Partners No More: Relational Transformation and the Turn to Litigation in Two Conservationist Organizations

The rise in litigation against administrative bodies by environmental and other political interest groups worldwide has been explained predominantly through the liberalization of standing doctrines. Under this explanation, termed here the floodgate model, restrictive standing rules have dammed the flow of suits that groups were otherwise ready and eager to pursue. I examine this hypothesis by analyzing processes of institutional transformation in two conservationist organizations: the Sierra Club in the United States and the Society for the Protection of Nature in Israel (SPNI). Rather than an eagerness to embrace newly available litigation opportunities, as the floodgate model would predict, the groups\u27 history reveals a gradual process of transformation marked by internal, largely intergenerational divisions between those who abhorred conflict with state institutions and those who saw such conflict as not only appropriate but necessary to the mission of the group. Furthermore, in contrast to the pluralist interactions that the floodgate model imagines, both groups\u27 relations with pertinent agencies in earlier eras better accorded with the partnership-based corporatist paradigm. Sociolegal research has long indicated the importance of relational distance to the transformation of interpersonal disputes. I argue that, at the group level as well, the presence or absence of a (national) partnership-centered relationship determines propensities to bring political issues to court. As such, well beyond change in groups\u27 legal capacity and resources, current increases in levels of political litigation suggest more fundamental transformations in the structure and meaning of relations between citizen groups and the state

The Lys-Specific Molecular Tweezer, CLR01, Modulates Aggregation of the Mutant p53 DNA Binding Domain and Inhibits Its Toxicity

The tumor suppressor p53 plays a unique role as a central hub of numerous cell proliferation and apoptotic pathways, and its malfunction due to mutations is a major cause of various malignancies. Therefore, it serves as an attractive target for developing novel anticancer therapeutics. Because of its intrinsically unstable DNA binding domain, p53 unfolds rapidly at physiological temperature. Certain mutants shift the equilibrium toward the unfolded state and yield high-molecular weight, nonfunctional, and cytotoxic β-sheet-rich aggregates that share tinctorial and conformational similarities with amyloid deposits found in various protein misfolding diseases. Here, we examined the effect of a novel protein assembly modulator, the lysine (Lys)-specific molecular tweezer, CLR01, on different aggregation stages of misfolded mutant p53 <i>in vitro</i> and on the cytotoxicity of the resulting p53 aggregates in cell culture. We found that CLR01 induced rapid formation of β-sheet-rich, intermediate-size p53 aggregates yet inhibited further p53 aggregation and reduced the cytotoxicity of the resulting aggregates. Our data suggest that aggregation modulators, such as CLR01, could prevent the formation of toxic p53 aggregates