By Jeffrey Rosen | The Atlantic | June 3, 2016

Louis Brandeis, who was confirmed to the Supreme Court exactly 100 years ago, was America’s greatest critic of bigness since Thomas Jefferson. Denouncing big banks as well as big government as symptoms of what he called a “curse of bigness,” Brandeis was determined to diminish concentrated financial and federal power, which he viewed as a menace to liberty and democracy. He is also the Jeffersonian prophet who has been most consistently vindicated. The “people’s lawyer,” who predicted the stock-market crash of 1929, was a ferocious critic of economic and political consolidation in an earlier age of “too big to fail.” More than any other Supreme Court justice, he shows the importance of translating values of privacy and free speech in an age of technological change.

By Amy N. Shore, Chi-Hsuan Chang, Oh-Joon Kwon, Matthew C. Weston, Mei Zhang, Li Xi, and Jeffrey M. Rosen | Developmental Biology | October 23, 2015

Abstract:

In the mammary gland, PTEN loss in luminal and basal epithelial cells results in differentiation defects and enhanced proliferation, leading to the formation of tumors with basal epithelial characteristics. In breast cancer, PTEN loss is associated with a hormone receptor-negative, basal-like subtype that is thought to originate in a luminal epithelial cell. Here, we show that luminal-specific PTEN loss results in distinct effects on epithelial homeostasis and mammary tumor formation. Luminal PTEN loss increased proliferation of hormone receptor-negative cells, thereby decreasing the percentage of hormone receptor-positive cells. Moreover, luminal PTEN loss led to misoriented cell divisions and mislocalization of cells to the intraluminal space of mammary ducts. Despite their elevated levels of activated AKT, Pten-null intraluminal cells showed increased levels of apoptosis. One year after Pten deletion, the ducts had cleared and no palpable mammary tumors were detected. These data establish PTEN as a critical regulator of luminal epithelial homeostasis and integrity in the adult mammary gland, and further show that luminal PTEN loss alone is not sufficient to promote the progression of mammary tumorigenesis.

Read the full article here.

By Chi-Hsuan Chang, Mei Zhang, Kimal Rajapakshe, Cristian Coarfa, Dean Edwards, Shixia Huang, and Jeffrey M. Rosen | Stem Cell Reports | August 20, 2015

Summary:

Adult stem cells and tumor-initiating cells (TICs) often employ different mechanisms of DNA damage response (DDR) as compared to other tissue cell types. However, little is known about how mammary stem cells (MaSCs) and mammary TICs respond to DNA damage. Using the mouse mammary gland and syngeneic p53-null tumors as models, we investigated the molecular and physiological consequences of DNA damage in wild-type MaSCs, p53-null MaSCs, and p53-null TICs. We showed that wild-type MaSCs and basal cells are more resistant to apoptosis and exhibit increased non-homologous end joining (NHEJ) activity. Loss of p53 in mammary epithelium affected both cell-cycle regulation and DNA repair efficiency. In p53-null tumors, we showed that TICs are more resistant to ionizing radiation (IR) due to decreased apoptosis, elevated NHEJ activity, and more-rapid DNA repair. These results have important implications for understanding DDR mechanisms involved in both tumorigenesis and therapy resistance.

Read the full article here.

Brandon Monroe for the New York Times

I. Mr. Weinstein’s Cyst When historians of the future try to identify the moment that neuroscience began to transform the American legal system, they may point to a little-noticed case from the early 1990s. The case involved Herbert Weinstein, a 65-year-old ad executive who was charged with strangling his wife, Barbara, to death and then, in an effort to make the murder look like a suicide, throwing her body out the window of their 12th-floor apartment on East 72nd Street in Manhattan. Before the trial began, Weinstein’s lawyer suggested that his client should not be held responsible for his actions because of a mental defect — namely, an abnormal cyst nestled in his arachnoid membrane, which surrounds the brain like a spider web.

The implications of the claim were considerable. American law holds people criminally responsible unless they act under duress (with a gun pointed at the head, for example) or if they suffer from a serious defect in rationality — like not being able to tell right from wrong. But if you suffer from such a serious defect, the law generally doesn’t care why — whether it’s an unhappy childhood or an arachnoid cyst or both. To suggest that criminals could be excused because their brains made them do it seems to imply that anyone whose brain isn’t functioning properly could be absolved of responsibility. But should judges and juries really be in the business of defining the normal or properly working brain? And since all behavior is caused by our brains, wouldn’t this mean all behavior could potentially be excused?

Read the full article in the New York Times. By Jeffrey Rosen, CLBB Faculty member, commentator on US legal affairs, and President and CEO of the National Constitution Center in Philadelphia. Published March 11, 2007.