The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity

The pregnane X receptor (PXR) is the molecular target for catatoxic steroids such as pregnenolone 16α-carbonitrile (PCN), which induce cytochrome P450 3A (CYP3A) expression and protect the body from harmful chemicals. In this study, we demonstrate that PXR is activated by the toxic bile acid lithocholic acid (LCA) and its 3-keto metabolite. Furthermore, we show that PXR regulates the expression of genes involved in the biosynthesis, transport, and metabolism of bile acids including cholesterol 7α-hydroxylase (Cyp7a1) and the Na+-independent organic anion transporter 2 (Oatp2). Finally, we demonstrate that activation of PXR protects against severe liver damage induced by LCA. Based on these data, we propose that PXR serves as a physiological sensor of LCA, and coordinately regulates gene expression to reduce the concentrations of this toxic bile acid. These findings suggest that PXR agonists may prove useful in the treatment of human cholestatic liver disease.

Comparison of Couples' Normal Life Cycle Development and Intimacy Distance Regulation

When conceptualizing healthy couple relationships, it is tempting to use a simple framework as a panacea. Unfortunately, this desire for simplicity can lead to a narrow and naive perspective. Individuals interact and are influenced by a variety of factors (i.e., various social systems, multiple context memberships, complex interconnecting exchanges, etc.); consequently, it is necessary to guard against an overly narrow interpretation when examining healthy couple interactions. It is the purpose of this paper to develop one aspect of a complex perspective for healthy couple relationships by comparing couple life cycle development with couple intimacy-distance regulation.

Fortification and Frontier: The Project Drawn up by Juan Martín Zermeño for Puebla de Sanabria in 1766

Following the death of engineer General Jorge Próspero de Verboom in 1744 and after a few years of transition in the management of Spanish fortifications, Juan Martín Zermeño took on the role, initially with a temporary mandate, but then definitively during a second period that ran from 1766 until his death in 1772. He began this second period with a certain amount of concern because of what had taken place during the last period of conflict. The Seven Years War (1756–1763) which had brought Spain into conflict with Portugal and England in the Caribbean had also lead to conflict episodes along the Spanish–Portuguese border. Zermeño’s efforts as a planner and general engineer gave priority to the northern part of the Spanish–Portuguese border. After studying the territory and the existing fortifications on both sides of the border, Zermeño drew up three important projects in 1766. The outposts that needed to be reinforced were located, from north to south, at Puebla de Sanabria, Zamora and Ciudad Rodrigo, which is where he is believed to have come from. This latter township already had a modern installation built immediately after the war of the Spanish Succession and reinforced with the Fort of La Concepción. However, Zamora and Puebla de Sanabria had some obsolete fortifications that needed modernising. Since the middle of the 15th century Puebla de Sanabria had had a modern castle with rounded turrets, that of the counts of benavente. During the 16th and 17th centuries it had also been equipped with a walled enclosure with small bastions. During the war of the Spanish Succession the Portuguese had enlarged the enclosure and had erected a tentative offshoot to the west. In order to draw up the ambitious Puebla de Sanabria project Zermeño had the aid of some previous reports and projects, such as those by the count of robelin in 1722, the one by Antonio de Gaver in 1752, and Pedro Moreau’s report dated June 1755. This study includes a technical analysis of Zermeño’s project and its strategic position within the system of fortifications along the Spanish–Portuguese border.

1794, Catalogus eorum qui in Universitate Harvardiana, Cantabrigiae, in republica Massachusettensi, ab anno MDCXLII, ad annum MDCCXCIV. Alicujus gradû laureâ donati sunt.

Modern hardcover binding around original handsewn paper binding. Missing title page and first page of text. Key to abbreviations titled "Explination" on flyleaf with abbreviations for Massachusetts, New Hampshire, Connecticut, Rhode Island, Long Island, New York, Martha's Vineyard, New Jersey, Pensylvania [sic], Virginia, South Carolina, Georgia, West Indies, Great Britain, Episcopalian, and Baptist. Heavily annotated with residence locations. Asterisks added next to the names of alumni who died after the Catalogue's publication, generally in 1795. Also includes a tipped-in page at front of volume with the names of thirteen alumni of various classes from 1650 through 1756, in one hand, a note "Joseph Lovett was of Beverly, and a minister in a town of Connecticut the name of which I do not recollect. JW" in a different hand, and a final note "I believe there was a Lovett at Norwich" in the original hand.

Alphabetical catalog of Harvard College graduates through 1767, 1767

This hard-bound manuscript catalog alphabetically lists the men who graduated from Harvard College between 1642 and 1767. It is believed to be the first such list compiled. Entries contain each graduate's surname (in English), given name (in Latin), year of graduation, and occasional additional information. Francis Foxcroft (A.B. 1712) compiled the catalog. Entries for those who graduated between 1764 and 1767 have been added at the end of each alphabetical section.

Salutatory address of Abiel Abbot, 1792

Six-unlined pages containing a handwritten copy of the salutatory address composed by Abiel Abbot in Latin for the 1792 Harvard College Commencement. The text includes edits and struck-through words. The first page includes the title "Autore Abiele Abbot" and has a penciled note: "This must be gr. grandfather's Latin oration when he graduated from Harvard, with honors, in 1792."

Cincinnati, Ohio, ca. 1840 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of Cincinnati, Covington & Newport, drawn by B. Oertly. It was lithographed and published by Otto Onken, ca. 1840. Scale [ca. 1:10,500]. Covers also a portion of Northern Kentucky. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Ohio South State Plane NAD 1983 coordinate system (in Feet) (Fipszone 3402). 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, city ward boundaries, cemeteries, canals, and more. Includes also indexes and inset map of Millcreek Township.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.

Denver, Colorado, 1890 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Rollandet's map of the city of Denver, compiled, drawn and published by Edward Rollandet. It was published by Edward Rollandet in 1890. Scale [ca. 1:21,250]. The image inside the map neatline is georeferenced to the surface of the earth and fit to the HARN State Plane Colorado Central Zone NAD 1983 coordinate system (in Feet) (Fipszone 0502). 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, selected names of landowners, additions, subdivisions, township and range, parks, and more. Includes index and views of buildings.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.

Madison, Wisconsin, 1855 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of Madison and the Four Lake Country : Dane Co. Wis. It was published in 1855. Scale [ca. 1:53,000]. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Wisconsin South NAD 1983 coordinate system (in Feet) (Fipszone 4803). 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 (active and projected), drainage, selected points of interest, township and range boundaries, and more. Includes index and text.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.

Coastal Massachusetts, Marblehead to Hampton Harbor, New Hampshire, Nautical Chart, 1776 (Image 1 of 2) (Raster Image)

This layer is a georeferenced raster image of the untitled, historic nautical chart: [A chart of the harbours of Hampton, Newbury, Ipswich, Jebeka, Squam, Cape Ann, Manchester, Beverly, Salem, Marble Head &c.] (sheet originally published in 1776). The map is [sheet 23] from the Atlantic Neptune atlas Vol. 3 : Charts of the coast and harbors of New England, from surveys taken by Samuel Holland and published by J.F.W. Des Barres, 1781. Scale [ca. 1:50,000]. This layer is image 1 of 2 total images of the two sheet source map, representing the southern portion of the map. Covers coastal Massachusetts from Ipswich Harbor to Marblehead. The image is georeferenced to the surface of the earth and fit to the 'World Mercator' (WGS 84) projected coordinate system. All map collar information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, or other information associated with the principal map. This map shows coastal features such as harbors, inlets, rocks, channels, points, coves, shoals, islands, and more. Includes also selected land features such as cities and towns, buildings, and roads. Relief is shown by hachures; depths by soundings. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection. The entire Atlantic Neptune atlas Vol. 3 : Charts of the coast and harbors of New England has been scanned and georeferenced as part of this selection.

Coastal Massachusetts, Marblehead to Hampton Harbor, New Hampshire, Nautical Chart, 1776 (Image 2 of 2) (Raster Image)

This layer is a georeferenced raster image of the untitled, historic nautical chart: [A chart of the harbours of Hampton, Newbury, Ipswich, Jebeka, Squam, Cape Ann, Manchester, Beverly, Salem, Marble Head &c.] (sheet originally published in 1776). The map is [sheet 24] from the Atlantic Neptune atlas Vol. 3 : Charts of the coast and harbors of New England, from surveys taken by Samuel Holland and published by J.F.W. Des Barres, 1781. Scale [ca. 1:50,000]. This layer is image 2 of 2 total images of the two sheet source map, representing the northern portion of the map. Covers coastal Massachusetts and New Hampshire from Ipswich Harbor, Massachusetts to Hampton Harbor, New Hampshire. The image is georeferenced to the surface of the earth and fit to the 'World Mercator' (WGS 84) projected coordinate system. All map collar information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, or other information associated with the principal map. This map shows coastal features such as harbors, inlets, rocks, channels, points, coves, shoals, islands, and more. Includes also selected land features such as cities and towns, buildings, and roads. Relief is shown by hachures; depths by soundings. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection. The entire Atlantic Neptune atlas Vol. 3 : Charts of the coast and harbors of New England has been scanned and georeferenced as part of this selection.

New England, 1862 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: G. Woolworth Colton's railroad, township & distance map of New England : with adjacent portions of New York, Canada & New Brunswick, drawn, engraved & published by G. Woolworth Colton. It was published in 1862. Scale 1:900,000. The image inside the map neatline is georeferenced to the surface of the earth and fit to the USA Contiguous Albers Equal Area Conic projection (Meters). 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, or other information associated with the principal map. This map shows features such as roads, railroads, drainage, state, county, and town boundaries, and more. Relief shown by hachures. Includes table of distances and inset: The eastern portion of Massachusetts on an enlarged scale. Scale 1:350,000. This layer is part of a selection of digitally scanned and georeferenced historic maps of New England from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

New Hampshire, 1816 (Image 1 of 6) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: New Hampshire by recent survey : made under the supreme authority and published according to law by Philip Carrigain ; J.J. Barralet, del. ; W. Harrison, sct., Philada. It was published by Philip Carrigain in 1816. Scale [ca. 1:200,000]. This layer is image 1 of 6 total images, representing the northeast portion of the six sheet source map. The image inside the map neatline is georeferenced to the surface of the earth and fit to the New Hampshire State Plane coordinate system (NAD 1983 in Feet) (Fipszone 2800). 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, public buildings, schools, churches, industry locations (e.g. mills, factories, mines, etc.), selected private buildings with names of property owners, town boundaries, land grants, and more. Relief shown pictorially and by hachures. Includes area notes, text, and table of population. Also includes illustrations: View of the Great Boars Head and Hampton Beach -- The Cap of the White Mountains -- View of the White Mountains from Shelburne; inset maps: States of the Union east of the Hudson with the adjacent British colonies. Scale [ca. 1:1,920,000] -- The middle, southern and western sections of the United States with the territories. Scale [ca. 1:4,900,000]. Includes: ms. additions with updated county boundary & township names.This layer is part of a selection of digitally scanned and georeferenced historic maps of New England from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of regions, originators, ground condition dates, scales, and map purposes.