The interaction of the general anesthetic etomidate with the γ-aminobutyric acid type A receptor is influenced by a single amino acid

The γ-aminobutyric acid type A (GABAA) receptor is a transmitter-gated ion channel mediating the majority of fast inhibitory synaptic transmission within the brain. The receptor is a pentameric assembly of subunits drawn from multiple classes (α1–6, β1–3, γ1–3, δ1, and ɛ1). Positive allosteric modulation of GABAA receptor activity by general anesthetics represents one logical mechanism for central nervous system depression. The ability of the intravenous general anesthetic etomidate to modulate and activate GABAA receptors is uniquely dependent upon the β subunit subtype present within the receptor. Receptors containing β2- or β3-, but not β1 subunits, are highly sensitive to the agent. Here, chimeric β1/β2 subunits coexpressed in Xenopus laevis oocytes with human α6 and γ2 subunits identified a region distal to the extracellular N-terminal domain as a determinant of the selectivity of etomidate. The mutation of an amino acid (Asn-289) present within the channel domain of the β3 subunit to Ser (the homologous residue in β1), strongly suppressed the GABA-modulatory and GABA-mimetic effects of etomidate. The replacement of the β1 subunit Ser-290 by Asn produced the converse effect. When applied intracellularly to mouse L(tk−) cells stably expressing the α6β3γ2 subunit combination, etomidate was inert. Hence, the effects of a clinically utilized general anesthetic upon a physiologically relevant target protein are dramatically influenced by a single amino acid. Together with the lack of effect of intracellular etomidate, the data argue against a unitary, lipid-based theory of anesthesia.

Purification of the Drosophila RNA polymerase II general transcription factors.

We describe a fractionation and purification scheme for the Drosophila RNA polymerase II general transcription factors. Drosophila TFIIE, TFIIF, TFIIH, and RNA polymerase II have been purified to greater than 50% homogeneity from Drosophila embryo nuclear extracts. TFIID has been purified 80-fold and is not significantly contaminated with any of the other general factors. This is the first reported identification and purification of Drosophila TFIIH and TFIIE. Further analysis shows that, similar to their mammalian counterparts, Drosophila TFIIH is composed of eight polypeptides sized between 30 and 100 kDa, and Drosophila TFIIE is composed of two polypeptides sized at 34 and 60 kDa. When all of these fractions are combined with recombinant Drosophila TFlIB, a highly purified in vitro transcription system is generated that has not previously been available in Drosophila. The TFIID fraction can be replaced with recombinant Drosophila TBP to give a transcription system that is nearly free of contaminating proteins.

Members of the General Court, 1798-1799

Notebook with paper cover containing a handwritten list of the members of the Massachusetts General Court arranged by county and town. Pearson identified characteristics of the politicians including whether they were chosen by the people or Legislature, were for or against the College, were for or against the Virginia Resolutions, and whether they were "a good Federalist."

Burma, 1824 (Image 3 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 3 of 4 total images of the four sheet source map, representing the central south 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.

Burma, 1824 (Image 4 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 4 of 4 total images of the four sheet source map, representing the south 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.

Reference guide to post-government service employment activities of Department of the Navy personnel.

Mode of access: Internet.

Author and title list of the most important accessions to the War Department Library : with subject entries in biography, military history, and military science, and index of periodicals received during the calendar year, 1904.

"Office of the Chief of Staff, Second (Military Information) Division."

Public land system of the United States. : Historical outline /

At head of title: Department of the interior. General land office.

Crusaders of the jungle /

"The origin, growth, and decline of the principal missions on the frontiers of tropical South America during the colonial period."--Pref.

The Health consequences of smoking : a Public Health Service review.

Mode of access: Internet.

Public papers of the Presidents of the United States.

"Containing the public messages, speeches, and statements of the President", <1956-1992>.

Agriculture, Rural Development, Food and Drug Administration, and related agencies appropriations for 2006 : hearings before a Subcommittee of the Committee on Appropriations, House of Representatives, One Hundred Ninth Congress, first session /

Shipping list no. : 2005-0156-P (pt. 1A), 2005-0131-P (pt. 1B), 2005-0136-P (pt. 2), 2005-0172-P (pt. 3-5, 7), 2005-0185-P (pt. 6), 2005-0168-P (pt. 8), 2006-0066-P (pt. 9).

Senior citizens and how they live: an analysis of 1960 census data. [Report prepared by the Statistical Reports Staff] Office of Program Policy.

Mode of access: Internet.

A history of the Office of Censorship [microform].

Accompanied by: A guide to History of the Office of Censorship / edited by Paul Kesaris (6 p. ; 22 cm.).

Information bulletin : monthly magazine of the Office of United States High Commissioner for Germany.

First two issues continue the numbering of the title it supersedes and are called no. 170 and 171.