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Burdock Root

Washington Post Column Examines Issues Surrounding Supreme Court Confirmation Hearings
"When a Supreme Court nominee such as Judge Sonia Sotomayor comes before the Senate for confirmation, she is promised a full, fair hearing," yet "every nominee"s path is booby-trapped by the history of previous confirmation battles," Washington Post columnist David Broder writes. Broder examines prior confirmation hearings, noting that the "[o]ne thing that may make it harder to forget the partisan and ideological battles of the past is that President Obama found reasons to oppose" Chief Justice John Roberts and Justice Samuel Alito while he was in the Senate.During Roberts" confirmation hearing, Obama said that although he was "sorely tempted to vote for Judge Roberts," he had issues with Roberts in cases where "precedent and rules of construction" are insufficient and where justice "can only be determined on the basis of one"s deepest values." Obama added that the rights of women and minorities are dependent on cases in which "the critical ingredient is supplied by what is in the judge"s heart." Obama said Roberts" record on women"s rights and other issues was not strong enough to quell doubts about Roberts" "deepest values."Broder continues, "Based on the Obama precedent, the White House can hardly complain if Republicans push beyond the question of Sotomayor"s qualifications and examine her values -- and her biases." He concludes, "Someday, the Senate may again be satisfied to examine only professional credentials, recognizing the uncertain dynamics of a nine-person bench," but while past precedents survive, "that is not likely" (Broder, Washington Post, 6/4).
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FDA Ruling On Mercury Fillings Falls Short
In a disappointing move, the Food and Drug Administration (FDA) did an about face in issuing a final regulation classifying dental amalgam without calling for stringent precautions for pregnant women and children. Last June, a court settlement filed by the Consumers for Dental Choice required the FDA to withdraw claims of mercury amalgam"s safety from its Web site and issue an advisory indicating: "Dental amalgams contain mercury, which may have neurotoxic effects on the nervous systems of developing children and fetuses."
News of the day
Study Finds That Tobacco Companies Changed Design Of Cigarettes Without Alerting Smokers
As President Obama prepares to sign a bill giving the Food and Drug Administration (FDA) oversight of the tobacco industry, a new study from Harvard School of Public Health (HSPH) researchers shows that tobacco manufacturers have continually changed the ingredients and the design of their cigarettes over time, even if those changes have exceeded acceptable product variance guidelines. The result, say the researchers, is that consumers who buy the same brand of product are not made aware of how that product has been altered and what effect those alterations might have on their levels of addiction or harm.
Endocrinology

Context Is Key: Differential PI3K Signaling And Consequences For Targeted Therapy

In the July 15th issue of G and D, Dr. Suzanne Baker (St. Jude Children"s Research Hospital) and colleagues report on their surprising discovery of cell-type specificity of PI3K signaling in the mammalian brain. This finding highlights the complexity of this clinically significant cell signaling pathway, and its relevance to the design of small molecule PI3K pathway inhibitors, to both maximize efficacy and minimize side effects. The PI3K pathway is an intricate signaling cascade that regulates cell survival and growth under normal, as well as pathological conditions. In fact, the PI3K pathway is mutated in more cancer patients than any other. The signaling network is balanced by the PTEN tumor suppressor protein. PTEN (Phosphatase and Tensin Homologue Deleted from Chromosome-10) is recognized as one of the most frequently mutated tumor suppressors in human cancer, and has also been associated with neurological diseases like autism. It functions primarily as a phosphatase (phosphate-group-cleaving enzyme) to antagonize PI3K signaling by dephosphorylating PIP3, the lipid second messenger that signals activation of the PI3K signaling cascade. Loss of PTEN results in the upregulation of PI3K signaling, through the increased phosphorylation of PI3K effectors such as the molecule, AKT. Thus, the PTEN/PI3K/AKT pathway represents an important target for drug discovery. To study the role of the PI3K downstream effector molecule, PDK1, in mediating the effects of PTEN loss, Dr. Baker and colleagues generated a novel transgenic mouse strain deficient in both PDK1 and PTEN specifically in the brain. The researchers found that while some of the characteristic brain abnormalities arising from PTEN loss are corrected by the concomitant deletion of PDK1, others are not: Most notably, PDK1 did not rescue the migration defects associated with PTEN loss in neurons. PDK1-independent abnormalities in the brains of PTEN-deficient mice suggests that additional, alternate downstream effectors of the PI3K signal exist. This finding underscores the consideration that, as Dr. Baker explains, "inhibitors that block downstream effectors in PI3K signaling may not correct all of the defects caused by loss of PTEN function." Dr. Baker"s team also observed differential feedback regulation of the PI3K pathway in different CNS cell types. Clinical evidence has shown that some human tumors achieve chemoresistance through the increased phosphorylation of the PI3K downstream component, AKT. Quite surprisingly, Dr. Baker and colleagues found that PDK1 deletion caused a selective, dramatic increase in the phosphorylation of AKT in glial cells, but not neurons, indicating unanticipated cell-type specificity in PI3K feedback regulation in the brain. Further research will be needed to determine if PDK1, itself, represents a useful therapeutic target. However, this example of a cell type-specific response to PDK1 deletion supports the notion of personalized cancer treatment, in so far as emphasizing the relevance of tumor cell of origin and genotype to help predict which patients will respond positively to specific PI3K inhibitors. Dr. Baker emphasizes that, likewise, "There may be profound differences in the effects of inhibitors on different types of normal cells, which could be relevant in terms of side effects induced by systemic treatment with a pathway inhibitor." Heather Cosel-Pieper Cold Spring Harbor Laboratory


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