Environmental Law Confronts the New Industrial Revolution

This issue of the Pace Environmental Law Review presents a set of articles to shed new light on those questions in the case of the products of nanotechnology. For comparison, the issue also includes an article on the regulation of genetically modified organisms in agriculture in the United States and Brazil, an early effort to govern the risks of a major new technology

Lessons from a Lawyer’s Life

The author, scholar-in-residence at Pace Law School, received the 2013 ABA Award for Distinguished Achievement in Environmental Law and Policy. A pioneer in the early years of environmental protection, she expands in this space on her remarks in accepting the honor, drawing insights for today’s environmental professionals

Ending the Tyranny of the Status Quo: Building 21st Century Environmental Law

Over the past few years, the Environmental Law Institute (ELI or the Institute) has worked to assess the notable successes and current challenges of United States environmental law to inform a new agenda for the twenty-first century. Founded in 1969, at the beginning of modern environmental law, the Institute has been both participant and analyst of an impressive record of major accomplishments in pollution reduction, greater protection of public health, and more intelligent conservation and management of natural resources, in both the public and the private sector. Like the majority of environmental lawyers and policy professionals examining today\u27s challenges, we also see that the United States confronts even more complex environmental and natural resource impacts today. These include climate change, growth in human consumption and population, the consequences of these changes for water supplies, food security, and preservation of biodiversity, and the general sustainability of economic and social development supported by a diminished and inequitably distributed base of natural resources. To undertake this assessment, we began by surveying the many reports and articles written on reform of environmental protection over the past twenty-five years and by conducting interviews of many of the early leaders in environmental law, environmental futurists, and current law students to obtain their insight and ideas for improvement. We then outlined a potential program (1) to envision what America\u27s environmental future should look like in 2050 and (2) to consider what ethical norms, objectives, implementation strategies, and public- and private-sector roles and responsibilities might form a sturdy platform to advance toward the objectives. This article offers a summary of our findings and a proposal for future dialogue

Structural Insights into the Evolution of a Non-Biological Protein: Importance of Surface Residues in Protein Fold Optimization

Phylogenetic profiling of amino acid substitution patterns in proteins has led many to conclude that most structural information is carried by interior core residues that are solvent inaccessible. This conclusion is based on the observation that buried residues generally tolerate only conserved sequence changes, while surface residues allow more diverse chemical substitutions. This notion is now changing as it has become apparent that both core and surface residues play important roles in protein folding and stability. Unfortunately, the ability to identify specific mutations that will lead to enhanced stability remains a challenging problem. Here we discuss two mutations that emerged from an in vitro selection experiment designed to improve the folding stability of a non-biological ATP binding protein. These mutations alter two solvent accessible residues, and dramatically enhance the expression, solubility, thermal stability, and ligand binding affinity of the protein. The significance of both mutations was investigated individually and together, and the X-ray crystal structures of the parent sequence and double mutant protein were solved to a resolution limit of 2.8 and 1.65 Å, respectively. Comparative structural analysis of the evolved protein to proteins found in nature reveals that our non-biological protein evolved certain structural features shared by many thermophilic proteins. This experimental result suggests that protein fold optimization by in vitro selection offers a viable approach to generating stable variants of many naturally occurring proteins whose structures and functions are otherwise difficult to study

Alkylation of the Tumor Suppressor PTEN Activates Akt and β-Catenin Signaling: A Mechanism Linking Inflammation and Oxidative Stress with Cancer

PTEN, a phosphoinositide-3-phosphatase, serves dual roles as a tumor suppressor and regulator of cellular anabolic/catabolic metabolism. Adaptation of a redox-sensitive cysteinyl thiol in PTEN for signal transduction by hydrogen peroxide may have superimposed a vulnerability to other mediators of oxidative stress and inflammation, especially reactive carbonyl species, which are commonly occurring by-products of arachidonic acid peroxidation. Using MCF7 and HEK-293 cells, we report that several reactive aldehydes and ketones, e.g. electrophilic α,β-enals (acrolein, 4-hydroxy-2-nonenal) and α,β-enones (prostaglandin A2, Δ12-prostaglandin J2 and 15-deoxy-Δ-12,14-prostaglandin J2) covalently modify and inactivate cellular PTEN, with ensuing activation of PKB/Akt kinase; phosphorylation of Akt substrates; increased cell proliferation; and increased nuclear β-catenin signaling. Alkylation of PTEN by α,β-enals/enones and interference with its restraint of cellular PKB/Akt signaling may accentuate hyperplastic and neoplastic disorders associated with chronic inflammation, oxidative stress, or aging