The Search for Low Energy Conformational Families of Small Peptides: Searching for Active Conformations of Small Peptides in the Absence of a Known Receptor

Breast cancer is the most common cancer among women. Tamoxifen is the preferred drug for estrogen receptor-positive breast cancer treatment, yet many of these cancers are intrinsically resistant to tamoxifen or acquire resistance during treatment. Therefore, scientists are searching for breast cancer drugs that have different molecular targets. Previous work revealed that 8-mer and cyclic 9-mer peptides inhibit breast cancer in mouse and rat model systems, interacting with an unknown receptor, while peptides smaller than eight amino acids did not inhibit breast cancer. We have shown that the use of replica exchange molecular dynamics predicts structure and dynamics of active peptides, leading to the discovery of smaller peptides with full biological activity. These simulations identified smaller peptide analogs with a conserved turn, a β-turn formed in the larger peptides. These analogs inhibit estrogen-dependent cell growth in a mouse uterine growth assay, a test showing reliable correlation with human breast cancer inhibition. We outline the computational methods that were tried and used with the experimental information that led to the successful completion of this research.

Im/possible Lives: Gender, Class, Self-Fashioning, and Affinal Solidarity in Modern South Asia

Drawing on ethnographic research and employing a micro-historical approach that recognizes not only the transnational but also the culturally specific manifestations of modernity, this article centers on the efforts of a young woman to negotiate shifting and conflicting discourses about what a good life might consist of for a highly educated and high caste Hindu woman living at the margins of a nonetheless globalized world. Newly imaginable worlds in contemporary Mithila,South Asia, structure feeling and action in particularly gendered and classed ways, even as the capacity of individuals to actualize those worlds and the “modern” selves envisioned within them are constrained by both overt and subtle means. In the context of shifting cultural anchors, new practices of silence, literacy, and even behaviors interpreted as “mental illness” may become tactics in an individual’s negotiation of conflicting self-representations. The confluence of forces at play in contemporary Mithila, moreover, is creating new structures of feeling that may begin to reverse long-standing locally held assumptions about strong solidarities between natal families and daughters, on the one hand, and weak solidarities between affinal families and new daughters-in-law, on the other.

Working With Families of Impaired Elderly

In this article, several approaches to working with the complexity of family relationships in later adulthood are described. Basic information on family forms and the pattern of family support for older adults is discussed. In addition, several examples of interventions with family members of older adults are reviewed. The goal of these activities is to increase the range of options available to older adults and their family caregivers.

Transnational Marriage: Modern Imaginings, Relational Realignments, and Persistent Inequalities

In the context of shifting cultural anchors as well as unstable global economic conditions, new practices of intimacy and sexuality may become tactics in an individual’s negotiation of conflicting desires and potentials. This article offers reflection on the interface between global forces, powerful transcultural narratives, and state policies, on the one hand, and local, even individual, constructions and tactics in regard to sexuality, marriage, migration, and work, on the other. The article focuses on the life trajectory of Gudiya, an ambitious young Hindu woman who started out life with little social capital and few economic resources in a dusty corner of what was then the tiny kingdom of Nepal. Gudiya’s story highlights the ways in which she has engaged in relational realignments aimed at bringing her closer to the life she imagines, even as she has encountered new and persistent forms of inequality both local and transnational in scale.