Over 1 billion people are estimated to be overweight, placing them at risk for diabetes, cardiovascular disease, and cancer. We performed a systems-level genetic dissection of adiposity regulation using genome-wide RNAi screening in adult Drosophila. As a follow-up, the resulting approximately 500 candidate obesity genes were functionally classified using muscle-, oenocyte-, fat-body-, and neuronal-specific knockdown in vivo and revealed hedgehog signaling as the top-scoring fat-body-specific pathway. To extrapolate these findings into mammals, we generated fat-specific hedgehog-activation mutant mice. Intriguingly, these mice displayed near total loss of white, but not brown, fat compartments. Mechanistically, activation of hedgehog signaling irreversibly blocked differentiation of white adipocytes through direct, coordinate modulation of early adipogenic factors. These findings identify a role for hedgehog signaling in white/brown adipocyte determination and link in vivo RNAi-based scanning of the Drosophila genome to regulation of adipocyte cell fate in mammals.

The binding of RGD peptides to integrins offers an excellent system to study the multivalent mediated changes in affinity that arise when peptides, displayed on the surface of a nanoparticle carrier, bind to integrins displayed on the cell membrane. The IC50 of an RGD nanoparticle for endothelial adhesion was 1.0 nM nanoparticle or 20 nM peptide (20 peptide/nanoparticle) and was associated with strong multivalent effects, defined as a multivalent enhancement factor (MVE) of 38 (MVE=IC50 (peptide)/IC50 (peptide when displayed by nanoparticle)). The attachment of RGD peptides to nanoparticles resulted in an extension of the peptide blood half-life from 13 to 180 min. Based on the multivalent enhancement of affinity and extension of blood half-life, multivalent RGD nanoparticle-sized materials should be potent inhibitors of the alpha(V)beta(3) function on endothelial cells in vivo.

In the assessment of normal corneas, the Pentacam measured CCT values closer to ultrasound pachymetry and with less variability compared with Orbscan. The (interobserver) reproducibility with the Pentacam was highest of all 3 modalities.

Optical imaging of specific molecular targets and pathways in vivo has recently become possible through continued developments in imaging equipment, reconstruction algorithms, and more importantly the availability of imaging reporter molecules. These reporter molecules encompass photoproteins expressed in vivo and exogenously administered probes detectable by fluorescence and/or bioluminescence imaging. One particularly enticing aspect of optical imaging is the ability to design activatible probes with inherent amplification. This review summarizes our experience in developing novel near-infrared fluorescent (NIRF) imaging agents that report on protease activities. These agents are designed to be biocompatible, highly activatible, and able to produce bright NIRF following protease cleavage.