Paradoxical enhancement of fear extinction memory and synaptic plasticity by inhibition of the histone acetyltransferase p300

It is well established that the coordinated regulation of activity-dependent gene expression by the histone acetyltransferase (HAT) family of transcriptional coactivators is crucial for the formation of contextual fear and spatial memory, and for hippocampal synaptic plasticity. However, no studies have examined the role of this epigenetic mechanism within the infralimbic prefrontal cortex (ILPFC), an area of the brain that is essential for the formation and consolidation of fear extinction memory. Here we report that a postextinction training infusion of a combined p300/CBP inhibitor (Lys-CoA-Tat), directly into the ILPFC, enhances fear extinction memory in mice. Our results also demonstrate that the HAT p300 is highly expressed within pyramidal neurons of the ILPFC and that the small-molecule p300-specific inhibitor (C646) infused into the ILPFC immediately after weak extinction training enhances the consolidation of fear extinction memory. C646 infused 6 h after extinction had no effect on fear extinction memory, nor did an immediate postextinction training infusion into the prelimbic prefrontal cortex. Consistent with the behavioral findings, inhibition of p300 activity within the ILPFC facilitated long-term potentiation (LTP) under stimulation conditions that do not evoke long-lasting LTP. These data suggest that one function of p300 activity within the ILPFC is to constrain synaptic plasticity, and that a reduction in the function of this HAT is required for the formation of fear extinction memory.

The Anodic Polishing of Copper in Solutions of Orthophosphoric Acid

The electrolytic cleaning of metals by anodic methods has been known for many years. It was recognized long ago that when the temperature and concentration of the electro­lyte were properly regulated, bright clean surfaces were obtained.

An attempt to simplify English grammar : with observations on the method of teaching it /

Mode of access: Internet.

A dictionary of derivations; or, An introduction to etymology, on a new plan.

Mode of access: Internet.

An outline of the general regulations and methods of teaching in the male national model schools, for the use of the teachers in training.

Cover title.

Loss of glial glutamate transporters and induction of neuronal expression of GLT-1B in the hypoxic neonatal pig brain

The homeostasis of glutamate is critical to normal brain function; deficiencies in the regulation of extracellular glutamate are thought to be a major determinant of damage in hypoxic brains. Extracellular levels of glutamate are regulated mainly by plasmalemmal glutamate transporters. We have evaluated the distribution of the glutamate transporter GLAST and two splice variants of GLT-1 in the hypoxic neonatal pig brain using this as model of neonatal humans. In response to severe hypoxic insults, we observe a rapid loss of two glial glutamate transporters from specific brain regions, such as the CA1 region of the hippocampus, but not the dentate gyrus. The spatial distribution of loss accords with patterns of damage in these brains. Conversely, we demonstrate that hypoxia evokes the expression of a splice variant of GLT-1 in neurons. We suggest that this expression may be induced in response to elevated extracellular glutamate around these neurons, and that this splice variant may represent a useful marker for direct quantification of the extent of likely neuronal damage in hypoxic brains. © 2004 Elsevier B.V. All rights reserved.

Copyright, Licences, and Statutory Fraud

In this article we explore the interplay between the law of copyright, contract, and statutory fraud within the digital environment, and in particular with respect to the business of commercial image licensing within the UK.

Photograph - Robert Stanfield and Sean O'Sullivan, 1972

A photograph of Robert Stanfield with Sean O'Sullivan in his office, House of Commons, June 1972.

Correspondence - Sean O'Sullivan with Robert L. Stanfield, 1974

A correspondence between Robert L. Stanfield and Sean O'Sullivan regarding the future of the St. Lawrence Seaway and the Great Lakes. In the first letter, Mr. Stanfield requests to hear about O'Sullivan's progress. The second letter is from O'Sullivan with an update of his assignment. The third letter is from Mr. Stanfield thanking O'Sullivan for his work thus far and acknowledging the difficulties of such a project.

Sullivan Agent Confesses, [1948]

The National Seaman’s Association was a labour recruiter hiding behind a union-like name. It was run by H.N. McMaster who collected fees from companies and dues from workers. With McMaster in charge, shipping interests could claim that their seamen had a union, but ship-owners were free to push their vessels and their workers to the breaking point. In 1935, the members on the Great Lakes decided to strike. One year later, they created their own union and amalgamated with a Montreal-based independent body to create the Canadian Seamen’s Union headed by a ship’s cook who became a union leader, John Allan Patrick “Pat” Sullivan. By the late 1940s, almost all sailors on Canadian ships were CSU members. Right from its inception in 1936, Communists were prominent among the leaders of the union. Sullivan had been recruited to the Communist party that year and the union had a close rapport with the party. On June 8, 1940, Pat Sullivan was arrested because of his affiliation with the Communist party. He was incarcerated until March 20, 1942. No charges were laid, no bail was set and there was no trial. After his release, Sullivan was elected second vice-president of the Trades and Labour Congress of Canada. In 1943, Percy Bengough was elected as president and Sullivan was elected as secretary treasurer of the TLC while maintaining his role as president of the CSU. On March 14, 1947 Sullivan made a shocking announcement that he was resigning from the CSU and the Labor-Progressive Party. He claimed that the CSU was under the full control of the Communists. Within a month of this announcement, he emerged as the president of the Canadian Lake Seamen’s Union. Ship-owners never really reconciled themselves to having their industry unionized, and in 1946 there was a seamen’s strike in which the union won the eight-hour day. In 1949, the shipping companies had a plan to get rid of the union and were negotiating behind their back with the Seafarers International Union (SIU). In a brutal confrontation, led by Hal Banks, an American ex-convict, the SIU was able to roust the CSU and take over the bargaining rights of Canadian seamen. On July 15, 1948, Robert Lindsay, who was Sullivan’s Welland business agent said that to the best of his knowledge, Sullivan’s outfit, the CLSU, was under the control of some of the Steamship Companies. Lindsay had heard that there was a movement to get rid of Bengough of the Trades and Labour Congress as well as elements of the CSU. He also had heard that the CLSU wanted to affiliate with the American Federation of Labor. Lindsay’s allegations raised the questions: Were the ship-owners powerful enough to oust Percy Bengough because he supported the seamen? Could the CLSU get an affiliation with the American Federation of Labor? and Would the American Federation of Labor actually affiliate with a union that was siding with employers against a locked-out union?

Letter - Sean O'Sullivan to J. Diefenbaker, November 1969

A letter from Sean O'Sullivan to John Diefenbaker, 29 November 1969. O'Sullivan mentions a confrontation between Diefenbaker and Prime Minister Trudeau, during which Trudeau made an error and apologized to the House. Instead of seizing the moment to ridicule, Diefenbaker crossed the floor to accept the apology. O'Sullivan remarks "The gesture you made brought new honour to Parliament; an honour far too often lacking; and serves to remind all Canadians of the difference between a true leader and a petty political opportunist". He ends his letter by mentioning graffiti on the walls of Brock University that reads: "Mickey Mouse wears a Robert Stanfield watch".