Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter.

A second isoform of the human vesicular monoamine transporter (hVMAT) has been cloned from a pheochromocytoma cDNA library. The contribution of the two transporter isoforms to monoamine storage in human neuroendocrine tissues was examined with isoform-specific polyclonal antibodies against hVMAT1 and hVMAT2. Central, peripheral, and enteric neurons express only VMAT2. VMAT1 is expressed exclusively in neuroendocrine, including chromaffin and enterochromaffin, cells. VMAT1 and VMAT2 are coexpressed in all chromaffin cells of the adrenal medulla. VMAT2 alone is expressed in histamine-storing enterochromaffin-like cells of the oxyntic mucosa of the stomach. The transport characteristics and pharmacology of each VMAT isoform have been directly compared after expression in digitonin-permeabilized fibroblastic (CV-1) cells, providing information about substrate feature recognition by each transporter and the role of vesicular monoamine storage in the mechanism of action of psychopharmacologic and neurotoxic agents in human. Serotonin has a similar affinity for both transporters. Catecholamines exhibit a 3-fold higher affinity, and histamine exhibits a 30-fold higher affinity, for VMAT2. Reserpine and ketanserin are slightly more potent inhibitors of VMAT2-mediated transport than of VMAT1-mediated transport, whereas tetrabenazine binds to and inhibits only VMAT2. N-methyl-4-phenylpyridinium, phenylethylamine, amphetamine, and methylenedioxymethamphetamine are all more potent inhibitors of VMAT2 than of VMAT1, whereas fenfluramine is a more potent inhibitor of VMAT1-mediated monamine transport than of VMAT2-mediated monoamine transport. The unique distributions of hVMAT1 and hVMAT2 provide new markers for multiple neuroendocrine lineages, and examination of their transport properties provides mechanistic insights into the pharmacology and physiology of amine storage in cardiovascular, endocrine, and central nervous system function.

Nerve growth factor in the anterior pituitary: localization in mammotroph cells and cosecretion with prolactin by a dopamine-regulated mechanism.

Nerve growth factor (NGF) is well characterized for its neurotrophic actions on peripheral sensory and sympathetic neurons and on central cholinergic neurons of the basal forebrain. Recent evidence, however, has shown high levels of NGF to be present in a variety of biological fluids after inflammatory and autoimmune responses, suggesting that NGF is a mediator of immune interactions. Increased NGF serum levels have been reported in both humans and experimental animal models of psychological and physical stress, thus implicating NGF in neuroendocrine interactions as well. The possible source(s) and the regulatory mechanisms involved in the control of serum NGF levels, however, still remain to be elucidated. We now report the presence of both NGF gene transcripts and protein in the anterior pituitary. Immunofluorescence analysis indicated that hypophysial NGF is selectively localized in mammotroph cells and stored in secretory granules. NGF is cosecreted with prolactin from mammotroph cells by a neurotransmitter-dependent mechanism that can be pharmacologically regulated. Activation of the dopamine D2 receptor subtype, which physiologically controls prolactin release, resulted in a complete inhibition of vasoactive intestinal peptide-stimulated NGF secretion in vitro, whereas the specific D2 antagonist (-)-sulpiride stimulated NGF secretion in vivo, suggesting that the anterior pituitary is a possible source of circulating NGF. Given the increased NGF serum levels in stressful conditions and the newly recognized immunoregulatory function of this protein, NGF, together with prolactin, may thus be envisaged as an immunological alerting signal under neuronal control.

One of Us: Joseph Conrad's Under Western Eyes and A Personal Record

Author: Torgeir Ehler Title: One of Us: Joseph Conrad's Under Western Eyes and A Personal Record Advisor: Jan Gorak Degree Date: June 2009 Abstract This present work explores the relationship of Joseph Conrad's status as a Polish exile to his creative and biographical work. Its main focus is on the tandem publications of the novel Under Western Eyes and his autobiographical volume A Personal Record, both published within a year of each other and written contemporaneously. The first chapter is a short biographical survey of Conrad's life and addresses some later biographical works by his wife, among others. An overview of critical works that deal with Under Western Eyes is presented in the second chapter. An investigation into narrative structure and its use in creating a heteroglossic text is investigated in the third chapter. How this strategy reflects Conrad's personal stake in the novel and how the novel and its creation affected the author's ability to cope with his own homo-duplex geographies is also addressed herein. The fourth chapter then concerns itself with Conrad's attempt to create a truly heteroglossic, autobiographically based persona for public consumption in Britain, while keeping true to his function as a `cultural bridge'. An early effort at communicating the exile's predicament and failure to bridge the cultural divide in the story `Amy Foster' is taken up in the fifth and final chapter. The legacy of Conrad's effort is also discussed herein as relevant to the work of Milan Kundera and Erich Maria Remarque.

Portland, Oregon, 1901 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of Portland, Oregon. It was published by C.H. Crocker Co. Lith. in 1901. Scale [ca. 1:22,000]. Covers portions of Portland and Beaverton, Oregon. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Oregon North State Plane NAD 1983 (in Feet) (Fipszone 3601). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads and stations, drainage, selected buildings, property lots and numbers, city and ward boundaries, parks and cemeteries, and more. Depths shown by soundings. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

EU Democratic Legitimacy and National Parliaments. CEPS Essay No. 7, 25 November 2013

The role of national parliaments in the EU has been at the centre of a long debate. Since the Maastricht treaty, new powers to the EU level have been accompanied not only by an increasing role of the European Parliament (EP) in the legislative process, but also by a number of declarations and protocols to ensure that national parliaments received the information and documents required to effectively monitor their governments in EU affairs. The Lisbon Treaty extended the guarantees and also included new modes of direct participation. The proper use of the mechanisms in place, namely, the subsidiarity checks, the political dialogue with the Commission and the inter-parliamentary cooperation with the European Parliament, has become of vital importance in view of recent developments in EU economic policy and beyond. The choice for increasing inter-governmentalism in decision-making and the centralisation of the implementing and supervisory powers in the Commission and the Central Bank have raised questions about political accountability and the appropriate involvement of parliaments. However, the extent to which national parliaments should be more involved is also rather controversial. This essay examines the difficulty of defining and addressing the question of the democratic legitimacy in the EU. It examines the role of the national parliaments in the treaties and explores ways in which they can contribute to improving that legitimacy.

Nord Stream II-testing EU and credibility. EPC Commentary, 16 December 2015

In September 2015, Gazprom and major European energy companies (Germany's E.ON and BASF/Wintershall, Austria's OMV, France’s ENGIE and Royal Dutch Shell) signed an agreement to double the Nord Stream gas pipeline’s capacity by 2019. The plan is to transport up to 55 billion additional cubic metres of gas a year to Germany through the Baltic Sea, bypassing Ukraine and other Central-Eastern European countries.

Detrital zircon geochronology data, petrographic point count data and paleocurrent indicator data of Triassic turbidites in the Nanpanjiang Basin, South China

Triassic turbidites of the Nanpanjiang basin of south China represent the most expansive and voluminous siliciclastic turbidite accumulation in south China. The Nanpanjiang basin occurs at a critical junction between the southern margin of the south China plate and the Indochina, Siamo and Sibumasu plates to the south and southwest. The Triassic Yangtze carbonate shelf and isolated carbonated platforms in the basin have been extensively studied, but silicilastic turbidites in the basin have received relatively little attention. Deciphering the facies, paleocurrent indicators and provenance of the Triassic turbidites is important for several reasons: it promises to help resolve the timing of plate collisions along suture zones bordering the basin to the south and southwest, it will enable evaluation of which suture zones and Precambrian massifs were source areas, and it will allow an evaluation of the impact of the siliciclastic flux on carbonate platform evolution within the basin. Turbidites in the basin include the Early Triassic Shipao Formation and the Middle-Late Triassic Baifeng, Xinyuan, Lanmu Bianyang and Laishike formations. Each ranges upward of 700 m and the thickest is nearly 3 km. The turbidites contain very-fine sand in the northern part of the basin whereas the central and southern parts of the basin also commonly contain fine and rarely medium sand size. Coarser sand sizes occur where paleocurrents are from the south, and in this area some turbidites exhibit complete bouma sequences with graded A divisions. Successions contain numerous alternations between mud-rich and sand-rich intervals with thickness trends corresponding to proximal/ distal fan components. Spectacularly preserved sedimentary structures enable robust evaluation of turbidite systems and paleocurrent analyses. Analysis of paleocurrent measurements indicates two major directions of sediment fill. The northern part of the basin was sourced primarily by the Jiangnan massif in the northeast, and the central and southern parts of the basin were sourced primarily from suture zones and the Yunkai massif to the south and southeast respectively. Sandstones of the Lower Triassic Shipao Fm. have volcaniclastic composition including embayed quartz and glass shards. Middle Triassic sandstones are moderately mature, matrix-rich, lithic wackes. The average QFL ratio from all point count samples is 54.1/18.1/27.8% and the QmFLt ratio is 37.8/ 18.1/ 44.1%. Lithic fragments are dominantly claystone and siltstone clasts and metasedimentary clasts such as quartz mica tectonite. Volcanic lithics are rare. Most samples fall in the recycled orogen field of QmFLt plots, indicating a relatively quartz and lithic rich composition consistent with derivation from Precambrian massifs such as the Jiangnan, and Yunkai. A few samples from the southwest part of the basin fall into the dissected arc field, indicating a somewhat more lithic and feldspar-rich composition consistent with derivation from a suture zone Analysis of detrial zircon populations from 17 samples collected across the basin indicate: (1) Several samples contain zircons with concordant ages greater than 3000 Ma, (2) there are widespread peaks across the basin at 1800 Ma and 2500, (3) a widespread 900 Ma population, (3) a widespread population of zircons at 440 Ma, and (5) a larger population of younger zircons about 250 Ma in the southwestern part which is replaced to the north and northwest by a somewhat older population around 260-290 Ma. The 900 Ma provenance fits derivation from the Jiangnan Massif, the 2500, 1800, and 440 Ma provenance fits the Yunkai massif, and the 250 Ma is consistent with convergence and arc development in suture zones bordering the basin on the south or southwest. Early siliciclastic turbidite flux, proximal to source areas impacted carbonate platform evolution by infilling the basin, reducing accommodation space, stabilizing carbonate platform margins and promoting margin progradation. Late arrival, in areas far from source areas caused margin aggradation over a starved basin, development of high relief aggradational escarpments and unstable scalloped margins.

The development of an improved railroad-highway grade crossing risk factor. Executive summry report.

Ohio Department of Transportation, Columbus

The development of an improved railroad-highway grade crossing risk factor. Final report.

Ohio Department of Transportation, Columbus