Conformational change and enhanced stabilization of the vitamin D receptor by the 1,25-dihydroxyvitamin D3 analog KH1060.

The 1,25-dihydroxyvitamin D3 [1,25-(OH)2vitamin D3] analog KH1060 exerts very potent effects on cell proliferation and cell differentiation via the vitamin D receptor (VDR). However, the activities of KH1060 are not associated with an increased affinity for the VDR. We now show that increased stabilization of the VDR-KH1060 complex could be an explanation for its high potencies. VDR half-life studies performed with cycloheximide-translational blocked rat osteoblast-like ROS 17/2.8 cells demonstrated that, in the absence of ligand, VDR levels rapidly decreased. After 2 hr, less than 10% of the initial VDR level could be measured. In the presence of 1,25-(OH)2vitamin D3, the VDR half-life was 15 hr. After 24 hr. less than 20% of the initial VDR content was detectable, whereas, at this time-point, when the cells were incubated with KH1060 80% of the VDR was still present. Differences in 1,25-(OH)2vitamin D3- and KH1060-induced conformational changes of the VDR could underlie the increased VDR stability. As assessed by limited proteolytic digestion analysis, both 1,25-(OH)2vitamin D3 and KH1060 caused a specific conformational change of the VDR. Compared with 1,25-(OH)2vitamin D3, KH1060 induced a conformational change that led to a far more dramatic protection of the VDR against proteolytic degradation. In conclusion, the altered VDR stability and the possibly underlying change in VDR conformation caused by KH1060 could be an explanation for its enhanced bioactivity.

The expenses of a dinner provided at the installation of the Rev'd. Professor Williams, 1780 May 2

Handwritten one-page itemized list of costs for food and supplies purchased for the installation dinner of Samuel Williams (1743-1817) for his appointment as Hollis Professor Mathematics and Natural Philosophy at Harvard College. Signed by Caleb Gannett.

Primary Raw Materials (1986-89) Volume 1 (Summary Reports of the R&D Programme). EUR 13647/I EN, 1992

"This document contains the Summary Reports of cost sharing Research and Development contracts funded under the "Primary Raw Materials" subprogramme of the Commission of the European Communities. This programme was part of the research and development programme on "Raw Materials and Advanced Materials" (1986 - 1989). The main objectives of the "Primary Raw Materials" subprogramme were to enhance the competitiveness of the European Community mining and metallurgical Industries and to reduce European Community vulnerability for minerals, particularly those of critical or strategic interest." Three research areas: Research and development exploration; Mining technology; Mineral processing.

Remarks on the life and death of the fam'd Mr. Blood : giving an account [brace]of his plot in Ireland, to surprize Dublin Castle; several transactions in his head-quarters in the city; rescue of Captain Mason at Doncaster; attempt on the person of his Grace the Duke of Ormond; seizing on the crown and scepter in the Tower; coming into favour with his Prince; concern about his Grace the Duke of Buckingham; sickness, death, and twice interment : published for publick information.

Leaf A₂ mis-signed as A₁.

Boyer's French dictionary: comprising all the additions and improvements of the latest Paris and London editions, with a very large number of useful words and phrases, now first selected from the modern dictionaries of Boiste, Wailly, Catineau, and others; with the pronunciation of each word, according to the dictionary of the Abbé Tardy: to which are prefixed, rules for the pronunciation of French vowels, diphthongs, and final consonants, chiefly collected from the prosody of the Abbé d'Olivet, with a table of French verbs, &c.

Acompañado de: An English-French dictionary, designed as a second part to the Boston edition of Boyer's French dictionary, with Tardy's pronunciation.

Programs and services of the Area D Community Mental Health Center.

On cover: The Area D Community Mental Health Center; programs and services, 1971.

King of the Golden River

Mode of access: Internet.

King of the thundering herd : the biography of an American bison /

Mode of access: Internet.

The King of the Hurons /

Republished in England as "Blanche Montaigne".