological gambling (PG), classified in the DSM-IV among impulse control disorders, is defined as inappropriate, persistent gaming for money with serious personal, family, and social consequences. Offenses are frequently committed to obtain money for gambling. Pathological gambling, a planned and structured behavioral disorder, has often been described as a complication of dopamine agonist treatment in patients with Parkinson's disease. It has never been described in patients with schizophrenia receiving dopamine agonists. We present two patients with schizophrenia, previously treated with antipsychotic drugs without any suggestion of PG, who a short time after starting aripiprazole, a dopamine partial agonist, developed PG and criminal behavior, which totally resolved when aripiprazole was discontinued. Based on recent advances in research on PG and adverse drug reactions to dopamine agonists in Parkinson's disease, we postulate a link between aripiprazole and PG in both our patients with schizophrenia and raise the question of criminal responsibility. © 2010 American Academy of Forensic Sciences.

  10. Insulin reduces neuronal excitability by turning on GABA(A channels that generate tonic current.

    Directory of Open Access Journals (Sweden)

    Zhe Jin

    Full Text Available Insulin signaling to the brain is important not only for metabolic homeostasis but also for higher brain functions such as cognition. GABA (γ-aminobutyric acid decreases neuronal excitability by activating GABA(A channels that generate phasic and tonic currents. The level of tonic inhibition in neurons varies. In the hippocampus, interneurons and dentate gyrus granule cells normally have significant tonic currents under basal conditions in contrast to the CA1 pyramidal neurons where it is minimal. Here we show in acute rat hippocampal slices that insulin (1 nM "turns on" new extrasynaptic GABA(A channels in CA1 pyramidal neurons resulting in decreased frequency of action potential firing. The channels are activated by more than million times lower GABA concentrations than synaptic channels, generate tonic currents and show outward rectification. The single-channel current amplitude is related to the GABA concentration resulting in a single-channel GABA affinity (EC(50 in intact CA1 neurons of 17 pM with the maximal current amplitude reached with 1 nM GABA. They are inhibited by GABA(A antagonists but have novel pharmacology as the benzodiazepine flumazenil and zolpidem are inverse agonists. The results show that tonic rather than synaptic conductances regulate basal neuronal excitability when significant tonic conductance is expressed and demonstrate an unexpected hormonal control of the inhibitory channel subtypes and excitability of hippocampal neurons. The insulin-induced new channels provide a specific target for rescuing cognition in health and disease.

  11. Chesapeake Bay plume dynamics from LANDSAT

    Science.gov (United States)

    Munday, J. C., Jr.; Fedosh, M. S.

    1981-01-01

    LANDSAT images with enhancement and density slicing show that the Chesapeake Bay plume usually frequents the Virginia coast south of the Bay mouth. Southwestern (compared to northern) winds spread the plume easterly over a large area. Ebb tide images (compared to flood tide images) show a more dispersed plume. Flooding waters produce high turbidity levels over the shallow northern portion of the Bay mouth.

  12. Sedimentological characteristics and depositional processes of sediment gravity flows in rift basins: The Palaeogene Dongying and Shahejie formations, Bohai Bay Basin, China

    Science.gov (United States)

    Liu, Lei; Chen, Hongde; Zhong, Yijiang; Wang, Jun; Xu, Changgui; Chen, Anqing; Du, Xiaofeng

    2017-10-01

    Sediment gravity flow deposits are common, particularly in sandy formations, but their origin has been a matter of debate and there is no consensus about the classification of such deposits. However, sediment gravity flow sandstones are economically important and have the potential to meet a growing demand in oil and gas exploration, so there is a drive to better understand them. This study focuses on sediment gravity flow deposits identified from well cores in Palaeogene deposits from the Liaodong Bay Depression in Bohai Bay Basin, China. We classify the sediment gravity flow deposits into eight lithofacies using lithological characteristics, grain size, and sedimentary structures, and interpret the associated depositional processes. Based on the scale, spatial distribution, and contact relationships of sediment gravity flow deposits, we defined six types of lithofacies associations (LAs) that reflect transformation processes and depositional morphology: LA1 (unconfined proximal breccia deposits), LA2 (confined channel deposits), LA3 (braided-channel lobe deposits), LA4 (unconfined lobe deposits), LA5 (distal sheet deposits), and LA6 (non-channelized sheet deposits). Finally, we established three depositional models that reflect the sedimentological characteristics and depositional processes of sediment gravity flow deposits: (1) slope-apron gravel-rich depositional model, which involves cohesive debris flows deposited as LA1 and dilute turbidity currents deposited as LA5; (2) non-channelized surge-like turbidity current depositional model, which mainly comprises sandy slumping, suspended load dominated turbidity currents, and dilute turbidity currents deposited as LA5 and LA6; and (3) channelized subaqueous-fan depositional model, which consists of non-cohesive bedload dominated turbidity currents, suspended load dominated turbidity currents, and dilute turbidity currents deposited as LA2-LA5, originating from sustained extrabasinal turbidity currents

  13. Beryllium-10 in Chesapeake Bay sediments: an indicator of sediment provenance

    International Nuclear Information System (INIS)

    Helz, G.R.; Valette-Silver, Nathalie

    1992-01-01

    In a plot of 10 Be vs. Fe, central Chesapeake Bay sediments can be segregated into distinct units. This plot reveals an unexpected, statistically significant difference between sediments on the eastern and western flanks of the main channel, implying different origins. Although the 10 Be concentrations in sediments from these two regions span as much as an order of magnitude range, the 10 Be/Fe ratios vary by an amount approximating analytical error alone. The large concentration ranges are ascribed to hydraulic sorting, which can produce variance in composition while not affecting ratios between grain surface components such as Fe and Be. On the basis of 10 Be/Fe signatures, sediments on the western flank of the main channel appear to have been derived from the Susquehanna or another Piedmont/Appalachian river. Sediments on the eastern flank may have been transported from the south, by landward flowing bottom currents, or may be relics of a Pleistocene estuarine system. Conditions under which 10 Be may prove a useful tool in sediment provenance studies elsewhere are discussed. (Author)

  14. Inward rectifier K+ channel and T-type Ca2+ channel contribute to enhancement of GABAergic transmission induced by β1-adrenoceptor in the prefrontal cortex.

    Science.gov (United States)

    Luo, Fei; Zheng, Jian; Sun, Xuan; Tang, Hua

    2017-02-01

    The functions of prefrontal cortex (PFC) are sensitive to norepinephrine (NE). Endogenously released NE influences synaptic transmission through activation of different subtypes of adrenergic receptors in PFC including α 1 , α 2 , β 1 or β 2 -adrenoceptor. Our recent study has revealed that β 1 -adrenoceptor (β 1 -AR) activation modulates glutamatergic transmission in the PFC, whereas the roles of β 1 -AR in GABAergic transmission are elusive. In the current study, we probed the effects of the β 1 -AR agonist dobutamine (Dobu) on GABAergic transmission onto pyramidal neurons in the PFC of juvenile rats. Dobu increased both the frequency and amplitude of miniature IPSCs (mIPSCs). Ca 2+ influx through T-type voltage-gated Ca 2+ channel was required for Dobu-enhanced mIPSC frequency. We also found that Dobu facilitated GABA release probability and the number of releasable vesicles through regulating T-type Ca 2+ channel. Dobu depolarized GABAergic fast-spiking (FS) interneurons with no effects on the firing rate of action potentials (APs) of interneurons. Dobu-induced depolarization of FS interneurons required inward rectifier K + channel (Kir). Our results suggest that Dobu increase GABA release via inhibition of Kir, which further depolarizes FS interneurons resulting in Ca 2+ influx via T-type Ca 2+ channel. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Small-molecule agonists for the glucagon-like peptide 1 receptor

    DEFF Research Database (Denmark)

    Knudsen, Lotte Bjerre; Kiel, Dan; Teng, Min

    2007-01-01

    and independent agonists. Potency of GLP-1 was not changed by the allosteric agonists, but affinity of GLP-1 for the receptor was increased. The most potent compound identified stimulates glucose-dependent insulin release from normal mouse islets but, importantly, not from GLP-1 receptor knockout mice. Also...

  16. Effect of beta-agonists on LAM progression and treatment.

    Science.gov (United States)

    Le, Kang; Steagall, Wendy K; Stylianou, Mario; Pacheco-Rodriguez, Gustavo; Darling, Thomas N; Vaughan, Martha; Moss, Joel

    2018-01-30

    Lymphangioleiomyomatosis (LAM), a rare disease of women, is associated with cystic lung destruction resulting from the proliferation of abnormal smooth muscle-like LAM cells with mutations in the tuberous sclerosis complex (TSC) genes TSC1 and/or TSC2 The mutant genes and encoded proteins are responsible for activation of the mechanistic target of rapamycin (mTOR), which is inhibited by sirolimus (rapamycin), a drug used to treat LAM. Patients who have LAM may also be treated with bronchodilators for asthma-like symptoms due to LAM. We observed stabilization of forced expiratory volume in 1 s over time in patients receiving sirolimus and long-acting beta-agonists with short-acting rescue inhalers compared with patients receiving only sirolimus. Because beta-agonists increase cAMP and PKA activity, we investigated effects of PKA activation on the mTOR pathway. Human skin TSC2 +/- fibroblasts or LAM lung cells incubated short-term with isoproterenol (beta-agonist) showed a sirolimus-independent increase in phosphorylation of S6, a downstream effector of the mTOR pathway, and increased cell growth. Cells incubated long-term with isoproterenol, which may lead to beta-adrenergic receptor desensitization, did not show increased S6 phosphorylation. Inhibition of PKA blocked the isoproterenol effect on S6 phosphorylation. Thus, activation of PKA by beta-agonists increased phospho-S6 independent of mTOR, an effect abrogated by beta-agonist-driven receptor desensitization. In agreement, retrospective clinical data from patients with LAM suggested that a combination of bronchodilators in conjunction with sirolimus may be preferable to sirolimus alone for stabilization of pulmonary function.

  17. Geology and structure of the North Boqueron Bay-Punta Montalva Fault System

    Science.gov (United States)

    Roig Silva, Coral Marie

    The North Boqueron Bay-Punta Montalva Fault Zone is an active fault system that cuts across the Lajas Valley in southwestern Puerto Rico. The fault zone has been recognized and mapped based upon detailed analysis of geophysical data, satellite images and field mapping. The fault zone consists of a series of Cretaceous bedrock faults that reactivated and deformed Miocene limestone and Quaternary alluvial fan sediments. The fault zone is seismically active (ML < 5.0) with numerous locally felt earthquakes. Focal mechanism solutions and structural field data suggest strain partitioning with predominantly east-west left-lateral displacements with small normal faults oriented mostly toward the northeast. Evidence for recent displacement consists of fractures and small normal faults oriented mostly northeast found in intermittent streams that cut through the Quaternary alluvial fan deposits along the southern margin of the Lajas Valley, Areas of preferred erosion, within the alluvial fan, trend toward the west-northwest parallel to the on-land projection of the North Boqueron Bay Fault. Beyond the faulted alluvial fan and southeast of the Lajas Valley, the Northern Boqueron Bay Fault joins with the Punta Montalva Fault. The Punta Montalva Fault is defined by a strong topographic WNW lineament along which stream channels are displaced left laterally 200 meters and Miocene strata are steeply tilted to the south. Along the western end of the fault zone in northern Boqueron Bay, the older strata are only tilted 3° south and are covered by flat lying Holocene sediments. Focal mechanisms solutions along the western end suggest NW-SE shortening, which is inconsistent with left lateral strain partitioning along the fault zone. The limited deformation of older strata and inconsistent strain partitioning may be explained by a westerly propagation of the fault system from the southwest end. The limited geomorphic structural expression along the North Boqueron Bay Fault segment

  18. Conotoxins as Tools to Understand the Physiological Function of Voltage-Gated Calcium (CaV Channels

    Directory of Open Access Journals (Sweden)

    David Ramírez

    2017-10-01

    Full Text Available Voltage-gated calcium (CaV channels are widely expressed and are essential for the completion of multiple physiological processes. Close regulation of their activity by specific inhibitors and agonists become fundamental to understand their role in cellular homeostasis as well as in human tissues and organs. CaV channels are divided into two groups depending on the membrane potential required to activate them: High-voltage activated (HVA, CaV1.1–1.4; CaV2.1–2.3 and Low-voltage activated (LVA, CaV3.1–3.3. HVA channels are highly expressed in brain (neurons, heart, and adrenal medulla (chromaffin cells, among others, and are also classified into subtypes which can be distinguished using pharmacological approaches. Cone snails are marine gastropods that capture their prey by injecting venom, “conopeptides”, which cause paralysis in a few seconds. A subset of conopeptides called conotoxins are relatively small polypeptides, rich in disulfide bonds, that target ion channels, transporters and receptors localized at the neuromuscular system of the animal target. In this review, we describe the structure and properties of conotoxins that selectively block HVA calcium channels. We compare their potency on several HVA channel subtypes, emphasizing neuronal calcium channels. Lastly, we analyze recent advances in the therapeutic use of conotoxins for medical treatments.

  19. Generalized concentration addition: a method for examining mixtures containing partial agonists.

    Science.gov (United States)

    Howard, Gregory J; Webster, Thomas F

    2009-08-07

    Environmentally relevant toxic exposures often consist of simultaneous exposure to multiple agents. Methods to predict the expected outcome of such combinations are critical both to risk assessment and to an accurate judgment of whether combinations are synergistic or antagonistic. Concentration addition (CA) has commonly been used to assess the presence of synergy or antagonism in combinations of similarly acting chemicals, and to predict effects of combinations of such agents. CA has the advantage of clear graphical interpretation: Curves of constant joint effect (isoboles) must be negatively sloped straight lines if the mixture is concentration additive. However, CA cannot be directly used to assess combinations that include partial agonists, although such agents are of considerable interest. Here, we propose a natural extension of CA to a functional form that may be applied to mixtures including full agonists and partial agonists. This extended definition, for which we suggest the term "generalized concentration addition," encompasses linear isoboles with slopes of any sign. We apply this approach to the simple example of agents with dose-response relationships described by Hill functions with slope parameter n=1. The resulting isoboles are in all cases linear, with negative, zero and positive slopes. Using simple mechanistic models of ligand-receptor systems, we show that the same isobole pattern and joint effects are generated by modeled combinations of full and partial agonists. Special cases include combinations of two full agonists and a full agonist plus a competitive antagonist.

  20. Short Term Sediment Exchange Between Marshes and Bays Using Beryllium-7 as a Tracer, Fourleague Bay, Louisiana.

    Science.gov (United States)

    Restreppo, G. A.; Bentley, S. J.; Xu, K.; Wang, J.

    2016-12-01

    Modern delta models focus on the availability and exchange of coarse sediment as one of the major factors of deltaic growth or decay. Fine-grained sediment exchange within a river's delta is relatively poorly understood, as is the impact that this exchange has on land building and land loss. To better understand the dynamics of fine grain sediment exchange between river mouth, adjacent bays, and marshland, sediment cores from Fourleague Bay, LA, were collected and analyzed for 7Be, a naturally occurring radioisotope that serves as a marker for recently deposited sediment. Time-series push cores were collected every two months at ten sites, five located across a longitudinal transect in the middle bay and five located along adjacent marshes, from May 2015 to May 2016. All sites fall within 11 to 28 km of the Atchafalaya Delta, along a gradient extending towards the open ocean. Cores were extruded in 2 cm intervals, dried, ground, and analyzed via gamma spectrometry for the presence of 7Be. Inventories of 7Be were then calculated and used to determine bimonthly sedimentation rates over the course twelve months. Sediment deposition on the bay floor and marsh surface were then compared to Atchafalaya River discharge, wind speed and direction, and wave action. Preliminary results indicate patterns of initial fluvial sediment transfer from river to bay floor, then bay floor to marsh surface, with decreasing fluvial influence towards the open ocean. Sediment transport from bay to marsh appears to be coupled with meteorological forcing that induces bay-floor sediment resuspension and the flooding of marsh surfaces. This indirect mechanism of fluvial sediment supply to wetland surfaces may extend the region of influence for sediment delivery from man-made river-sediment diversions.

  1. The antipsychotic drug loxapine is an opener of the sodium-activated potassium channel slack (Slo2.2).

    Science.gov (United States)

    Biton, B; Sethuramanujam, S; Picchione, Kelly E; Bhattacharjee, A; Khessibi, N; Chesney, F; Lanneau, C; Curet, O; Avenet, P

    2012-03-01

    Sodium-activated potassium (K(Na)) channels have been suggested to set the resting potential, to modulate slow after-hyperpolarizations, and to control bursting behavior or spike frequency adaptation (Trends Neurosci 28:422-428, 2005). One of the genes that encodes K(Na) channels is called Slack (Kcnt1, Slo2.2). Studies found that Slack channels were highly expressed in nociceptive dorsal root ganglion neurons and modulated their firing frequency (J Neurosci 30:14165-14172, 2010). Therefore, Slack channel openers are of significant interest as putative analgesic drugs. We screened the library of pharmacologically active compounds with recombinant human Slack channels expressed in Chinese hamster ovary cells, by using rubidium efflux measurements with atomic absorption spectrometry. Riluzole at 500 μM was used as a reference agonist. The antipsychotic drug loxapine and the anthelmintic drug niclosamide were both found to activate Slack channels, which was confirmed by using manual patch-clamp analyses (EC(50) = 4.4 μM and EC(50) = 2.9 μM, respectively). Psychotropic drugs structurally related to loxapine were also evaluated in patch-clamp experiments, but none was found to be as active as loxapine. Loxapine properties were confirmed at the single-channel level with recombinant rat Slack channels. In dorsal root ganglion neurons, loxapine was found to behave as an opener of native K(Na) channels and to increase the rheobase of action potential. This study identifies new K(Na) channel pharmacological tools, which will be useful for further Slack channel investigations.

  2. The Good, the Bad, and the Ugly: Agonistic Behaviour in Juvenile Crocodilians

    OpenAIRE

    Brien, Matthew L.; Lang, Jeffrey W.; Webb, Grahame J.; Stevenson, Colin; Christian, Keith A.

    2013-01-01

    We examined agonistic behaviour in seven species of hatchling and juvenile crocodilians held in small groups (N = 4) under similar laboratory conditions. Agonistic interactions occurred in all seven species, typically involved two individuals, were short in duration (5-15 seconds), and occurred between 1600-2200 h in open water. The nature and extent of agonistic interactions, the behaviours displayed, and the level of conspecific tolerance varied among species. Discrete postures, non-contact...

  3. Five hTRPA1 Agonists Found in Indigenous Korean Mint, Agastache rugosa.

    Directory of Open Access Journals (Sweden)

    Hana Moon

    Full Text Available Transient receptor potential ankyrin1 (TRPA1 and transient receptor potential vanilloid 1 (TRPV1 are members of the TRP superfamily of structurally related, nonselective cation channels and mediators of several signaling pathways. Previously, we identified methyl syringate as an hTRPA1 agonist with efficacy against gastric emptying. The aim of this study was to find hTRPA1 and/or hTRPV1 activators in Agastache rugosa (Fisch. et Meyer O. Kuntze (A.rugosa, commonly known as Korean mint to improve hTRPA1-related phenomena. An extract of the stem and leaves of A.rugosa (Labiatae selectively activated hTRPA1 and hTRPV1. We next investigated the effects of commercially available compounds found in A.rugosa (acacetin, 4-allylanisole, p-anisaldehyde, apigenin 7-glucoside, L-carveol, β-caryophyllene, trans-p-methoxycinnamaldehyde, methyl eugenol, pachypodol, and rosmarinic acid on cultured hTRPA1- and hTRPV1-expressing cells. Of the ten compounds, L-carveol, trans-p-methoxycinnamaldehyde, methyl eugenol, 4-allylanisole, and p-anisaldehyde selectively activated hTRPA1, with EC50 values of 189.1±26.8, 29.8±14.9, 160.2±21.9, 1535±315.7, and 546.5±73.0 μM, respectively. The activities of these compounds were effectively inhibited by the hTRPA1 antagonists, ruthenium red and HC-030031. Although the five active compounds showed weaker calcium responses than allyl isothiocyanate (EC50=7.2±1.4 μM, our results suggest that these compounds from the stem and leaves of A.rugosa are specific and selective agonists of hTRPA1.

  4. Prolonging survival of corneal transplantation by selective sphingosine-1-phosphate receptor 1 agonist.

    Directory of Open Access Journals (Sweden)

    Min Gao

    Full Text Available Corneal transplantation is the most used therapy for eye disorders. Although the cornea is somewhat an immune privileged organ, immune rejection is still the major problem that reduces the success rate. Therefore, effective chemical drugs that regulate immunoreactions are needed to improve the outcome of corneal transplantations. Here, a sphingosine-1-phosphate receptor 1 (S1P1 selective agonist was systematically evaluated in mouse allogeneic corneal transplantation and compared with the commonly used immunosuppressive agents. Compared with CsA and the non-selective sphingosine 1-phosphate (S1P receptor agonist FTY720, the S1P1 selective agonist can prolong the survival corneal transplantation for more than 30 days with a low immune response. More importantly, the optimal dose of the S1P1 selective agonist was much less than non-selective S1P receptor agonist FTY720, which would reduce the dose-dependent toxicity in drug application. Then we analyzed the mechanisms of the selected S1P1 selective agonist on the immunosuppression. The results shown that the S1P1 selective agonist could regulate the distribution of the immune cells with less CD4+ T cells and enhanced Treg cells in the allograft, moreover the expression of anti-inflammatory cytokines TGF-β1 and IL-10 unregulated which can reduce the immunoreactions. These findings suggest that S1P1 selective agonist may be a more appropriate immunosuppressive compound to effectively prolong mouse allogeneic corneal grafts survival.

  5. BOOK REVIEW OF "CHESAPEAKE BAY BLUES: SCIENCE, POLITICS, AND THE STRUGGLE TO SAVE THE BAY"

    Science.gov (United States)

    This is a book review of "Chesapeake Bay Blues: Science, Politics, and the Struggle to Save the Bay". This book is very well written and provides an easily understandable description of the political challenges faced by those proposing new or more stringent environmental regulat...

  6. Long-term impacts due to sediment supply changes towards the San Francisco Bay-Delta system

    Science.gov (United States)

    Achete, F.; Van der Wegen, M. V.; Jaffe, B. E.

    2012-12-01

    The Sacramento-San Joaquin Delta and Watershed is the main source of fresh water and sediment to San Francisco Bay. Mid 19th century hydraulic mining in the catchment caused an excessive supply of sediment. After mining activities stopped, in the first part of the 20th century several hydraulic structures were built deviating fresh water and trapping sediment upstream. The main purpose of most of these structures is water storage for irrigation and/or water supply Wright and Schoellhamer (2004) show that from 1957 to 2001 the sediment load carried to San Francisco Bay has decreased by about one half. The lack of sediments may lead to a different erosion/deposition pattern in the Bay-Delta system causing problems like mud flat erosion, shift in navigation channel, land subsidence and changing habitat for endemic species. The objective of this work is to identify and quantify morphological shifts in the Bay-Delta system due to variation in fresh water and sediment supply. In this study, we couple the Delta and Bay in a unique model network (the Delta-Bay model). This coupling allows tracking of sediment from Sacramento via the Delta and Bay and through the Golden Gate, making it possible to identify erosion and deposition areas. The numerical model applied is an unstructured, process-based model (D-Flow Flexible Mesh developed by Deltares). It simulates the hydrodynamics and morphodynamics of the area on a detailed, 64000-node mesh (10-200m mesh length scale) on a timescale of minutes. The morphological impact is assessed for multiple scenarios with different input of sediment and fresh water. A statistical analysis is performed to account for uncertainty of model parameters and climate change impacts. The fresh water discharge already has a strong natural seasonal and inter-annual variation. The human impact by foreseen different water pumping strategies due to the peripheral canal will be considered. Jaffe et al. (2007) has shown that substantial morphological

  7. Force spectroscopy measurements show that cortical neurons exposed to excitotoxic agonists stiffen before showing evidence of bleb damage.

    Directory of Open Access Journals (Sweden)

    Shan Zou

    Full Text Available In ischemic and traumatic brain injury, hyperactivated glutamate (N-methyl-D-aspartic acid, NMDA and sodium (Nav channels trigger excitotoxic neuron death. Na(+, Ca(++ and H2O influx into affected neurons elicits swelling (increased cell volume and pathological blebbing (disassociation of the plasma membrane's bilayer from its spectrin-actomyosin matrix. Though usually conflated in injured tissue, cell swelling and blebbing are distinct processes. Around an injury core, salvageable neurons could be mildly swollen without yet having suffered the bleb-type membrane damage that, by rendering channels leaky and pumps dysfunctional, exacerbates the excitotoxic positive feedback spiral. Recognizing when neuronal inflation signifies non-lethal osmotic swelling versus blebbing should further efforts to salvage injury-penumbra neurons. To assess whether the mechanical properties of osmotically-swollen versus excitotoxically-blebbing neurons might be cytomechanically distinguishable, we measured cortical neuron elasticity (gauged via atomic force microscopy (AFM-based force spectroscopy upon brief exposure to hypotonicity or to excitotoxic agonists (glutamate and Nav channel activators, NMDA and veratridine. Though unperturbed by solution exchange per se, elasticity increased abruptly with hypotonicity, with NMDA and with veratridine. Neurons then invariably softened towards or below the pre-treatment level, sometimes starting before the washout. The initial channel-mediated stiffening bespeaks an abrupt elevation of hydrostatic pressure linked to NMDA or Nav channel-mediated ion/H2O fluxes, together with increased [Ca(++]int-mediated submembrane actomyosin contractility. The subsequent softening to below-control levels is consistent with the onset of a lethal level of bleb damage. These findings indicate that dissection/identification of molecular events during the excitotoxic transition from stiff/swollen to soft/blebbing is warranted and should be

  8. Long-acting beta 2-agonists in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Llewellyn-Jones, Carol

    2002-01-01

    Until recently, the use of long-acting beta 2-agonists in chronic obstructive pulmonary disease has been understated. There is now evidence that they may offer benefits beyond bronchodilation. This article reviews the management of chronic obstructive pulmonary disease and looks at the place of long-acting beta 2-agonists as a first-line treatment option.

  9. Non-Acidic Free Fatty Acid Receptor 4 Agonists with Antidiabetic Activity

    DEFF Research Database (Denmark)

    Goncalves de Azavedo, Carlos M. B. P.; Watterson, Kenneth R; Wargent, Ed T

    2016-01-01

    The free fatty acid receptor 4 (FFA4 or GPR120) has appeared as an interesting potential target for the treatment of metabolic disorders. At present, most FFA4 ligands are carboxylic acids that are assumed to mimic the endogenous long-chain fatty acid agonists. Here, we report preliminary structure......-activity relationship studies of a previously disclosed non-acidic sulfonamide FFA4 agonist. Mutagenesis studies indicate that the compounds are orthosteric agonists despite the absence of a carboxylate function. The preferred compounds showed full agonist activity on FFA4 and complete selectivity over FFA1, although...... a significant fraction of these non-carboxylic acids also showed partial antagonistic activity on FFA1. Studies in normal and diet-induced obese (DIO) mice with the preferred compound 34 showed improved glucose tolerance after oral dosing in an oral glucose tolerance test. Chronic dosing of 34 in DIO mice...

  10. Thermo-sensitive TRP channels in peripheral nerve injury: a review of their role in cold intolerance.

    Science.gov (United States)

    Kambiz, S; Duraku, L S; Holstege, J C; Hovius, S E R; Ruigrok, T J H; Walbeehm, E T

    2014-05-01

    One of the sensory complications of traumatic peripheral nerve injury is thermal intolerance, which manifests in humans mainly as cold intolerance. It has a major effect on the quality of life, and adequate therapy is not yet available. In order to better understand the pathophysiological background of thermal intolerance, we focus first on the various transient receptor potential (TRP) channels that are involved in temperature sensation, including their presence in peripheral nerves and in keratinocytes. Second, the role of thermo-sensitive TRP channels in cold and heat intolerance is described showing three different mechanisms that contribute to thermal intolerance in the skin: (a) an increased expression of TRP channels on nerve fibres and on keratinocytes, (b) a lower activation threshold of TRP channels and (c) the sprouting of non-injured nerve fibres. Finally, the data that are available on the effects of TRP channel agonists and antagonists and their clinical use are discussed. In conclusion, TRP channels play a major role in temperature sensation and in cold and heat intolerance. Unfortunately, the available pharmaceutical agents that successfully target TRP channels and counteract thermal intolerance are still very limited. Yet, our focus should remain on TRP channels since it is difficult to imagine a reliable treatment for thermal intolerance that will not involve TRP channels. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  11. A conserved aspartic acid is important for agonist (VUAA1 and odorant/tuning receptor-dependent activation of the insect odorant co-receptor (Orco.

    Directory of Open Access Journals (Sweden)

    Brijesh N Kumar

    Full Text Available Insect odorant receptors function as heteromeric odorant-gated cation channels comprising a conventional odorant-sensitive tuning receptor, and a conserved co-receptor (Orco. An Orco agonist, VUAA1, is able to activate both heteromeric and homomeric Orco-containing channels. Very little is known about specific residues in Orco that contribute to cation permeability and gating. We investigated the importance of two conserved Asp residues, one in each of transmembrane domains 5 and 7, for channel function by mutagenesis. Drosophila melanogaster Orco and its substitution mutants were expressed in HEK cells and VUAA1-stimulated channel activity was determined by Ca(2+ influx and whole-cell patch clamp electrophysiology. Substitution of D466 in transmembrane 7 with amino acids other than glutamic acid resulted in a substantial reduction in channel activity. The D466E Orco substitution mutant was ~2 times more sensitive to VUAA1. The permeability of the D466E Orco mutant to cations was unchanged relative to wild-type Orco. When D466E Orco is co-expressed with a conventional tuning odorant receptor, the heteromeric complex also shows increased sensitivity to an odorant. Thus, the effect of the D466E mutation is not specific to VUAA1 agonism or dependent on homomeric Orco assembly. We suggest the gain-of-activation characteristic of the D466E mutant identifies an amino acid that is likely to be important for activation of both heteromeric and homomeric insect odorant receptor channels.

  12. Towards a sustainable future in Hudson Bay

    International Nuclear Information System (INIS)

    Okrainetz, G.

    1991-01-01

    To date, ca $40-50 billion has been invested in or committed to hydroelectric development on the rivers feeding Hudson Bay. In addition, billions more have been invested in land uses such as forestry and mining within the Hudson Bay drainage basin. However, there has never been a study of the possible impacts on Hudson Bay resulting from this activity. Neither has there been any federal environmental assessment on any of the economic developments that affect Hudson Bay. To fill this gap in knowledge, the Hudson Bay Program was established. The program will not conduct scientific field research but will rather scan the published literature and consult with leading experts in an effort to identify biophysical factors that are likely to be significantly affected by the cumulative influence of hydroelectric and other developments within and outside the region. An annotated bibliography on Hudson Bay has been completed and used to prepare a science overview paper, which will be circulated for comment, revised, and used as the basis for a workshop on cumulative effects in Hudson Bay. Papers will then be commissioned for a second workshop to be held in fall 1993. A unique feature of the program is its integration of traditional ecological knowledge among the Inuit and Cree communities around Hudson Bay with the scientific approach to cumulative impact assessment. One goal of the program is to help these communities bring forward their knowledge in such a way that it can be integrated into the cumulative effects assessment

  13. Bidirectional shifts of TRPM8 channel gating by temperature and chemical agents modulate the cold sensitivity of mammalian thermoreceptors.

    Science.gov (United States)

    Mälkiä, Annika; Madrid, Rodolfo; Meseguer, Victor; de la Peña, Elvira; Valero, María; Belmonte, Carlos; Viana, Félix

    2007-05-15

    TRPM8, a member of the melastatin subfamily of transient receptor potential (TRP) cation channels, is activated by voltage, low temperatures and cooling compounds. These properties and its restricted expression to small sensory neurons have made it the ion channel with the most advocated role in cold transduction. Recent work suggests that activation of TRPM8 by cold and menthol takes place through shifts in its voltage-activation curve, which cause the channel to open at physiological membrane potentials. By contrast, little is known about the actions of inhibitors on the function of TRPM8. We investigated the chemical and thermal modulation of TRPM8 in transfected HEK293 cells and in cold-sensitive primary sensory neurons. We show that cold-evoked TRPM8 responses are effectively suppressed by inhibitor compounds SKF96365, 4-(3-chloro-pyridin-2-yl)-piperazine-1-carboxylic acid (4-tert-butyl-phenyl)-amide (BCTC) and 1,10-phenanthroline. These antagonists exert their effect by shifting the voltage dependence of TRPM8 activation towards more positive potentials. An opposite shift towards more negative potentials is achieved by the agonist menthol. Functionally, the bidirectional shift in channel gating translates into a change in the apparent temperature threshold of TRPM8-expressing cells. Accordingly, in the presence of the antagonist compounds, the apparent response-threshold temperature of TRPM8 is displaced towards colder temperatures, whereas menthol sensitizes the response, shifting the threshold in the opposite direction. Co-application of agonists and antagonists produces predictable cancellation of these effects, suggesting the convergence on a common molecular process. The potential for half maximal activation of TRPM8 activation by cold was approximately 140 mV more negative in native channels compared to recombinant channels, with a much higher open probability at negative membrane potentials in the former. In functional terms, this difference translates

  14. The fine sand Abra alba community of the Bay of Morlaix twenty years after the Amoco Cadiz oil spill

    Energy Technology Data Exchange (ETDEWEB)

    Dauvin, J.-C. [CNRS-UPRES-A Elico, Wimereux (France). Station Marine de Wimereux

    1998-09-01

    The fine sand Abra alba community from the Bay of Morlaix (western English Channel) was strongly affected by the Amoco Cadiz oil spill of April 1978. The long term changes in the community (1977-1996) show that reconstitution of this community is slow (over 10 yr). A progressive recolonization by amphipod Ampelisca populations constituting the dominant species is observed. The results show that it is necessary to survey the affected communities for a long period of time (> 10 yr) after an event to identify the real ecological impact of an oil spill. The abiotic and biotic factor existing in the Bay of Morlaix are favorable to the establishment and the persistence of stable dominant Ampelisca populations in time. The 'climax' concept seems to be applicable to this type of stable environment. The soft-bottom Abra alba community of the Bay of Morlaix may only support a maximal carrying capacity ofapproximately 10-11 g m{sup -2} (mean annual biomass in decalcified dry weight). The deficit of production during 11 annual cycles may have affected the fish biomass feeding on this community. (author)

  15. Mesozooplankton production, grazing and respiration in the Bay of Bengal: Implications for net heterotrophy

    Science.gov (United States)

    Fernandes, Veronica; Ramaiah, N.

    2016-03-01

    Mesozooplankton samples were collected from the mixed layer along a central (along 88°E) and a western transect in the Bay of Bengal during four seasons covered between 2001 and 2006 in order to investigate spatio-temporal variability in their biomass. At these stations, grazing and respiration rates were measured from live zooplankton hauled in from the surface during December 2005. Akin to the mesozooplankton "paradox" in the central and eastern Arabian Sea, biomass in the mixed layer was more or less invariant in the central and western Bay of Bengal, even as the chl a showed marginal temporal variation. By empirical equation, the mesozooplankton production rate calculated to be 70-246 mg C m- 2 d- 1 is on par with the Arabian Sea. Contrary to the conventional belief, mesozooplankton grazing impact was up to 83% on primary production (PP). Low PP coupled with very high zooplankton production (70% of PP) along with abundant bacterial production (50% of the PP; Ramaiah et al., 2009) is likely to render the Bay of Bengal net heterotrophic, especially during the spring intermonsoon. Greater estimates of fecal pellet-carbon egestion by mesozooplankton compared to the average particulate organic carbon flux in sediment traps, implies that much of the matter is recycled by heterotrophic communities in the mixed layer facilitating nutrient regeneration for phytoplankton growth. We also calculated that over a third of the primary production is channelized for basin-wide zooplankton respiration that accounts for 52 Mt C annually. In the current scenario of global warming, if low (primary) productive warm pools like the Bay of Bengal continue to be net heterotrophic, negative implications like enhanced emission of CO2 to the atmosphere, increased particulate flux to the deeper waters and greater utilization of dissolved oxygen resulting in expansion of the existing oxygen minimum zone are imminent.

  16. Diel use of a saltwater creek by white-tip reef sharks Triaenodon obesus (Carcharhiniformes: Carcharhinidae in Academy Bay, Galapagos Islands

    Directory of Open Access Journals (Sweden)

    César Peñaherrera

    2012-06-01

    Full Text Available White-tip reef sharks are common inhabitants of the shallow waters surrounding the Galapagos Islands, where several known aggregation sites have become touristic attractions. With the aim to describe site fidelity and residency patterns of the white-tip reef sharks in a saltwater creek, we used the ultrasonic telemetry method. The study was undertaken in a saltwater channel South of Academy Bay, Santa Cruz Island, from May 2008-September 2009. A total of nine transmitters were attached to sharks and ultrasonic receivers were deployed at the inner and outside areas of the creek. From the total of fitted sharks, four lost their transmitters. The results obtained with the remaining sharks showed an elevated use of the inner area of the channel during the day, with more use of the external area during the night. However, none of the sharks were detected at the site every day, suggesting that they may have a number of preferred sites within their home range. More studies are needed to detail the home range and habitat use of this species, and to guide its protection level in the AcademyBay area. Rev. Biol. Trop. 60 (2: 735-743. Epub 2012 June 01.

  17. POTENTIAL HAZARDS OF SEDIMENT IN KENDARI BAY, SOUTHEAST SULAWESI

    Directory of Open Access Journals (Sweden)

    Nur Adi Kristanto

    2017-07-01

    Full Text Available Kendari bay is located in front of Kendari city. There are two harbors in the inner part of bay which very important to support economic activities such as shipping and passenger transportation. The result of coastal characteristic mapping and physical oceanography survey show various coastal morphology, vegetation, weathering processes, sedimentation, currents, and water depth and sea floor morphology. Kendari bay is an enclosed bay; the area is wide in the inner part and narrow in mouth of bay (outlet, the morphology look like a bottle’s neck. Numerous mouth rivers are concentrate around the bay. The rivers load material from land since erosion on land is intensive enough. There is indication that sediment supplies from land trough river mouth not equivalent with outlet capacity. Sediment load is trapped in the inner bay caused the outlet morphology. So high sediment rate play an important role in the process of shallow of water depth in Kendari bay. This condition make the Kendari bay is a prone area of sediment hazard due to height rate of sedimentary process. Therefore, to anticipate the hazards, precaution should be taken related to the Kendari bay as the center of activities in southeast of Sulawesi. The further survey is needed such as marine geotechnique and on land environmental to collect data, which can be used as database for development planning. Key words: Potential hazard, sediment, Kendari Bay Teluk

  18. Contamination with retinoic acid receptor agonists in two rivers in the Kinki region of Japan.

    Science.gov (United States)

    Inoue, Daisuke; Nakama, Koki; Sawada, Kazuko; Watanabe, Taro; Takagi, Mai; Sei, Kazunari; Yang, Min; Hirotsuji, Junji; Hu, Jianying; Nishikawa, Jun-ichi; Nakanishi, Tsuyoshi; Ike, Michihiko

    2010-04-01

    This study was conducted to investigate the agonistic activity against human retinoic acid receptor (RAR) alpha in the Lake Biwa-Yodo River and the Ina River in the Kinki region of Japan. To accomplish this, a yeast two-hybrid assay was used to elucidate the spatial and temporal variations and potential sources of RARalpha agonist contamination in the river basins. RARalpha agonistic activity was commonly detected in the surface water samples collected along two rivers at different periods, with maximum all-trans retinoic acid (atRA) equivalents of 47.6 ng-atRA/L and 23.5 ng-atRA/L being observed in Lake Biwa-Yodo River and Ina River, respectively. The results indicated that RARalpha agonists are always present and widespread in the rivers. Comparative investigation of RARalpha and estrogen receptor alpha agonistic activities at 20 stations along each river revealed that the spatial variation pattern of RARalpha agonist contamination was entirely different from that of the estrogenic compound contamination. This suggests that the effluent from municipal wastewater treatment plants, a primary source of estrogenic compounds, seemed not to be the cause of RARalpha agonist contamination in the rivers. Fractionation using high performance liquid chromatography (HPLC) directed by the bioassay found two bioactive fractions from river water samples, suggesting the presence of at least two RARalpha agonists in the rivers. Although a trial conducted to identify RARalpha agonists in the major bioactive fraction was not completed as part of this study, comparison of retention times in HPLC analysis and quantification with liquid chromatography-mass spectrometry analysis revealed that the major causative contaminants responsible for the RARalpha agonistic activity were not RAs (natural RAR ligands) and 4-oxo-RAs, while 4-oxo-RAs were identified as the major RAR agonists in sewage in Beijing, China. These findings suggest that there are unknown RARalpha agonists with high

  19. Targeted Delivery of LXR Agonist Using a Site-Specific Antibody-Drug Conjugate.

    Science.gov (United States)

    Lim, Reyna K V; Yu, Shan; Cheng, Bo; Li, Sijia; Kim, Nam-Jung; Cao, Yu; Chi, Victor; Kim, Ji Young; Chatterjee, Arnab K; Schultz, Peter G; Tremblay, Matthew S; Kazane, Stephanie A

    2015-11-18

    Liver X receptor (LXR) agonists have been explored as potential treatments for atherosclerosis and other diseases based on their ability to induce reverse cholesterol transport and suppress inflammation. However, this therapeutic potential has been hindered by on-target adverse effects in the liver mediated by excessive lipogenesis. Herein, we report a novel site-specific antibody-drug conjugate (ADC) that selectively delivers a LXR agonist to monocytes/macrophages while sparing hepatocytes. The unnatural amino acid para-acetylphenylalanine (pAcF) was site-specifically incorporated into anti-CD11a IgG, which binds the α-chain component of the lymphocyte function-associated antigen 1 (LFA-1) expressed on nearly all monocytes and macrophages. An aminooxy-modified LXR agonist was conjugated to anti-CD11a IgG through a stable, cathepsin B cleavable oxime linkage to afford a chemically defined ADC. The anti-CD11a IgG-LXR agonist ADC induced LXR activation specifically in human THP-1 monocyte/macrophage cells in vitro (EC50-27 nM), but had no significant effect in hepatocytes, indicating that payload delivery is CD11a-mediated. Moreover, the ADC exhibited higher-fold activation compared to a conventional synthetic LXR agonist T0901317 (Tularik) (3-fold). This novel ADC represents a fundamentally different strategy that uses tissue targeting to overcome the limitations of LXR agonists for potential use in treating atherosclerosis.

  20. MODELING THE 1958 LITUYA BAY MEGA-TSUNAMI, II

    Directory of Open Access Journals (Sweden)

    Charles L. Mader

    2002-01-01

    Full Text Available Lituya Bay, Alaska is a T-Shaped bay, 7 miles long and up to 2 miles wide. The two arms at the head of the bay, Gilbert and Crillon Inlets, are part of a trench along the Fairweather Fault. On July 8, 1958, an 7.5 Magnitude earthquake occurred along the Fairweather fault with an epicenter near Lituya Bay.A mega-tsunami wave was generated that washed out trees to a maximum altitude of 520 meters at the entrance of Gilbert Inlet. Much of the rest of the shoreline of the Bay was denuded by the tsunami from 30 to 200 meters altitude.In the previous study it was determined that if the 520 meter high run-up was 50 to 100 meters thick, the observed inundation in the rest of Lituya Bay could be numerically reproduced. It was also concluded that further studies would require full Navier-Stokes modeling similar to those required for asteroid generated tsunami waves.During the Summer of 2000, Hermann Fritz conducted experiments that reproduced the Lituya Bay 1958 event. The laboratory experiments indicated that the 1958 Lituya Bay 524 meter run-up on the spur ridge of Gilbert Inlet could be caused by a landslide impact.The Lituya Bay impact landslide generated tsunami was modeled with the full Navier- Stokes AMR Eulerian compressible hydrodynamic code called SAGE with includes the effect of gravity.

  1. Radionuclides in sediments from Port Phillip Bay, Australia

    International Nuclear Information System (INIS)

    Smith, J.D.; Tinker, R.A.; Towler, P.H.

    1998-01-01

    Full text: Sediment cores were collected from two sites in Port Phillip Bay, Australia, in 1994 and 1995. The concentration of 210 Pb and parameters including water content were measured. The sites chosen were near the centre of the bay where fine sediment accumulates, and towards the northern end of the bay closer to the mouth of the Yarra River. The mid-bay sediment had a high water content (about 1.8 g water per g dry sediment) and a supported 210 Pb activity of about 22 mBq per g of dry sediment. The sediments from further north in the bay were more consolidated, with a lower water content (about 0.6 g water per g dry sediment), and had a supported 210 Pb activity of about 6 mBq per g of dry sediment. Unsupported 210 Pb occurred to depths of about 10 cm in the mid-bay sediment and about 20 cm in sediment from further north in the bay. Models incorporating the water and 210 Pb contents of the sediments were used to calculate possible rates of sediment accumulation and mixing. The distribution of other radionuclides was used as an aid in understanding the sediment behaviour in Port Phillip Bay

  2. Allosteric enhancers, allosteric agonists and ago-allosteric modulators: where do they bind and how do they act?

    DEFF Research Database (Denmark)

    Schwartz, Thue W; Holst, Birgitte

    2007-01-01

    Many small-molecule agonists also display allosteric properties. Such ago-allosteric modulators act as co-agonists, providing additive efficacy--instead of partial antagonism--and they can affect--and often improve--the potency of the endogenous agonist. Surprisingly, the apparent binding sites...... different binding modes. In another, dimeric, receptor scenario, the endogenous agonist binds to one protomer while the ago-allosteric modulator binds to the other, 'allosteric' protomer. It is suggested that testing for ago-allosteric properties should be an integral part of the agonist drug discovery...... process because a compound that acts with--rather than against--the endogenous agonist could be an optimal agonist drug....

  3. The treatment of Parkinson's disease with dopamine agonists

    Directory of Open Access Journals (Sweden)

    Frank, Wilhelm

    2008-06-01

    Full Text Available Parkinson’s disease is a chronic degenerative organic disease with unknown causes. A disappearance of cells with melanin in the substantia nigra is considered as biological artefact of the disease, which causes a degenerative loss of neurons in the corpus striatum of mesencephalon. This structure produces also the transmitter substance dopamine. Due to this disappearance of cells dopamine is not produced in a sufficient quantity which is needed for movement of the body. The questions of this report are concerned the efficiency and safety of a treatment with dopamine agonists. Furthermore the cost-effectiveness is investigated as well as ethic questions. The goal is to give recommendation for the use of dopamine agonists to the German health system. A systematic literature search was done. The identified studies have different methodological quality and investigate different hypothesis and different outcome criteria. Therefore a qualitative method of information synthesis was chosen. Since the introduction of L-Dopa in the 1960´s it is considered as the most effective substance to reduce all the cardinal symptoms of Parkinson disease. This substance was improved in the course of time. Firstly some additional substances were given (decarbonxylase inhibitors, catechol-o-transferase inhibitors (COMT-inhibitors, monoaminoxydase-inhibitors (MAO-inhibitors and NMDA-antagonists (N-Methyl-d-aspartat-antagonists. In the practical therapy of Parkinson dopamine agonists play an important role, because they directly use the dopamine receptors. The monotherapy of Parkinson disease is basically possible and is used in early stages of the disease. Clinical practise has shown, that an add on therapy with dopamine agonists can led to a reduction of the dose of L-dopa and a reduction of following dyskinesia. The studies for effectiveness include studies for the initial therapy, monotherapy and add-on-therapy. Basically there is a good effectiveness of dopamine

  4. Hurricane Ike Deposits on the Bolivar Peninsula, Galveston Bay, Texas

    Science.gov (United States)

    Evans, Cynthia A.; Wilkinson, M. J.; Eppler, Dean

    2011-01-01

    In September 2008, Hurricane Ike made landfall on Galveston Bay, close to the NASA Johnson Space Center (JSC). The storm flooded much of the area with a storm surge ranging from 11 -20 feet. The Bolivar peninsula, the southeastern coast of Galveston Bay, experienced the brunt of the surge. Several agencies collected excellent imagery baselines before the storm and complementary data a few days afterward that helped define the impacts of the storm. In April of 2011, a team of scientists and astronauts from JSC conducted field mapping exercises along the Bolivar Peninsula, the section of the Galveston Bay coast most impacted by the storm. Astronauts routinely observe and document coastal changes from orbit aboard the International Space Station. As part of their basic Earth Science training, scientists at the Johnson Space Center take astronauts out for field mapping exercises so that they can better recognize and understand features and processes that they will later observe from the International Space Station. Using pre -storm baseline images of the Bolivar Peninsula near Rollover Pass and Gilchrist (NOAA/Google Earth Imagery and USGS aerial imagery and lidar data), the astronauts mapped current coastline positions at defined locations, and related their findings to specific coastal characteristics, including channel, jetties, and other developments. In addition to mapping, we dug trenches along both the Gulf of Mexico coast as well as the Galveston Bay coast of the Bolivar peninsula to determine the depth of the scouring from the storm on the Gulf side, and the amount of deposition of the storm surge deposits on the Bay side of the peninsula. The storm signature was easy to identify by sharp sediment transitions and, in the case of storm deposits, a layer of storm debris (roof shingles, PVC pipes, etc) and black, organic rich layers containing buried sea grasses in areas that were marshes before the storm. The amount of deposition was generally about 20 -25 cm

  5. Mutations in the voltage-sensing domain affect the alternative ion permeation pathway in the TRPM3 channel.

    Science.gov (United States)

    Held, Katharina; Gruss, Fabian; Aloi, Vincenzo Davide; Janssens, Annelies; Ulens, Chris; Voets, Thomas; Vriens, Joris

    2018-03-31

    Mutagenesis at positively charged amino acids (arginines and lysines) (R1-R4) in the voltage-sensor domain (transmembrane segment (S) 4) of voltage-gated Na + , K + and Ca 2+ channels can lead to an alternative ion permeation pathway distinct from the central pore. Recently, a non-canonical ion permeation pathway was described in TRPM3, a member of the transient receptor potential (TRP) superfamily. The non-canonical pore exists in the native TRPM3 channel and can be activated by co-stimulation of the endogenous agonist pregnenolone sulphate and the antifungal drug clotrimazole or by stimulation of the synthetic agonist CIM0216. Alignment of the voltage sensor of Shaker K + channels with the entire TRPM3 sequence revealed the highest degree of similarity in the putative S4 region of TRPM3, and suggested that only one single gating charge arginine (R2) in the putative S4 region is conserved. Mutagenesis studies in the voltage-sensing domain of TRPM3 revealed several residues in the voltage sensor (S4) as well as in S1 and S3 that are crucial for the occurrence of the non-canonical inward currents. In conclusion, this study provides evidence for the involvement of the voltage-sensing domain of TRPM3 in the formation of an alternative ion permeation pathway. Transient receptor potential (TRP) channels are cationic channels involved in a broad array of functions, including homeostasis, motility and sensory functions. TRP channel subunits consist of six transmembrane segments (S1-S6), and form tetrameric channels with a central pore formed by the region encompassing S5 and S6. Recently, evidence was provided for the existence of an alternative ion permeation pathway in TRPM3, which allows large inward currents upon hyperpolarization independently of the central pore. However, very little knowledge is available concerning the localization of this alternative pathway in the native TRPM3 channel protein. Guided by sequence homology with Shaker K + channels, in which

  6. Dopamine agonist activity of EMD 23,448

    International Nuclear Information System (INIS)

    Martin, G.E.; Pettibone, D.J.

    1985-01-01

    EMD 23,448 was examined in tests of dopaminergic function and was found to be an atypical dopamine (DA) agonist. EMD 23,448 was a weak or inactive DA agonist when examined in tests of normal postsynaptic DA receptor function: production of stereotypy in the rat (ED 50 greater than sign 5.0 mg/kg.i.p.); production of emesis in beagles (minimum effective dose = 81μg/kg i.v.); and, enhanced locomotor activity of the mouse (no excitation in doses 3 H]-apomorphine binding to rat striatal membranes (Ki, 205 nM). On the other hand, this indolyl-3-butylamine did activate supersensitive postsynaptic DA receptors. Specifically, it elicited contralateral turning in rats with a unilateral 6-hydroxydopamine lesion of the substantia nigra (ED 50 value = 0.9 mg/kg) and did elicit stereotypy in rats given chronic daily haloperidol treatments. EMD 23,448 also exerted pharmacological effects in tests designed to measure activation of dopamine autoreceptors. It inhibited the γ-butyrolactone-induced increase in striatal dopa levels (ED 50 = 1 mg/kg i.p.) and produced a dose-related fall in the locomotor activity of the mouse. The results are discussed and contrasted with data derived for apomorphine and the putatively selective autoreceptor agonist (+-)-3-PPP. (Author)

  7. Daya bay reactor neutrino experiment

    International Nuclear Information System (INIS)

    Cao Jun

    2010-01-01

    Daya Bay Reactor Neutrino Experiment is a large international collaboration experiment under construction. The experiment aims to precisely determine the neutrino mixing angle θ 13 by detecting the neutrinos produced by the Daya Bay Nuclear Power Plant. θ 13 is one of two unknown fundamental parameters in neutrino mixing. Its magnitude is a roadmap of the future neutrino physics, and very likely related to the puzzle of missing antimatter in our universe. The precise measurement has very important physics significance. The detectors of Daya Bay is under construction now. The full operation is expected in 2011. Three years' data taking will reach the designed the precision, to determine sin 2 2θ 13 to better than 0.01. Daya Bay neutrino detector is an underground large nuclear detector of low background, low energy, and high precision. In this paper, the layout of the experiment, the design and fabrication progress of the detectors, and some highlighted nuclear detecting techniques developed in the detector R and D are introduced. (author)

  8. Analysis of agonist dissociation constants as assessed by functional antagonism in guinea pig left atria

    International Nuclear Information System (INIS)

    Molenaar, P.; Malta, E.

    1986-01-01

    In electrically driven guinea pig left atria, positive inotropic responses to (-)-isoprenaline and the selective beta 1-adrenoceptor agonist RO363 were obtained in the absence and in the presence of the functional antagonists adenosine, carbachol, gallopamil, nifedipine, and Ro 03-7894. Each of the functional antagonists reduced the maximum response to both agonists and produced nonparallel rightward shifts in the cumulative concentration effect curves. For both agonists, dissociation constants (KA) were calculated using the equation described by Furchgott (1966) for irreversible antagonism. For RO363, which is a partial agonist with high agonist activity, the equations outlined for functional interaction by Mackay (1981) were also employed to calculate KA values. The KA values obtained by each method were compared with the dissociation constants (KD) for the two agonists determined from their ability to displace the radioligand (-)-[ 125 I]iodocyanopindolol from beta 1-adrenoceptors in guinea pig left atrial membrane preparations. The estimates of KA varied substantially from KD values. The KD values were taken as more accurate estimates of the true values for the dissociation constants because a high degree of correlation exists between pKD and pD2 values for a number of other beta-adrenoceptor agonists that behave as partial agonists and between pKD and pKB values for a number of beta-adrenoceptor antagonists. Thus, it appears that there are serious limitations in the current theory for using functional antagonism as a means of obtaining agonist dissociation constants

  9. Comparison of the effects of the K(+)-channel openers cromakalim and minoxidil sulphate on vascular smooth muscle.

    Science.gov (United States)

    Wickenden, A. D.; Grimwood, S.; Grant, T. L.; Todd, M. H.

    1991-01-01

    1 The actions of the potassium channel openers, cromakalim and minoxidil sulphate, were compared in a range of isolated blood vessel preparations. 2 Cromakalim and minoxidil sulphate inhibited spontaneous mechanical activity of the guinea-pig portal vein and relaxed the noradrenaline precontracted rat aorta with similar potency. In contrast, minoxidil sulphate was less potent than cromakalim in inhibiting spontaneous activity in the rat portal vein and was essentially inactive in the noradrenaline precontracted rat mesenteric artery and rabbit aorta. 3 Minoxidil sulphate did not antagonize the effects of cromakalim in the rabbit aorta indicating it was not acting as a partial 'agonist'. 4 Charybdotoxin, noxiustoxin and rubidium failed to discriminate between cromakalim and minoxidil sulphate indicating that the apparently selective effects of minoxidil sulphate were not mediated by either Ca(2+)-activated potassium channels, delayed rectifiers or rubidium impermeable potassium channels. 5 Glibenclamide antagonized the effects of cromakalim in an apparently competitive manner whereas the effects of minoxidil sulphate were antagonized in a non-competitive manner. The involvement of subtypes of ATP-sensitive potassium channels is discussed. PMID:1878752

  10. 226Ra and 228Ra in the mixing zones of the Pee Dee River-Winyah Bay, Yangtze River and Delaware Bay Estuaries

    International Nuclear Information System (INIS)

    Elsinger, R.J.; Moore, W.S.

    1984-01-01

    226 Ra and 228 Ra have non-conservative excess concentrations in the mixing zones of the Pee Dee River-Winyah Bay estuary, the Yangtze River estuary, and the Delaware Bay estuary. Laboratory experiments, using Pee Dee River sediment, indicate desorption of 226 Ra to increase with increasing salinities up to 20 per mille. In Winyah Bay desorption from river-borne sediments could contribute almost all of the increases for both isotopes. Desorption adds only a portion of the excess 228 Ra measured in the Yangtze River and adjacent Shelf waters and Delaware Bay. In the Yangtze River the mixing zone extends over a considerable portion of the Continental Shelf where 228 Ra is added to the water column by diffusion from bottom sediments, while 226 Ra concentrations decrease from dilution. Diffusion of 228 Ra from bottom sediments in Delaware Bay primarily occurs in the upper part of the bay ( 228 Ra of 0.33 dpm cm -2 year was determined for Delaware Bay. (author)

  11. The Neoglacial landscape and human history of Glacier Bay, Glacier Bay National Park and Preserve, southeast Alaska, USA

    Science.gov (United States)

    Connor, C.; Streveler, G.; Post, A.; Monteith, D.; Howell, W.

    2009-01-01

    The Neoglacial landscape of the Huna Tlingit homeland in Glacier Bay is recreated through new interpretations of the lower Bay's fjordal geomorphology, late Quaternary geology and its ethnographic landscape. Geological interpretation is enhanced by 38 radiocarbon dates compiled from published and unpublished sources, as well as 15 newly dated samples. Neoglacial changes in ice positions, outwash and lake extents are reconstructed for c. 5500?????"200 cal. yr ago, and portrayed as a set of three landscapes at 1600?????"1000, 500?????"300 and 300?????"200 cal. yr ago. This history reveals episodic ice advance towards the Bay mouth, transforming it from a fjordal seascape into a terrestrial environment dominated by glacier outwash sediments and ice-marginal lake features. This extensive outwash plain was building in lower Glacier Bay by at least 1600 cal. yr ago, and had filled the lower bay by 500 cal. yr ago. The geologic landscape evokes the human-described landscape found in the ethnographic literature. Neoglacial climate and landscape dynamism created difficult but endurable environmental conditions for the Huna Tlingit people living there. Choosing to cope with environmental hardship was perhaps preferable to the more severely deteriorating conditions outside of the Bay as well as conflicts with competing groups. The central portion of the outwash plain persisted until it was overridden by ice moving into Icy Strait between AD 1724?????"1794. This final ice advance was very abrupt after a prolonged still-stand, evicting the Huna Tlingit from their Glacier Bay homeland. ?? 2009 SAGE Publications.

  12. Organic Matter Remineralization Predominates Phosphorus Cycling in the Mid-Bay Sediments in the Chesapeake Bay

    Energy Technology Data Exchange (ETDEWEB)

    Sunendra, Joshi R.; Kukkadapu, Ravi K.; Burdige, David J.; Bowden, Mark E.; Sparks, Donald L.; Jaisi, Deb P.

    2015-05-19

    The Chesapeake Bay, the largest and most productive estuary in the US, suffers from varying degrees of water quality issues fueled by both point and non–point source nutrient sources. Restoration of the bay is complicated by the multitude of nutrient sources, their variable inputs and hydrological conditions, and complex interacting factors including climate forcing. These complexities not only restrict formulation of effective restoration plans but also open up debates on accountability issues with nutrient loading. A detailed understanding of sediment phosphorus (P) dynamics enables one to identify the exchange of dissolved constituents across the sediment- water interface and aid to better constrain mechanisms and processes controlling the coupling between the sediments and the overlying waters. Here we used phosphate oxygen isotope ratios (δ18Op) in concert with sediment chemistry, XRD, and Mössbauer spectroscopy on the sediment retrieved from an organic rich, sulfidic site in the meso-haline portion of the mid-bay to identify sources and pathway of sedimentary P cycling and to infer potential feedback effect on bottom water hypoxia and surface water eutrophication. Isotope data indicate that the regeneration of inorganic P from organic matter degradation (remineralization) is the predominant, if not sole, pathway for authigenic P precipitation in the mid-bay sediments. We interpret that the excess inorganic P generated by remineralization should have overwhelmed any bottom-water and/or pore-water P derived from other sources or biogeochemical processes and exceeded saturation with respect to authigenic P precipitation. It is the first research that identifies the predominance of remineralization pathway against remobilization (coupled Fe-P cycling) pathway in the Chesapeake Bay. Therefore, these results are expected to have significant implications for the current understanding of P cycling and benthic-pelagic coupling in the bay, particularly on the

  13. Regional Sediment Management Studies of Matagorda Ship Channel and Matagorda Bay System, Texas

    Science.gov (United States)

    2013-08-01

    undisturbed free water surface.” The USACE presently has no standardized method to measure the fluid mud to determine nautical depth. The Engineer Manual...structural member in the bottom of the hull and channel bottom) is used to account for parameters such as ship motion from waves, squat , safety...distance between the nautical bottom and undisturbed free water surface. To complete the definition of nautical bottom, the physical characteristic(s) on

  14. Low-dose add-back therapy during postoperative GnRH agonist treatment

    Directory of Open Access Journals (Sweden)

    Hsiao-Wen Tsai

    2016-02-01

    Conclusion: Low dose add-back therapy could effectively ameliorate hypoestrogenic side effects and simultaneously maintain the therapeutic response of GnRH agonist treatment. The treatment dropout was lower compared with a regular dose. Therefore, low dose add-back therapy can be considered a treatment choice during postoperative GnRH agonist treatment.

  15. Point mutation of a conserved aspartate, D69, in the muscarinic M2 receptor does not modify voltage-sensitive agonist potency.

    Science.gov (United States)

    Ågren, Richard; Sahlholm, Kristoffer; Nilsson, Johanna; Århem, Peter

    2018-01-29

    The muscarinic M 2 receptor (M 2 R) has been shown to display voltage-sensitive agonist binding, based on G protein-activated inward rectifier potassium channel (GIRK) opening and radioligand binding at different membrane voltages. A conserved aspartate in transmembrane segment (TM) II of M 2 R, D69, has been proposed as the voltage sensor. While a recent paper instead presented evidence of tyrosines in TMs III, VI, and VII acting as voltage sensors, these authors were not able to record GIRK channel activation by a D69N mutant M 2 R. In the present study, we succeeded in recording ACh-induced GIRK channel activation by this mutant at -80 and 0 mV. The acetylcholine EC 50 was about 2.5-fold higher at 0 mV, a potency shift very similar to that observed at wild-type M 2 R, indicating that voltage sensitivity persists at the D69N mutant. Thus, our present observations corroborate the notion that D69 is not responsible for voltage sensitivity of the M 2 R. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Algae Reefs in Shark Bay, Western Australia, Australia

    Science.gov (United States)

    1990-01-01

    Numerous algae reefs are seen in Shark Bay, Western Australia, Australia (26.0S, 113.5E) especially in the southern portions of the bay. The south end is more saline because tidal flow in and out of the bay is restricted by sediment deposited at the north and central end of the bay opposite the mouth of the Wooramel River. This extremely arid region produces little sediment runoff so that the waters are very clear, saline and rich in algae.

  17. Scaffold-based pan-agonist design for the PPARα, PPARβ and PPARγ receptors.

    Directory of Open Access Journals (Sweden)

    Li-Song Zhang

    Full Text Available As important members of nuclear receptor superfamily, Peroxisome proliferator-activated receptors (PPAR play essential roles in regulating cellular differentiation, development, metabolism, and tumorigenesis of higher organisms. The PPAR receptors have 3 identified subtypes: PPARα, PPARβ and PPARγ, all of which have been treated as attractive targets for developing drugs to treat type 2 diabetes. Due to the undesirable side-effects, many PPAR agonists including PPARα/γ and PPARβ/γ dual agonists are stopped by US FDA in the clinical trials. An alternative strategy is to design novel pan-agonist that can simultaneously activate PPARα, PPARβ and PPARγ. Under such an idea, in the current study we adopted the core hopping algorithm and glide docking procedure to generate 7 novel compounds based on a typical PPAR pan-agonist LY465608. It was observed by the docking procedures and molecular dynamics simulations that the compounds generated by the core hopping and glide docking not only possessed the similar functions as the original LY465608 compound to activate PPARα, PPARβ and PPARγ receptors, but also had more favorable conformation for binding to the PPAR receptors. The additional absorption, distribution, metabolism and excretion (ADME predictions showed that the 7 compounds (especially Cpd#1 hold high potential to be novel lead compounds for the PPAR pan-agonist. Our findings can provide a new strategy or useful insights for designing the effective pan-agonists against the type 2 diabetes.

  18. The good, the bad, and the ugly: agonistic behaviour in juvenile crocodilians.

    Directory of Open Access Journals (Sweden)

    Matthew L Brien

    Full Text Available We examined agonistic behaviour in seven species of hatchling and juvenile crocodilians held in small groups (N = 4 under similar laboratory conditions. Agonistic interactions occurred in all seven species, typically involved two individuals, were short in duration (5-15 seconds, and occurred between 1600-2200 h in open water. The nature and extent of agonistic interactions, the behaviours displayed, and the level of conspecific tolerance varied among species. Discrete postures, non-contact and contact movements are described. Three of these were species-specific: push downs by C. johnstoni; inflated tail sweeping by C. novaeguineae; and, side head striking combined with tail wagging by C. porosus. The two long-snouted species (C. johnstoni and G. gangeticus avoided contact involving the head and often raised the head up out of the way during agonistic interactions. Several behaviours not associated with aggression are also described, including snout rubbing, raising the head up high while at rest, and the use of vocalizations. The two most aggressive species (C. porosus, C. novaeguineae appeared to form dominance hierarchies, whereas the less aggressive species did not. Interspecific differences in agonistic behaviour may reflect evolutionary divergence associated with morphology, ecology, general life history and responses to interspecific conflict in areas where multiple species have co-existed. Understanding species-specific traits in agonistic behaviour and social tolerance has implications for the controlled raising of different species of hatchlings for conservation, management or production purposes.

  19. Structure and biological activity of endogenous and synthetic agonists of GPR119

    Science.gov (United States)

    Tyurenkov, I. N.; Ozerov, A. A.; Kurkin, D. V.; Logvinova, E. O.; Bakulin, D. A.; Volotova, E. V.; Borodin, D. D.

    2018-02-01

    A G-protein-coupled receptor, GPR119, is a promising pharmacological target for a new class of hypoglycaemic drugs with an original mechanism of action, namely, increase in the glucose-dependent incretin and insulin secretion. In 2005, the first ligands were found and in the subsequent years, a large number of GPR119 agonists were synthesized in laboratories in various countries; the safest and most promising agonists have entered phase I and II clinical trials as agents for the treatment of type 2 diabetes mellitus and obesity. The review describes the major endogenous GPR119 agonists and the main trends in the design and modification of synthetic structures for increasing the hypoglycaemic activity. The data on synthetic agonists are arranged according to the type of the central core of the molecules. The bibliography includes 104 references.

  20. Interleukin-24 as a target cytokine of environmental aryl hydrocarbon receptor agonist exposure in the lung

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Yueh-Hsia; Kuo, Yu-Chun; Tsai, Ming-Hsien; Ho, Chia-Chi; Tsai, Hui-Ti; Hsu, Chin-Yu; Chen, Yu-Cheng; Lin, Pinpin, E-mail: pplin@nhri.org.tw

    2017-06-01

    Exposure to environmental aryl hydrocarbon receptor (AhR) agonists, such as halogenated aromatic hydrocarbons and polycyclic aromatic hydrocarbons (PAHs), has great impacts on the development of various lung diseases. As emerging molecular targets for AhR agonists, cytokines may contribute to the inflammatory or immunotoxic effects of environmental AhR agonists. However, general cytokine expression may not specifically indicate environmental AhR agonist exposure. By comparing cytokine and chemokine expression profiles in human lung adenocarcinoma cell line CL5 treated with AhR agonists and the non-AhR agonist polychlorinated biphenyl (PCB) 39, we identified a target cytokine of environmental AhR agonist exposure of in the lungs. Thirteen cytokine and chemokine genes were altered in the AhR agonists-treated cells, but none were altered in the PCB39-treated cells. Interleukin (IL)-24 was the most highly induced gene among AhR-modulated cytokines. Cotreatment with AhR antagonist completely prevented IL-24 induction by AhR agonists in the CL5 cells. Knockdown AhR expression with short-hairpin RNA (shRNA) significantly reduced benzo[a]pyrene (BaP)-induced IL-24 mRNA levels. We further confirmed that gene transcription, but not mRNA stability, was involved in IL-24 upregulation by BaP. Particulate matter (PM) in the ambient air contains some PAHs and is reported to activate AhR. Oropharyngeal aspiration of PM significantly increased IL-24 levels in lung epithelia and in bronchoalveolar lavage fluid of mice 4 weeks after treatment. Thus, our data suggests that IL-24 is a pulmonary exposure target cytokine of environmental AhR agonists. - Graphical abstract: (A) Cytokine and chemokine gene expressions were examined in CL5 cells treated with AhR and non-AhR agonists. Thirteen cytokines and chemokines genes were altered in the AhR agonist-treated cells, but not in the non-AhR agonist-treated cells. IL-24 was the most highly induced gene among the AhR-modulated cytokines. (B

  1. Unique thermal record in False Bay

    CSIR Research Space (South Africa)

    Grundlingh, ML

    1993-10-01

    Full Text Available Over the past decade False Bay has assumed a prime position in terms of research in to large South African bays. This is manifested by investigations that cover flow conditions modelling, thermal structure, management, biology and nutrients, geology...

  2. Do Agonistic Motives Matter More Than Anger? Three Studies of Cardiovascular Risk in Adolescents

    Science.gov (United States)

    Ewart, Craig K.; Elder, Gavin J.; Smyth, Joshua M.; Sliwinski, Martin J.; Jorgensen, Randall S.

    2011-01-01

    Objective Three motivational profiles have been associated with recurring psychological stress in low-income youth and young adults: Striving to control others (agonistic striving), striving to control the self (transcendence striving), and not asserting control (dissipated striving); Agonistic Striving has been associated with elevated ambulatory blood pressure during daily activities. Three studies tested the hypotheses that: (1) Agonistic Striving is associated with poor anger regulation, and (2) Agonistic Striving and poor anger regulation interactively elevate blood pressure. Design Motivational profiles, anger regulation, and ambulatory blood pressure were assessed in a multiethnic sample of 264 urban youth. Main outcome measures (1) Anger regulation/recovery during laboratory challenge; (2) anger / blood pressure during daily activities (48 hours). Results and conclusion Replication of the profiles in distant cities showed they occur with similar frequency across differences of region, race, and gender. Analyses controlling for body size, race, and gender revealed that individuals with the Agonistic Striving profile had higher ambulatory pressure, especially during social encounters. They became more openly angry and aggressive when challenged, but did not exhibit difficulty regulating anger in the laboratory, nor did they feel more angry during monitoring. However, individuals with the Agonistic Striving profile who did display poor anger regulation in the lab had the highest blood pressure; deficient self-regulatory capability amplified the positive association between Agonistic Striving and cardiovascular risk in both genders and all ethnic groups. Although anger is thought to increase cardiovascular risk, present findings suggest that anger and elevated blood pressure are co-effects of agonistic struggles to control others. PMID:21534673

  3. NUMERICAL MODELS AS TOOLS TO UNDERSTAND THE DYNAMICS IN BAYS: CASE OF STUDY CHETUMAL BAY, QUINTANA ROO

    Directory of Open Access Journals (Sweden)

    David Avalos-Cueva

    2017-07-01

    Full Text Available In this study performed the simulation of currents generated by the wind on the Bay of Chetumal, Quintana Roo through the use of a stationary shallow-water model. A homogeneous climatic wind was used for the entire Bay, with a velocity of 3m·s-1 , and directions North, South, Northeast, Northwest, East, Southeast, Southwest and West. The results showed a rather complex dynamics in Chetumal Bay, in which important turns were observed in deep areas, with speeds reaching up to 13 cm·s-1 .

  4. Non-nucleotide Agonists Triggering P2X7 Receptor Activation and Pore Formation

    Directory of Open Access Journals (Sweden)

    Francesco Di Virgilio

    2018-02-01

    Full Text Available The P2X7 receptor (P2X7R is a ligand-gated plasma membrane ion channel belonging to the P2X receptor subfamily activated by extracellular nucleotides. General consensus holds that the physiological (and maybe the only agonist is ATP. However, scattered evidence generated over the last several years suggests that ATP might not be the only agonist, especially at inflammatory sites. Solid data show that NAD+ covalently modifies the P2X7R of mouse T lymphocytes, thus lowering the ATP threshold for activation. Other structurally unrelated agents have been reported to activate the P2X7R via a poorly understood mechanism of action: (a the antibiotic polymyxin B, possibly a positive allosteric P2X7R modulator, (b the bactericidal peptide LL-37, (c the amyloidogenic β peptide, and (d serum amyloid A. Some agents, such as Alu-RNA, have been suggested to activate the P2X7R acting on the intracellular N- or C-terminal domains. Mode of P2X7R activation by these non-nucleotide ligands is as yet unknown; however, these observations raise the intriguing question of how these different non-nucleotide ligands may co-operate with ATP at inflammatory or tumor sites. New information obtained from the cloning and characterization of the P2X7R from exotic mammalian species (e.g., giant panda and data from recent patch-clamp studies are strongly accelerating our understanding of P2X7R mode of operation, and may provide hints to the mechanism of activation of P2X7R by non-nucleotide ligands.

  5. 76 FR 31851 - Safety Zone; Put-in-Bay Fireworks, Fox's the Dock Pier; South Bass Island, Put-in-Bay, OH

    Science.gov (United States)

    2011-06-02

    ... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 165 [Docket No. USCG-2011-0417] RIN 1625-AA00 Safety Zone; Put-in-Bay Fireworks, Fox's the Dock Pier; South Bass Island, Put-in-Bay, OH AGENCY.... Add Sec. 165.T09-0417 as follows: Sec. 165.T09-0417 Safety Zone; Put-In-Bay Fireworks, Fox's the Dock...

  6. Characterization of a series of anabaseine-derived compounds reveals that the 3-(4)-dimethylaminocinnamylidine derivative is a selective agonist at neuronal nicotinic alpha 7/125I-alpha-bungarotoxin receptor subtypes.

    Science.gov (United States)

    de Fiebre, C M; Meyer, E M; Henry, J C; Muraskin, S I; Kem, W R; Papke, R L

    1995-01-01

    Investigation of the naturally occurring, nicotinic agonist anabaseine and novel derivatives has shown that these compounds have cytoprotective and memory-enhancing effects. The hypothesis that these arise at least in part through actions on brain nicotinic receptors was evaluated by examining the ability of these compounds to displace the binding of nicotinic ligands and to affect the function of the alpha 4 beta 2 and alpha 7 receptor subtypes expressed in Xenopus oocytes. The derivative 3-(4)-dimethylaminocinnamylidine anabaseine (DMAC) was found to be a selective alpha 7 receptor agonist; it was more potent than nicotine, acetylcholine, anabaseine, and other derivatives at activating the alpha 7 receptor subtype, while displaying little agonist activity at alpha 4 beta 2 and other receptor subtypes. Compared with anabaseine and the other derivatives, DMAC was the most potent at displacing 125I-alpha-bungarotoxin binding (putative alpha 7) and the least potent at displacing [3H]cytisine binding (putative alpha 4 beta 2) to brain membranes. Independently of agonist activities, all of the novel compounds displayed secondary inhibitory activity at both receptor subtypes. At the alpha 4 beta 2 receptor subtype, inhibition by the 3-(2,4)-dimethoxybenzylidene derivative was enhanced by coapplication of acetylcholine, suggesting a noncompetitive form of inhibition. Anabaseine and nicotine prolonged the time course of activation of alpha 4 beta 2 receptors, compared with acetylcholine, suggesting sequential channel-blocking activity. As selective agonists, anabaseine derivatives such as DMAC may be useful for elucidating the function of alpha 7 nicotinic receptors, including their potential role(s) in the cytoprotective and memory-enhancing effects of nicotinic agents.

  7. Reverse mode Na+/Ca2+ exchange mediated by STIM1 contributes to Ca2+ influx in airway smooth muscle following agonist stimulation

    Directory of Open Access Journals (Sweden)

    Fox Jane

    2010-12-01

    Full Text Available Abstract Background Agonist stimulation of airway smooth muscle (ASM results in IP3 mediated Ca2+ release from the sarcoplasmic reticulum followed by the activation of store operated and receptor operated non-selective cation channels. Activation of these non-selective channels also results in a Na+ influx. This localised increase in Na+ levels can potentially switch the Na+/Ca2+ exchanger into reverse mode and so result in a further influx of Ca2+. The aim of this study was to characterise the expression and physiological function of the Na+/Ca2+ exchanger in cultured human bronchial smooth muscle cells and determine its contribution to agonist induced Ca2+ influx into these cells. Methods The expression profile of NCX (which encodes the Na+/Ca2+ exchanger homologues in cultured human bronchial smooth muscle cells was determined by reverse transcriptase PCR. The functional activity of reverse mode NCX was investigated using a combination of whole cell patch clamp, intracellular Ca2+ measurements and porcine airway contractile analyses. KB-R7943 (an antagonist for reverse mode NCX and target specific siRNA were utilised as tools to inhibit NCX function. Results NCX1 protein was detected in cultured human bronchial smooth muscle cells (HBSMC cells and NCX1.3 was the only mRNA transcript variant detected. A combination of intracellular Na+ loading and addition of extracellular Ca2+ induced an outwardly rectifying current which was augmented following stimulation with histamine. This outwardly rectifying current was inhibited by 10 μM KB-R7943 (an antagonist of reverse mode NCX1 and was reduced in cells incubated with siRNA against NCX1. Interestingly, this outwardly rectifying current was also inhibited following knockdown of STIM1, suggesting for the first time a link between store operated cation entry and NCX1 activation. In addition, 10 μM KB-R7943 inhibited agonist induced changes in cytosolic Ca2+ and induced relaxation of porcine

  8. Chesapeake Bay under stress

    Science.gov (United States)

    According to extensive data obtained over its 13,000 km of shoreline, the Chesapeake Bay has been suffering a major, indeed unprecedented, reduction in submerged vegetation. Chesapeake Bay is alone in experiencing decline in submerged vegetation. Other estuary systems on the east coast of the United States are not so affected. These alarming results were obtained by the synthesis of the findings of numerous individual groups in addition to large consortium projects on the Chesapeake done over the past decade. R. J. Orth and R. A. Moore of the Virginia Institute of Marine Science pointed to the problem of the severe decline of submerged grasses on the Bay and along its tributaries. In a recent report, Orth and Moore note: “The decline, which began in the 1960's and accelerated in the 1970's, has affected all species in all areas. Many major river systems are now totally devoid of any rooted vegetation” (Science, 222, 51-53, 1983).

  9. Chondrichthyan occurrence and abundance trends in False Bay ...

    African Journals Online (AJOL)

    Commercial fishing in False Bay, South Africa, began in the 1600s. Today chondrichthyans are regularly taken in fisheries throughout the bay. Using a combination of catch, survey and life history data, the occurrence and long-term changes in populations of chondrichthyans in False Bay are described. Analyses of time ...

  10. Dopamine agonist activity of EMD 23,448

    Energy Technology Data Exchange (ETDEWEB)

    Martin, G E; Pettibone, D J [Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania (USA). Dept. of Pharmacology

    1985-01-01

    EMD 23,448 was examined in tests of dopaminergic function and was found to be an atypical dopamine (DA) agonist. EMD 23,448 was a weak or inactive DA agonist when examined in tests of normal postsynaptic DA receptor function: production of stereotypy in the rat (ED/sub 50/ greater than sign 5.0 mg/kg.i.p.); production of emesis in beagles (minimum effective dose = 81..mu..g/kg i.v.); and, enhanced locomotor activity of the mouse (no excitation in doses <=50 mg/i.p.). Moreover, EMD 23,448 was relatively weak in competing for (/sup 3/H)-apomorphine binding to rat striatal membranes (Ki, 205 nM). On the other hand, this indolyl-3-butylamine did activate supersensitive postsynaptic DA receptors. Specifically, it elicited contralateral turning in rats with a unilateral 6-hydroxydopamine lesion of the substantia nigra (ED/sub 50/ value = 0.9 mg/kg) and did elicit stereotypy in rats given chronic daily haloperidol treatments. EMD 23,448 also exerted pharmacological effects in tests designed to measure activation of dopamine autoreceptors. It inhibited the ..gamma..-butyrolactone-induced increase in striatal dopa levels (ED/sub 50/ = 1 mg/kg i.p.) and produced a dose-related fall in the locomotor activity of the mouse. The results are discussed and contrasted with data derived for apomorphine and the putatively selective autoreceptor agonist (+-)-3-PPP.

  11. Toxic phytoplankton in San Francisco Bay

    Science.gov (United States)

    Rodgers, Kristine M.; Garrison, David L.; Cloern, James E.

    1996-01-01

    The Regional Monitoring Program (RMP) was conceived and designed to document the changing distribution and effects of trace substances in San Francisco Bay, with focus on toxic contaminants that have become enriched by human inputs. However, coastal ecosystems like San Francisco Bay also have potential sources of naturally-produced toxic substances that can disrupt food webs and, under extreme circumstances, become threats to public health. The most prevalent source of natural toxins is from blooms of algal species that can synthesize metabolites that are toxic to invertebrates or vertebrates. Although San Francisco Bay is nutrient-rich, it has so far apparently been immune from the epidemic of harmful algal blooms in the world’s nutrient-enriched coastal waters. This absence of acute harmful blooms does not imply that San Francisco Bay has unique features that preclude toxic blooms. No sampling program has been implemented to document the occurrence of toxin-producing algae in San Francisco Bay, so it is difficult to judge the likelihood of such events in the future. This issue is directly relevant to the goals of RMP because harmful species of phytoplankton have the potential to disrupt ecosystem processes that support animal populations, cause severe illness or death in humans, and confound the outcomes of toxicity bioassays such as those included in the RMP. Our purpose here is to utilize existing data on the phytoplankton community of San Francisco Bay to provide a provisional statement about the occurrence, distribution, and potential threats of harmful algae in this Estuary.

  12. Heavy metals in superficial sediment of Algiers Bay

    International Nuclear Information System (INIS)

    Benamar, M.A.; Toumert, C.L.; Chaouch, L.; Bacha, L.; Tobbeche, S.

    1996-01-01

    Sediment samples were collected in 33 stations from the bay of Algiers for the potential sources of pollution. the analyses were made x-ray fluorescence (XRF) and atomic absorption spectrometry (AAS) the results give information about level of concentrations morphology of the bay (funnel form of bay). only Co,Mn,Fe, and Cd present a particular repartition (unrelated to the sedimentary facies). the level pollution bu heavy metals of the bottom sediments in algiers bay have been compared with those of Surkouk considered as a region with low anthropogenic activities

  13. Hierarchical mixtures of naive Bayes classifiers

    NARCIS (Netherlands)

    Wiering, M.A.

    2002-01-01

    Naive Bayes classifiers tend to perform very well on a large number of problem domains, although their representation power is quite limited compared to more sophisticated machine learning algorithms. In this pa- per we study combining multiple naive Bayes classifiers by using the hierar- chical

  14. Integrating science and resource management in Tampa Bay, Florida

    Science.gov (United States)

    Yates, Kimberly K.; Greening, Holly; Morrison, Gerold

    2011-01-01

    Tampa Bay is recognized internationally for its remarkable progress towards recovery since it was pronounced "dead" in the late 1970s. Due to significant efforts by local governments, industries and private citizens throughout the watershed, water clarity in Tampa Bay is now equal to what it was in 1950, when population in the watershed was less than one-quarter of what it is today. Seagrass extent has increased by more than 8,000 acres since the mid-1980s, and fish and wildlife populations are increasing. Central to this successful turn-around has been the Tampa Bay resource management community's long-term commitment to development and implementation of strong science-based management strategies. Research institutions and agencies, including Eckerd College, the Florida Wildlife Commission Fish and Wildlife Research Institute, Mote Marine Laboratory, National Oceanic and Atmospheric Administration, the Southwest Florida Water Management District, University of South Florida, U.S. Environmental Protection Agency, U.S. Geological Survey, local and State governments, and private companies contribute significantly to the scientific basis of our understanding of Tampa Bay's structure and ecological function. Resource management agencies, including the Tampa Bay Regional Planning Council's Agency on Bay Management, the Southwest Florida Water Management District's Surface Water Improvement and Management Program, and the Tampa Bay Estuary Program, depend upon this scientific basis to develop and implement regional adaptive management programs. The importance of integrating science with management has become fully recognized by scientists and managers throughout the region, State and Nation. Scientific studies conducted in Tampa Bay over the past 10–15 years are increasingly diverse and complex, and resource management programs reflect our increased knowledge of geology, hydrology and hydrodynamics, ecology and restoration techniques. However, a synthesis of this

  15. Dopamine agonists and risk: impulse control disorders in Parkinson's disease.

    Science.gov (United States)

    Voon, Valerie; Gao, Jennifer; Brezing, Christina; Symmonds, Mkael; Ekanayake, Vindhya; Fernandez, Hubert; Dolan, Raymond J; Hallett, Mark

    2011-05-01

    Impulse control disorders are common in Parkinson's disease, occurring in 13.6% of patients. Using a pharmacological manipulation and a novel risk taking task while performing functional magnetic resonance imaging, we investigated the relationship between dopamine agonists and risk taking in patients with Parkinson's disease with and without impulse control disorders. During functional magnetic resonance imaging, subjects chose between two choices of equal expected value: a 'Sure' choice and a 'Gamble' choice of moderate risk. To commence each trial, in the 'Gain' condition, individuals started at $0 and in the 'Loss' condition individuals started at -$50 below the 'Sure' amount. The difference between the maximum and minimum outcomes from each gamble (i.e. range) was used as an index of risk ('Gamble Risk'). Sixteen healthy volunteers were behaviourally tested. Fourteen impulse control disorder (problem gambling or compulsive shopping) and 14 matched Parkinson's disease controls were tested ON and OFF dopamine agonists. Patients with impulse control disorder made more risky choices in the 'Gain' relative to the 'Loss' condition along with decreased orbitofrontal cortex and anterior cingulate activity, with the opposite observed in Parkinson's disease controls. In patients with impulse control disorder, dopamine agonists were associated with enhanced sensitivity to risk along with decreased ventral striatal activity again with the opposite in Parkinson's disease controls. Patients with impulse control disorder appear to have a bias towards risky choices independent of the effect of loss aversion. Dopamine agonists enhance sensitivity to risk in patients with impulse control disorder possibly by impairing risk evaluation in the striatum. Our results provide a potential explanation of why dopamine agonists may lead to an unconscious bias towards risk in susceptible individuals.

  16. Whose Bay Street? Competing Narratives of Nassau's City Centre

    Directory of Open Access Journals (Sweden)

    Nona Patara Martin

    2009-05-01

    Full Text Available Bay Street has always been at the centre of commercial, cultural and political life in the Bahama Islands. It also acts as a gateway for millions of tourists who come to Nassau, the Bahamian capital, via cruise ships every year. Not surprisingly, Bahamians and non-Bahamians have widely divergent impressions of Bay Street. The need to accommodate the tourists who are critical to the Bahamian economy has meant that Bay Street, despite its deep social significance for Bahamians, has increasingly become a tourist space. With reference to the ‘sense of place’ and place attachment literature, this paper traces the transformation of Bay Street and attempts to tease out the most obvious tensions between the Bay Street that Bahamians experience and Bay Street as a port of call.

  17. Detection of glucocorticoid receptor agonists in effluents from sewage treatment plants in Japan.

    Science.gov (United States)

    Suzuki, Go; Sato, Kentaro; Isobe, Tomohiko; Takigami, Hidetaka; Brouwer, Abraham; Nakayama, Kei

    2015-09-15

    Glucocorticoids (GCs) are widely used as anti-inflammatory drugs. Our previous study demonstrated that several GCs such as cortisol and dexamethasone (Dex) were frequently detected in effluents collected from Japanese sewage treatment plants (STPs) in 2012. In this study, we used the GC-Responsive Chemical-Activated LUciferase gene eXpression (GR-CALUX) assay to elucidate GC receptor (GR) agonistic activities of ten pure synthetic GCs and selected STP effluents in Japan for assessment of the risks associated with the presence of GR agonists. The tested GCs demonstrated dose-dependent agonistic effects in the GR-CALUX assay and their EC50 values were calculated for estimation of relative potencies (REPs) compared to Dex. The GR agonistic potency was in the rank of: clobetasol propionate > clobetasone butyrate > betamethasone 17-valerate > difluprednate > betamethasone 17,21-dipropionate > Dex > betamethasone > 6α-methylprednisolone > prednisolone > cortisol. The GR agonistic activity in STP effluents as measured in Dex-equivalent (Dex-EQ) activities ranged from effluents in Japan. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Citral sensing by Transient [corrected] receptor potential channels in dorsal root ganglion neurons.

    Science.gov (United States)

    Stotz, Stephanie C; Vriens, Joris; Martyn, Derek; Clardy, Jon; Clapham, David E

    2008-05-07

    Transient receptor potential (TRP) ion channels mediate key aspects of taste, smell, pain, temperature sensation, and pheromone detection. To deepen our understanding of TRP channel physiology, we require more diverse pharmacological tools. Citral, a bioactive component of lemongrass, is commonly used as a taste enhancer, as an odorant in perfumes, and as an insect repellent. Here we report that citral activates TRP channels found in sensory neurons (TRPV1 and TRPV3, TRPM8, and TRPA1), and produces long-lasting inhibition of TRPV1-3 and TRPM8, while transiently blocking TRPV4 and TRPA1. Sustained citral inhibition is independent of internal calcium concentration, but is state-dependent, developing only after TRP channel opening. Citral's actions as a partial agonist are not due to cysteine modification of the channels nor are they a consequence of citral's stereoisoforms. The isolated aldehyde and alcohol cis and trans enantiomers (neral, nerol, geranial, and geraniol) each reproduce citral's actions. In juvenile rat dorsal root ganglion neurons, prolonged citral inhibition of native TRPV1 channels enabled the separation of TRPV2 and TRPV3 currents. We find that TRPV2 and TRPV3 channels are present in a high proportion of these neurons (94% respond to 2-aminoethyldiphenyl borate), consistent with our immunolabeling experiments and previous in situ hybridization studies. The TRPV1 activation requires residues in transmembrane segments two through four of the voltage-sensor domain, a region previously implicated in capsaicin activation of TRPV1 and analogous menthol activation of TRPM8. Citral's broad spectrum and prolonged sensory inhibition may prove more useful than capsaicin for allodynia, itch, or other types of pain involving superficial sensory nerves and skin.

  19. Platelet-activating factor receptor agonists mediate xeroderma pigmentosum A photosensitivity.

    Science.gov (United States)

    Yao, Yongxue; Harrison, Kathleen A; Al-Hassani, Mohammed; Murphy, Robert C; Rezania, Samin; Konger, Raymond L; Travers, Jeffrey B

    2012-03-16

    To date, oxidized glycerophosphocholines (Ox-GPCs) with platelet-activating factor (PAF) activity produced non-enzymatically have not been definitively demonstrated to mediate any known disease processes. Here we provide evidence that these Ox-GPCs play a pivotal role in the photosensitivity associated with the deficiency of the DNA repair protein xeroderma pigmentosum type A (XPA). It should be noted that XPA-deficient cells are known to have decreased antioxidant defenses. These studies demonstrate that treatment of human XPA-deficient fibroblasts with the pro-oxidative stressor ultraviolet B (UVB) radiation resulted in increased reactive oxygen species and PAF receptor (PAF-R) agonistic activity in comparison with gene-corrected cells. The UVB irradiation-generated PAF-R agonists were inhibited by antioxidants. UVB irradiation of XPA-deficient (Xpa-/-) mice also resulted in increased PAF-R agonistic activity and skin inflammation in comparison with control mice. The increased UVB irradiation-mediated skin inflammation and TNF-α production in Xpa-/- mice were blocked by systemic antioxidants and by PAF-R antagonists. Structural characterization of PAF-R-stimulating activity in UVB-irradiated XPA-deficient fibroblasts using mass spectrometry revealed increased levels of sn-2 short-chain Ox-GPCs along with native PAF. These studies support a critical role for PAF-R agonistic Ox-GPCs in the pathophysiology of XPA photosensitivity.

  20. Long-term outcome of patients with macroprolactinomas initially treated with dopamine agonists

    NARCIS (Netherlands)

    Kars, Marleen; Pereira, Alberto M.; Smit, Johannes W.; Romijn, Johannes A.

    2009-01-01

    Dopamine agonists are the first line therapy for the treatment of prolactinomas. The aim of this study was to assess the outcome of macroprolactinomas during long-term follow-up after initial treatment with dopamine agonists. Retrospective follow-up study. We included 72 consecutive patients (age

  1. The therapeutic potential of nicotinic acetylcholine receptor agonists for pain control.

    Science.gov (United States)

    Decker, M W; Meyer, M D; Sullivan, J P

    2001-10-01

    Due to the limitations of currently available analgesics, a number of novel alternatives are currently under investigation, including neuronal nicotinic acetylcholine receptor (nAChR) agonists. During the 1990s, the discovery of the antinociceptive properties of the potent nAChR agonist epibatidine in rodents sparked interest in the analgesic potential of this class of compounds. Although epibatidine also has several mechanism-related toxicities, the identification of considerable nAChR diversity suggested that the toxicities and therapeutic actions of the compound might be mediated by distinct receptor subtypes. Consistent with this view, a number of novel nAChR agonists with antinociceptive activity and improved safety profiles in preclinical models have now been identified, including A-85380, ABT-594, DBO-83, SIB-1663 and RJR-2403. Of these, ABT-594 is the most advanced and is currently in Phase II clinical evaluation. Nicotinically-mediated antinociception has been demonstrated in a variety of rodent pain models and is likely mediated by the activation of descending inhibitory pathways originating in the brainstem with the predominant high-affinity nicotine site in brain, the alpha4beta2 subtype, playing a critical role. Thus, preclinical findings suggest that nAChR agonists have the potential to be highly efficacious treatments in a variety of pain states. However, clinical proof-of-principle studies will be required to determine if nAChR agonists are active in pathological pain.

  2. Fecal indicator bacteria at Havana Bay

    International Nuclear Information System (INIS)

    Lopez Perez, Lisse; Gomez D'Angelo, Yamiris; Beltran Gonzalez, Jesus; Alvarez Valiente, Reinaldo

    2013-01-01

    Aims: Fecal indicator bacteria concentrations were evaluated in Havana Bay. Methods: Concentrations of traditional fecal indicator bacteria were calculated between April 2010 and February 2011, by MPN methods. Concentrations of thermo tolerant coliform (CTT), Escherichia coli, fecal streptococci (EF), intestinal enterococci (ENT) in seawater, and Clostridium perfringens in sediment surface, were determined. Results: CTT and E. coli levels were far above Cuban water quality standard for indirect contact with water, showing the negative influence of sewage and rivers on the bay. The EF and ENT were measured during sewage spills at the discharge site and they were suitable indicators of fecal contamination, but these indicators didn't show the same behavior in other selected sites. This result comes from its well-known inactivation by solar light in tropical zones and the presumable presence of humid acids in the waters of the bay. Conclusion: Fecal indicator bacteria and its statistical relationships reflect recent and chronic fecal contamination at the bay and near shores.

  3. Citral Sensing by TRANSient Receptor Potential Channels in Dorsal Root Ganglion Neurons

    Science.gov (United States)

    Stotz, Stephanie C.; Vriens, Joris; Martyn, Derek; Clardy, Jon; Clapham, David E.

    2008-01-01

    Transient receptor potential (TRP) ion channels mediate key aspects of taste, smell, pain, temperature sensation, and pheromone detection. To deepen our understanding of TRP channel physiology, we require more diverse pharmacological tools. Citral, a bioactive component of lemongrass, is commonly used as a taste enhancer, as an odorant in perfumes, and as an insect repellent. Here we report that citral activates TRP channels found in sensory neurons (TRPV1 and TRPV3, TRPM8, and TRPA1), and produces long-lasting inhibition of TRPV1–3 and TRPM8, while transiently blocking TRPV4 and TRPA1. Sustained citral inhibition is independent of internal calcium concentration, but is state-dependent, developing only after TRP channel opening. Citral's actions as a partial agonist are not due to cysteine modification of the channels nor are they a consequence of citral's stereoisoforms. The isolated aldehyde and alcohol cis and trans enantiomers (neral, nerol, geranial, and geraniol) each reproduce citral's actions. In juvenile rat dorsal root ganglion neurons, prolonged citral inhibition of native TRPV1 channels enabled the separation of TRPV2 and TRPV3 currents. We find that TRPV2 and TRPV3 channels are present in a high proportion of these neurons (94% respond to 2-aminoethyldiphenyl borate), consistent with our immunolabeling experiments and previous in situ hybridization studies. The TRPV1 activation requires residues in transmembrane segments two through four of the voltage-sensor domain, a region previously implicated in capsaicin activation of TRPV1 and analogous menthol activation of TRPM8. Citral's broad spectrum and prolonged sensory inhibition may prove more useful than capsaicin for allodynia, itch, or other types of pain involving superficial sensory nerves and skin. PMID:18461159

  4. Tidal and meteorological forcing of sediment transport in tributary mudflat channels.

    Science.gov (United States)

    Ralston, David K; Stacey, Mark T

    2007-06-01

    Field observations of flow and sediment transport in a tributary channel through intertidal mudflats indicate that suspended sediment was closely linked to advection and dispersion of a tidal salinity front. During calm weather when tidal forcing was dominant, high concentrations of suspended sediment advected up the mudflat channel in the narrow region between salty water from San Francisco Bay and much fresher runoff from the small local watershed. Salinity and suspended sediment dispersed at similar rates through each tidal inundation, such that during receding ebbs the sediment pulse had spread spatially and maximum concentrations had decreased. Net sediment transport was moderately onshore during the calm weather, as asymmetries in stratification due to tidal straining of the salinity front enhanced deposition, particularly during weaker neap tidal forcing. Sediment transport by tidal forcing was periodically altered by winter storms. During storms, strong winds from the south generated wind waves and temporarily increased suspended sediment concentrations. Increased discharge down the tributary channels due to precipitation had more lasting impact on sediment transport, supplying both buoyancy and fine sediment to the system. Net sediment transport depended on the balance between calm weather tidal forcing and perturbations by episodic storms. Net transport in the tributary channel was generally off-shore during storms and during calm weather spring tides, and on-shore during calm weather neap tides.

  5. Cryo-EM structures of the human endolysosomal TRPML3 channel in three distinct states.

    Science.gov (United States)

    Zhou, Xiaoyuan; Li, Minghui; Su, Deyuan; Jia, Qi; Li, Huan; Li, Xueming; Yang, Jian

    2017-12-01

    TRPML3 channels are mainly localized to endolysosomes and play a critical role in the endocytic pathway. Their dysfunction causes deafness and pigmentation defects in mice. TRPML3 activity is inhibited by low endolysosomal pH. Here we present cryo-electron microscopy (cryo-EM) structures of human TRPML3 in the closed, agonist-activated, and low-pH-inhibited states, with resolutions of 4.06, 3.62, and 4.65 Å, respectively. The agonist ML-SA1 lodges between S5 and S6 and opens an S6 gate. A polycystin-mucolipin domain (PMD) forms a luminal cap. S1 extends into this cap, forming a 'gating rod' that connects directly to a luminal pore loop, which undergoes dramatic conformational changes in response to low pH. S2 extends intracellularly and interacts with several intracellular regions to form a 'gating knob'. These unique structural features, combined with the results of electrophysiological studies, indicate a new mechanism by which luminal pH and other physiological modulators such as PIP 2 regulate TRPML3 by changing S1 and S2 conformations.

  6. Role of TRPV1 channels in ischemia/reperfusion-induced acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Lan Chen

    Full Text Available OBJECTIVES: Transient receptor potential vanilloid 1 (TRPV1 -positive sensory nerves are widely distributed in the kidney, suggesting that TRPV1-mediated action may participate in the regulation of renal function under pathophysiological conditions. Stimulation of TRPV1 channels protects against ischemia/reperfusion (I/R-induced acute kidney injury (AKI. However, it is unknown whether inhibition of these channels is detrimental in AKI or not. We tested the role of TRPV1 channels in I/R-induced AKI by modulating these channels with capsaicin (TRPV1 agonist, capsazepine (TRPV1 antagonist and using Trpv1-/- mice. METHODS AND RESULTS: Anesthetized C57BL/6 mice were subjected to 25 min of renal ischemia and 24 hrs of reperfusion. Mice were pretreated with capsaicin (0.3 mg/kg body weight or capsazepine (50 mg/kg body weight. Capsaicin ameliorated the outcome of AKI, as measured by serum creatinine levels, tubular damage,neutrophil gelatinase-associated lipocalin (NGAL abundance and Ly-6B.2 positive polymorphonuclear inflammatory cells in injured kidneys. Neither capsazepine nor deficiency of TRPV1 did deteriorate renal function or histology after AKI. Measurements of endovanilloids in kidney tissue indicate that 20-hydroxyeicosatetraeonic acid (20-HETE or epoxyeicosatrienoic acids (EETs are unlikely involved in the beneficial effects of capsaicin on I/R-induced AKI. CONCLUSIONS: Activation of TRPV1 channels ameliorates I/R-induced AKI, but inhibition of these channels does not affect the outcome of AKI. Our results may have clinical implications for long-term safety of renal denervation to treat resistant hypertension in man, with respect to the function of primary sensory nerves in the response of the kidney to ischemic stimuli.

  7. Oceanographic studies in Harrison Bay and the Colville River Delta, Alaska, to support the development of oil spill response strategies

    International Nuclear Information System (INIS)

    Owens, E.H.; Taylor, E.; Hale, B.

    2003-01-01

    The risk of an oil spill resulting from the development of the Alpine oil field is considered to be low. The field is located on the North Slope of Alaska adjacent to the Alaskan Beaufort Sea and reaches coastal waters from the distributary channels of the Colville River Delta. The physical environmental (hydrodynamic) conditions that would affect the transport and fate of spilled oil was investigated to further reduce the risk. During the open-water season of 2001 in Harrison Bay, near shore current meters were deployed and data on weather and surface currents was analyzed. Ocean current and wind measurements were examined to evaluate the relationship between meteorology and water levels during the open-water season. The objective was to gain a better understanding of the near shore hydrodynamic processes at play in Harrison Bay, in order to plan the most appropriate spill response strategies. The results obtained indicate that surface currents within the bay adjacent to the Colville Delta are variable. They respond to wind forces as well as other possible mechanisms like estuarine circulation. The surface currents reach maximum speeds of 0.26 metre per second. For the late July-September deployment, the calculated net surface drift was a 0.02 metre per second current to the east southeast. In both Harrison Bay and Colville Delta, prevailing southwest and northeast winds, respectively, induced water level changes of more than 0.5 metre above and below the average. 7 refs., 3 tabs., 7 figs

  8. Heme oxygenase-1 mediates BAY 11-7085 induced ferroptosis.

    Science.gov (United States)

    Chang, Ling-Chu; Chiang, Shih-Kai; Chen, Shuen-Ei; Yu, Yung-Luen; Chou, Ruey-Hwang; Chang, Wei-Chao

    2018-03-01

    Ferroptosis is a form of oxidative cell death and has become a chemotherapeutic target for cancer treatment. BAY 11-7085 (BAY), which is a well-known IκBα inhibitor, suppressed viability in cancer cells via induction of ferroptotic death in an NF-κB-independent manner. Reactive oxygen species scavenging, relief of lipid peroxidation, replenishment of glutathione and thiol-containing agents, as well as iron chelation, rescued BAY-induced cell death. BAY upregulated a variety of Nrf2 target genes related to redox regulation, particularly heme oxygenase-1 (HO-1). Studies with specific inhibitors and shRNA interventions suggested that the hierarchy of induction is Nrf2-SLC7A11-HO-1. SLC7A11 inhibition by erastin, sulfasalazine, or shRNA interference sensitizes BAY-induced cell death. Overexperession of SLC7A11 attenuated BAY-inhibited cell viability. The ferroptotic process induced by hHO-1 overexpression further indicated that HO-1 is a key mediator of BAY-induced ferroptosis that operates through cellular redox regulation and iron accumulation. BAY causes compartmentalization of HO-1 into the nucleus and mitochondrion, and followed mitochondrial dysfunctions, leading to lysosome targeting for mitophagy. In this study, we first discovered that BAY induced ferroptosis via Nrf2-SLC7A11-HO-1 pathway and HO-1 is a key mediator by responding to the cellular redox status. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Changing Salinity Patterns in Biscayne Bay, Florida

    Science.gov (United States)

    ,

    2004-01-01

    Biscayne Bay, Fla., is a 428-square-mile (1,109-square-kilometer) subtropical estuarine ecosystem that includes Biscayne National Park, the largest marine park in the U.S. national park system (fig. 1). The bay began forming between 5,000 and 3,000 years ago as sea level rose and southern Florida was flooded. Throughout most of its history, the pristine waters of the bay supported abundant and diverse fauna and flora, and the bay was a nursery for the adjacent coral-reef and marine ecosystems. In the 20th century, urbanization of the Miami-Dade County area profoundly affected the environment of the bay. Construction of powerplants, water-treatment plants, and solid-waste sites and large-scale development along the shoreline stressed the ecosystem. Biscayne National Monument was established in 1968 to ?preserve and protect for the education, inspiration, recreation and enjoyment of present and future generations a rare combination of terrestrial, marine, and amphibious life in a tropical setting of great natural beauty? (Public Law 90?606). The monument was enlarged in 1980 and designated a national park.

  10. A strong CO2 sink enhanced by eutrophication in a tropical coastal embayment (Guanabara Bay, Rio de Janeiro, Brazil)

    Science.gov (United States)

    Cotovicz, L. C., Jr.; Knoppers, B. A.; Brandini, N.; Costa Santos, S. J.; Abril, G.

    2015-10-01

    In contrast to its small surface area, the coastal zone plays a disproportionate role in the global carbon cycle. Carbon production, transformation, emission and burial rates at the land-ocean interface are significant at the global scale but still poorly known, especially in tropical regions. Surface water pCO2 and ancillary parameters were monitored during nine field campaigns between April 2013 and April 2014 in Guanabara Bay, a tropical eutrophic to hypertrophic semi-enclosed estuarine embayment surrounded by the city of Rio de Janeiro, southeast Brazil. Water pCO2 varied between 22 and 3715 ppmv in the bay, showing spatial, diurnal and seasonal trends that mirrored those of dissolved oxygen (DO) and chlorophyll a (Chl a). Marked pCO2 undersaturation was prevalent in the shallow, confined and thermally stratified waters of the upper bay, whereas pCO2 oversaturation was restricted to sites close to the small river mouths and small sewage channels, which covered only 10 % of the bay's area. Substantial daily variations in pCO2 (up to 395 ppmv between dawn and dusk) were also registered and could be integrated temporally and spatially for the establishment of net diurnal, seasonal and annual CO2 fluxes. In contrast to other estuaries worldwide, Guanabara Bay behaved as a net sink of atmospheric CO2, a property enhanced by the concomitant effects of strong radiation intensity, thermal stratification, and high availability of nutrients, which promotes phytoplankton development and net autotrophy. The calculated CO2 fluxes for Guanabara Bay ranged between -9.6 and -18.3 mol C m-2 yr-1, of the same order of magnitude as the organic carbon burial and organic carbon inputs from the watershed. The positive and high net community production (52.1 mol C m-2 yr-1) confirms the high carbon production in the bay. This autotrophic metabolism is apparently enhanced by eutrophication. Our results show that global CO2 budgetary assertions still lack information on tropical

  11. A large CO2 sink enhanced by eutrophication in a tropical coastal embayment (Guanabara Bay, Rio de Janeiro, Brazil)

    Science.gov (United States)

    Cotovicz, L. C., Jr.; Knoppers, B. A.; Brandini, N.; Costa Santos, S. J.; Abril, G.

    2015-03-01

    In contrast to its small surface area, the coastal zone plays a disproportionate role in the global carbon cycle. Carbon production, transformation, emission and burial rates at the land-ocean interface are still poorly known, especially in tropical regions. Surface water pCO2 and ancillary parameters were monitored during nine field campaigns between April 2013 and April 2014 in Guanabara Bay, a tropical eutrophic to hypertrophic semi-enclosed estuarine embayment surrounded by the city of Rio de Janeiro, SE-Brazil. Water pCO2 varied between 22 and 3715 ppmv in the Bay showing spatial, diurnal and seasonal trends that mirrored those of dissolved oxygen (DO) and Chlorophyll a (Chl a). Marked pCO2 undersaturation was prevalent in the shallow, confined and thermally stratified waters of the upper bay, whereas pCO2 oversaturation was restricted to sites close to the small river mouths and small sewage channels, which covered only 10% of the bay's area. Substantial daily variations in pCO2 (up to 395 ppmv between dawn and dusk) were also registered and could be integrated temporally and spatially for the establishment of net diurnal, seasonal and annual CO2 fluxes. In contrast to other estuaries worldwide, Guanabara Bay behaved as a net sink of atmospheric CO2, a property enhanced by the concomitant effects of strong radiation intensity, thermal stratification, and high availability of nutrients, which promotes phytoplankton development and net autotrophy. In the inner part of the bay, the calculated annual CO2 sink (-19.6 mol C m2 yr-1) matched the organic carbon burial in the sediments reported in the literature. The carbon sink and autotrophy of Guanabara Bay was driven by planktonic primary production promoted by eutrophication, and by its typology of marine embayment lacking the classical extended estuarine mixing zone, in contrast to river-dominated estuarine systems, which are generally net heterotrophic and CO2 emitters. Our results show that global CO2

  12. Study of recent changes in sedimentation regime inside Cienfuegos Cuban bay, using 210Pb and 137Cs as tracers

    International Nuclear Information System (INIS)

    Alonso Hernandez, C.M.; Diaz Asencio, M.; Munnoz Caravaca, A.; Delfanti, R.; Papucci, C.

    2001-01-01

    Cienfuegos Bay is a semi closed bay with a surface area of 90 km2 and an average depth of 14m, connected to the Caribbean Sea by a narrow channel of about 3 km long. The bay is divided in two well defined hydro graphic cells, due to the presence of a submerged ridge about 1m below the water surface. The northern cell receives most of the anthropic impact from the outfall of Cienfuegos city, industrial pole in the country, and the fluvial supply of Damuji and Salado rivers. The southern cell receives a lower anthropic impact from the Caonao and Arimao river inputs. Part of this southern cell is a natural protected park, which represents a niche of migratory birds and marine species in conservation status.The bay represents the most important natural resource in the province, due to fishing activities, maritime transport, tourism industry, and natural parks. In the last three decades, deleterious ecological signers in the area have been observed. Declining of biodiversity in the ecosystem, bethonic communities' movement, reduction of size and capture levels of commercial marine species, erosion of coastline, could be associated with changes of sedimentation regime in the bay. The distribution of 210Pb, 137Cs in sediments provide, insight into the sedimentation processes in the last 100 years. The main goal of the present study was the application of 210Pb, 137Cs dating techniques to estimate the recent sedimentation rates in the bay. Two sediment cores, (S and N) have been collected in 1999 using a gravity corer. The lengths of the cores were 0.93m. The cores were extruded and sliced immediately in 1.5cm intervals. Aliquots of 5g of each core sections were used for complementary analyses. The remaining parts were dried and placed in standard geometry for the determination of 210Pb and 137Cs activities, by g spectrometry with an hyper pure Germanium detector coupled with multichannel analyzer. Both core profiles show that important environmental changes have been

  13. Incident wave run-up into narrow sloping bays and estuaries

    Science.gov (United States)

    Sinan Özeren, M.; Postacioglu, Nazmi; Canlı, Umut

    2015-04-01

    The problem is investigated using Carrier Greenspan hodograph transformations.We perform a quasi-one-dimensional solution well into the bay, far enough of the mouth of the bay. The linearized boundary conditions at the mouth of the bay lead to an integral equation for 2-D geometry. A semi analytical optimization method has been developed to solve this integral equation. When the wavelength of the incident wave is much larger than the width of the bay, the conformalmapping of the bay and the semi infinite sea onto upper complex plane provides a solution of the integral equation in closed form. Particular emphasis is placed on the case where the frequency of the incident waves matches the real-part of the natural frequency of the oscillation of the bay. These natural frequencies are complex because of the radiation conditions imposed at the mouth of the bay. It is found that the complex part of these natural frequencies decreases with decreasing width of the bay. Thus the trapping of the waves in narrower bays leads to a strong resonance phenomenon when the frequency of the incident wave is equal to the real part of the natural frequency.

  14. Elemental analysis of Uranouchi bay seabed sludge using PIXE

    International Nuclear Information System (INIS)

    Kabir, M. Hasnat; Narusawa, Tadashi; Nishiyama, Fumitaka; Sumi, Katsuhiro

    2006-01-01

    Elemental analyses were carried out for the seabed sludge collected from Uranouchi bay (Kochi, Japan) using Particle Induced X-ray Emission (PIXE). Seabed-sludge contamination with heavy metals as well as toxic elements becomes one of the most serious environmental problems. The aim of the present study is to investigate the polluted areas in the bay by heavy and toxic elements. As a results of analyses of samples collected from eleven different places in the bay, seventeen elements including toxic ones were detected. The results suggest that the center region of the bay is seriously contaminated by heavy and toxic elements in comparison with the other areas in the bay. (author)

  15. Preclinical evaluation of SMM-189, a cannabinoid receptor 2-specific inverse agonist.

    Science.gov (United States)

    Presley, Chaela; Abidi, Ammaar; Suryawanshi, Satyendra; Mustafa, Suni; Meibohm, Bernd; Moore, Bob M

    2015-08-01

    Cannabinoid receptor 2 agonists and inverse agonists are emerging as new therapeutic options for a spectrum of autoimmune-related disease. Of particular interest, is the ability of CB2 ligands to regulate microglia function in neurodegenerative diseases and traumatic brain injury. We have previously reported the receptor affinity of 3',5'-dichloro-2,6-dihydroxy-biphenyl-4-yl)-phenyl-methanone (SMM-189) and the characterization of the beneficial effects of SMM-189 in the mouse model of mild traumatic brain injury. Herein, we report the further characterization of SMM-189 as a potent and selective CB2 inverse agonist, which acts as a noncompetitive inhibitor of CP 55,940. The ability of SMM-189 to regulate microglial activation, in terms of chemokine expression and cell morphology, has been determined. Finally, we have determined that SMM-189 possesses acceptable biopharmaceutical properties indicating that the triaryl class of CB2 inverse agonists are viable compounds for continued preclinical development for the treatment of neurodegenerative disorders and traumatic brain injury.

  16. South Bay Salt Pond Mercury Studies Project

    Science.gov (United States)

    Information about the SFBWQP South Bay Salt Pond Mercury Studies Project, part of an EPA competitive grant program to improve SF Bay water quality focused on restoring impaired waters and enhancing aquatic resources.

  17. Interactions of dopaminergic agonists and antagonists with dopaminergic D3 binding sites in rat striatum. Evidence that [3H]dopamine can label a high affinity agonist-binding state of the D1 dopamine receptor

    International Nuclear Information System (INIS)

    Leff, S.E.; Creese, I.

    1985-01-01

    The interactions of dopaminergic agonists and antagonists with 3 H-agonist labeled D3 dopaminergic binding sites of rat striatum have been characterized by radioligand-binding techniques. When the binding of [ 3 H]dopamine and [ 3 H]apomorphine to D2 dopamine receptors is blocked by the inclusion of D2 selective concentrations of unlabeled spiroperidol or domperidone, these ligands appear to label selectively the previously termed D3 binding site. Antagonist/[ 3 H]dopamine competition curves are of uniformly steep slope (nH . 1.0), suggesting the presence of a single D3 binding site. The relative potencies of antagonists to inhibit D3 specific [ 3 H]dopamine binding are significantly correlated with their potencies to block D1 dopamine receptors as measured by the inhibition of both dopamine-stimulated adenylate cyclase and [ 3 H]flupentixol-binding activities. The affinities of agonists to inhibit D3 specific [ 3 H]dopamine binding are also correlated with estimates of these agonists affinities for the high affinity binding component of agonist/[ 3 H]flupentixol competition curves. Both D3 specific [ 3 H] dopamine binding and the high affinity agonist-binding component of dopamine/[ 3 H]flupentixol competition curves show a similar sensitivity to guanine nucleotides. Taken together, these data strongly suggest that the D3 binding site is related to a high affinity agonist-binding state of the D1 dopamine receptor

  18. In silico discovery of novel Retinoic Acid Receptor agonist structures

    Directory of Open Access Journals (Sweden)

    Samuels Herbert H

    2001-06-01

    Full Text Available Abstract Background Several Retinoic Acid Receptors (RAR agonists have therapeutic activity against a variety of cancer types; however, unacceptable toxicity profiles have hindered the development of drugs. RAR agonists presenting novel structural and chemical features could therefore open new avenues for the discovery of leads against breast, lung and prostate cancer or leukemia. Results We have analysed the induced fit of the active site residues upon binding of a known ligand. The derived binding site models were used to dock over 150,000 molecules in silico (or virtually to the structure of the receptor with the Internal Coordinates Mechanics (ICM program. Thirty ligand candidates were tested in vitro. Conclusions Two novel agonists resulting from the predicted receptor model were active at 50 nM. One of them displays novel structural features which may translate into the development of new ligands for cancer therapy.

  19. The convulsive and electroencephalographic changes produced by nonpeptidic delta-opioid agonists in rats: comparison with pentylenetetrazol.

    Science.gov (United States)

    Jutkiewicz, Emily M; Baladi, Michelle G; Folk, John E; Rice, Kenner C; Woods, James H

    2006-06-01

    delta-Opioid agonists produce convulsions and antidepressant-like effects in rats. It has been suggested that the antidepressant-like effects are produced through a convulsant mechanism of action either through overt convulsions or nonconvulsive seizures. This study evaluated the convulsive and seizurogenic effects of nonpeptidic delta-opioid agonists at doses that previously were reported to produce antidepressant-like effects. In addition, delta-opioid agonist-induced electroencephalographic (EEG) and behavioral changes were compared with those produced by the chemical convulsant pentylenetetrazol (PTZ). For these studies, EEG changes were recorded using a telemetry system before and after injections of the delta-opioid agonists [(+)-4-[(alphaR)-alpha-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-methoxyphenyl)methyl]-N,N-diethylbenz (SNC80) and [(+)-4-[alpha(R)-alpha-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-hydroxyphenyl)methyl]-N,N-diethylbenzamide [(+)-BW373U86]. Acute administration of nonpeptidic delta-opioid agonists produced bilateral ictal and paroxysmal spike and/or sharp wave discharges. delta-Opioid agonists produced brief changes in EEG recordings, and tolerance rapidly developed to these effects; however, PTZ produced longer-lasting EEG changes that were exacerbated after repeated administration. Studies with antiepileptic drugs demonstrated that compounds used to treat absence epilepsy blocked the convulsive effects of nonpeptidic delta-opioid agonists. Overall, these data suggest that delta-opioid agonist-induced EEG changes are not required for the antidepressant-like effects of these compounds and that neural circuitry involved in absence epilepsy may be related to delta-opioid agonist-induced convulsions. In terms of therapeutic development, these data suggest that it may be possible to develop delta-opioid agonists devoid of convulsive properties.

  20. DEVELOP Chesapeake Bay Watershed Hydrology - UAV Sensor Web

    Science.gov (United States)

    Holley, S. D.; Baruah, A.

    2008-12-01

    The Chesapeake Bay is the largest estuary in the United States, with a watershed extending through six states and the nation's capital. Urbanization and agriculture practices have led to an excess runoff of nutrients and sediment into the bay. Nutrients and sediment loading stimulate the growth of algal blooms associated with various problems including localized dissolved oxygen deficiencies, toxic algal blooms and death of marine life. The Chesapeake Bay Program, among other stakeholder organizations, contributes greatly to the restoration efforts of the Chesapeake Bay. These stakeholders contribute in many ways such as monitoring the water quality, leading clean-up projects, and actively restoring native habitats. The first stage of the DEVELOP Chesapeake Bay Coastal Management project, relating to water quality, contributed to the restoration efforts by introducing NASA satellite-based water quality data products to the stakeholders as a complement to their current monitoring methods. The second stage, to be initiated in the fall 2008 internship term, will focus on the impacts of land cover variability within the Chesapeake Bay Watershed. Multiple student led discussions with members of the Land Cover team at the Chesapeake Bay Program Office in the DEVELOP GSFC 2008 summer term uncovered the need for remote sensing data for hydrological mapping in the watershed. The Chesapeake Bay Program expressed in repeated discussions on Land Cover mapping that significant portions of upper river areas, streams, and the land directly interfacing those waters are not accurately depicted in the watershed model. Without such hydrological mapping correlated with land cover data the model will not be useful in depicting source areas of nutrient loading which has an ecological and economic impact in and around the Chesapeake Bay. The fall 2008 DEVELOP team will examine the use of UAV flown sensors in connection with in-situ and Earth Observation satellite data. To maximize the

  1. PPAR Agonists and Metabolic Syndrome: An Established Role?

    Directory of Open Access Journals (Sweden)

    Margherita Botta

    2018-04-01

    Full Text Available Therapeutic approaches to metabolic syndrome (MetS are numerous and may target lipoproteins, blood pressure or anthropometric indices. Peroxisome proliferator-activated receptors (PPARs are involved in the metabolic regulation of lipid and lipoprotein levels, i.e., triglycerides (TGs, blood glucose, and abdominal adiposity. PPARs may be classified into the α, β/δ and γ subtypes. The PPAR-α agonists, mainly fibrates (including newer molecules such as pemafibrate and omega-3 fatty acids, are powerful TG-lowering agents. They mainly affect TG catabolism and, particularly with fibrates, raise the levels of high-density lipoprotein cholesterol (HDL-C. PPAR-γ agonists, mainly glitazones, show a smaller activity on TGs but are powerful glucose-lowering agents. Newer PPAR-α/δ agonists, e.g., elafibranor, have been designed to achieve single drugs with TG-lowering and HDL-C-raising effects, in addition to the insulin-sensitizing and antihyperglycemic effects of glitazones. They also hold promise for the treatment of non-alcoholic fatty liver disease (NAFLD which is closely associated with the MetS. The PPAR system thus offers an important hope in the management of atherogenic dyslipidemias, although concerns regarding potential adverse events such as the rise of plasma creatinine, gallstone formation, drug–drug interactions (i.e., gemfibrozil and myopathy should also be acknowledged.

  2. Suppression of atherosclerosis by synthetic REV-ERB agonist

    Energy Technology Data Exchange (ETDEWEB)

    Sitaula, Sadichha [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Billon, Cyrielle [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States); Kamenecka, Theodore M.; Solt, Laura A. [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Burris, Thomas P., E-mail: burristp@slu.edu [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States)

    2015-05-08

    The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice. Atherosclerotic plaque size was significantly reduced (p < 0.05) in mice administered SR9009 (100 mg/kg) for seven weeks compared to control mice (n = 10 per group). SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to proinflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Our results suggest that pharmacological targeting of REV-ERBs may be a viable therapeutic option for treatment of atherosclerosis. - Highlights: • Synthetic REV-ERB agonist treatment reduced atherosclerosis in a mouse model. • Pharmacological activation of REV-ERB decreased M1 macrophage polarization. • Pharmacological activation of REV-ERB increased M2 macrophage polarization.

  3. Identification of adiponectin receptor agonist utilizing a fluorescence polarization based high throughput assay.

    Directory of Open Access Journals (Sweden)

    Yiyi Sun

    Full Text Available Adiponectin, the adipose-derived hormone, plays an important role in the suppression of metabolic disorders that can result in type 2 diabetes, obesity, and atherosclerosis. It has been shown that up-regulation of adiponectin or adiponectin receptor has a number of therapeutic benefits. Given that it is hard to convert the full size adiponectin protein into a viable drug, adiponectin receptor agonists could be designed or identified using high-throughput screening. Here, we report on the development of a two-step screening process to identify adiponectin agonists. First step, we developed a high throughput screening assay based on fluorescence polarization to identify adiponectin ligands. The fluorescence polarization assay reported here could be adapted to screening against larger small molecular compound libraries. A natural product library containing 10,000 compounds was screened and 9 hits were selected for validation. These compounds have been taken for the second-step in vitro tests to confirm their agonistic activity. The most active adiponectin receptor 1 agonists are matairesinol, arctiin, (--arctigenin and gramine. The most active adiponectin receptor 2 agonists are parthenolide, taxifoliol, deoxyschizandrin, and syringin. These compounds may be useful drug candidates for hypoadiponectin related diseases.

  4. Humboldt Bay, California Benthic Habitats 2009 Geoform

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Humboldt Bay is the largest estuary in California north of San Francisco Bay and represents a significant resource for the north coast region. Beginning in 2007 the...

  5. Humboldt Bay, California Benthic Habitats 2009 Substrate

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Humboldt Bay is the largest estuary in California north of San Francisco Bay and represents a significant resource for the north coast region. Beginning in 2007 the...

  6. Humboldt Bay Benthic Habitats 2009 Aquatic Setting

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Humboldt Bay is the largest estuary in California north of San Francisco Bay and represents a significant resource for the north coast region. Beginning in 2007 the...

  7. Humboldt Bay, California Benthic Habitats 2009 Geodatabase

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Humboldt Bay is the largest estuary in California north of San Francisco Bay and represents a significant resource for the north coast region. Beginning in 2007 the...

  8. Beta-Estradiol Regulates Voltage-Gated Calcium Channels and Estrogen Receptors in Telocytes from Human Myometrium

    Directory of Open Access Journals (Sweden)

    Adela Banciu

    2018-05-01

    Full Text Available Voltage-gated calcium channels and estrogen receptors are essential players in uterine physiology, and their association with different calcium signaling pathways contributes to healthy and pathological conditions of the uterine myometrium. Among the properties of the various cell subtypes present in human uterine myometrium, there is increasing evidence that calcium oscillations in telocytes (TCs contribute to contractile activity and pregnancy. Our study aimed to evaluate the effects of beta-estradiol on voltage-gated calcium channels and estrogen receptors in TCs from human uterine myometrium and to understand their role in pregnancy. For this purpose, we employed patch-clamp recordings, ratiometric Fura-2-based calcium imaging analysis, and qRT-PCR techniques for the analysis of cultured human myometrial TCs derived from pregnant and non-pregnant uterine samples. In human myometrial TCs from both non-pregnant and pregnant uterus, we evidenced by qRT-PCR the presence of genes encoding for voltage-gated calcium channels (Cav3.1, Ca3.2, Cav3.3, Cav2.1, estrogen receptors (ESR1, ESR2, GPR30, and nuclear receptor coactivator 3 (NCOA3. Pregnancy significantly upregulated Cav3.1 and downregulated Cav3.2, Cav3.3, ESR1, ESR2, and NCOA3, compared to the non-pregnant condition. Beta-estradiol treatment (24 h, 10, 100, 1000 nM downregulated Cav3.2, Cav3.3, Cav1.2, ESR1, ESR2, GRP30, and NCOA3 in TCs from human pregnant uterine myometrium. We also confirmed the functional expression of voltage-gated calcium channels by patch-clamp recordings and calcium imaging analysis of TCs from pregnant human myometrium by perfusing with BAY K8644, which induced calcium influx through these channels. Additionally, we demonstrated that beta-estradiol (1000 nM antagonized the effect of BAY K8644 (2.5 or 5 µM in the same preparations. In conclusion, we evidenced the presence of voltage-gated calcium channels and estrogen receptors in TCs from non-pregnant and pregnant

  9. Beta-Estradiol Regulates Voltage-Gated Calcium Channels and Estrogen Receptors in Telocytes from Human Myometrium.

    Science.gov (United States)

    Banciu, Adela; Banciu, Daniel Dumitru; Mustaciosu, Cosmin Catalin; Radu, Mihai; Cretoiu, Dragos; Xiao, Junjie; Cretoiu, Sanda Maria; Suciu, Nicolae; Radu, Beatrice Mihaela

    2018-05-09

    Voltage-gated calcium channels and estrogen receptors are essential players in uterine physiology, and their association with different calcium signaling pathways contributes to healthy and pathological conditions of the uterine myometrium. Among the properties of the various cell subtypes present in human uterine myometrium, there is increasing evidence that calcium oscillations in telocytes (TCs) contribute to contractile activity and pregnancy. Our study aimed to evaluate the effects of beta-estradiol on voltage-gated calcium channels and estrogen receptors in TCs from human uterine myometrium and to understand their role in pregnancy. For this purpose, we employed patch-clamp recordings, ratiometric Fura-2-based calcium imaging analysis, and qRT-PCR techniques for the analysis of cultured human myometrial TCs derived from pregnant and non-pregnant uterine samples. In human myometrial TCs from both non-pregnant and pregnant uterus, we evidenced by qRT-PCR the presence of genes encoding for voltage-gated calcium channels (Cav3.1, Ca3.2, Cav3.3, Cav2.1), estrogen receptors (ESR1, ESR2, GPR30), and nuclear receptor coactivator 3 (NCOA3). Pregnancy significantly upregulated Cav3.1 and downregulated Cav3.2, Cav3.3, ESR1, ESR2, and NCOA3, compared to the non-pregnant condition. Beta-estradiol treatment (24 h, 10, 100, 1000 nM) downregulated Cav3.2, Cav3.3, Cav1.2, ESR1, ESR2, GRP30, and NCOA3 in TCs from human pregnant uterine myometrium. We also confirmed the functional expression of voltage-gated calcium channels by patch-clamp recordings and calcium imaging analysis of TCs from pregnant human myometrium by perfusing with BAY K8644, which induced calcium influx through these channels. Additionally, we demonstrated that beta-estradiol (1000 nM) antagonized the effect of BAY K8644 (2.5 or 5 µM) in the same preparations. In conclusion, we evidenced the presence of voltage-gated calcium channels and estrogen receptors in TCs from non-pregnant and pregnant human uterine

  10. Contaminant transport in Massachusetts Bay

    Science.gov (United States)

    Butman, Bradford

    Construction of a new treatment plant and outfall to clean up Boston Harbor is currently one of the world's largest public works projects, costing about $4 billion. There is concern about the long-term impact of contaminants on Massachusetts Bay and adjacent Gulf of Maine because these areas are used extensively for transportation, recreation, fishing, and tourism, as well as waste disposal. Public concern also focuses on Stellwagen Bank, located on the eastern side of Massachusetts Bay, which is an important habitat for endangered whales. Contaminants reach Massachusetts Bay not only from Boston Harbor, but from other coastal communities on the Gulf of Maine, as well as from the atmosphere. Knowledge of the pathways, mechanisms, and rates at which pollutants are transported throughout these coastal environments is needed to address a wide range of management questions.

  11. Bayes linear statistics, theory & methods

    CERN Document Server

    Goldstein, Michael

    2007-01-01

    Bayesian methods combine information available from data with any prior information available from expert knowledge. The Bayes linear approach follows this path, offering a quantitative structure for expressing beliefs, and systematic methods for adjusting these beliefs, given observational data. The methodology differs from the full Bayesian methodology in that it establishes simpler approaches to belief specification and analysis based around expectation judgements. Bayes Linear Statistics presents an authoritative account of this approach, explaining the foundations, theory, methodology, and practicalities of this important field. The text provides a thorough coverage of Bayes linear analysis, from the development of the basic language to the collection of algebraic results needed for efficient implementation, with detailed practical examples. The book covers:The importance of partial prior specifications for complex problems where it is difficult to supply a meaningful full prior probability specification...

  12. Agonist-induced desensitization of adenylyl cyclase in Y1 adrenocortical tumor cells

    International Nuclear Information System (INIS)

    Olson, M.F.; Tsao, J.; Pon, D.J.; Schimmer, B.P.

    1991-01-01

    Y1 adrenocortical tumor cells (Y1DS) and Y1 mutants resistant to ACTH-induced desensitization of adenylyl cyclase (Y1DR) were transfected with a gene encoding the mouse beta 2-adrenergic receptor (beta 2-AR). Transfectants expressed beta 2-ARs that were able to stimulate adenylyl cyclase activity and steroid biosynthesis. These transfectants were used to explore the basis for the DR mutation in Y1 cells. The authors demonstrate that beta-adrenergic agonists desensitize the adenylyl cyclase system in transfected Y1DS cells whereas transfected Y1DR cells are resistant to desensitization by beta-adrenergic agonists. The fate of the beta 2-ARs during desensitization was evaluated by photoaffinity labelling with [125I]iodocyanopindolol diazerine. Desensitization of Y1DS transfectants was accompanied by a modest loss in receptor density that was insufficient to account for the complete loss of responsiveness to beta-adrenergic agonists. The extent of receptor loss induced by beta-adrenergic agonists in Y1DR transfectants exceeded that in the Y1DS transfectants indicating that the mutation which protects Y1DR cells from agonist-induced desensitization is prior to receptor down-regulation in the desensitization pathway. From these results we infer that ACTH and isoproterenol desensitize adenylyl cyclase by a common pathway and that receptor loss is not a major component of the desensitization process in these cells

  13. Bathymetry and digital elevation models of Coyote Creek and Alviso Slough, South San Francisco Bay, California

    Science.gov (United States)

    Foxgrover, Amy C.; Finlayson, David P.; Jaffe, Bruce E.; Fregoso, Theresa A.

    2012-01-05

    In 2010 the U.S. Geological Survey (USGS), Pacific Coastal and Marine Science Center completed three cruises to map the bathymetry of the main channel and shallow intertidal mudflats in the southernmost part of south San Francisco Bay. The three surveys were merged to generate comprehensive maps of Coyote Creek (from Calaveras Point east to the railroad bridge) and Alviso Slough (from the bay to the town of Alviso) to establish baseline bathymetry prior to the breaching of levees adjacent to Alviso and Guadalupe Sloughs as part of the South Bay Salt Pond Restoration Project (http://www.southbayrestoration.org). Since 2010 the USGS has conducted twelve additional surveys to monitor bathymetric change in this region as restoration progresses.The bathymetry surveys were conducted using the state-of-the-art research vessel R/V Parke Snavely outfitted with an interferometric sidescan sonar for swath mapping in extremely shallow water. This publication provides high-resolution bathymetric data collected by the USGS. For the 2010 baseline survey we have merged the bathymetry with aerial lidar data that were collected for the USGS during the same time period to create a seamless, high-resolution digital elevation model (DEM) of the study area. The series of bathymetry datasets are provided at 1 m resolution and the 2010 bathymetric/topographic DEM at 2 m resolution. The data are formatted as both X, Y, Z text files and ESRI Arc ASCII files that are accompanied by Federal Geographic Data Committee (FGDC) compliant metadata.

  14. Coastal circulation and sediment dynamics in Maunalua Bay, Oahu, Hawaii, measurements of waves, currents, temperature, salinity, and turbidity; November 2008-February 2009

    Science.gov (United States)

    Storlazzi, Curt D.; Presto, M. Katherine; Logan, Joshua B.; Field, Michael E.

    2010-01-01

    the U.S. Coral Reef Task Force's (USCRTF) Hawaiian Local Action Strategy to address Land-Based Pollution (LAS-LBP) threats to coral reefs adjacent to the urbanized watersheds of Manualua Bay. Study Area Maunalua Bay is on the south side of Oahu, Hawaii, and is approximately 10 km long and 3 km wide. The bay is flanked by two large, dormant craters: Koko Head to the east and Diamond Head to the west. Rainfall in the watersheds that drain into Maunalua Bay ranges from more than 200 cm/year at the top of the Ko'olau Range that borders the northwestern part of the bay to less than 70 cm/year to the east at Koko Head. Seven major channels flow into the bay, and all but one have been altered by engineering structures.

  15. Mex Bay

    African Journals Online (AJOL)

    user

    2015-02-23

    Feb 23, 2015 ... surveys to assess the vulnerability of the most important physical and eutrophication parameters along. El- Mex Bay coast. As a result of increasing population and industrial development, poorly untreated industrial waste, domestic sewage, shipping industry and agricultural runoff are being released to the.

  16. PPAR agonists reduce steatosis in oleic acid-overloaded HepaRG cells

    International Nuclear Information System (INIS)

    Rogue, Alexandra; Anthérieu, Sébastien; Vluggens, Aurore; Umbdenstock, Thierry; Claude, Nancy; Moureyre-Spire, Catherine de la; Weaver, Richard J.; Guillouzo, André

    2014-01-01

    Although non-alcoholic fatty liver disease (NAFLD) is currently the most common form of chronic liver disease there is no pharmacological agent approved for its treatment. Since peroxisome proliferator-activated receptors (PPARs) are closely associated with hepatic lipid metabolism, they seem to play important roles in NAFLD. However, the effects of PPAR agonists on steatosis that is a common pathology associated with NAFLD, remain largely controversial. In this study, the effects of various PPAR agonists, i.e. fenofibrate, bezafibrate, troglitazone, rosiglitazone, muraglitazar and tesaglitazar on oleic acid-induced steatotic HepaRG cells were investigated after a single 24-hour or 2-week repeat treatment. Lipid vesicles stained by Oil-Red O and triglycerides accumulation caused by oleic acid overload, were decreased, by up to 50%, while fatty acid oxidation was induced after 2-week co-treatment with PPAR agonists. The greatest effects on reduction of steatosis were obtained with the dual PPARα/γ agonist muraglitazar. Such improvement of steatosis was associated with up-regulation of genes related to fatty acid oxidation activity and down-regulation of many genes involved in lipogenesis. Moreover, modulation of expression of some nuclear receptor genes, such as FXR, LXRα and CAR, which are potent actors in the control of lipogenesis, was observed and might explain repression of de novo lipogenesis. Conclusion: Altogether, our in vitro data on steatotic HepaRG cells treated with PPAR agonists correlated well with clinical investigations, bringing a proof of concept that drug-induced reversal of steatosis in human can be evaluated in in vitro before conducting long-term and costly in vivo studies in animals and patients. - Highlights: • There is no pharmacological agent approved for the treatment of NAFLD. • This study demonstrates that PPAR agonists can reduce fatty acid-induced steatosis. • Some nuclear receptors appear to be potent actors in the control

  17. PPAR agonists reduce steatosis in oleic acid-overloaded HepaRG cells

    Energy Technology Data Exchange (ETDEWEB)

    Rogue, Alexandra [Inserm UMR 991, 35043 Rennes Cedex (France); Université de Rennes 1, Faculté des Sciences Pharmaceutiques et Biologiques, 35043 Rennes Cedex (France); Biologie Servier, Gidy (France); Anthérieu, Sébastien; Vluggens, Aurore [Inserm UMR 991, 35043 Rennes Cedex (France); Université de Rennes 1, Faculté des Sciences Pharmaceutiques et Biologiques, 35043 Rennes Cedex (France); Umbdenstock, Thierry [Technologie Servier, Orléans (France); Claude, Nancy [Institut de Recherches Servier, Courbevoie (France); Moureyre-Spire, Catherine de la; Weaver, Richard J. [Biologie Servier, Gidy (France); Guillouzo, André, E-mail: Andre.Guillouzo@univ-rennes1.fr [Inserm UMR 991, 35043 Rennes Cedex (France); Université de Rennes 1, Faculté des Sciences Pharmaceutiques et Biologiques, 35043 Rennes Cedex (France)

    2014-04-01

    Although non-alcoholic fatty liver disease (NAFLD) is currently the most common form of chronic liver disease there is no pharmacological agent approved for its treatment. Since peroxisome proliferator-activated receptors (PPARs) are closely associated with hepatic lipid metabolism, they seem to play important roles in NAFLD. However, the effects of PPAR agonists on steatosis that is a common pathology associated with NAFLD, remain largely controversial. In this study, the effects of various PPAR agonists, i.e. fenofibrate, bezafibrate, troglitazone, rosiglitazone, muraglitazar and tesaglitazar on oleic acid-induced steatotic HepaRG cells were investigated after a single 24-hour or 2-week repeat treatment. Lipid vesicles stained by Oil-Red O and triglycerides accumulation caused by oleic acid overload, were decreased, by up to 50%, while fatty acid oxidation was induced after 2-week co-treatment with PPAR agonists. The greatest effects on reduction of steatosis were obtained with the dual PPARα/γ agonist muraglitazar. Such improvement of steatosis was associated with up-regulation of genes related to fatty acid oxidation activity and down-regulation of many genes involved in lipogenesis. Moreover, modulation of expression of some nuclear receptor genes, such as FXR, LXRα and CAR, which are potent actors in the control of lipogenesis, was observed and might explain repression of de novo lipogenesis. Conclusion: Altogether, our in vitro data on steatotic HepaRG cells treated with PPAR agonists correlated well with clinical investigations, bringing a proof of concept that drug-induced reversal of steatosis in human can be evaluated in in vitro before conducting long-term and costly in vivo studies in animals and patients. - Highlights: • There is no pharmacological agent approved for the treatment of NAFLD. • This study demonstrates that PPAR agonists can reduce fatty acid-induced steatosis. • Some nuclear receptors appear to be potent actors in the control

  18. Transient receptor potential (TRP) channels as drug targets for diseases of the digestive system

    Science.gov (United States)

    Holzer, Peter

    2011-01-01

    Approximately 20 of the 30 mammalian transient receptor potential (TRP) channel subunits are expressed by specific neurons and cells within the alimentary canal. They subserve important roles in taste, chemesthesis, mechanosensation, pain and hyperalgesia and contribute to the regulation of gastrointestinal motility, absorptive and secretory processes, blood flow, and mucosal homeostasis. In a cellular perspective, TRP channels operate either as primary detectors of chemical and physical stimuli, as secondary transducers of ionotropic or metabotropic receptors, or as ion transport channels. The polymodal sensory function of TRPA1, TRPM5, TRPM8, TRPP2, TRPV1, TRPV3 and TRPV4 enables the digestive system to survey its physical and chemical environment, which is relevant to all processes of digestion. TRPV5 and TRPV6 as well as TRPM6 and TRPM7 contribute to the absorption of Ca2+ and Mg2+, respectively. TRPM7 participates in intestinal pacemaker activity, and TRPC4 transduces muscarinic acetylcholine receptor activation to smooth muscle contraction. Changes in TRP channel expression or function are associated with a variety of diseases/disorders of the digestive system, notably gastro-esophageal reflux disease, inflammatory bowel disease, pain and hyperalgesia in heartburn, functional dyspepsia and irritable bowel syndrome, cholera, hypomagnesemia with secondary hypocalcemia, infantile hypertrophic pyloric stenosis, esophageal, gastrointestinal and pancreatic cancer, and polycystic liver disease. These implications identify TRP channels as promising drug targets for the management of a number of gastrointestinal pathologies. As a result, major efforts are put into the development of selective TRP channel agonists and antagonists and the assessment of their therapeutic potential. PMID:21420431

  19. Review article: transient receptor potential channels as possible therapeutic targets in irritable bowel syndrome.

    Science.gov (United States)

    Beckers, A B; Weerts, Z Z R M; Helyes, Z; Masclee, A A M; Keszthelyi, D

    2017-11-01

    Abdominal pain in irritable bowel syndrome (IBS) remains challenging to treat effectively. Researchers have attempted to elucidate visceral nociceptive processes in order to guide treatment development. Transient receptor potential (TRP) channels have been implied in the generation (TRPV1, TRPV4, TRPA1) and inhibition (TRPM8) of visceral pain signals. Pathological changes in their functioning have been demonstrated in inflammatory conditions, and appear to be present in IBS as well. To provide a comprehensive review of the current literature on TRP channels involved in visceral nociception. In particular, we emphasise the clinical implications of these nociceptors in the treatment of IBS. Evidence to support this review was obtained from an electronic database search via PubMed using the search terms "visceral nociception," "visceral hypersensitivity," "irritable bowel syndrome" and "transient receptor potential channels." After screening the abstracts the articles deemed relevant were cross-referenced for additional manuscripts. Recent studies have resulted in significant advances in our understanding of TRP channel mediated visceral nociception. The diversity of TRP channel sensitization pathways is increasingly recognised. Endogenous TRP agonists, including poly-unsaturated fatty acid metabolites and hydrogen sulphide, have been implied in augmented visceral pain generation in IBS. New potential targets for treatment development have been identified (TRPA1 and TRPV4,) and alternative means of affecting TRP channel signalling (partial antagonists, downstream targeting and RNA-based therapy) are currently being explored. The improved understanding of mechanisms involved in visceral nociception provides a solid basis for the development of new treatment strategies for abdominal pain in IBS. © 2017 John Wiley & Sons Ltd.

  20. Investigation of the mechanism of radioprotective action of adrenoceptor agonists

    International Nuclear Information System (INIS)

    Kulinskij, V.I.; Klimova, A.D.; Yashunskij, V.G.; Alpatova, T.V.; 4205700SU)

    1986-01-01

    α-Adrenoceptor agonists of both main groups, i.e. arylalkylamines and imidazolines, have a pronounced radioprotective effect. Their chemical analogs, which fail to stimulate α-adrenoceptors, do not protect mice. The effect of phenylephrine, adrenaline, and noradrenaline comes into play via α 1 -adrenoceptors and that of clonidine, via α 2 -adrenoceptors and also via α 1 -adrenoceptors. Adrenoceptor agonists can probably manifest their radioprotective action via both subtypes of α-adrenoceptors. Possible intracellular mechanisms of the radioprotective action are discussed

  1. San Francisco Bay Water Quality Improvement Fund

    Science.gov (United States)

    EPAs grant program to protect and restore San Francisco Bay. The San Francisco Bay Water Quality Improvement Fund (SFBWQIF) has invested in 58 projects along with 70 partners contributing to restore wetlands, water quality, and reduce polluted runoff.,

  2. PEMANFATAN TEOREMA BAYES DALAM PENENTUAN PENYAKIT THT

    Directory of Open Access Journals (Sweden)

    Sri Winiarti

    2008-07-01

    Full Text Available Dalam konsep pelacakan dalam mencari solusi dengan pendekatan artificial inteligent, ada berbagai metode yang dapat diterapkan untuk mengatasi masalah ketidakpastian saat proses pelacakan terjadi. Salah satunya adalah teorema bayes. Adanya ketidakpastian pada proses pelacakan dapat terjadi karena adanya perubahan pengetahuan yang ada di dalam sistem. Untuk itu diperlukan adanya suatu metode untuk mengatasi permasalahan tersebut. Dalam penelitian ini telah diterapkan suatu metode untuk mengatasi ketidakpastian dengan teorema Bayes pada kasus pelacakan untuk mendiagnosa penyakit pada THT (Telinga,Hidung dan Tenggorokan. Subjek pada penelitian ini adalah proses pelacakan untuk menentukan penyakit THT dengan model penalaran forward chaining dan metode kepastiannya menggunakan teorema bayes dengan cara menghitung nilai probabilitas suatu penyakit dan membandingkan probabilitas setiap gejalanya. Model pengembangan perangkat lunak yang digunakan dalam penelitian ini adalah Waterfall. Metode Waterfall diawali dengan analisis data, perancangan sistem, pengkodean menggunakan Visual Basic 6.0, pengujian sistem dengan black box test dan alfa test. Dari penelitian yang dilakukan menghasilkan sebuah perangkat lunak yaitu yang mampu menentukan penyakit pada THT dengan menerapkan metode bayes untuk mengatasi ketidakpastian. Hasil uji coba sistem menujukkan bahwa aplikasi ini layak dan dapat digunakan. Kata kunci : Penyakit, THT, Teorema Bayes.

  3. Geochemistry of sediments in the Back Bay and Yellowknife Bay of the Great Slave Lake

    International Nuclear Information System (INIS)

    Mudroch, A.; Joshi, S.R.; Sutherland, D.; Mudroch, P.; Dickson, K.M.

    1989-01-01

    Gold mining activities have generated wastes with high concentrations of arsenic and zinc in the vicinity of Yellowknife, Northwest Territories, Canada. Some of the waste material has been discharged into Yellowknife Bay of Great Slave Lake. Concentrations of arsenic and zinc were determined in sediment cores collected at the depositional areas of Yellowknife Bay. Sedimentation rates were estimated using two different radiometric approaches: the depth profiles of cesium 137 and lead 210. Geochemical analysis of the sediment cores indicated input of similar material into sampling areas over the past 50 yr. Age profiles of the sediment constructed from the radionuclide measurements were used to determine historical trends of arsenic and zinc inputs into Yellowknife Bay. The historical record was in good agreement with implemented remedial actions and the usage patterns of both elements. 16 refs., 6 figs., 3 tabs

  4. Citral sensing by Transient [corrected] receptor potential channels in dorsal root ganglion neurons.

    Directory of Open Access Journals (Sweden)

    Stephanie C Stotz

    2008-05-01

    Full Text Available Transient receptor potential (TRP ion channels mediate key aspects of taste, smell, pain, temperature sensation, and pheromone detection. To deepen our understanding of TRP channel physiology, we require more diverse pharmacological tools. Citral, a bioactive component of lemongrass, is commonly used as a taste enhancer, as an odorant in perfumes, and as an insect repellent. Here we report that citral activates TRP channels found in sensory neurons (TRPV1 and TRPV3, TRPM8, and TRPA1, and produces long-lasting inhibition of TRPV1-3 and TRPM8, while transiently blocking TRPV4 and TRPA1. Sustained citral inhibition is independent of internal calcium concentration, but is state-dependent, developing only after TRP channel opening. Citral's actions as a partial agonist are not due to cysteine modification of the channels nor are they a consequence of citral's stereoisoforms. The isolated aldehyde and alcohol cis and trans enantiomers (neral, nerol, geranial, and geraniol each reproduce citral's actions. In juvenile rat dorsal root ganglion neurons, prolonged citral inhibition of native TRPV1 channels enabled the separation of TRPV2 and TRPV3 currents. We find that TRPV2 and TRPV3 channels are present in a high proportion of these neurons (94% respond to 2-aminoethyldiphenyl borate, consistent with our immunolabeling experiments and previous in situ hybridization studies. The TRPV1 activation requires residues in transmembrane segments two through four of the voltage-sensor domain, a region previously implicated in capsaicin activation of TRPV1 and analogous menthol activation of TRPM8. Citral's broad spectrum and prolonged sensory inhibition may prove more useful than capsaicin for allodynia, itch, or other types of pain involving superficial sensory nerves and skin.

  5. Optimasi Naive Bayes Dengan Pemilihan Fitur Dan Pembobotan Gain Ratio

    Directory of Open Access Journals (Sweden)

    I Guna Adi Socrates

    2016-03-01

    Full Text Available Naïve Bayes merupakan salah satu metode data mining yang umum digunakan dalam klasifikasi dokumen berbasis text. Kelebihan dari metode ini adalah algoritma yang sederhana dengan  kompleksitas  perhitungan  yang  rendah.  Akan  tetapi,  pada  metode  Naïve  Bayes terdapat kelemahan dimana sifat independensi dari fitur Naïve Bayes tidak dapat selalu diterapkan sehingga akan berpengaruh pada tingkat akurasi perhitungan. Maka dari itu, metode Naïve Bayes perlu dioptimasi dengan cara pemberian bobot mengunakan Gain Ratio. Namun, pemberian bobot pada Naïve Bayes menimbulkan permasalahan pada penghitungan probabilitas setiap    dokumen, dimana fitur  yang tidak  merepresentasikan kelas  yang diuji banyak muncul sehingga terjadi kesalahan klasifikasi. Oleh karena itu, pembobotan Naïve Bayes   masih   belum   optimal.   Paper   ini mengusulkan  optimasi  metode   Naïve   Bayes mengunakan pembobotan Gain Ratio yang ditambahkan dengan metode pemilihan fitur pada kasus klasifikasi teks. Hasil penelitian ini menunjukkan bahwa optimasi metode Naïve Bayes menggunakan pemilihan fitur dan pembobotan menghasilkan akurasi sebesar 94%.

  6. Recent results from Daya Bay

    Directory of Open Access Journals (Sweden)

    Chua Ming-chung

    2016-01-01

    Full Text Available Utilizing powerful nuclear reactors as antineutrino sources, high mountains to provide ample shielding from cosmic rays in the vicinity, and functionally identical detectors with large target volume for near-far relative measurement, the Daya Bay Reactor Neutrino Experiment has achieved unprecedented precision in measuring the neutrino mixing angle θ13 and the neutrino mass squared difference |Δm2ee|. I will report the latest Daya Bay results on neutrino oscillations and light sterile neutrino search.

  7. 77 FR 30443 - Safety Zone; Alexandria Bay Chamber of Commerce, St. Lawrence River, Alexandria Bay, NY

    Science.gov (United States)

    2012-05-23

    ...The Coast Guard proposes to establish a temporary safety zone on the St. Lawrence River, Alexandria Bay, NY. This proposed rule is intended to restrict vessels from a portion of the St. Lawrence River during the Alexandria Bay Chamber of Commerce fireworks display. The safety zone established by this proposed rule is necessary to protect spectators and vessels from the hazards associated with a fireworks display.

  8. Holocene evolution of Apalachicola Bay, Florida

    Science.gov (United States)

    Osterman, L.E.; Twichell, D.C.; Poore, R.Z.

    2009-01-01

    A program of geophysical mapping and vibracoring was conducted to better understand the geologic evolution of Apalachicola Bay. Analyses of the geophysical data and sediment cores along with age control provided by 34 AMS 14C dates on marine shells and wood reveal the following history. As sea level rose in the early Holocene, fluvial deposits filled the Apalachicola River paleochannel, which extended southward under the central part of the bay and seaward across the continental shelf. Sediments to either side of the paleochannel contain abundant wood fragments, with dates documenting that those areas were forested at 8,000 14C years b.p. As sea level continued to rise, spits formed of headland prodelta deposits. Between ???6,400 and ???2,500 14C years b.p., an Apalachicola prodelta prograded and receded several times across the inner shelf that underlies the western part of the bay. An eastern deltaic lobe was active for a shorter time, between ???5,800 and 5,100 14C years b.p. Estuarine benthic foraminiferal assemblages occurred in the western bay as early as 6,400 14C years b.p., and indicate that there was some physical barrier to open-ocean circulation and shelf species established by that time. It is considered that shoals formed in the region of the present barrier islands as the rising sea flooded an interstream divide. Estuarine conditions were established very early in the post-glacial flooding of the bay. ?? 2009 US Government.

  9. The contribution of TRPM8 and TRPA1 channels to cold allodynia and neuropathic pain.

    Science.gov (United States)

    Caspani, Ombretta; Zurborg, Sandra; Labuz, Dominika; Heppenstall, Paul A

    2009-10-08

    Cold allodynia is a common feature of neuropathic pain however the underlying mechanisms of this enhanced sensitivity to cold are not known. Recently the transient receptor potential (TRP) channels TRPM8 and TRPA1 have been identified and proposed to be molecular sensors for cold. Here we have investigated the expression of TRPM8 and TRPA1 mRNA in the dorsal root ganglia (DRG) and examined the cold sensitivity of peripheral sensory neurons in the chronic construction injury (CCI) model of neuropathic pain in mice.In behavioral experiments, chronic constriction injury (CCI) of the sciatic nerve induced a hypersensitivity to both cold and the TRPM8 agonist menthol that developed 2 days post injury and remained stable for at least 2 weeks. Using quantitative RT-PCR and in situ hybridization we examined the expression of TRPM8 and TRPA1 in DRG. Both channels displayed significantly reduced expression levels after injury with no change in their distribution pattern in identified neuronal subpopulations. Furthermore, in calcium imaging experiments, we detected no alterations in the number of cold or menthol responsive neurons in the DRG, or in the functional properties of cold transduction following injury. Intriguingly however, responses to the TRPA1 agonist mustard oil were strongly reduced.Our results indicate that injured sensory neurons do not develop abnormal cold sensitivity after chronic constriction injury and that alterations in the expression of TRPM8 and TRPA1 are unlikely to contribute directly to the pathogenesis of cold allodynia in this neuropathic pain model.

  10. The contribution of TRPM8 and TRPA1 channels to cold allodynia and neuropathic pain.

    Directory of Open Access Journals (Sweden)

    Ombretta Caspani

    Full Text Available Cold allodynia is a common feature of neuropathic pain however the underlying mechanisms of this enhanced sensitivity to cold are not known. Recently the transient receptor potential (TRP channels TRPM8 and TRPA1 have been identified and proposed to be molecular sensors for cold. Here we have investigated the expression of TRPM8 and TRPA1 mRNA in the dorsal root ganglia (DRG and examined the cold sensitivity of peripheral sensory neurons in the chronic construction injury (CCI model of neuropathic pain in mice.In behavioral experiments, chronic constriction injury (CCI of the sciatic nerve induced a hypersensitivity to both cold and the TRPM8 agonist menthol that developed 2 days post injury and remained stable for at least 2 weeks. Using quantitative RT-PCR and in situ hybridization we examined the expression of TRPM8 and TRPA1 in DRG. Both channels displayed significantly reduced expression levels after injury with no change in their distribution pattern in identified neuronal subpopulations. Furthermore, in calcium imaging experiments, we detected no alterations in the number of cold or menthol responsive neurons in the DRG, or in the functional properties of cold transduction following injury. Intriguingly however, responses to the TRPA1 agonist mustard oil were strongly reduced.Our results indicate that injured sensory neurons do not develop abnormal cold sensitivity after chronic constriction injury and that alterations in the expression of TRPM8 and TRPA1 are unlikely to contribute directly to the pathogenesis of cold allodynia in this neuropathic pain model.

  11. [Effects of GLP-1 receptor agonists on carbohydrate metabolism control].

    Science.gov (United States)

    Fernández-García, José Carlos; Colomo, Natalia; Tinahones, Francisco José

    2014-09-01

    Glucagon-like peptide-1 (GLP-1) receptor agonists are a new group of drugs for the treatment of type 2 diabetes mellitus (DM2). In the present article, we review the available evidence on the efficacy of GLP-1 receptor agonists as glucose-lowering agents, their place in therapeutic algorithms, and the clinical factors associated with a favorable treatment response. Finally, we describe the clinical characteristics of patients who may benefit from these drugs. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  12. Dopamine receptors on adrenal chromaffin cells modulate calcium uptake and catecholamine release

    Energy Technology Data Exchange (ETDEWEB)

    Bigornia, L; Suozzo, M; Ryan, K A; Napp, D; Schneider, A S

    1988-10-01

    The presence of dopamine-containing cells in sympathetic ganglia, i.e., small, intensely fluorescent cells, has been known for some time. However, the role of dopamine as a peripheral neurotransmitter and its mechanism of action are not well understood. Previous studies have demonstrated the presence of D2 dopamine receptors on the surface of bovine adrenal chromaffin cells using radioligand binding methods and dopamine receptor inhibition of catecholamine release from perfused adrenal glands. In the present study, we provide evidence confirming a role of dopamine receptors as inhibitory modulators of adrenal catecholamine release from bovine chromaffin cell cultures and further show that the mechanism of modulation involves inhibition of stimulated calcium uptake. Apomorphine gave a dose-dependent inhibition (IC50 = 1 microM) of 45Ca2+ uptake stimulated by either nicotine (10 microM) or membrane depolarization with an elevated K+ level (60 mM). This inhibition was reversed by a series of specific (including stereospecific) dopamine receptor antagonists: haloperidol, spiperone, sulpiride, and (+)-butaclamol, but not (-)-butaclamol. In addition, the calcium channel agonist Bay K 8644 was used to stimulate uptake of 45Ca2+ into chromaffin cells, and this uptake was also inhibited by the dopamine receptor agonist apomorphine. The combined results suggest that dopamine receptors on adrenal chromaffin cells alter Ca2+ channel conductance, which, in turn, modulates catecholamine release.

  13. Legacy effects of colonial millponds on floodplain sedimentation, bank erosion, and channel morphology, MID-Atlantic, USA

    Science.gov (United States)

    Schenk, E.R.; Hupp, C.R.

    2009-01-01

    Many rivers and streams of the Mid-Atlantic Region, United States (U.S.) have been altered by postcolonial floodplain sedimentation (legacy sediment) associated with numerous milldams. Little Conestoga Creek, Pennsylvania, a tributary to the Susquehanna River and the Chesapeake Bay, is one of these streams. Floodplain sedimentation rates, bank erosion rates, and channel morphology were measured annually during 2004-2007 at five sites along a 28-km length of Little Conestoga Creek with nine colonial era milldams (one dam was still in place in 2007). This study was part of a larger cooperative effort to quantify floodplain sedimentation, bank erosion, and channel morphology in a high sediment yielding region of the Chesapeake Bay watershed. Data from the five sites were used to estimate the annual volume and mass of sediment stored on the floodplain and eroded from the banks for 14 segments along the 28-km length of creek. A bank and floodplain reach based sediment budget (sediment budget) was constructed for the 28 km by summing the net volume of sediment deposited and eroded from each segment. Mean floodplain sedimentation rates for Little Conestoga Creek were variable, with erosion at one upstream site (-5 mm/year) to deposition at the other four sites (highest = 11 mm/year) despite over a meter of floodplain aggradation from postcolonial sedimentation. Mean bank erosion rates range between 29 and 163 mm/year among the five sites. Bank height increased 1 m for every 10.6 m of channel width, from upstream to downstream (R2 = 0.79, p channel and the floodplain. Floodplain sedimentation and bank erosion rates also appear to be affected by the proximity of the segments to one existing milldam, which promotes deposition upstream and scouring downstream. The floodplain and bank along the 28-km reach produced a net mean sediment loss of 5,634 Mg/year for 2004-2007, indicating that bank erosion was exceeding floodplain sedimentation. In particular, the three segments

  14. Topobathymetric model of Mobile Bay, Alabama

    Science.gov (United States)

    Danielson, Jeffrey J.; Brock, John C.; Howard, Daniel M.; Gesch, Dean B.; Bonisteel-Cormier, Jamie M.; Travers, Laurinda J.

    2013-01-01

    Topobathymetric Digital Elevation Models (DEMs) are a merged rendering of both topography (land elevation) and bathymetry (water depth) that provides a seamless elevation product useful for inundation mapping, as well as for other earth science applications, such as the development of sediment-transport, sea-level rise, and storm-surge models. This 1/9-arc-second (approximately 3 meters) resolution model of Mobile Bay, Alabama was developed using multiple topographic and bathymetric datasets, collected on different dates. The topographic data were obtained primarily from the U.S. Geological Survey (USGS) National Elevation Dataset (NED) (http://ned.usgs.gov/) at 1/9-arc-second resolution; USGS Experimental Advanced Airborne Research Lidar (EAARL) data (2 meters) (http://pubs.usgs.gov/ds/400/); and topographic lidar data (2 meters) and Compact Hydrographic Airborne Rapid Total Survey (CHARTS) lidar data (2 meters) from the U.S. Army Corps of Engineers (USACE) (http://www.csc.noaa.gov/digitalcoast/data/coastallidar/). Bathymetry was derived from digital soundings obtained from the National Oceanic and Atmospheric Administration’s (NOAA) National Geophysical Data Center (NGDC) (http://www.ngdc.noaa.gov/mgg/geodas/geodas.html) and from water-penetrating lidar sources, such as EAARL and CHARTS. Mobile Bay is ecologically important as it is the fourth largest estuary in the United States. The Mobile and Tensaw Rivers drain into the bay at the northern end with the bay emptying into the Gulf of Mexico at the southern end. Dauphin Island (a barrier island) and the Fort Morgan Peninsula form the mouth of Mobile Bay. Mobile Bay is 31 miles (50 kilometers) long by a maximum width of 24 miles (39 kilometers) with a total area of 413 square miles (1,070 square kilometers). The vertical datum of the Mobile Bay topobathymetric model is the North American Vertical Datum of 1988 (NAVD 88). All the topographic datasets were originally referenced to NAVD 88 and no transformations

  15. Parameter Identification by Bayes Decision and Neural Networks

    DEFF Research Database (Denmark)

    Kulczycki, P.; Schiøler, Henrik

    1994-01-01

    The problem of parameter identification by Bayes point estimation using neural networks is investigated.......The problem of parameter identification by Bayes point estimation using neural networks is investigated....

  16. Chesapeake Bay baseline data acquisition, toxics in the Chesapeake Bay. Final preliminary report, 1946-78

    International Nuclear Information System (INIS)

    1978-07-01

    This report identifies researchers, research activities, and data files applicable to the Chesapeake Bay estuarine system. The identified data were generated after 1973 on the following: submerged aquatic vegetation, shellfish bed closures, eutrophication, toxics accumulation in the food chain, dredging and spoil disposal, hydrologic modifications, modification of fisheries, shoreline erosion, wetlands alterations, and the effects of boating and shipping on water quality. Major past and current program monitoring in the Bay and its tributaries are summarized according to frequency

  17. Wind-Driven Waves in Tampa Bay, Florida

    Science.gov (United States)

    Gilbert, S. A.; Meyers, S. D.; Luther, M. E.

    2002-12-01

    Turbidity and nutrient flux due to sediment resuspension by waves and currents are important factors controlling water quality in Tampa Bay. During December 2001 and January 2002, four Sea Bird Electronics SeaGauge wave and tide recorders were deployed in Tampa Bay in each major bay segment. Since May 2002, a SeaGauge has been continuously deployed at a site in middle Tampa Bay as a component of the Bay Regional Atmospheric Chemistry Experiment (BRACE). Initial results for the summer 2002 data indicate that significant wave height is linearly dependent on wind speed and direction over a range of 1 to 12 m/s. The data were divided into four groups according to wind direction. Wave height dependence on wind speed was examined for each group. Both northeasterly and southwesterly winds force significant wave heights that are about 30% larger than those for northwesterly and southeasterly winds. This difference is explained by variations in fetch due to basin shape. Comparisons are made between these observations and the results of a SWAN-based model of Tampa Bay. The SWAN wave model is coupled to a three-dimensional circulation model and computes wave spectra at each model grid cell under observed wind conditions and modeled water velocity. When SWAN is run without dissipation, the model results are generally similar in wave period but about 25%-50% higher in significant wave height than the observations. The impact of various dissipation mechanisms such as bottom drag and whitecapping on the wave state is being investigated. Preliminary analyses on winter data give similar results.

  18. PPARα agonists up-regulate organic cation transporters in rat liver cells

    International Nuclear Information System (INIS)

    Luci, Sebastian; Geissler, Stefanie; Koenig, Bettina; Koch, Alexander; Stangl, Gabriele I.; Hirche, Frank; Eder, Klaus

    2006-01-01

    It has been shown that clofibrate treatment increases the carnitine concentration in the liver of rats. However, the molecular mechanism is still unknown. In this study, we observed for the first time that treatment of rats with the peroxisome proliferator activated receptor (PPAR)-α agonist clofibrate increases hepatic mRNA concentrations of organic cation transporters (OCTNs)-1 and -2 which act as transporters of carnitine into the cell. In rat hepatoma (Fao) cells, treatment with WY-14,643 also increased the mRNA concentration of OCTN-2. mRNA concentrations of enzymes involved in carnitine biosynthesis were not altered by treatment with the PPARα agonists in livers of rats and in Fao cells. We conclude that PPARα agonists increase carnitine concentrations in livers of rats and cells by an increased uptake of carnitine into the cell but not by an increased carnitine biosynthesis

  19. Characterization of 12 GnRH peptide agonists - a kinetic perspective.

    Science.gov (United States)

    Nederpelt, Indira; Georgi, Victoria; Schiele, Felix; Nowak-Reppel, Katrin; Fernández-Montalván, Amaury E; IJzerman, Adriaan P; Heitman, Laura H

    2016-01-01

    Drug-target residence time is an important, yet often overlooked, parameter in drug discovery. Multiple studies have proposed an increased residence time to be beneficial for improved drug efficacy and/or longer duration of action. Currently, there are many drugs on the market targeting the gonadotropin-releasing hormone (GnRH) receptor for the treatment of hormone-dependent diseases. Surprisingly, the kinetic receptor-binding parameters of these analogues have not yet been reported. Therefore, this project focused on determining the receptor-binding kinetics of 12 GnRH peptide agonists, including many marketed drugs. A novel radioligand-binding competition association assay was developed and optimized for the human GnRH receptor with the use of a radiolabelled peptide agonist, [(125) I]-triptorelin. In addition to radioligand-binding studies, a homogeneous time-resolved FRET Tag-lite™ method was developed as an alternative assay for the same purpose. Two novel competition association assays were successfully developed and applied to determine the kinetic receptor-binding characteristics of 12 high-affinity GnRH peptide agonists. Results obtained from both methods were highly correlated. Interestingly, the binding kinetics of the peptide agonists were more divergent than their affinities with residence times ranging from 5.6 min (goserelin) to 125 min (deslorelin). Our research provides new insights by incorporating kinetic, next to equilibrium, binding parameters in current research and development that can potentially improve future drug discovery targeting the GnRH receptor. © 2015 The British Pharmacological Society.

  20. Discovery of Azetidinone Acids as Conformationally-Constrained Dual PPARalpha/gamma Agonists

    Energy Technology Data Exchange (ETDEWEB)

    Wang, W.; Devasthale, P; Farrelly, D; Gu, L; Harrity, T; Cap, M; Chu, C; Kunselman, L; Morgan, N; et. al.

    2008-01-01

    A novel class of azetidinone acid-derived dual PPAR{alpha}/{gamma} agonists has been synthesized for the treatment of diabetes and dyslipidemia. The preferred stereochemistry in this series for binding and functional agonist activity against both PPARa and PPAR? receptors was shown to be 3S,4S. Synthesis, in vitro and in vivo activities of compounds in this series are described. A high-yielding method for N-arylation of azetidinone esters is also described.

  1. Phytoplankton growth, dissipation, and succession in estuarine environments. [Chesapeake Bay

    Energy Technology Data Exchange (ETDEWEB)

    Seliger, H H

    1976-01-01

    Two major advances in a study of phytoplankton ecology in the Chesapeake Bay are reported. The annual subsurface transport of a dinoflagellate species (Prorocentrum mariae labouriae) from the mouth of the bay a distance northward of 120 nautical miles to the region of the Bay Bridge was followed. Prorocentrum is a major seasonal dinoflagellate in the Chespeake Bay and annually has been reported to form mahogany tides, dense reddish-brown patches, in the northern bay beginning in late spring and continuing through the summer. Subsequent to this annual appearance the Prorocentrum spread southward and into the western tributary estuaries. The physiological behavioral characteristics of the Prorocentrum were correlated with the physical water movements in the bay. A phytoplankton cage technique for the measurement in situ of the growth rates of natural mixed populations is described. (CH)

  2. Mobile Bay turbidity study

    Science.gov (United States)

    Crozier, G. F.; Schroeder, W. W.

    1978-01-01

    The termination of studies carried on for almost three years in the Mobile Bay area and adjacent continental shelf are reported. The initial results concentrating on the shelf and lower bay were presented in the interim report. The continued scope of work was designed to attempt a refinement of the mathematical model, assess the effectiveness of optical measurement of suspended particulate material and disseminate the acquired information. The optical characteristics of particulate solutions are affected by density gradients within the medium, density of the suspended particles, particle size, particle shape, particle quality, albedo, and the angle of refracted light. Several of these are discussed in detail.

  3. Transcranial Random Noise Stimulation-induced plasticity is NMDA-receptor independent but sodium-channel blocker and benzodiazepines sensitive

    Directory of Open Access Journals (Sweden)

    Leila eChaieb

    2015-04-01

    Full Text Available Background: Application of transcranial random noise stimulation (tRNS between 0.1 and 640 Hz of the primary motor cortex (M1 for 10 minutes induces a persistent excitability increase lasting for at least 60 minutes. However, the mechanism of tRNS-induced cortical excitability alterations is not yet fully understood. Objective: The main aim of this study was to get first efficacy data with regard to the possible neuronal effect of tRNS. Methods: Single-pulse transcranial magnetic stimulation (TMS was used to measure levels of cortical excitability before and after combined application of tRNS at an intensity of 1mA for 10mins stimulation duration and a pharmacological agent (or sham on 8 healthy male participants. Results: The sodium channel blocker carbamazepine showed a tendency towards inhibiting MEPs 5-60 mins poststimulation. The GABAA agonist lorazepam suppressed tRNS-induced cortical excitability increases at 0-20 and 60 min time points. The partial NMDA receptor agonist D-cycloserine, the NMDA receptor antagonist dextromethorphan and the D2/D3 receptor agonist ropinirole had no significant effects on the excitability increases seen with tRNS.Conclusions: In contrast to transcranial direct current stimulation (tDCS, aftereffects of tRNS are seem to be not NMDA receptor dependent and can be suppressed by benzodiazepines suggesting that tDCS and tRNS depend upon different mechanisms.

  4. Humboldt Bay Orthoimages

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set consists of 0.5-meter pixel resolution, four band orthoimages covering the Humboldt Bay area. An orthoimage is remotely sensed image data in which...

  5. With Prudhoe Bay in decline

    International Nuclear Information System (INIS)

    Davis, J.M.; Pollock, J.R.

    1992-01-01

    Almost every day, it seems, someone is mentioning Prudhoe Bay---its development activities, the direction of its oil production, and more recently its decline rate. Almost as frequently, someone is mentioning the number of companies abandoning exploration in Alaska. The state faces a double-edged dilemma: decline of its most important oil field and a diminished effort to find a replacement for the lost production. ARCO has seen the Prudhoe Bay decline coming for some time and has been planning for it. We have reduced staff, and ARCO and BP Exploration are finding cost-effective ways to work more closely together through such vehicles as shared services. At the same time, ARCO is continuing its high level of Alaskan exploration. This article will assess the future of Prudhoe Bay from a technical perspective, review ARCO's exploration plans for Alaska, and suggest what the state can do to encourage other companies to invest in this crucial producing region and exploratory frontier

  6. Bayes Empirical Bayes Inference of Amino Acid Sites Under Positive Selection

    DEFF Research Database (Denmark)

    Yang, Ziheng; Wong, Wendy Shuk Wan; Nielsen, Rasmus

    2005-01-01

    , with > 1 indicating positive selection. Statistical distributions are used to model the variation in among sites, allowing a subset of sites to have > 1 while the rest of the sequence may be under purifying selection with ... probabilities that a site comes from the site class with > 1. Current implementations, however, use the naive EB (NEB) approach and fail to account for sampling errors in maximum likelihood estimates of model parameters, such as the proportions and ratios for the site classes. In small data sets lacking...... information, this approach may lead to unreliable posterior probability calculations. In this paper, we develop a Bayes empirical Bayes (BEB) approach to the problem, which assigns a prior to the model parameters and integrates over their uncertainties. We compare the new and old methods on real and simulated...

  7. The Holocene History of Placentia Bay, Newfoundland

    DEFF Research Database (Denmark)

    Sheldon, Christina; Seidenkrantz, Marit-Solveig; Reynisson, Njall

    2013-01-01

    Marine sediments analyzed from cores taken in Placentia Bay, Newfoundland, located in the Labrador Sea, captured oceanographic and climatic changes from the end of the Younger Dryas through the Holocene. Placentia Bay is an ideal site to capture changes in both the south-flowing Labrador Current ...

  8. Copper-induced activation of TRP channels promotes extracellular calcium entry and activation of CaMs and CDPKs leading to copper entry and membrane depolarization in Ulva compressa

    Directory of Open Access Journals (Sweden)

    Melissa eGómez

    2015-03-01

    Full Text Available In order to identify channels involved in membrane depolarization, Ulva compressa was incubated with agonists of TRP channels C5, A1 and V1 and the level of intracellular calcium was detected. Agonists of TRPC5, A1 and V1 induced increases in intracellular calcium at 4, 9 and 12 min of exposure, respectively, and antagonists of TRPC5, A1 and V1 corresponding to SKF-96365 (SKF, HC-030031 (HC and capsazepin (CPZ, respectively, inhibited calcium increases indicating that functional TRPs exist in U. compressa. In addition, copper excess induced increases in intracellular calcium at 4, 9 and 12 min which were inhibited by SKF, HC and CPZ, respectively, indicating that copper activate TRPC5, A1 and V1 channels. Moreover, copper-induced calcium increases were inhibited by EGTA, a non-permeable calcium chelating agent, but not by thapsigargin, an inhibitor of endoplasmic reticulum (ER calcium ATPase, indicating that activation of TRPs leads to extracellular calcium entry. Furthermore, copper-induced calcium increases were not inhibited by W-7, an inhibitor of CaMs, and staurosporine, an inhibitor of CDPKs, indicating that extracellular calcium entry did not require CaMs and CDPKs activation. In addition, copper induced membrane depolarization events at 4, 8 and 11 min and these events were inhibited by SKF, HC, CPZ and bathocuproine, a specific copper chelating agent, indicating copper entry through TRP channels leading to membrane depolarization. Moreover, membrane depolarization events were inhibited by W-7 and staurosporine, indicating that CaMs and CDPKs are required in order to activate TRPs to allow copper entry. Thus, light-dependent copper-induced activation TRPC5, A1 and V1 promotes extracellular calcium entry leading to activation of CaMs and CDPKs which, in turn, promotes copper entry through these TRP channels leading to membrane depolarization.

  9. Benthic harpacticoid copepods of Jiaozhou Bay, Qingdao

    Science.gov (United States)

    Ma, Lin; Li, Xinzheng

    2017-09-01

    The species richness of benthic harpacticoid copepod fauna in Jiaozhou Bay, Qingdao, on the southern coast of Shandong Peninsula, has not been comprehensively studied. We present a preliminary inventory of species for this region based on material found in nine sediment samples collected from 2011 to 2012. Our list includes 15 species belonging to 15 genera in 9 families, the most speciose family was the Miraciidae Dana, 1846 (seven species); all other families were represented by single species only. Sediment characteristics and depth are determined to be important environmental determinants of harpacticoid distribution in this region. We briefly detail the known distributions of species and provide a key to facilitate their identification. Both harpacticoid species richness and the species/genus ratio in Jiaozhou Bay are lower than in Bohai Gulf and Gwangyang Bay. The poor knowledge of the distribution of benthic harpacticoids, in addition to low sampling effort in Jiaozhou Bay, likely contribute to low species richness.

  10. Estradiol agonists inhibit human LoVo colorectal-cancer cell proliferation and migration through p53.

    Science.gov (United States)

    Hsu, Hsi-Hsien; Kuo, Wei-Wen; Ju, Da-Tong; Yeh, Yu-Lan; Tu, Chuan-Chou; Tsai, Ying-Lan; Shen, Chia-Yao; Chang, Sheng-Huang; Chung, Li-Chin; Huang, Chih-Yang

    2014-11-28

    To investigate the effects of 17β-estradiol via estrogen receptors (ER) or direct administration of ER agonists on human colorectal cancer. LoVo cells were established from the Bioresource Collection and Research Center and cultured in phenol red-free DMEM (Sigma, United States). To investigate the effects of E2 and/or ER selective agonists on cellular proliferation, LoVo colorectal cells were treated with E2 or ER-selective agonists for 24 h and 48 h and subjected to the MTT (Sigma) assay to find the concentration. And investigate the effects of E2 and/or ER selective agonists on cell used western immunoblotting to find out the diversification of signaling pathways. In order to observe motility and migration the wound healing assay and a transwell chamber (Neuro Probe) plate were tased. For a quantitative measure, we counted the number of migrating cells to the wound area post-wounding for 24 h. We further examined the cellular migration-regulating factors urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA) and matrix metalloproteinase (MMP)-9 in human LoVo cells so gelatin zymography that we used and gelatinolytic activity was visualized by Coomassie blue staining. And these results are presented as means ± SE, and statistical comparisons were made using Student's t-test. The structure was first compared with E2 and ER agonists. We then treated the LoVo cells with E2 and ER agonists (10(-8) mol/L) for 24 h and 48 h and subsequently measured the cell viability using MTT assay. Our results showed that treatment with 17β-estradiol and/or ER agonists in human LoVo colorectal cancer cells activated p53 and then up-regulated p21 and p27 protein levels, subsequently inhibiting the downstream target gene, cyclin D1, which regulates cell proliferation. Taken together, our findings demonstrate the anti-tumorigenesis effects of 17β-estradiol and/or ER agonists and suggest that these compounds may prove to be a potential alternative

  11. Concentrations of PAHs (Polycyclicaromatic Hydrocarbons Pollutant in Sediment of The Banten Bay

    Directory of Open Access Journals (Sweden)

    Khozanah Munawir

    2018-02-01

    Full Text Available Banten Bay is end of stream for a few rivers from Banten mainland where many manufactures and petrochemical industries are built. This may give environmental pressure of water quality of the bay due to pollutant input, such as Polycyclic Aromatic Hydrocarbons (PAHs. This study is to identify those pollutants and determine their total concentration and distribution in sediments. Surface sediment samples were collected in four zones: inner coastline within the bay, middle bay, coastline off the bay and outer of the Bay in April 2016. PAH components were extracted and measured using a gas chromatography-mass spectrometry. Levels of total PAHs in sediments in inner coastline within the bay ranged between 0.381-2.654 ppm with an average of 1.288 ppm, middle of the bay ranged between 0.747-1.762 ppm with an average of 1.198 ppm, outer of the bay ranged between 0.192-1.394 ppm with an average of 0.921 ppm, and east coast of the bay ranged between 0.191-1.394 ppm and an average of 0.778 ppm. The levels of total PAH contamination is apparently lower than those of PAH threshold in sediments (i.e. 4.5 ppm. Keywords: PAHs (Polycyclic Aromatic Hydrocarbons, Banten Bay

  12. Rapid Crustal Uplift at Birch Bay, Washington

    Science.gov (United States)

    Sherrod, B. L.; Kelsey, H. M.; Blakely, R. J.

    2010-12-01

    Geomorphology and coastal marsh stratigraphy suggest late Holocene uplift of the shoreline at Birch Bay, located northwest of Bellingham, Washington, during an earthquake on a shallow fault. LiDAR images show a raised, late Holocene shoreline along Birch Bay, with ~1 m of elevation difference between the modern shoreline and the inferred paleoshoreline. Commercial seismic reflection images reveal an anticline in Tertiary and possibly Quaternary deposits underlying Birch Bay. NW-trending magnetic anomalies are likely associated with the Birch Bay anticline and other nearby structures. Taken together, the geophysical data and lidar images suggest uplift of young deposits along a NW-trending blind reverse fault. Stratigraphy from Terrell Creek marsh, located just south of Birch Bay, shows freshwater peat buried by lower intertidal muds, indicating local submergence ~1300 yr BP. Stratigraphy of a 70-cm sediment core from Birch Bay marsh, sitting astride the anticline imaged with seismic reflection data, shows mud buried by detrital peat. One radiocarbon age from the core places the abrupt change from mud to peat prior to 1520-1700 yr BP. We divide fossil diatom assemblages straddling the mud-peat contact at Birch Bay into three zones. The oldest zone consists primarily of intertidal and marine diatoms, dominated by Paralia sulcata, Scoleoneis tumida, Grammataphora oceanica, and Gyrosigma balticum. An intermediate zone, beginning at the sharp contact between mud and overlying peat, consists of a mixture of brackish marsh and freshwater species, dominated by Diploneis interrupta, with lesser amounts of Aulacoseira sp., Pinnularia viridis, Eunotia pectinalis, and Paralia sulcata. A third and youngest zone lies in the upper half of the peat and is dominated by poorly preserved freshwater diatoms, mostly Aulacoseira cf. crassapuntata, Pinnularia viridis, P. maior, Eunotia pectinalis, and E. praerupta. Paleoecological inferences, based on distributions of modern diatoms

  13. Defining a data management strategy for USGS Chesapeake Bay studies

    Science.gov (United States)

    Ladino, Cassandra

    2013-01-01

    The mission of U.S. Geological Survey’s (USGS) Chesapeake Bay studies is to provide integrated science for improved understanding and management of the Chesapeake Bay ecosystem. Collective USGS efforts in the Chesapeake Bay watershed began in the 1980s, and by the mid-1990s the USGS adopted the watershed as one of its national place-based study areas. Great focus and effort by the USGS have been directed toward Chesapeake Bay studies for almost three decades. The USGS plays a key role in using “ecosystem-based adaptive management, which will provide science to improve the efficiency and accountability of Chesapeake Bay Program activities” (Phillips, 2011). Each year USGS Chesapeake Bay studies produce published research, monitoring data, and models addressing aspects of bay restoration such as, but not limited to, fish health, water quality, land-cover change, and habitat loss. The USGS is responsible for collaborating and sharing this information with other Federal agencies and partners as described under the President’s Executive Order 13508—Strategy for Protecting and Restoring the Chesapeake Bay Watershed signed by President Obama in 2009. Historically, the USGS Chesapeake Bay studies have relied on national USGS databases to store only major nationally available sources of data such as streamflow and water-quality data collected through local monitoring programs and projects, leaving a multitude of other important project data out of the data management process. This practice has led to inefficient methods of finding Chesapeake Bay studies data and underutilization of data resources. Data management by definition is “the business functions that develop and execute plans, policies, practices and projects that acquire, control, protect, deliver and enhance the value of data and information.” (Mosley, 2008a). In other words, data management is a way to preserve, integrate, and share data to address the needs of the Chesapeake Bay studies to better

  14. Influence of net freshwater supply on salinity in Florida Bay

    Science.gov (United States)

    Nuttle, William K.; Fourqurean, James W.; Cosby, Bernard J.; Zieman, Joseph C.; Robblee, Michael B.

    2000-01-01

    An annual water budget for Florida Bay, the large, seasonally hypersaline estuary in the Everglades National Park, was constructed using physically based models and long‐term (31 years) data on salinity, hydrology, and climate. Effects of seasonal and interannual variations of the net freshwater supply (runoff plus rainfall minus evaporation) on salinity variation within the bay were also examined. Particular attention was paid to the effects of runoff, which are the focus of ambitious plans to restore and conserve the Florida Bay ecosystem. From 1965 to 1995 the annual runoff from the Everglades into the bay was less than one tenth of the annual direct rainfall onto the bay, while estimated annual evaporation slightly exceeded annual rainfall. The average net freshwater supply to the bay over a year was thus approximately zero, and interannual variations in salinity appeared to be affected primarily by interannual fluctuations in rainfall. At the annual scale, runoff apparently had little effect on the bay as a whole during this period. On a seasonal basis, variations in rainfall, evaporation, and runoff were not in phase, and the net freshwater supply to the bay varied between positive and negative values, contributing to a strong seasonal pattern in salinity, especially in regions of the bay relatively isolated from exchanges with the Gulf of Mexico and Atlantic Ocean. Changes in runoff could have a greater effect on salinity in the bay if the seasonal patterns of rainfall and evaporation and the timing of the runoff are considered. One model was also used to simulate spatial and temporal patterns of salinity responses expected to result from changes in net freshwater supply. Simulations in which runoff was increased by a factor of 2 (but with no change in spatial pattern) indicated that increased runoff will lower salinity values in eastern Florida Bay, increase the variability of salinity in the South Region, but have little effect on salinity in the Central

  15. Hyperglycemia and Diabetes Downregulate the Functional Expression of TRPV4 Channels in Retinal Microvascular Endothelium

    Science.gov (United States)

    Monaghan, Kevin; McNaughten, Jennifer; McGahon, Mary K.; Kelly, Catriona; Kyle, Daniel; Yong, Phaik Har

    2015-01-01

    Retinal endothelial cell dysfunction is believed to play a key role in the etiology and pathogenesis of diabetic retinopathy. Numerous studies have shown that TRPV4 channels are critically involved in maintaining normal endothelial cell function. In the current paper, we demonstrate that TRPV4 is functionally expressed in the endothelium of the retinal microcirculation and that both channel expression and activity is downregulated by hyperglycaemia. Quantitative PCR and immunostaining demonstrated molecular expression of TRPV4 in cultured bovine retinal microvascular endothelial cells (RMECs). Functional TRPV4 activity was assessed in cultured RMECs from endothelial Ca2+-responses recorded using fura-2 microfluorimetry and electrophysiological recordings of membrane currents. The TRPV4 agonist 4α-phorbol 12,13-didecanoate (4-αPDD) increased [Ca2+]i in RMECs and this response was largely abolished using siRNA targeted against TRPV4. These Ca2+-signals were completely inhibited by removal of extracellular Ca2+, confirming their dependence on influx of extracellular Ca2+. The 4-αPDD Ca2+-response recorded in the presence of cyclopiazonic acid (CPA), which depletes the intracellular stores preventing any signal amplification through store release, was used as a measure of Ca2+-influx across the cell membrane. This response was blocked by HC067047, a TRPV4 antagonist. Under voltage clamp conditions, the TRPV4 agonist GSK1016790A stimulated a membrane current, which was again inhibited by HC067047. Following incubation with 25mM D-glucose TRPV4 expression was reduced in comparison with RMECs cultured under control conditions, as were 4αPDD-induced Ca2+-responses in the presence of CPA and ion currents evoked by GSK1016790A. Molecular expression of TRPV4 in the retinal vascular endothelium of 3 months’ streptozotocin-induced diabetic rats was also reduced in comparison with that in age-matched controls. We conclude that hyperglycaemia and diabetes reduce the

  16. Safety culture development at Daya Bay NPP

    International Nuclear Information System (INIS)

    Zhang Shanming

    2001-01-01

    From view on Organization Behavior theory, the concept, development and affecting factors of safety culture are introduced. The focuses are on the establishment, development and management practice for safety culture at Daya Bay NPP. A strong safety culture, also demonstrated, has contributed greatly to improving performance at Daya Bay

  17. Antibodies to the extracellular pore loop of TRPM8 act as antagonists of channel activation.

    Directory of Open Access Journals (Sweden)

    Silke Miller

    Full Text Available The mammalian transient receptor potential melastatin channel 8 (TRPM8 is highly expressed in trigeminal and dorsal root ganglia. TRPM8 is activated by cold temperature or compounds that cause a cooling sensation, such as menthol or icilin. TRPM8 may play a role in cold hypersensitivity and hyperalgesia in various pain syndromes. Therefore, TRPM8 antagonists are pursued as therapeutics. In this study we explored the feasibility of blocking TRPM8 activation with antibodies. We report the functional characterization of a rabbit polyclonal antibody, ACC-049, directed against the third extracellular loop near the pore region of the human TRPM8 channel. ACC-049 acted as a full antagonist at recombinantly expressed human and rodent TRPM8 channels in cell based agonist-induced 45Ca2+ uptake assays. Further, several poly-and monoclonal antibodies that recognize the same region also blocked icilin activation of not only recombinantly expressed TRPM8, but also endogenous TRPM8 expressed in rat dorsal root ganglion neurons revealing the feasibility of generating monoclonal antibody antagonists. We conclude that antagonist antibodies are valuable tools to investigate TRPM8 function and may ultimately pave the way for development of therapeutic antibodies.

  18. The GABAA receptor agonist THIP is neuroprotective in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Kristensen, Bjarne Winther; Noraberg, Jens; Zimmer, Jens

    2003-01-01

    The potential neuroprotective effects of the GABA(A) receptor agonists THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) and muscimol, and the selective GluR5 kainate receptor agonist ATPA ((RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid), which activates GABAergic interneu......The potential neuroprotective effects of the GABA(A) receptor agonists THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) and muscimol, and the selective GluR5 kainate receptor agonist ATPA ((RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid), which activates GABAergic...... interneurons, were examined in hippocampal slice cultures exposed to N-methyl-D-aspartate (NMDA). The NMDA-induced excitotoxicity was quantified by densitometric measurements of propidium iodide (PI) uptake. THIP (100-1000 microM) was neuroprotective in slice cultures co-exposed to NMDA (10 microM) for 48 h......, while muscimol (100-1000 microM) and ATPA (1-3 microM) were without effect. The results demonstrate that direct GABA(A) agonism can mediate neuroprotection in the hippocampus in vitro as previously suggested in vivo....

  19. Lost lake - restoration of a Carolina bay

    Energy Technology Data Exchange (ETDEWEB)

    Hanlin, H.G.; McLendon, J.P. [Univ. of South Carolina, Aiken, SC (United States). Dept. of Biology and Geology; Wike, L.D. [Univ. of South Carolina, Aiken, SC (United States). Dept. of Biology and Geology]|[Westinghouse Savannah River Co., Aiken, SC (United States). Savannah River Technology Center; Dietsch, B.M. [Univ. of South Carolina, Aiken, SC (United States). Dept. of Biology and Geology]|[Univ. of Georgia, Aiken, SC (United States)

    1994-09-01

    Carolina bays are shallow wetland depressions found only on the Atlantic Coastal Plain. Although these isolated interstream wetlands support many types of communities, they share the common features of having a sandy margin, a fluctuating water level, an elliptical shape, and a northwest to southeast orientation. Lost Lake, an 11.3 hectare Carolina bay, was ditched and drained for agricultural production before establishment of the Savannah River Site in 1950. Later it received overflow from a seepage basin containing a variety of chemicals, primarily solvents and some heavy metals. In 1990 a plan was developed for the restoration of Lost Lake, and restoration activities were complete by mid-1991. Lost Lake is the first known project designed for the restoration and recovery of a Carolina bay. The bay was divided into eight soil treatment zones, allowing four treatments in duplicate. Each of the eight zones was planted with eight species of native wetland plants. Recolonization of the bay by amphibians and reptiles is being evaluated by using drift fences with pitfall traps and coverboard arrays in each of the treatment zones. Additional drift fences in five upland habitats were also established. Hoop turtle traps, funnel minnow traps, and dip nets were utilized for aquatic sampling. The presence of 43 species common to the region has been documented at Lost Lake. More than one-third of these species show evidence of breeding populations being established. Three species found prior to the restoration activity and a number of species common to undisturbed Carolina bays were not encountered. Colonization by additional species is anticipated as the wetland undergoes further succession.

  20. Alpha-2 adrenergic agonists for the prevention of cardiac complications among adults undergoing surgery.

    Science.gov (United States)

    Duncan, Dallas; Sankar, Ashwin; Beattie, W Scott; Wijeysundera, Duminda N

    2018-03-06

    The surgical stress response plays an important role on the pathogenesis of perioperative cardiac complications. Alpha-2 adrenergic agonists attenuate this response and may help prevent postoperative cardiac complications. To determine the efficacy and safety of α-2 adrenergic agonists for reducing mortality and cardiac complications in adults undergoing cardiac surgery and non-cardiac surgery. We searched CENTRAL (2017, Issue 4), MEDLINE (1950 to April Week 4, 2017), Embase (1980 to May 2017), the Science Citation Index, clinical trial registries, and reference lists of included articles. We included randomized controlled trials that compared α-2 adrenergic agonists (i.e. clonidine, dexmedetomidine or mivazerol) against placebo or non-α-2 adrenergic agonists. Included trials had to evaluate the efficacy and safety of α-2 adrenergic agonists for preventing perioperative mortality or cardiac complications (or both), or measure one or more relevant outcomes (i.e. death, myocardial infarction, heart failure, acute stroke, supraventricular tachyarrhythmia and myocardial ischaemia). Two authors independently assessed trial quality, extracted data and independently performed computer entry of abstracted data. We contacted study authors for additional information. Adverse event data were gathered from the trials. We evaluated included studies using the Cochrane 'Risk of bias' tool, and the quality of the evidence underlying pooled treatment effects using GRADE methodology. Given the clinical heterogeneity between cardiac and non-cardiac surgery, we analysed these subgroups separately. We expressed treatment effects as pooled risk ratios (RR) with 95% confidence intervals (CI). We included 47 trials with 17,039 participants. Of these studies, 24 trials only included participants undergoing cardiac surgery, 23 only included participants undergoing non-cardiac surgery and eight only included participants undergoing vascular surgery. The α-2 adrenergic agonist studied

  1. Antineoplastic Effects of PPARγ Agonists, with a Special Focus on Thyroid Cancer.

    Science.gov (United States)

    Ferrari, Silvia Martina; Materazzi, Gabriele; Baldini, Enke; Ulisse, Salvatore; Miccoli, Paolo; Antonelli, Alessandro; Fallahi, Poupak

    2016-01-01

    Peroxisome Proliferator-Activated Receptor-γ (PPARγ) is a ligand-activated nuclear hormone receptor that functions as transcription factor and plays an important role in lipid metabolism and insulin sensitization. Recent studies have shown that PPARγ is overexpressed in many tumor types, including cancers of breast, lung, pancreas, colon, glioblastoma, prostate and thyroid differentiated/anaplastic cancers. These data suggest a role of PPARγ in tumor development and/or progression. PPARγ is emerging as a growth-limiting and differentiation-promoting factor, and it exerts a tumor suppressor role. Moreover, naturally-occurring and synthetic PPARγ agonists promote growth inhibition and apoptosis. Thiazolidinediones (TZDs) are synthetic agonists of PPARγ that were developed to treat type II diabetes. These compounds also display anticancer effects which appear mainly to be independent of their PPARγ agonist activity. Various preclinical and clinical studies strongly suggest a role for TZDs both alone and in combination with existing chemotherapeutic agents, for the treatment of cancer. Differentiation therapy involves the use of agents with the ability to induce differentiation in cells that have lost this ability, i.e. cancer cells, targeting pathways capable of re-activating blocked terminal differentiation programs. PPARγ agonists have been shown to induce differentiation in solid tumors such as thyroid differentiated/ anaplastic cancers and sarcomas. However, emerging data suggest that chronic use of TZDs is associated with increased risk of adverse cardiovascular events. The exploration of newer PPARγ agonists can help in unveiling the underlying mechanisms of these drugs, providing new molecules that are able to treat cancer, without increasing the cardiovascular risk of neoplastic patients.

  2. The putative imidazoline receptor agonist, harmane, promotes intracellular calcium mobilisation in pancreatic beta-cells.

    Science.gov (United States)

    Squires, Paul E; Hills, Claire E; Rogers, Gareth J; Garland, Patrick; Farley, Sophia R; Morgan, Noel G

    2004-10-06

    beta-Carbolines (including harmane and pinoline) stimulate insulin secretion by a mechanism that may involve interaction with imidazoline I(3)-receptors but which also appears to be mediated by actions that are additional to imidazoline receptor agonism. Using the MIN6 beta-cell line, we now show that both the imidazoline I(3)-receptor agonist, efaroxan, and the beta-carboline, harmane, directly elevate cytosolic Ca(2+) and increase insulin secretion but that these responses display different characteristics. In the case of efaroxan, the increase in cytosolic Ca(2+) was readily reversible, whereas, with harmane, the effect persisted beyond removal of the agonist and resulted in the development of a repetitive train of Ca(2+)-oscillations whose frequency, but not amplitude, was concentration-dependent. Initiation of the Ca(2+)-oscillations by harmane was independent of extracellular calcium but was sensitive to both dantrolene and high levels (20 mM) of caffeine, suggesting the involvement of ryanodine receptor-gated Ca(2+)-release. The expression of ryanodine receptor-1 and ryanodine receptor-2 mRNA in MIN6 cells was confirmed using reverse transcription-polymerase chain reaction (RT-PCR) and, since low concentrations of caffeine (1 mM) or thimerosal (10 microM) stimulated increases in [Ca(2+)](i), we conclude that ryanodine receptors are functional in these cells. Furthermore, the increase in insulin secretion induced by harmane was attenuated by dantrolene, consistent with the involvement of ryanodine receptors in mediating this response. By contrast, the smaller insulin secretory response to efaroxan was unaffected by dantrolene. Harmane-evoked changes in cytosolic Ca(2+) were maintained by nifedipine-sensitive Ca(2+)-influx, suggesting the involvement of L-type voltage-gated Ca(2+)-channels. Taken together, these data imply that harmane may interact with ryanodine receptors to generate sustained Ca(2+)-oscillations in pancreatic beta-cells and that this effect

  3. 76 FR 70480 - Otay River Estuary Restoration Project, South San Diego Bay Unit of the San Diego Bay National...

    Science.gov (United States)

    2011-11-14

    ... River Estuary Restoration Project, South San Diego Bay Unit of the San Diego Bay National Wildlife...), intend to prepare an environmental impact statement (EIS) for the proposed Otay River Estuary Restoration... any one of the following methods. Email: [email protected] . Please include ``Otay Estuary NOI'' in the...

  4. PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR (PPAR) AGONISTS AS PROMISING NEW MEDICATIONS FOR DRUG ADDICTION: PRECLINICAL EVIDENCE

    Science.gov (United States)

    Foll, Bernard Le; Ciano, Patricia Di; Panlilio, Leigh V.; Goldberg, Steven R.; Ciccocioppo, Roberto

    2013-01-01

    This review examines the growing literature on the role of peroxisome proliferator-activated receptors (PPARs) in addiction. There are two subtypes of PPAR receptors that have been studied in addiction: PPAR-α and PPAR-γ. The role of each PPAR subtype in common models of addictive behavior, mainly pre-clinical models, is summarized. In particular, studies are reviewed that investigated the effects of PPAR-α agonists on relapse, sensitization, conditioned place preference, withdrawal and drug intake, and effects of PPAR-γ agonists on relapse, withdrawal and drug intake. Finally, studies that investigated the effects of PPAR agonists on neural pathways of addiction are reviewed. Taken together this preclinical data indicates that PPAR agonists are promising new medications for drug addiction treatment. PMID:23614675

  5. PENERAPAN ALGORITMA NAIVE BAYES UNTUK MENGKLASIFIKASI DATA NASABAH ASURANSI

    Directory of Open Access Journals (Sweden)

    Bustami Bustami

    2014-01-01

    Full Text Available Data mining adalah teknik yang memanfaatkan data dalam jumlah yang besar untuk memperoleh informasi berharga yang sebelumnya tidak diketahui dan dapat dimanfaatkan untuk pengambilan keputusan penting. Pada penelitian ini, penulis berusaha menambang data (data mining nasabah sebuah perusahaan asuransi untuk mengetahui lancar, kurang lancar atau tidak lancarnya nasabah tersebut. Data yang ada dianalisis menggunakan algoritma Naive Bayes. Naive Bayes merupakan salah satu meode pada probabilistic reasoning. Algoritma Naive Bayes bertujuan untuk melakukan klasifikasi data pada kelas tertentu, kemudian pola tersebut dapat digunakan untuk memperkirakan nasabah yang bergabung, sehingga perusahaan bisa mengambil keputusan menerima atau menolak calon nasabah tersebut. Kata Kunci : data mining, asuransi, klasifikasi, algoritma Naive Bayes

  6. Automation in tube finishing bay

    International Nuclear Information System (INIS)

    Bhatnagar, Prateek; Satyadev, B.; Raghuraman, S.; Syama Sundara Rao, B.

    1997-01-01

    Automation concept in tube finishing bay, introduced after the final pass annealing of PHWR tubes resulted in integration of number of sub-systems in synchronisation with each other to produce final cut fuel tubes of specified length, tube finish etc. The tube finishing bay which was physically segregated into four distinct areas: 1. tube spreader and stacking area, 2. I.D. sand blasting area, 3. end conditioning, wad blowing, end capping and O.D. wet grinding area, 4. tube inspection, tube cutting and stacking area has been studied

  7. Reports of pathological gambling, hypersexuality, and compulsive shopping associated with dopamine receptor agonist drugs.

    Science.gov (United States)

    Moore, Thomas J; Glenmullen, Joseph; Mattison, Donald R

    2014-12-01

    Severe impulse control disorders involving pathological gambling, hypersexuality, and compulsive shopping have been reported in association with the use of dopamine receptor agonist drugs in case series and retrospective patient surveys. These agents are used to treat Parkinson disease, restless leg syndrome, and hyperprolactinemia. To analyze serious adverse drug event reports about these impulse control disorders received by the US Food and Drug Administration (FDA) and to assess the relationship of these case reports with the 6 FDA-approved dopamine receptor agonist drugs. We conducted a retrospective disproportionality analysis based on the 2.7 million serious domestic and foreign adverse drug event reports from 2003 to 2012 extracted from the FDA Adverse Event Reporting System. Cases were selected if they contained any of 10 preferred terms in the Medical Dictionary for Regulatory Activities (MedDRA) that described the abnormal behaviors. We used the proportional reporting ratio (PRR) to compare the proportion of target events to all serious events for the study drugs with a similar proportion for all other drugs. We identified 1580 events indicating impulse control disorders from the United States and 21 other countries:710 fordopamine receptor agonist drugs and 870 for other drugs. The dopamine receptor agonist drugs had a strong signal associated with these impulse control disorders (n = 710; PRR = 277.6, P < .001). The association was strongest for the dopamine agonists pramipexole (n = 410; PRR = 455.9, P < .001) and ropinirole (n = 188; PRR = 152.5, P < .001), with preferential affinity for the dopamine D3 receptor. A signal was also seen for aripiprazole, an antipsychotic classified as a partial agonist of the D3 receptor (n = 37; PRR = 8.6, P < .001). Our findings confirm and extend the evidence that dopamine receptor agonist drugs are associated with these specific impulse control disorders. At present

  8. Pharmacological characterization of 30 human melanocortin-4 receptor polymorphisms with the endogenous proopiomelanocortin-derived agonists, synthetic agonists, and the endogenous agouti-related protein antagonist.

    Science.gov (United States)

    Xiang, Zhimin; Proneth, Bettina; Dirain, Marvin L; Litherland, Sally A; Haskell-Luevano, Carrie

    2010-06-08

    The melanocortin-4 receptor (MC4R) is a G-protein-coupled receptor (GPCR) that is expressed in the central nervous system and has a role in regulating feeding behavior, obesity, energy homeostasis, male erectile response, and blood pressure. Since the report of the MC4R knockout mouse in 1997, the field has been searching for links between this genetic biomarker and human obesity and type 2 diabetes. More then 80 single nucleotide polymorphisms (SNPs) have been identified from human patients, both obese and nonobese controls. Many significant studies have been performed examining the pharmacological characteristics of these hMC4R SNPs in attempts to identify a molecular defects/insights that might link a genetic factor to the obese phenotype observed in patients possessing these mutations. Our laboratory has previously reported the pharmacological characterization of 40 of these polymorphic hMC4 receptors with multiple endogenous and synthetic ligands. The goal of the current study is to perform a similar comprehensive side-by-side characterization of 30 additional human hMC4R with single nucleotide polymorphisms using multiple endogenous agonists [alpha-, beta-, and gamma(2)-melanocyte stimulating hormones (MSH) and adrenocorticotropin (ACTH)], the antagonist agouti-related protein hAGRP(87-132), and synthetic agonists [NDP-MSH, MTII, and the tetrapeptide Ac-His-dPhe-Arg-Trp-NH(2) (JRH887-9)]. These in vitro data, in some cases, provide a putative molecular link between dysfunctional hMC4R's and human obesity. These 30 hMC4R SNPs include R7H, R18H, R18L, S36Y, P48S, V50M, F51L, E61K, I69T, D90N, S94R, G98R, I121T, A154D, Y157S, W174C, G181D, F202L, A219 V, I226T, G231S, G238D, N240S, C271R, S295P, P299L, E308K, I317V, L325F, and 750DelGA. All but the N240S hMC4R were identified in obese patients. Additionally, we have characterized a double I102T/V103I hMC4R. In addition to the pharmacological characterization, the hMC4R variants were evaluated for cell surface

  9. Agonist-induced desensitization of human β3-adrenoceptors expressed in human embryonic kidney cells

    NARCIS (Netherlands)

    Michel-Reher, Martina B.; Michel, Martin C.

    2013-01-01

    β3-Adrenoceptors are resistant to agonist-induced desensitization in some cell types but susceptible in others including transfected human embryonic kidney (HEK) cells. Therefore, we have studied cellular and molecular changes involved in agonist-induced β3-adrenoceptor desensitization in HEK cells.

  10. Anti-calmodulins and tricyclic adjuvants in pain therapy block the TRPV1 channel.

    Directory of Open Access Journals (Sweden)

    Zoltán Oláh

    2007-06-01

    Full Text Available Ca(2+-loaded calmodulin normally inhibits multiple Ca(2+-channels upon dangerous elevation of intracellular Ca(2+ and protects cells from Ca(2+-cytotoxicity, so blocking of calmodulin should theoretically lead to uncontrolled elevation of intracellular Ca(2+. Paradoxically, classical anti-psychotic, anti-calmodulin drugs were noted here to inhibit Ca(2+-uptake via the vanilloid inducible Ca(2+-channel/inflamatory pain receptor 1 (TRPV1, which suggests that calmodulin inhibitors may block pore formation and Ca(2+ entry. Functional assays on TRPV1 expressing cells support direct, dose-dependent inhibition of vanilloid-induced (45Ca(2+-uptake at microM concentrations: calmidazolium (broad range > or = trifluoperazine (narrow range chlorpromazine/amitriptyline>fluphenazine>>W-7 and W-13 (only partially. Most likely a short acidic domain at the pore loop of the channel orifice functions as binding site either for Ca(2+ or anti-calmodulin drugs. Camstatin, a selective peptide blocker of calmodulin, inhibits vanilloid-induced Ca(2+-uptake in intact TRPV1(+ cells, and suggests an extracellular site of inhibition. TRPV1(+, inflammatory pain-conferring nociceptive neurons from sensory ganglia, were blocked by various anti-psychotic and anti-calmodulin drugs. Among them, calmidazolium, the most effective calmodulin agonist, blocked Ca(2+-entry by a non-competitive kinetics, affecting the TRPV1 at a different site than the vanilloid binding pocket. Data suggest that various calmodulin antagonists dock to an extracellular site, not found in other Ca(2+-channels. Calmodulin antagonist-evoked inhibition of TRPV1 and NMDA receptors/Ca(2+-channels was validated by microiontophoresis of calmidazolium to laminectomised rat monitored with extracellular single unit recordings in vivo. These unexpected findings may explain empirically noted efficacy of clinical pain adjuvant therapy that justify efforts to develop hits into painkillers, selective to sensory Ca(2

  11. Development of specific dopamine D-1 agonists and antagonists

    International Nuclear Information System (INIS)

    Sakolchai, S.

    1987-01-01

    To develop potentially selective dopamine D-1 agonists and to investigate on the structural requirement for D-1 activity, the derivatives of dibenzocycloheptadiene are synthesized and pharmacologically evaluated. The target compounds are 5-aminomethyl-10,11-dihydro-1,2-dihydroxy-5H-dibenzo[a,d]cycloheptene hydrobromide 10 and 9,10-dihydroxy-1,2,3,7,8,12b-hexahydrobenzo[1,2]cyclohepta[3,4,5d,e]isoquinoline hydrobromide 11. In a dopamine-sensitive rat retinal adenylate cyclase assay, a model for D-1 activity, compound 10 is essentially inert for both agonist and antagonist activity. In contrast, compound 11 is approximately equipotent to dopamine in activation of the D-1 receptor. Based on radioligand and binding data, IC 50 of compound 11 for displacement of 3 H-SCH 23390, a D-1 ligand, is about 7 fold less than that for displacement of 3 H-spiperone, a D-2 ligand. These data indicate that compound 11 is a potent selective dopamine D-1 agonist. This study provides a new structural class of dopamine D-1 acting agent: dihydroxy-benzocycloheptadiene analog which can serve as a lead compound for further drug development and as a probe for investigation on the nature of dopamine D-1 receptor

  12. 46 CFR 7.110 - Mamala Bay, HI.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Mamala Bay, HI. 7.110 Section 7.110 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Hawaii § 7.110 Mamala Bay, HI. A line drawn from Barbers Point Light to Diamond Head Light. Pacific Coast ...

  13. 33 CFR 165.1187 - Security Zones; Golden Gate Bridge and the San Francisco-Oakland Bay Bridge, San Francisco Bay...

    Science.gov (United States)

    2010-07-01

    ... Limited Access Areas Eleventh Coast Guard District § 165.1187 Security Zones; Golden Gate Bridge and the... Golden Gate Bridge and the San Francisco-Oakland Bay Bridge, in San Francisco Bay, California. (b... siren, radio, flashing light, or other means, the operator of a vessel shall proceed as directed. [COTP...

  14. Serotonin 2A receptor agonist binding in the human brain with [C]Cimbi-36

    DEFF Research Database (Denmark)

    Ettrup, A.; da Cunha-Bang, S.; McMahon, Barry P.

    2014-01-01

    [C]Cimbi-36 was recently developed as a selective serotonin 2A (5-HT) receptor agonist radioligand for positron emission tomography (PET) brain imaging. Such an agonist PET radioligand may provide a novel, and more functional, measure of the serotonergic system and agonist binding is more likely ....... Thus, we here describe [C]Cimbi-36 as the first agonist PET radioligand to successfully image and quantify 5-HT receptors in the human brain.Journal of Cerebral Blood Flow & Metabolism advance online publication, 30 April 2014; doi:10.1038/jcbfm.2014.68....... than antagonist binding to reflect 5-HT levels in vivo. Here, we show data from a first-in-human clinical trial with [C]Cimbi-36. In 29 healthy volunteers, we found high brain uptake and distribution according to 5-HT receptors with [C]Cimbi-36 PET. The two-tissue compartment model using arterial input...

  15. Effects of the small molecule HERG activator NS1643 on Kv11.3 channels.

    Directory of Open Access Journals (Sweden)

    Arne Bilet

    Full Text Available NS1643 is one of the small molecule HERG (Kv11.1 channel activators and has also been found to increase erg2 (Kv11.2 currents. We now investigated whether NS1643 is also able to act as an activator of Kv11.3 (erg3 channels expressed in CHO cells. Activation of rat Kv11.3 current occurred in a dose-dependent manner and maximal current increasing effects were obtained with 10 µM NS1643. At this concentration, steady-state outward current increased by about 80% and the current increase was associated with a significant shift in the voltage dependence of activation to more negative potentials by about 15 mV. In addition, activation kinetics were accelerated, whereas deactivation was slowed. There was no significant effect on the kinetics of inactivation and recovery from inactivation. The strong current-activating agonistic effect of NS1643 did not result from a shift in the voltage dependence of Kv11.3 channel inactivation and was independent from external Na(+ or Ca(2+. At the higher concentration of 20 µM, NS1643 induced clearly less current increase. The left shift in the voltage dependence of activation reversed and the voltage sensitivity of activation dramatically decreased along with a slowing of Kv11.3 channel activation. These data show that, in comparison to other Kv11 family members, NS1643 exerts distinct effects on Kv11.3 channels with especially pronounced partial antagonistic effects at higher concentration.

  16. Channel Power in Multi-Channel Environments

    NARCIS (Netherlands)

    M.G. Dekimpe (Marnik); B. Skiera (Bernd)

    2004-01-01

    textabstractIn the literature, little attention has been paid to instances where companies add an Internet channel to their direct channel portfolio. However, actively managing multiple sales channels requires knowing the customers’ channel preferences and the resulting channel power. Two key

  17. Tectonic framework of the Hanoe Bay area, southern Baltic Sea

    International Nuclear Information System (INIS)

    Wannaes, K.O.; Floden, T.

    1994-06-01

    The tectonic framework and the general geologic development of the Hanoe Bay, from the Scanian coast in the west to south of Oeland in the east, has been investigated by means of reflection seismic methods. The Hanoe Bay is in this paper subdivided into four areas of different geologic settings. These are: 1) The Hanoe Bay slope, which forms a southward dipping continuation of the rigid Blekinge coastal plain. 2) The eastward dipping Kalmarsund Slope, which southwards from Oeland forms the western part of the Paleozoic Baltic Syneclise. 3) The Mesozoic Hanoe Bay Halfgraben, which forms the central and southern parts of the Hanoe Bay. The ongoing subsidence of the Halfgraben is estimated to be in the order of 20-60 m during the Quaternary. 4) The Yoldia Structural Element, which forms a deformed, tilted and possibly rotated block of Paleozoic bedrock located east of the Hanoe Bay Halfgraben. Two tectonic phases dominate the post-Paleozoic development of the Hanoe Bay, these are: 1) The Early Kimmerian phase, which initiated subsidence and reactivated older faults. 2) The Late Cretaceous phase, which is the main subsidence phase of the Hanoe Bay Halfgraben. The tectonic fault pattern of the Hanoe Bay is dominated by three directions, i.e. NW-SE, NE-SW and WNW-ESE. The two main tectonic elements of the area are the Kullen-Christiansoe Ridge System (NW-SE) and the Bornholm Gat Tectonic Zone (NE-SW). Sinistral strike-slip movements in order of 2-3 km are interpreted to have occurred along the Bornholm Gat Tectonic Zone during the late Cretaceous. 20 refs, 19 figs

  18. Measuring Macrobenthos Biodiversity at Oyster Aquaculture Sites in the Delaware Inland Bays

    Science.gov (United States)

    Fuoco, M. J.; Ozbay, G.

    2016-12-01

    The Delaware Inland Bays consists of three shallow coastal bays located in the southern portion of Delaware. Anthropogenic activities have led to the degradation of water quality, because the bays are surrounded by highly developed areas and have low flushing rates. This results in loss of biodiversity and abundance of organisms. Ongoing degradation of the bays has led to a dramatic decline in local oyster populations since the late 1800s. Oysters are keystone species, which provide habitats for organisms and help to improve water quality. This study aims to find if the introduction of oyster aquaculture improves local biodiversity and abundance of macrobenthos. The study was conducted in Rehoboth Bay, Indian River Bay and Little Assawoman Bay. Aquaculture gear was placed at one location in each of the bays and 24 sediment core samples were taken once a month. From these core samples all worms were fixed and stained in a 10% Formalin Rose Bengal solution and preserved in 70% Ethanol for later identification. Stable carbon and nitrogen isotope analysis of oyster tissue will also be performed to assess the health of the bay. The goals of this research are to better understand the role of oyster aquaculture in restoring the viability and health of the Delaware Inland Bays.

  19. Use of Geographic Information Systems to examine cumulative impacts of development on Mobile Bay, AL and Galveston Bay, TX

    International Nuclear Information System (INIS)

    Rosigno, P.F.; McNiff, M.E.; Watzin, M.C.; Ji, W.

    1993-01-01

    Databases from Mobile Bay, Alabama and Galveston Bay, Texas were compiled using ARC/INFO Geographic Information Systems (GIS) to examine the cumulative impacts from urbanization and industrialization on these two Gulf of Mexico estuaries. The databases included information on wetland habitats, pollution sources, metal contamination, bird-nesting sites, and oyster reefs, among others. A series of maps were used to represent the impacts within and between each ecosystem. These two estuaries share many similarities in the types of developmental pressures that each experience. However, difference in the magnitude of industrial activity, pollution loading, and urban growth coupled with distinct hydrodynamic and geochemical differences in sediment mineralogy, freshwater inflows and salinity regimens results in differing responses. With growing human population and extensive oil and gas development, the demands on Galveston Bay are quite different than those placed on Mobile Bay which has lower growth and less extensive oil and gas infrastructure. Mobile Bay tends to retain whatever contamination enters into the system because of the high levels of clay and organic carbon found in its sediment. Some of these chemicals bioaccumulate, posing an extra risk to natural resources. Geographic Information Systems provide natural resource managers with the technology to manage complex databases. The analytical and mapping capabilities of GIS can be used to consider cumulative effects in a regional context and to develop plans to protect ecologically sensitive areas

  20. Relationships between precipitation and surface water chemistry in three Carolina bays

    International Nuclear Information System (INIS)

    Monegue, R.L.; Jagoe, C.H.

    1995-01-01

    Carolina Bays are shallow freshwater wetlands, the only naturally occurring lentic systems on the southeastern coastal plain. Bays are breeding sites for many amphibian species, but data on precipitation/surface water relationships and long-term chemical trends are lacking. Such data are essential to interpret major fluctuations in amphibian populations. Surface water and bulk precipitation were sampled bi-weekly for over two years at three bays along a 25 km transect on the Savannah River Site in South Carolina. Precipitation chemistry was similar at all sites; average pH was 4.56, and the major ions were H + (30.8 % of total), and SO 4 (50.3% of total). H + was positively correlated with SO 4 , suggesting the importance of anthropogenic acids to precipitation chemistry. All three bays, Rainbow Bay (RB), Thunder Bay (TB), and Ellenton Bay (EB), contained soft (specific conductivity 5--90 microS/cm), acidic water (pH 4.0--5.9) with DOM from 4--40 mg/L. The major cation for RB, TB, and EB, respectively, was: Mg (30.8 % of total); Na (27% of total); and Ca (34.2% of total). DOM was the major anion for all bays, and SO 4 represented 13 to 28 % of total anions. H + was not correlated to DOM or SO, in RB; H + was positively correlated to DOM and SO 4 in TB, and negatively correlated to DOM and SO 4 in EB. Different biogeochemical processes probably control pH and other chemical variables in each bay. While surface water H + was not directly correlated with precipitation H + , NO 3 , or SO 4 , precipitation and shallow groundwater are dominant water sources for these bays. Atmospheric inputs of anthropogenic acids and other chemicals are important factors influencing bay chemistry

  1. Hydrodynamics and water quality models applied to Sepetiba Bay

    Science.gov (United States)

    Cunha, Cynara de L. da N.; Rosman, Paulo C. C.; Ferreira, Aldo Pacheco; Carlos do Nascimento Monteiro, Teófilo

    2006-10-01

    A coupled hydrodynamic and water quality model is used to simulate the pollution in Sepetiba Bay due to sewage effluent. Sepetiba Bay has a complicated geometry and bottom topography, and is located on the Brazilian coast near Rio de Janeiro. In the simulation, the dissolved oxygen (DO) concentration and biochemical oxygen demand (BOD) are used as indicators for the presence of organic matter in the body of water, and as parameters for evaluating the environmental pollution of the eastern part of Sepetiba Bay. Effluent sources in the model are taken from DO and BOD field measurements. The simulation results are consistent with field observations and demonstrate that the model has been correctly calibrated. The model is suitable for evaluating the environmental impact of sewage effluent on Sepetiba Bay from river inflows, assessing the feasibility of different treatment schemes, and developing specific monitoring activities. This approach has general applicability for environmental assessment of complicated coastal bays.

  2. Inputs and spatial distribution patterns of Cr in Jiaozhou Bay

    Science.gov (United States)

    Yang, Dongfang; Miao, Zhenqing; Huang, Xinmin; Wei, Linzhen; Feng, Ming

    2018-03-01

    Cr pollution in marine bays has been one of the critical environmental issues, and understanding the input and spatial distribution patterns is essential to pollution control. In according to the source strengths of the major pollution sources, the input patterns of pollutants to marine bay include slight, moderate and heavy, and the spatial distribution are corresponding to three block models respectively. This paper analyzed input patterns and distributions of Cr in Jiaozhou Bay, eastern China based on investigation on Cr in surface waters during 1979-1983. Results showed that the input strengths of Cr in Jiaozhou Bay could be classified as moderate input and slight input, and the input strengths were 32.32-112.30 μg L-1 and 4.17-19.76 μg L-1, respectively. The input patterns of Cr included two patterns of moderate input and slight input, and the horizontal distributions could be defined by means of Block Model 2 and Block Model 3, respectively. In case of moderate input pattern via overland runoff, Cr contents were decreasing from the estuaries to the bay mouth, and the distribution pattern was parallel. In case of moderate input pattern via marine current, Cr contents were decreasing from the bay mouth to the bay, and the distribution pattern was parallel to circular. The Block Models were able to reveal the transferring process of various pollutants, and were helpful to understand the distributions of pollutants in marine bay.

  3. The effects of the dopamine agonist rotigotine on hemispatial neglect following stroke

    OpenAIRE

    Gorgoraptis, Nikos; Mah, Yee-Haur; Machner, Bjoern; Singh-Curry, Victoria; Malhotra, Paresh; Hadji-Michael, Maria; Cohen, David; Simister, Robert; Nair, Ajoy; Kulinskaya, Elena; Ward, Nick; Greenwood, Richard; Husain, Masud

    2012-01-01

    Hemispatial neglect following right-hemisphere stroke is a common and disabling disorder, for which there is currently no effective pharmacological treatment. Dopamine agonists have been shown to play a role in selective attention and working memory, two core cognitive components of neglect. Here, we investigated whether the dopamine agonist rotigotine would have a beneficial effect on hemispatial neglect in stroke patients. A double-blind, randomized, placebo-controlled ABA design was used, ...

  4. Bayes and Networks

    NARCIS (Netherlands)

    Gao, F.

    2017-01-01

    The dissertation consists of research in three subjects in two themes—Bayes and networks: The first studies the posterior contraction rates for the Dirichlet-Laplace mixtures in a deconvolution setting (Chapter 1). The second subject regards the statistical inference in preferential attachment

  5. Trends in Accretion Rates of Riverine Sediments in a Distal Bay and Wetlands Using 7-Beryllium as a Tracer: Fourleague Bay, Louisiana.

    Science.gov (United States)

    Restreppo, G. A.; Bentley, S. J.; Wang, J.; Xu, K.

    2017-12-01

    To combat land loss along the Mississippi River Delta, Louisiana has launched a historic campaign to sustain and regrow coastal lands using, in part, sediment diversions. Previous research has focused primarily on sand sized sediment load, which is usually deposited proximal to a river's delta or a diversion's outlet. Fine sediments constitute the majority of sediment load in the Mississippi, but are under-studied with respect to dispersal processes, particularly in terms of sediment supply to distal deltaic bays and wetlands. The Atchafalaya River and associated wetlands serve as prime study areas for this purpose. Bimonthly time-series push cores were collected from May 2015 to May 2016 along ten sites within Fourleague Bay, Louisiana. Fourleague Bay has remained stable against the deteriorative effects of relative sea level rise, standing out along Louisiana's declining coastline. Of the ten field sites, five are located across a longitudinal transect in the middle bay, while the other five are located in adjacent marshes. All sites fall within 10 to 30 km of the Atchafalaya Delta, extending south towards the Gulf of Mexico. Cores were extruded in 2 cm intervals, dried, ground, and analyzed via gamma spectrometry for the presence of 7Be. Inventories of 7Be were then calculated and used to determine daily mass accretion rate (MAR) over twelve months. Average MAR values for the bay and the marshes are compared with Atchafalaya River discharge, wind data, and atmospheric pressure through the year of sampling. Peak marsh MAR, 0.88 ± 0.20 kg m-2 d-1, occurs just after historically high river discharge. Peak bay MAR, 1.2 ± 0.67 kg m-2 d-1, occurs during seasonal low river discharge and calm winds. Average bay and marsh MARs have a moderate to strong, negative correlation when compared. Results indicate sediment bypass of the bay floor during periods of moderate to high river discharge, entering the marshes directly when inundation occurs and enhanced by the passage

  6. Potential of beta-adrenergic agonists for increasing protein deposition in ruminants in developing countries

    International Nuclear Information System (INIS)

    Berschauer, F.

    1989-01-01

    Various substituted phenylethanolamines, acting on the sympathetic nervous system, have been shown to increase protein retention (via decreased proteolysis) and reduce fat deposition (via increased lipolysis and reduced lipogenesis) in ruminants and monogastrics. Research with finishing lambs in developed countries show various beta-adrenergic agonists to improve growth rate (by 18%), feed conversion (by 12%) and carcass quality (28% increase in area of longissimus dorsi and 33% reduction in subcutaneous fat). Similar effects of beta-agonists on carcass composition of well fed cattle have been reported. The effects of beta-agonists on livestock in developing countries of the tropics have not yet been investigated, but their effects in increasing metabolic rate suggest that treated ruminants would be more vulnerable to hot environments. Beta-agonists appear to improve nitrogen retention to a greater extent in breeds with a lower potential for muscle growth. In view of this, they might be particularly effective in improving nitrogen retention in tropical breeds which have a low growth potential. This aspect, together with the response of undernourished animals in the developing countries, needs investigation. Beta-adrenergic agonists are not yet registered for use in animal production, but product licenses for some of them are expected to be granted soon. (author). 31 refs, 1 fig., 12 tabs

  7. Transcriptome analysis of endometrial tissues following GnRH agonist treatment in a mouse adenomyosis model

    Directory of Open Access Journals (Sweden)

    Guo S

    2017-03-01

    Full Text Available Song Guo,1,* Xiaowei Lu,1,* Ruihuan Gu,2 Di Zhang,3 Yijuan Sun,2 Yun Feng1 1Department of Obstetrics and Gynecology, Reproductive Medicine Center, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Gynecology, Shanghai Ji Ai Genetics & In Vitro Fertilization Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Gynecology and Obstetrics, Jinan Military General Hospital, Jinan, People’s Republic of China *These authors contributed equally to this work Purpose: Adenomyosis is a common, benign gynecological condition of the female reproductive tract characterized by heavy menstrual bleeding and dysmenorrhea. Gonadotropin-releasing hormone (GnRH agonists are one of the medications used in adenomyosis treatment; however, their underlying mechanisms are poorly understood. Moreover, it is difficult to obtain endometrial samples from women undergoing such treatment. To overcome this, we generated an adenomyosis mouse model, which we treated with an GnRH agonist to determine its effect on pregnancy outcomes. We also analyzed endometrial gene expression following GnRH agonist treatment to determine the mechanisms that may affect pregnancy outcome in individuals with adenomyosis.Methods: Neonatal female mice were divided into a control group, an untreated adenomyosis group, and an adenomyosis group treated with a GnRH agonist (n=6 each. The pregnancy outcome was observed and compared among the groups. Then, three randomly chosen transcriptomes from endometrial tissues from day 4 of pregnancy were analyzed between the adenomyosis group and the GnRH agonist treatment group by RNA sequencing and quantitative reverse transcription polymerase chain reaction (PCR.Results: The litter size was significantly smaller in the adenomyosis group than in the control group (7±0.28 vs 11±0.26; P<0.05. However, the average live litter

  8. Centennial record of anthropogenic impacts in Galveston Bay: Evidence from trace metals (Hg, Pb, Ni, Zn) and lignin oxidation products.

    Science.gov (United States)

    Al Mukaimi, Mohammad E; Kaiser, Karl; Williams, Joshua R; Dellapenna, Timothy M; Louchouarn, Patrick; Santschi, Peter H

    2018-06-01

    During the 20th century the impacts of industrialization and urbanization in Galveston Bay resulted in significant shifts in trace metals (Hg, Pb, Ni, Zn) and vascular plant biomarkers (lignin phenols) recorded within the surface sediments and sediment cores profile. A total of 22 sediment cores were collected in Galveston Bay in order to reconstruct the historical input of Hg, Pb, Ni, Zn and terrestrial organic matter. Total Hg (T-Hg) concentration ranged between 6 and 162 ng g -1 in surface sediments, and showed decreasing concentrations southward from the Houston Ship Channel (HSC) toward the open estuary. Core profiles of T-Hg and trace metals (Ni, Zn) showed substantial inputs starting in 1905, with peak concentrations between 1960 and 1970's, and decreasing thereafter with exception to Pb, which peaked around 1930-1940s. Stable carbon isotopes and lignin phenols showed an increasing input of terrestrial organic matter driven by urban development within the watershed in the early 1940s. Both the enrichment factor and the geoaccumulation index (I geo ) for T-Hg as a measure of the effectiveness of environmental management practices showed substantial improvements since the 1970s. The natural recovery rate in Galveston Bay since the peak input of T-Hg was non-linear and displayed a slow recovery during the twenty-first century. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Theories of transporting processes of Cu in Jiaozhou Bay

    Science.gov (United States)

    Yang, Dongfang; Su, Chunhua; Zhu, Sixi; Wu, Yunjie; Zhou, Wei

    2018-02-01

    Many marine bays have been polluted along with the rapid development of industry and population size, and understanding the transporting progresses of pollutants is essential to pollution control. In order to better understanding the transporting progresses of pollutants in marine, this paper carried on a comprehensive research of the theories of transporting processes of Cu in Jiaozhou Bay. Results showed that the transporting processes of Cu in this bay could be summarized into seven key theories including homogeneous theory, environmental dynamic theory, horizontal loss theory, source to waters transporting theory, sedimentation transporting theory, migration trend theory and vertical transporting theory, respectively. These theories helpful to better understand the migration progress of pollutants in marine bay.

  10. Innate Immune Responses to TLR2 and TLR4 Agonists Differ between Baboons, Chimpanzees and Humans

    Science.gov (United States)

    Brinkworth, Jessica F.; Pechenkina, Ekaterina A.; Silver, Jack; Goyert, Sanna M.

    2012-01-01

    Background African catarrhine primates differ in bacterial disease susceptibility. Methods Human, chimpanzee, and baboon blood was stimulated with TLR-detected bacterial agonists and cytokine/chemokine induction assessed by real-time pcr. Results Humans and chimpanzees shared similar cytokine/chemokine responses, while baboon cytokine/chemokine induction differed. Generally, responses were agonist-independent. Conclusions These primates tend to generate species rather than agonist–specific responses to bacterial agonists. PMID:22978822

  11. An integrated platform for simultaneous multi-well field potential recording and Fura-2-based calcium transient ratiometry in human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes.

    Science.gov (United States)

    Rast, Georg; Weber, Jürgen; Disch, Christoph; Schuck, Elmar; Ittrich, Carina; Guth, Brian D

    2015-01-01

    Human induced pluripotent stem cell-derived cardiomyocytes are available from various sources and they are being evaluated for safety testing. Several platforms are available offering different assay principles and read-out parameters: patch-clamp and field potential recording, imaging or photometry, impedance measurement, and recording of contractile force. Routine use will establish which assay principle and which parameters best serve the intended purpose. We introduce a combination of field potential recording and calcium ratiometry from spontaneously beating cardiomyocytes as a novel assay providing a complementary read-out parameter set. Field potential recording is performed using a commercial multi-well multi-electrode array platform. Calcium ratiometry is performed using a fiber optic illumination and silicon avalanche photodetectors. Data condensation and statistical analysis are designed to enable statistical inference of differences and equivalence with regard to a solvent control. Simultaneous recording of field potentials and calcium transients from spontaneously beating monolayers was done in a nine-well format. Calcium channel blockers (e.g. nifedipine) and a blocker of calcium store release (ryanodine) can be recognized and discriminated based on the calcium transient signal. An agonist of L-type calcium channels, FPL 64176, increased and prolonged the calcium transient, whereas BAY K 8644, another L-type calcium channel agonist, had no effect. Both FPL 64176 and various calcium channel antagonists have chronotropic effects, which can be discriminated from typical "chronotropic" compounds, like (±)isoprenaline (positive) and arecaidine propargyl ester (negative), based on their effects on the calcium transient. Despite technical limitations in temporal resolution and exact matching of composite calcium transient with the field potential of a subset of cells, the combined recording platform enables a refined interpretation of the field potential

  12. Involvement of Ca2+ Signaling in the Synergistic Effects between Muscarinic Receptor Antagonists and β2-Adrenoceptor Agonists in Airway Smooth Muscle

    Directory of Open Access Journals (Sweden)

    Kentaro Fukunaga

    2016-09-01

    Full Text Available Long-acting muscarinic antagonists (LAMAs and short-acting β2-adrenoceptor agonists (SABAs play important roles in remedy for COPD. To propel a translational research for development of bronchodilator therapy, synergistic effects between SABAs with LAMAs were examined focused on Ca2+ signaling using simultaneous records of isometric tension and F340/F380 in fura-2-loaded tracheal smooth muscle. Glycopyrronium (3 nM, a LAMA, modestly reduced methacholine (1 μM-induced contraction. When procaterol, salbutamol and SABAs were applied in the presence of glycopyrronium, relaxant effects of these SABAs are markedly enhanced, and percent inhibition of tension was much greater than the sum of those for each agent and those expected from the BI theory. In contrast, percent inhibition of F340/F380 was not greater than those values. Bisindolylmaleimide, an inhibitor of protein kinase C (PKC, significantly increased the relaxant effect of LAMA without reducing F340/F380. Iberiotoxin, an inhibitor of large-conductance Ca2+-activated K+ (KCa channels, significantly suppressed the effects of these combined agents with reducing F340/F380. In conclusion, combination of SABAs with LAMAs synergistically enhances inhibition of muscarinic contraction via decreasing both Ca2+ sensitization mediated by PKC and Ca2+ dynamics mediated by KCa channels. PKC and KCa channels may be molecular targets for cross talk between β2-adrenoceptors and muscarinic receptors.

  13. Hammond Bay Biological Station

    Data.gov (United States)

    Federal Laboratory Consortium — Hammond Bay Biological Station (HBBS), located near Millersburg, Michigan, is a field station of the USGS Great Lakes Science Center (GLSC). HBBS was established by...

  14. Inward rectifier potassium (Kir2.1) channels as end‐stage boosters of endothelium‐dependent vasodilators

    Science.gov (United States)

    Dalsgaard, Thomas; Bonev, Adrian D.; Nelson, Mark T.

    2016-01-01

    Key points Increase in endothelial cell (EC) calcium activates calcium‐sensitive intermediate and small conductance potassium (IK and SK) channels, thereby causing hyperpolarization and endothelium‐dependent vasodilatation.Endothelial cells express inward rectifier potassium (Kir) channels, but their role in endothelium‐dependent vasodilatation is not clear.In the mesenteric arteries, only ECs, but not smooth muscle cells, displayed Kir currents that were predominantly mediated by the Kir2.1 isoform.Endothelium‐dependent vasodilatations in response to muscarinic receptor, TRPV4 (transient receptor potential vanilloid 4) channel and IK/SK channel agonists were highly attenuated by Kir channel inhibitors and by Kir2.1 channel knockdown.These results point to EC Kir channels as amplifiers of vasodilatation in response to increases in EC calcium and IK/SK channel activation and suggest that EC Kir channels could be targeted to treat endothelial dysfunction, which is a hallmark of vascular disorders. Abstract Endothelium‐dependent vasodilators, such as acetylcholine, increase intracellular Ca2+ through activation of transient receptor potential vanilloid 4 (TRPV4) channels in the plasma membrane and inositol trisphosphate receptors in the endoplasmic reticulum, leading to stimulation of Ca2+‐sensitive intermediate and small conductance K+ (IK and SK, respectively) channels. Although strong inward rectifier K+ (Kir) channels have been reported in the native endothelial cells (ECs) their role in EC‐dependent vasodilatation is not clear. Here, we test the idea that Kir channels boost the EC‐dependent vasodilatation of resistance‐sized arteries. We show that ECs, but not smooth muscle cells, of small mesenteric arteries have Kir currents, which are substantially reduced in EC‐specific Kir2.1 knockdown (EC‐Kir2.1 −/−) mice. Elevation of extracellular K+ to 14 mm caused vasodilatation of pressurized arteries, which was prevented by endothelial

  15. Inward rectifier potassium (Kir2.1) channels as end-stage boosters of endothelium-dependent vasodilators.

    Science.gov (United States)

    Sonkusare, Swapnil K; Dalsgaard, Thomas; Bonev, Adrian D; Nelson, Mark T

    2016-06-15

    Increase in endothelial cell (EC) calcium activates calcium-sensitive intermediate and small conductance potassium (IK and SK) channels, thereby causing hyperpolarization and endothelium-dependent vasodilatation. Endothelial cells express inward rectifier potassium (Kir) channels, but their role in endothelium-dependent vasodilatation is not clear. In the mesenteric arteries, only ECs, but not smooth muscle cells, displayed Kir currents that were predominantly mediated by the Kir2.1 isoform. Endothelium-dependent vasodilatations in response to muscarinic receptor, TRPV4 (transient receptor potential vanilloid 4) channel and IK/SK channel agonists were highly attenuated by Kir channel inhibitors and by Kir2.1 channel knockdown. These results point to EC Kir channels as amplifiers of vasodilatation in response to increases in EC calcium and IK/SK channel activation and suggest that EC Kir channels could be targeted to treat endothelial dysfunction, which is a hallmark of vascular disorders. Endothelium-dependent vasodilators, such as acetylcholine, increase intracellular Ca(2+) through activation of transient receptor potential vanilloid 4 (TRPV4) channels in the plasma membrane and inositol trisphosphate receptors in the endoplasmic reticulum, leading to stimulation of Ca(2+) -sensitive intermediate and small conductance K(+) (IK and SK, respectively) channels. Although strong inward rectifier K(+) (Kir) channels have been reported in the native endothelial cells (ECs) their role in EC-dependent vasodilatation is not clear. Here, we test the idea that Kir channels boost the EC-dependent vasodilatation of resistance-sized arteries. We show that ECs, but not smooth muscle cells, of small mesenteric arteries have Kir currents, which are substantially reduced in EC-specific Kir2.1 knockdown (EC-Kir2.1(-/-) ) mice. Elevation of extracellular K(+) to 14 mm caused vasodilatation of pressurized arteries, which was prevented by endothelial denudation and Kir channel

  16. THE RESPONSE OF MONTEREY BAY TO THE 2010 CHILEAN EARTHQUAKE

    Directory of Open Access Journals (Sweden)

    Laurence C. Breaker

    2011-01-01

    Full Text Available The primary frequencies contained in the arrival sequence produced by the tsunami from the Chilean earthquake of 2010 in Monterey Bay were extracted to determine the seiche modes that were produced. Singular Spectrum Analysis (SSA and Ensemble Empirical Mode Decomposition (EEMD were employed to extract the primary frequencies of interest. The wave train from the Chilean tsunami lasted for at least four days due to multipath arrivals that may not have included reflections from outside the bay but most likely did include secondary undulations, and energy trapping in the form of edge waves, inside the bay. The SSA decomposition resolved oscillations with periods of 52-57, 34-35, 26-27, and 21-22 minutes, all frequencies that have been predicted and/or observed in previous studies. The EEMD decomposition detected oscillations with periods of 50-55 and 21-22 minutes. Periods in the range of 50-57 minutes varied due to measurement uncertainties but almost certainly correspond to the first longitudinal mode of oscillation for Monterey Bay, periods of 34-35 minutes correspond to the first transverse mode of oscillation that assumes a nodal line across the entrance of the bay, a period of 26- 27 minutes, although previously observed, may not represent a fundamental oscillation, and a period of 21-22 minutes has been predicted and observed previously. A period of ~37 minutes, close to the period of 34-35 minutes, was generated by the Great Alaskan Earthquake of 1964 in Monterey Bay and most likely represents the same mode of oscillation. The tsunamis associated with the Great Alaskan Earthquake and the Chilean Earthquake both entered Monterey Bay but initially arrived outside the bay from opposite directions. Unlike the Great Alaskan Earthquake, however, which excited only one resonant mode inside the bay, the Chilean Earthquake excited several modes suggesting that the asymmetric shape of the entrance to Monterey Bay was an important factor and that the

  17. Pärnu Bay Golf Club = Pärnu Bay Golf Club / Arhitekt11

    Index Scriptorium Estoniae

    2016-01-01

    Pärnu Bay Golf Club, arhitektid Jürgen Lepper, Anto Savi, Margus Soonets, Janar Toomesso (Arhitekt11), sisearhitektid Liina Vaino, Kaari Metslang, Hannelore Kääramees (Arhitekt11). Kultuurkapitali Arhitektuuri sihtkapitali aastapreemia nominent 2016

  18. The role of voltage-gated potassium channels in the regulation of mouse uterine contractility

    Directory of Open Access Journals (Sweden)

    Abel Peter W

    2007-11-01

    Full Text Available Abstract Background Uterine smooth muscle cells exhibit ionic currents that appear to be important in the control of uterine contractility, but how these currents might produce the changes in contractile activity seen in pregnant myometrium has not been established. There are conflicting reports concerning the role of voltage-gated potassium (Kv channels and large-conductance, calcium-activated potassium (BK channels in the regulation of uterine contractility. In this study we provide molecular and functional evidence for a role for Kv channels in the regulation of spontaneous contractile activity in mouse myometrium, and also demonstrate a change in Kv channel regulation of contractility in pregnant mouse myometrium. Methods Functional assays which evaluated the effects of channel blockers and various contractile agonists were accomplished by quantifying contractility of isolated uterine smooth muscle obtained from nonpregnant mice as well as mice at various stages of pregnancy. Expression of Kv channel proteins in isolated uterine smooth muscle was evaluated by Western blots. Results The Kv channel blocker 4-aminopyridine (4-AP caused contractions in nonpregnant mouse myometrium (EC50 = 54 micromolar, maximal effect at 300 micromolar but this effect disappeared in pregnant mice; similarly, the Kv4.2/Kv4.3 blocker phrixotoxin-2 caused contractions in nonpregnant, but not pregnant, myometrium. Contractile responses to 4-AP were not dependent upon nerves, as neither tetrodotoxin nor storage of tissues at room temperature significantly altered these responses, nor were responses dependent upon the presence of the endometrium. Spontaneous contractions and contractions in response to 4-AP did not appear to be mediated by BK, as the BK channel-selective blockers iberiotoxin, verruculogen, or tetraethylammonium failed to affect either spontaneous contractions or 4-AP-elicited responses. A number of different Kv channel alpha subunit proteins were

  19. Microbial biogeography of San Francisco Bay sediments

    Science.gov (United States)

    Lee, J. A.; Francis, C. A.

    2014-12-01

    The largest estuary on the west coast of North America, San Francisco Bay is an ecosystem of enormous biodiversity, and also enormous human impact. The benthos has experienced dredging, occupation by invasive species, and over a century of sediment input as a result of hydraulic mining. Although the Bay's great cultural and ecological importance has inspired numerous surveys of the benthic macrofauna, to date there has been almost no investigation of the microbial communities on the Bay floor. An understanding of those microbial communities would contribute significantly to our understanding of both the biogeochemical processes (which are driven by the microbiota) and the physical processes (which contribute to microbial distributions) in the Bay. Here, we present the first broad survey of bacterial and archaeal taxa in the sediments of the San Francisco Bay. We conducted 16S rRNA community sequencing of bacteria and archaea in sediment samples taken bimonthly for one year, from five sites spanning the salinity gradient between Suisun and Central Bay, in order to capture the effect of both spatial and temporal environmental variation on microbial diversity. From the same samples we also conducted deep sequencing of a nitrogen-cycling functional gene, nirS, allowing an assessment of evolutionary diversity at a much finer taxonomic scale within an important and widespread functional group of bacteria. We paired these sequencing projects with extensive geochemical metadata as well as information about macrofaunal distribution. Our data reveal a diversity of distinct biogeographical patterns among different taxa: clades ubiquitous across sites; clades that respond to measurable environmental drivers; and clades that show geographical site-specificity. These community datasets allow us to test the hypothesis that salinity is a major driver of both overall microbial community structure and community structure of the denitrifying bacteria specifically; and to assess

  20. Discovery of novel acetanilide derivatives as potent and selective beta3-adrenergic receptor agonists.

    Science.gov (United States)

    Maruyama, Tatsuya; Onda, Kenichi; Hayakawa, Masahiko; Matsui, Tetsuo; Takasu, Toshiyuki; Ohta, Mitsuaki

    2009-06-01

    In the search for potent and selective human beta3-adrenergic receptor (AR) agonists as potential drugs for the treatment of obesity and noninsulin-dependent (type II) diabetes, a novel series of acetanilide-based analogues were prepared and their biological activities were evaluated at the human beta3-, beta2-, and beta1-ARs. Among these compounds, 2-pyridylacetanilide (2f), pyrimidin-2-ylacetanilide (2u), and pyrazin-2-ylacetanilide (2v) derivatives exhibited potent agonistic activity at the beta3-AR with functional selectivity over the beta1- and beta2-ARs. In particular, compound 2u was found to be the most potent and selective beta3-AR agonist with an EC(50) value of 0.11 microM and no agonistic activity for either the beta1- or beta2-AR. In addition, 2f, 2u, and 2v showed significant hypoglycemic activity in a rodent diabetic model.