Engineering the Melanocortin-4 Receptor to Control Constitutive and Ligand-Mediated Gs Signaling In Vivo

The molecular and functional diversity of G protein–coupled receptors is essential to many physiological processes. However, this diversity presents a significant challenge to understanding the G protein–mediated signaling events that underlie a specific physiological response. To increase our understanding of these processes, we sought to gain control of the timing and specificity of Gs signaling in vivo. We used naturally occurring human mutations to develop two Gs-coupled engineered receptors that respond solely to a synthetic ligand (RASSLs). Our Gs-coupled RASSLs are based on the melanocortin-4 receptor, a centrally expressed receptor that plays an important role in the regulation of body weight. These RASSLs are not activated by the endogenous hormone α-melanocyte-stimulating hormone but respond potently to a selective synthetic ligand, tetrahydroisoquinoline. The RASSL variants reported here differ in their intrinsic basal activities, allowing the separation of the effects of basal signaling from ligand-mediated activation of the Gs pathway in vivo. These RASSLs can be used to activate Gs signaling in any tissue, but would be particularly useful for analyzing downstream events that mediate body weight regulation in mice. Our study also demonstrates the use of human genetic variation for protein engineering

One-dimensional ordering of Ge nanoclusters along atomically straight steps of Si(111)

Ge nanostructures grown by molecular beam epitaxy on a vicinal Si(111) surface with atomically well-defined steps are studied by means of scanning tunneling microscopy and spectroscopy. When the substrate temperature during deposition is around 250 degrees C, Ge nanoclusters of diameters less than 2.0 nm form a one-dimensional array of the periodicity 2.7 nm along each step. This self-organization is due to preferential nucleation of Ge on the unfaulted 7 x 7 half-unit cells at the upper step edges. Scanning tunneling spectroscopy reveals localized electronic states of the nanoclusters. (c) 2007 American Institute of Physics

Nanoscale charge transport measurements using a double-tip scanning tunneling microscope

We demonstrate the ability of a double-tip scanning tunneling microscope (STM) combined with a scanning electron microscope (SEM) to perform charge transport measurements on the nanoscale. The STM tips serve as electric probes that can be precisely positioned relative to the surface nanostructures using the SEM control and the height reference provided by the tunneling contact. The tips work in contact, noncontact, and tunneling modes. We present vertical transport measurements on nanosized GaAs/AlAs resonant tunneling diodes and lateral transport measurements on the conductive surface of 7 x 7 reconstructed Si(111). The high stability of the double-tip STM allows nondestructive electrical contacts to surfaces via the tunneling gaps. We performed two-point electrical measurements via tunneling contacts on the Si(111) (7x7) surface and evaluated them using a model for the charge transport on this surface. (C) 2008 American Institute of Physics. [DOI: 10.1063/1.3006891

Self-assembly of periodic nanoclusters of Si and Ge along atomically straight steps of a vicinal Si(111)

The very initial stage of the molecular beam epitaxy of Si and Ge on Si(111)-7x7 substrates with atomically straight steps has been studied by scanning tunneling microscopy and spectroscopy. The atomically straight steps have been prepared on a miscut Si(111) substrate by annealing at 830 degrees C with kink-up direct current. The length of the steps can be maximized by selecting a proper annealing time. The steps have a well-defined U(2, 0) step-edge structure. The growth of both Si and Ge at temperatures between 250 and 400 degrees C starts with formation of a single-adatom-row nanowire (0.67 nm in width) along the lower edge of each U(2, 0) step. Subsequent growth of Si and Ge at temperatures between 250 and 300 degrees C results in formation of one-dimensional arrays of nanoclusters (less than 2.0 nm in width) in the unfaulted halves of the 7x7 structure along the upper step edges. Scanning tunneling spectroscopy reveals localized electronic states of the nanoclusters. Differences between the growth of Si and Ge nanoclusters are discussed

Kinetic and strain-driven growth phenomena on Si(001)

Self-organization phenomena in semiconductors are usually based on strain-driven island growth during hetero epitaxial layer deposition. However, kinetic phenomena can become important and even dominating at the low growth temperatures usually employed during molecular beam epitaxy. We report on kinetic step bunching on Si(001), and identify the driving mechanism on the atomic scale via kinetic Monte Carlo simulations. Another phenomena discussed is facet formation during annealing of SiO2-covered Si(001) nanostructures at the relatively low temperatures usually employed for oxide desorption. Both phenomena are combined to facilitate perfect ordering of self-assembled Ge dots on facetted Si(001) nanostructure templates. (C) 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim