Mechanisms of endothelin-1 induced reactive oxygen species production in vascular adventitial fibroblasts

With the relationship between endothelin-1 (ET-1) stimulation and reactive oxygen species (ROS) production unknown in adventitial fibroblasts, I examined the ROS response to ET-1 and angiotensin (Ang II). ET-1 -induced ROS peaked following 4 hrs of ET-1 stimulation and was inhibited by an ETA receptor antagonist (BQ 123, 1 uM) an extracellular signal-regulated kinase (ERK) 1/2 inhibitor (PD98059, 10 uM), and by both a specific, apocynin (10 uM), and non-specific, diphenyleneiodonium (10 uM), NAD(P)H oxidase inhibitor. NOX2 knockout fibroblasts did not produce an ET-1 induced change in ROS levels. Ang II treatment increased ROS levels in a biphasic manner, with the second peak occurring 6 hrs following stimulation. The secondary phase of Ang II induced ROS was inhibited by an ATi receptor antagonist, Losartan (100 uM) and BQ 123. In conclusion, ET-1 induces ROS production primarily through an ETA-ERKl/2 NOX2 pathway, additionally, Ang II-induced ROS production also involves an ETa pathway.

The importance of hydrogen bonding in the alkylation of phenols

Hydrogen bond assisted alkylation of phenols is compared with the classical base assisted reactions. The influence of solvents on the fluoride assisted reactions is discussed,· with emphasis on the localization of hydrogen bond charge density. Polar aprotic solvents such as DMF favour a-alkylation, and nonpolar aprotic solvents such as toluene favourC-alkylation of phenol. For more reactive and soluble fluorides, such as tetrabu~ylammoniumfluoride, the polar aprotic solvent favours a-alkylation and nonpolar aprotic solvent favours fluorination. Freeze-dried potassium fluoride is a better catalytic agent in hydrogen bond assisted alkylation reactions of phenol than the oven-dried fluoride. The presence of water in the alkylation reactions reduces the expected yield drastically. The tolerance of the reaction to water has also been studied. The use ofa phase transfer catalyst such as tetrabutylammonium bromide in the alkylation reactions of phenol in the presence of potassium fluoride is very effective under anhydrous conditions. Sterically hindered phenols such as 2,6-ditertiarybutyl-4-methyl phenol could not be alkylated even by using the more reactive fluorides, such as tetrabutylammonium fluoride in either polar or nonpolar aprotic solvents. Attempts were also made to alkylate phenols in the presence of triphenylphosphine oxide.

Notice of Change in Reparation Agent- Quebec 1 May 1822

A notice of change in reparation agent between Robert Morrogh and Thomas Douglas from Quebec to Daniel Shannon in Niagara.

Psychopathic Traits and Endocrine Function as Predictors of Costly and Non-Costly Reactive Aggression

I investigated factors of psychopathy (fearless dominance, self-centered impulsivity) and hormones (testosterone, cortisol, estradiol) in predicting costly and non-costly reactive aggression. I hypothesized that whereas self-centred impulsivity (SCI) would promote costly aggression, fearless dominance (FD) would promote non-costly aggression. Costly aggression was measured using the Point Subtraction Aggression Paradigm and noncostly aggression was measured using one-shot dictator games. In women (n = 97; M age = 19.86 years), greater SCI and lower baseline estradiol predicted greater costly aggression; also, greater FD predicted greater non-costly aggression, particularly among women with lower SCI. In men (n = 104; M age = 20.15 years), psychopathy and endocrine function did not predict costly aggression; however, greater FD and greater increases in testosterone were associated with greater non-costly aggression. Thus, there are sex-specific links between psychopathic personality traits, hormones, and aggressive behaviour, and psychopathic traits and endocrine function predict aggressive behaviour independently of each other.

Cellular Mechanisms of Resveratrol's Interaction with Mitochondrial Reactive Oxygen Species Metabolism

Resveratrol, a polyphenol found naturally in red wines, has attracted great interest in both the scientific community and the general public for its reported ability to protect against many of the diseases facing Western society today. While the purported health effects of resveratrol are well characterized, details of the cellular mechanisms that give rise to these observations are unclear. Here, the mitochondrial antioxidant enzyme Mn superoxide dismutase (MnSOD) was identified as a proximal target of resveratrol in vitro and in vivo. MnSOD protein and activity levels increase significantly in cultured cells treated with resveratrol, and in the brain tissue of mice given resveratrol in a high fat diet. Preventing the increase in MnSOD levels eliminates two of resveratrol’s more interesting effects in the context of human health: inhibition of proliferative cell growth and cytoprotection. Thus, the induction of MnSOD is a critical step in the molecular mechanism of resveratrol. Mitochondrial morphology is a malleable property that is capable of impeding cell cycle progression and conferring resistance against stress induced cell death. Using confocal microscopy and a novel ‘cell free’ fusion assay it was determined that concurrent with changes in MnSOD protein levels, resveratrol treatment leads to a more fused mitochondrial reticulum. This observation may be important to resveratrol’s ability to slow proliferative cell growth and confer cytoprotection. Resveratrol's biological activities, including the ability to increase MnSOD levels, are strikingly similar to what is observed with estrogen treatment. Resveratrol fails to increase MnSOD levels, slow proliferative cell growth and confer cytoprotection in the presence of an estrogen receptor antagonist. Resveratrol's effects can be replicated with the specific estrogen receptor beta agonist diarylpropionitrile, and are absent in myoblasts lacking estrogen receptor beta. Four compounds that are structurally similar to resveratrol and seven phytoestrogens predicted to bind to estrogen receptor beta were screened for their effects on MnSOD, proliferative growth rates and stress resistance in cultured mammalian cells. Several of these compounds were able to mimic the effects of resveratrol on MnSOD levels, proliferative cell growth and stress resistance in vitro. Thus, I hypothesize that resveratrol interacts with estrogen receptor beta to induce the upregulation of MnSOD, which in turn affects cell cycle progression and stress resistance. These results have important implications for the understanding of RES’s biological activities and potential applications to human health.

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?

Advertisement (printed 1 page) advertising Charles Dwight, agent for The Western Bond Board of Kansas City

Advertisement (printed 1 page) advertising Charles Dwight, agent for The Western Bond Board of Kansas City, 1872, n.d.