Neurosecretory vesicles can be hybrids of synaptic vesicles and secretory granules.

We have investigated the relationship of the so-called small dense core vesicle (SDCV), the major catecholamine-containing neurosecretory vesicle of sympathetic neurons, to synaptic vesicles containing classic neurotransmitters and secretory granules containing neuropeptides. SDCVs contain membrane proteins characteristic of synaptic vesicles such as synaptophysin and synaptoporin. However, SDCVs also contain membrane proteins characteristic of certain secretory granules like the vesicular monoamine transporter and the membrane-bound form of dopamine beta-hydroxylase. In neurites of sympathetic neurons, synaptophysin and dopamine beta-hydroxylase are found in distinct vesicles, consistent with their transport from the trans-Golgi network to the site of SDCV formation in constitutive secretory vesicles and secretory granules, respectively. Hence, SDCVs constitute a distinct type of neurosecretory vesicle that is a hybrid of the synaptic vesicle and the secretory granule membranes and that originates from the contribution of both the constitutive and the regulated pathway of protein secretion.

Cloning and expression of two brain-specific inwardly rectifying potassium channels.

We have cloned two inwardly rectifying K+ channels that occur selectively in neurons in the brain and are designated BIRK (brain inwardly rectifying K+) channels. BIRK1 mRNA is extremely abundant and is enriched in specific brainstem nuclei, BIRK1 displays a consensus phosphate-binding loop, and expression in Xenopus oocytes has shown that its conductance is inhibited by ATP and adenosine 5'-[gamma-thio]triphosphate. BIRK2 is far less abundant and is selectively localized in telencephalic neurons. BIRK2 has a consensus sequence for cAMP-dependent phosphorylation.

Two cystic fibrosis transmembrane conductance regulator mutations have different effects on both pulmonary phenotype and regulation of outwardly rectified chloride currents.

Cystic fibrosis (CF), a disorder of electrolyte transport manifest in the lungs, pancreas, sweat duct, and vas deferens, is caused by mutations in the CF transmembrane conductance regulator (CFTR). The CFTR protein has been shown to function as a cAMP-activated chloride channel and also regulates a separate protein, the outwardly rectifying chloride channel (ORCC). To determine the consequence of disease-producing mutations upon these functions, mutant CFTR was transiently expressed in Xenopus oocytes and in human airway epithelial cells lacking functional CFTR. Both G551D, a mutation that causes severe lung disease, and A455E, a mutation associated with mild lung disease, altered but did not abolish CFTR's function as a chloride channel in Xenopus oocytes. Airway epithelial cells transfected with CFTR bearing either A455E or G551D had levels of chloride conductance significantly greater than those of mock-transfected and lower than those of wild-type CFTR-transfected cells, as measured by chloride efflux. A combination of channel blockers and analysis of current-voltage relationships were used to dissect the contribution of CFTR and the ORCC to whole cell currents of transfected cells. While CFTR bearing either mutation could function as a chloride channel, only CFTR bearing A455E retained the function of regulating the ORCC. These results indicate that CF mutations can affect CFTR functions differently and suggest that severity of pulmonary disease may be more closely associated with the regulatory rather than chloride channel function of CFTR.

Toulon, France, 1853 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Toulon : ancient Telo Martius, drawn by W.B. Clarke ; engraved by B.R. Davies. It was published by George Cox in 1853. Scale [ca. 1:6,100]. The image inside the map neatline is georeferenced to the surface of the earth and fit to the European Datum 1950, Universal Transverse Mercator (UTM) Zone 31N projected coordinate system. 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, drainage, built-up areas and selected buildings, fortifications, ground cover, shoreline features, docks, wharves, and more. Includes also inset: Panoramic view of Toulon from the outworks on the east.This layer is part of a selection of digitally scanned and georeferenced historic maps from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of originators, ground condition dates, scales, and map purposes.

San Francisco, California 1849 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of San Francisco, drawn on stone by F.W. Creen. It was published by W. B. Cooke & Co. ca. 1849. Scale [ca. 1:12,848]. The image inside the map neatline is georeferenced to the surface of the earth and fit to the California Zone III State Plane Coordinate System NAD83 (in Feet) (Fipszone 0403). 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, drainage, property lots and numbers, reserved government properties, and more. 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.

Chinatown, San Francisco, California 1885 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Official map of Chinatown in San Francisco, prepared under the supervision of the special committee of the board of supervisors, July 1885, W.B. Farwell, John E. Kunkler, E.B. Pond. It was engraved & printed by Bosqui Eng. & Print Co. in 1885. Scale [1:480]. This image consists of images of a two sheet source map that have been stitched together using image editing software to create one image. The image inside the map neatline is georeferenced to the surface of the earth and fit to the California Zone III State Plane Coordinate System NAD83 (in Feet) (Fipszone 0403). 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 cadastral map shows features such as roads, buildings with street addresses and types of businesses, and more. Buildings colored to show: general Chinese occupancy, Chinese gambling houses, Chinese prostitution, Chinese opium resorts, Chinese Joss houses, and White prostitution. 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.

Edinburgh, Scotland, United Kingdom, 1853 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Edinburgh, reduced under the Superintendence of the Society for the Diffusion of Useful Knowledge with the permission of Messrs. Laing and Forbes from their large plan; drawn by W.B. Clarke, Arch[t]; engraved by E. Turrell. It was published by the Society of the Diffusion of Useful Knowledge [by] George Cox in Jany. 1st, 1853. Scale [ca. 1:9,500]. Covers Edinburgh, Scotland, United Kingdom.The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'British National Grid' coordinate system. 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, drainage, built-up areas and selected buildings, ground cover, parks, and more. Relief shown by hachures. Includes also illustrations and inset: Edinburgh Castle.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.

Dublin, Ireland, 1853 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Dublin, drawn by W.B. Clarke, arch[t]; engraved by E. Turrell. It was published under superintendance of the Society of the Diffusion of Useful Knowledge [by] George Cox Jan[y] 1st 1853. Scale [ca.1:85,250]. Covers a portion of Dublin, Ireland. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Irish National Grid coordinate system. 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, drainage, built-up areas and selected buildings, parks, and more. 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.

Bordeaux, France, 1850 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Bordeaux, drawn by W.B. Clarke, arch[t]; engraved by J. Henshall. It was published by published under the superintendence of the Society for the Diffusion of Useful Knowledge [by] Charles Knight in 1850. Scale [ca. 1:12,000]. Covers Bordeaux, France. The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'European Datum 1950 UTM 30N' projected coordinate system. 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, drainage, built-up areas and selected buildings, fortification, ground cover, parks, and more. Depths shown by soundings. Includes views and index. 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.

Antwerp, Belgium, 1852 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Antwerp = (Antwerpen) (Anvers), drawn by W. B. Clarke ; engraved & printed by B. R. Davies. It was published under the Superintendance of the Society for the Diffusion of Useful Knowledge [by] George Cox, Jan. 1, 1852. Scale [ca. 1:4,700]. Covers Antwerp, Belgium.The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'Belge Lambert 1972' coordinate system. 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, drainage, canals, built-up areas and selected buildings, fortification, ground cover, and more. Relief shown by hachures. Includes inset map: Plan of the Scheldt & the Forts from Antwerp to Lillo, and views: Antwerp from the road to Mechlin Brussels and Louvain (from a print at the British Museum) and A Comparison of the Principal Buildings at Antwerp.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.

Brussels, Belgium, 1853 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Brussels = (Bruxelles), drawn by W.B. Clarke, archt. ; engraved by B.R. Davies. It was published under the superintendence of the Society for the Diffussion of Useful Knowledge [by] George Cox, Jany. 1st, 1853. Scale [ca. 1:120,000]. Covers Brussels, Belgium.The image inside the map neatline is georeferenced to the surface of the earth and fit to the Belgian Lambert 1972 coordinate system. 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, drainage, built-up areas and selected buildings, fortification, parks, and more. Includes illustrations of selected buildings and inset: Environs of Brussels. 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.

Frankfurt am Main, Germany, 1853 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Frankfort = (Frankfurt) (Am Mayn), drawn by W.B. Clarke, archt. ; engraved by T.E. Nicolson. It was published under the superintendence of the Society for the Diffusion of Useful Knowledge [by] George Cox, Jan. 1, 1853. Scale [ca. 1:6,450]. Covers Frankfurt am Main, Germany. Map primarily in English The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'Deutsches Hauptdreiecksnetz (DHDN) Gauss Kruger Zone 3, Rauenberg Datum' coordinate system. 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, canals, built-up areas and selected buildings, fortification, ground cover, and more. Includes: View of Frankfort from Sachsenhausen. 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.

Warsaw, Poland, 1831 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Warsaw = Warszawa, drawn by W.B. Clarke, Arch. ; engraved by T.E. Nicholson. It was published by Published under the superintendence of the Society for the Diffusion of Useful Knowledge [by] Baldwin & Cradock in 1831. Scale [ca. 1:17,000] Covers Warsaw, Poland. Map in English and Polish.The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'Pulkovo 1942 Adjust 1958 Poland Zone II' coordinate system. 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, drainage, built-up areas and selected buildings, fortification, ground cover, city district boundaries, and more. Relief shown by hachures. Includes profile views of selected buildings.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.

Madrid, Spain, 1831 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Madrid, W.B. Clarke, archt.; engraved by J. Henshall. It was published under the superintendence of the Society for the Diffusion of Useful Knowledge [by] Charles Knight & Co. Decr. 1, 1831. Scale [ca. 1:11,800]. Map in English and Spanish. The image inside the map neatline is georeferenced to the surface of the earth and fit to the European Datum 1950, UTM Zone 30N coordinate system. 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, drainage, built-up areas and selected buildings, ground cover, and more. Relief is shown by hachures. Includes illustrations. 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.