Inhibition of AP-1 binding and transcription by gold and selenium involving conserved cysteine residues in Jun and Fos.

Gold(I) salts and selenite, which have diverse therapeutic and biological effects, are noted for their reactivity with thiols. Since the binding of Jun-Jun and Jun-Fos dimers to the AP-1 DNA binding site is regulated in vitro by a redox process involving conserved cysteine residues, we hypothesized that some of the biological actions of gold and selenium are mediated via these residues. In electrophoretic mobility-shift analyses, AP-1 DNA binding was inhibited by gold(I) thiolates and selenite, with 50% inhibition occurring at approximately 5 microM and 1 microM, respectively. Thiomalic acid had no effect in the absence of gold(I), and other metal ions inhibited at higher concentrations, in a rank order correlating with their thiol binding affinities. Cysteine-to-serine mutants demonstrated that these effects of gold(I) and selenite require Cys272 and Cys154 in the DNA-binding domains of Jun and Fos, respectively. Gold(I) thiolates and selenite did not inhibit nonspecific protein binding to the AP-1 site and were at least an order of magnitude less potent as inhibitors of sequence-specific binding to the AP-2, TFIID, or NF1 sites compared with the AP-1 site. In addition, 10 microM gold(I) or 10 microM selenite inhibited expression of an AP-1-dependent reporter gene, but not an AP-2-dependent reporter gene. These data suggest a mechanism regulating transcription factor activity by inorganic ions which may contribute to the known antiarthritic action of gold and cancer chemoprevention by selenium.

The antiproliferative activity of c-myb and c-myc antisense oligonucleotides in smooth muscle cells is caused by a nonantisense mechanism.

Smooth muscle cell (SMC) proliferation is thought to play a major role in vascular restenosis after angioplasty and is a serious complication of the procedure. Developing antisense (AS) oligonucleotides as therapeutics is attractive because of the potentially high specificity of binding to their targets, and several investigators have reported inhibition of SMC proliferation in vitro and in vivo by using AS strategies. We report here the results of our experiments on vascular SMCs using AS oligonucleotides directed toward c-myb and c-myc. We found that significant inhibition of SMC proliferation occurred with these specific AS sequences but that this inhibition was clearly not via a hybridization-dependent AS mechanism. Rather, inhibition was due to the presence of four contiguous guanosine residues in the oligonucleotide sequence. This was demonstrated in vitro in primary cultures of SMCs and in arteries ex vivo. The ex vivo model developed here provides a rapid and effective system in which to screen potential oligonucleotide drugs for restenosis. We have further explored the sequence requirements of this non-AS effect and determined that phosphorothioate oligonucleotides containing at least two sets of three or four consecutive guanosine residues inhibit SMC proliferation in vitro and ex vivo. These results suggest that previous AS data obtained using these and similar, contiguous guanosine-containing AS sequences be reevaluated and that there may be an additional class of nucleic acid compounds that have potential as antirestenosis therapeutics.

Ecological chaos in the wake of invasion.

Irregularities in observed population densities have traditionally been attributed to discretization of the underlying dynamics. We propose an alternative explanation by demonstrating the evolution of spatiotemporal chaos in reaction-diffusion models for predator-prey interactions. The chaos is generated naturally in the wake of invasive waves of predators. We discuss in detail the mechanism by which the chaos is generated. By considering a mathematical caricature of the predator-prey models, we go on to explain the dynamical origin of the irregular behavior and to justify our assertion that the behavior we present is a genuine example of spatiotemporal chaos.

Investment behaviour of EU arable crop farms in selected EU countries and the impact of policy reforms. Factor Markets Working Document No. 42, May 2013

This deliverable provides a comparative analysis, among selected EU member states, of the investment demand of a sample of specialised field crop farms for farm buildings, machinery and equipment as determined by different types and levels of Common Agricultural Policy support. It allows for the existence of uncertainty in the price of output farmers receive and for both long- and short-run determinants of investment levels, as well as for the presence of irregularities in the cost adjustment function due to the existence of threshold-type behaviours. The empirical estimation reveals that three investment regimes are consistently identified in Germany and Hungary, across asset and support types, and in France for machinery and equipment. More traditional disinvestment-investment type behaviours characterise investment in farm building in France and the UK, across support types, and Italy for both asset classes under coupled payments. The long-run dynamic adjustment of capital stocks is consistently and significantly estimated to be towards a – mostly non-stationary – lower level of capitalisation of the farm analysed. By contrast, the expected largely positive short-run effects of an increase in output prices are often not significant. The effect of CAP support on both types of investment is positive, although seldom significant, while the proxy for uncertainty employed fails to be significant yet, in most cases, has the expected effect of reducing the investment levels.

The politicks on both sides, with regard to foreign affairs, stated from their own writings, and examined by the course of events. : With some observations on the present state of affairs in Great Britain, and the effects of our negotiations, for several years past.

Head-piece; initial.

Origines juridiciales, or Historical memorials of the English laws, courts of justice, forms of tryal, punishment in cases criminal, law-writers, law-books, grants and settlements of estates, degree of serjeant, Innes of court and chancery.

Head-pieces: a few manuscript marginal notes; the "Chronica series" covers the period 1067-1671, and is extended in manuscript through 1727 (with omission of last four columns, magist. rotulorum & c., for 1722-1727.

Gradual lessons in grammar, or, Guide to the construction of the English language by the analysis and composition of sentences /

On spine: Tower's English grammar.

The Law reports. Cases determined by the Chancery Division of the High Court of Justice, and by the Chief Judge in Bankruptcy, and by the Court of Appeal on appeal from the Chancery Division and the Chief Judge, and in lunacy.

Edited by G.W. Hemming.

In the news.

Occasional irregularities in numbering.

Lex, rex, or, The law and the prince : a dispute for the just prerogative of king and people, containing the reasons and causes of the most necessary defensive wars of the kingdom of Scotland and of their expedition for the aid and help of their dear brethren of England. In which their innocency is asserted and a full answer is given to a seditious pamphlet entituled, "Sacro-sancta regum majestas," or, The sacred and royal prerogative of Christian kings ; under the name of J.A., but penned by John Maxwell ... /

"De jure regni apud Scotos, a dialogue concerning the rights of the crown in Scotland" by George Buchanan -- pages [235]-283.

Outlines of a plan for the establishment of an agricultural model school in the province of Munster : as recommended by the Irish Relief Committee in London of 1822, who appropriated three thousand pounds of their remaning funds, to aid in carrying this object into effect.

Includes "Appendix. Report of the Committee of the N.W. Society concerning an agricultural seminary" and "Extracts from Travels in Switzerland by S. Simond, respecting Mr. Fellenberg's establishment at Hofwyl."

The Spanish empire in America : containing, a succinct relation of the discovery and settlement of its several colonies; a view of their respective situations, extent, commodities, trade, &c. : and a full and clear account of the commerce with Old Spain by the galleons, flota, &c. ; also of the contraband trade with the English, Dutch, French, Danes and Portuguese, with an exact description of Paraguay /

Memoir concerning the settlements of the Jesuits in Paraguay, by a French officer: p. 321-330.

Ideals of America; analyses of the guiding motives of contemporary American life by leaders in various fields of thought and action.

Can America's ideal be consciously shaped? by G. E. Hooker.--Ideals in politics, by F. D. Bramhall.--Ideals in law, by J. B. Winslow.--Ideals in labor, by J. P. Frey.--Ideals of science, by J. M. Coulter.--Ideals in education, by E. C. Moore.--Ideals in business, by A. E. Swanson.--Ideals in "society," by Elsie C. Parsons.--Ideals in music, by E. Dickinson.--Ideals in religion, by G. A. Coe.--Ideals in philosophy, by H. A. Overstreet.--Ideals in literature, by R. M. Lovett.--Human progress, by A. B. Pond.

People in Swimming Attire by River

Saline Valley Farms was an experiment in cooperative farming and living begun in 1932 by Harold S. Gray.

Dental health in children with phenylketonuria PKU and other inborn errors of amino acid metabolism managed by diet /

"Supported in part by Maternal and Child Health, Grant No. MCS-000252-16 and by contributions to Friends of Metabolic Research."