Protective immunity to HIV-1 in SCID/beige mice reconstituted with peripheral blood lymphocytes of exposed but uninfected individuals

Immunodeficiency typically appears many years after initial HIV infection. This long, essentially asymptomatic period contributes to the transmission of HIV in human populations. In rare instances, clearance of HIV-1 infection has been observed, particularly in infants. There are also reports of individuals who have been frequently exposed to HIV-1 but remain seronegative for the virus, and it has been hypothesized that these individuals are resistant to infection by HIV-1. However, little is known about the mechanism of immune clearance or protection against HIV-1 in these high-risk individuals because it is difficult to directly demonstrate in vivo protective immunity. Although most of these high-risk individuals show an HIV-1-specific cell-mediated immune response using in vitro assays, their peripheral blood lymphocytes (PBLs) are still susceptible to HIV infection in tissue culture. To study this further in vivo, we have established a humanized SCID mouse infection model whereby T-, B-, and natural killer-cell defective SCID/beige mice that have been reconstituted with normal human PBLs can be infected with HIV-1. When the SCID/beige mice were reconstituted with PBLs from two different multiply exposed HIV-1 seronegative individuals, the mice showed resistance to infection by two strains of HIV-1 (macrophage tropic and T cell tropic), although the same PBLs were easily infected in vitro. Mice reconstituted with PBLs from non-HIV-exposed controls were readily infected. When the same reconstituted mice were depleted of human CD8 T cells, however, they became susceptible to HIV-1 infection, indicating that the in vivo protection required CD8 T cells. This provides clear experimental evidence that some multiply exposed, HIV-1-negative individuals have in vivo protective immunity that is CD8 T cell-dependent. Understanding the mechanism of such protective immunity is critical to the design and testing of effective prophylactic vaccines and immunotherapeutic regimens.

Strategy for monitoring T cell responses to NY-ESO-1 in patients with any HLA class I allele

NY-ESO-1 elicits frequent antibody responses in cancer patients, accompanied by strong CD8+ T cell responses against HLA-A2-restricted epitopes. To broaden the range of cancer patients who can be assessed for immunity to NY-ESO-1, a general method was devised to detect T cell reactivity independent of prior characterization of epitopes. A recombinant adenoviral vector encoding the full cDNA sequence of NY-ESO-1 was used to transduce CD8-depleted peripheral blood lymphocytes as antigen-presenting cells. These modified antigen-presenting cells were then used to restimulate memory effector cells against NY-ESO-1 from the peripheral blood of cancer patients. Specific CD8+ T cells thus sensitized were assayed on autologous B cell targets infected with a recombinant vaccinia virus encoding NY-ESO-1. Strong polyclonal responses were observed against NY-ESO-1 in antibody-positive patients, regardless of their HLA profile. Because the vectors do not cross-react immunologically, only responses to NY-ESO-1 were detected. The approach described here allows monitoring of CD8+ T cell responses to NY-ESO-1 in the context of various HLA alleles and has led to the definition of NY-ESO-1 peptides presented by HLA-Cw3 and HLA-Cw6 molecules.

Overexpression of heme oxygenase-1 in human pulmonary epithelial cells results in cell growth arrest and increased resistance to hyperoxia.

Heme oxygenase (HO) catalyzes the rate-limiting step in the degradation of heme to biliverdin, which is reduced by biliverdin reductase to bilirubin. Heme oxygenase-1 (HO-1) is inducible not only by its heme substrate, but also by a variety of agents causing oxidative stress. Although much is known about the regulation of HO-1 expression, the functional significance of HO-1 induction after oxidant insult is still poorly understood. We hypothesize and provide evidence that HO-1 induction serves to protect cells against oxidant stress. Human pulmonary epithelial cells (A549 cells) stably transfected with the rat HO-1 cDNA exhibit marked increases of HO-1 mRNA levels which were correlated with increased HO enzyme activity. Cells that overexpress HO-1 (A549-A4) exhibited a marked decrease in cell growth compared with wild-type A549 (A549-WT) cells or A549 cells transfected with control DNA (A549-neo). This slowing of cell growth was associated with an increased number of cells in G0/G1 phase during the exponential growth phase and decreased entry into the S phase, as determined by flow cytometric analysis of propidium iodide-stained cells and pulse experiments with bromodeoxyuridine. Furthermore, the A549-A4 cells accumulated at the G2/M phase and failed to progress through the cell cycle when stimulated with serum, whereas the A549-neo control cells exhibited normal cell cycle progression. Interestingly, the A549-A4 cells also exhibited marked resistance to hyperoxic oxidant insult. Tin protoporphyrin, a selective inhibitor of HO, reversed the growth arrest and ablated the increased survival against hyperoxia observed in the A549-A4 cells overexpressing HO-1. Taken together, our data suggest that overexpression of HO-1 results in cell growth arrest, which may facilitate cellular protection against non-heme-mediated oxidant insult such as hyperoxia.

The transcriptional transactivator of simian foamy virus 1 binds to a DNA target element in the viral internal promoter.

The transcriptional transactivator (Tas) of simian foamy virus type 1 strongly augments gene expression directed by both the promoter in the viral long terminal repeat and the newly discovered internal promoter located within the env gene. A region of 121 bp, located immediately 5' to the TATA box in the internal promoter, is required for transactivation by Tas. The present study aimed to identify the precise Tas-responsive target(s) in this region and to determine the role of Tas in transcriptional regulation. By analysis of both clustered-site mutations and hybrid promoters in transient expression assays in murine and simian cells, two separate sequence elements within this 121-bp region were shown to be Tas-dependent transcriptional enhancers. These targets, each < 30 bp in length and displaying no apparent sequence homology one to the other, are designated the promoter-proximal and promoter-distal elements. By means of the gel electrophoresis mobility-shift assays, using purified glutathione S-transferase-Tas fusion protein expressed in Escherichia coli, the target proximal to the TATA box exhibited strong binding to glutathione S-transferase-Tas, whereas the distal element appears not to bind. In addition, footprint analysis revealed that 26 bp in the promoter proximal element was protected by glutathione S-transferase-Tas from DNase I. We propose a model for transactivation of the simian foamy virus type 1 internal promoter in which Tas interacts directly with the proximal target element positioned immediately 5' to the TATA box. In this model, Tas attached to this element is presumed to interact with a component(s) of the cellular RNA polymerase II initiation complex and thereby enhance transcription directed by the viral internal promoter.

Electrochemical synthesis at pre-pilot scale of 1-phenylethanol by cathodic reduction of acetophenone using a solid polymer electrolyte

The pre-pilot scale synthesis of 1-phenylethanol was carried out by the cathodic hydrogenation of acetophenone in a 100 cm2 (geometric area) Polymer Electrolyte Membrane Electrochemical Reactor. The cathode was a Pd/C electrode. Hydrogen oxidation on a gas diffusion electrode was chosen as anodic reaction in order to take advantage of the hydrogen evolved during the reduction. This hydrogen oxidation provides the protons needed for the synthesis. The synthesis performed with only a solid polymer electrolyte, spe, has lower fractional conversion although a higher selectivity than that carried out using a support–electrolyte–solvent together with a spe. However, the difference between these two cases is rather small and since the work-up and purification of the final product are much easier when only a spe is used, this last process was chosen for the pre-pilot electrochemical synthesis of 1-phenylethanol.

South America, 1825 (Image 1 of 2) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: General-Charte von Süd-America = Carte générale de L'Amerique Méridionale : en deux grandes feuilles. d'après les observations et les cartes spéciales, rapportées du Voyage dans l'intérieur du Brèsil, pendant les années 1817-1820..., par les Docteurs de Spix et de Martius, Chevaliers de L'Ordre civil de la Couronne de Bavière, membres de L'Académie Royale de Munich ; gestochen von Joh. Bapt. Seitz, Kupferstecher im topographischen Bureau des Kön. baier. General-Quartiermeister Stab. It was published by [M. Lindauer] in 1825. Scale [ca. 1:7,000,000]. This layer is image 1 of 2 total images of the two sheet source map, representing the southern portion of the map. Map in German and French. The image inside the map neatline is georeferenced to the surface of the earth and fit to the South America Lambert Conformal Conic 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 drainage, cities and other human settlements, territorial boundaries, roads, shoreline features, and more. Relief shown by hachures.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.

Jamaica, 1763 (Image 1 of 4) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: This map of the island of Jamaica; laid down from the papers and under the direction of Henry Moore, Esqr.; His Majesty's Lieutenant Governor and Commander in Chief of that island, in the years 1756, 57, 58, 59, 60 & 61; & from a great number of actual surveys performed by the publishers is humbly inscribed by his lordship's most obedient & most humble servants, Thos. Craskell, engineer, Jas. Simpson, surveyor. It was published by D. Fournier in 1763. Scale [ca 1:200,000]. This layer is image 1 of 4 total images of the four sheet map, representing the southwest portion of the map.The image inside the map neatline is georeferenced to the surface of the earth and fit to the Jamaica Grid 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 towns, villages, and other human settlements, roads, drainage, selected buildings, ground cover, shoreline features, and more. Relief shown pictorially. Includes also illustrations.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.

County of Cornwall, Jamaica, 1763 (Image 1 of 4) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: This map of the county of Cornwall, in the island of Jamaica; laid down from the papers, under the direction of, Henry Moore, Esqr., His Majesty's Lieutenant Governor, and Commander in Chief of that island, in the years 1756, 57, 58, 59, 60 & 61, & from a great number of actual surveys performed by the publishers is humbly inscribed by his lordship's most obedient & humble servants, Thos. Craskell, engineer, Jas. Simpson, surveyor. It was published by D. Fournier in 1763. Scale [ca. 1:95,000]. This layer is image 1 of 4 total images of the four sheet source map, representing the southwest portion of the map. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Jamaica Grid 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 towns, villages, and other human settlements, roads, parish boundaries, drainage, selected buildings and names of landowners, ground cover, shoreline features, shoals, channels, anchorage points, and more.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.

County of Middlesex, Jamaica, 1763 (Image 1 of 4) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: This map of the county of Middlesex in the island of Jamaica; laid down from the papers, and under the direction of Henry Moore, Esqr., His Majesty's Lieutenant Governor and Commander in Chief of that island, in the years 1756, 57, 58, 60, & 61 and from a great number of actual surveys performed by the publishers is humbly inscribed by his lordship's most obedient & most humble servants, Thos. Craskell, engineer, Jas. Simpson, surveyor. It was published by D. Fournier in 1763. Scale [ca. 1:95,000]. The layer is image 1 of 4 total images of the four sheet map, representing the southeast portion of the map.The image inside the map neatline is georeferenced to the surface of the earth and fit to the Jamaica Grid 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 towns, villages, and other human settlements, roads, parish boundaries, drainage, selected buildings and names of landowners, ground cover, shoreline features, shoals, channels, anchorage points, and more.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.

County of Surrey, Jamaica, 1763 (Image 1 of 4) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: This map of the county of Surry in the island of Jamaica; laid down from the papers and under the direction of Henry Moore, Esqr., His Majesty's Lieutenant Governor and Commander in Chief of that island, in the years 1756, 57, 58, 59, 60 & 61, & from a great number of actual surveys performed by the publishers is humbly inscribed, by his most obedient and humble servants, Thos. Craskell, engineer, Jas. Simpson, surveyor. It was published by D. Fournier in 1763. The layer is image 1 of 4 total images of the four sheet map, representing the northeast portion of the map. Scale ca. 1:100,000. Covers County of Surrey, Jamaica. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Jamaica Grid 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, cities and other human settlements, parish boundaries, shoreline features, plantations, and more. Includes also illustrations.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.

Coast, North Africa, Tunisia and Algeria, 1829 (Image 1 of 2) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Carte comparée des régences d'Alger et de Tunis, dressée par le Chev. Lapie, Géographe du Roi ; les noms anciens ont été revus par ... Hase ; les noms arabes par ... Taubert ; gravé par Flahaut ; écrit par Lallemand. It was published by Chez Ch. Picquet, Quai Conti, no. 17 in 1829. Scale [ca. 1:1,632,653], 16 km=9.8 cm. This layer is image 1 of 2 total images of the two sheet source map, representing the western portion of the map. Covers the coast of North Africa including Tunisia, Algeria, and portions of Morocco and Libya. Map in French. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Europe Lambert Conformal Conic 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 drainage, roads, cities and other human settlements, territorial boundaries, shoreline features, and more. Relief shown by hachures. 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.

Burma, 1824 (Image 1 of 4) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Geographical sketch of the Burmese Empire, drawn by H. Hamilton ; compiled at the office of the Surveyor General of India. It was published by Published at the Asiatic Lithographic Press in 1825. Scale [ca. 1:1,010,000]. This layer is image 1 of 4 total images of the four sheet source map, representing the north portion of the map. Covers Burma and bordering portions of India, Bangladesh, Thailand, and China.The image inside the map neatline is georeferenced to the surface of the earth and fit to the Asia North Lambert Conformal Conic 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 drainage, roads, cities and other human settlements, fortifications, territorial boundaries, shoreline features, ground cover, temples, and more. Relief shown by hachures. Includes also glossary and notes on the construction of the sketch and table of estimated road distances.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.

Queensland, Australia, 1896 (Image 1 of 2) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Queensland and British New Guinea : prepared for educational purposes, Survey Deptartment, Brisbane. It was published by The Dept. in 1896. Scale [ca. 1:1,710,720]. This layer is image 1 of 2 total images of the two sheet source map, representing north portion of the map. Covers primarily northeast Australia and a portion of Papua New Guinea.The image inside the map neatline is georeferenced to the surface of the earth and fit to the Geocentric Datum of Australia 1994 Map Grid of Australia Zone 54 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 and stations, drainage, coastal features, selected places of interest, administrative boundaries, and more. Relief shown by shading and spot heights. 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.

Uttar Pradesh, India, 1777 (Image 1 of 4) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: A map of the provinces of Delhi, Agrah, Oude, and Ellahabad : comprehending the countries lying between Delhi, and the Bengal Provinces, surveyed by Major James Rennell, Surveyor General to the Honourable East-India Company, and published by order of the court of directors of said company by Andrew Dury ; Wm. Haydon sculpt. It was published by Andrew Dury, Duke's Court, St. Martin's Lane in 1777. Scale [ca. 1:750,000]. This layer is image 1 of 4 total images of the four sheet source map, representing the northwest portion of the map. Covers primarily Uttar Pradesh, India.The image inside the map neatline is georeferenced to the surface of the earth and fit to the Asia North Lambert Conformal Conic 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, cities and other human settlements, forts, passes, fields of battle, territorial claims, and more. Relief shown pictorially. 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.

India, 1788 (Image 1 of 4) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: A map of Hindoostan, or the Mogul Empire : from the latest authorities. Inscribed to Sir Joseph Banks Bart., President of the Royal Society & c., & c. by his much obliged & faithful friend and servant, J. Rennell, 1st Jany. 1788 ; the map engraved by I. Phillips & W. Harrison ; writing by T. Harmar. It was published by James Rennell in 1788. Scale [ca. 1:3,000,000]. This layer is image 1 of 4 total images of the four sheet source map, covering the southwest portion of the map. Covers primarily India and adjacent portions of Asia.The image inside the map neatline is georeferenced to the surface of the earth and fit to the Asia North Lambert Conformal Conic 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 drainage, cities and other human settlements, roads, territorial boundaries, shoreline features, and more. Relief shown pictorially. 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.