Ligand-Specific Dynamics of the Androgen Receptor at Its Response Element in Living Cells

Androgens have key roles in normal physiology and in male sexual differentiation as well as in pathological conditions such as prostate cancer. Androgens act through the androgen receptor (AR), which is a ligand-modulated transcription factor. Antiandrogens block AR function and are widely used in disease states, but little is known about their mechanism of action in vivo. Here, we describe a rapid differential interaction of AR with target genomic sites in living cells in the presence of agonists which coincides with the recruitment of BRM ATPase complex and chromatin remodeling, resulting in transcriptional activation. In contrast, the interaction of antagonist-bound or mutant AR with its target was found to be kinetically different: it was dramatically faster, occurred without chromatin remodeling, and resulted in the lack of transcriptional inhibition. Fluorescent resonance energy transfer analysis of wild-type AR and a transcriptionally compromised mutant at the hormone response element showed that intramolecular interactions between the N and C termini of AR play a key functional role in vivo compared to intermolecular interactions between two neighboring ARs. These data provide a kinetic and mechanistic basis for regulation of gene expression by androgens and antiandrogens in living cells

Top-down synthesis of graphene: A comprehensive review

Graphene research has become an emerging frontier in materials science because of its potential as a versatile material in multiple applications, from electronics, sensors, water treatment, batteries, displays, advanced composites, and coatings to biomedical applications. While the community has witnessed tremendous advances in the laboratory-scale synthesis of graphene, it is crucial to focus on sustainable large-scale graphene production to adopt graphene-based technology at an industrial scale. Several top-down and bottom-up methods have been developed to realize affordable graphene production. However, a low-cost scalable graphene production method with acceptable quality remains a challenge; top-down processes are demonstrating their potential to offer a more straightforward solution. Herein, we present an overview of recent progress in the research and development of top-down graphene synthesis methods and their potential to scale-up graphene production. We cover the effect of different synthesis parameters on the quality control of graphene. In addition, we provide a brief overview of bottom-up methods. Finally, we discuss the existing challenges and future directions in top-down methods for large-scale graphene production