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Dekker F.J.,Max Planck Institute of Molecular Physiology | Dekker F.J.,University of Marburg | Dekker F.J.,University of Groningen | Rocks O.,Max Planck Institute of Molecular Physiology | And 25 more authors.
Nature Chemical Biology | Year: 2010

Cycles of depalmitoylation and repalmitoylation critically control the steady-state localization and function of various peripheral membrane proteins, such as Ras proto-oncogene products. Interference with acylation using small molecules is a strategy to modulate cellular localizationĝ€"and thereby unregulated signalingĝ€"caused by palmitoylated Ras proteins. We present the knowledge-based development and characterization of a potent inhibitor of acyl protein thioesterase 1 (APT1), a bona fide depalmitoylating enzyme that is, so far, poorly characterized in cells. The inhibitor, palmostatin B, perturbs the cellular acylation cycle at the level of depalmitoylation and thereby causes a loss of the precise steady-state localization of palmitoylated Ras. As a consequence, palmostatin B induces partial phenotypic reversion in oncogenic HRasG12V-transformed fibroblasts. We identify APT1 as one of the thioesterases in the acylation cycle and show that this protein is a cellular target of the inhibitor.

Finkelstein D.A.,Baker Laboratory | Kirtland J.D.,Cornell University | Mota N.D.,Baker Laboratory | Stroock A.D.,Cornell University | Abruna H.D.,Baker Laboratory
Journal of Physical Chemistry C | Year: 2011

Oxygen (O2) reduction has long been the factor limiting the power density of most fuel cells. Membraneless, microfluidic fuel cells are a promising new fuel cell technology, yet they are affected even more strongly by O2, as they usually require a dissolved oxidant, and O2 has minimal solubility in most solvents. Here we offer a detailed, analytical comparison of the performance of previously employed alternative oxidants, H2O2, MnO4 ?, VO2 +, and ClO?, at Pt, Au, and glassy carbon (GC) rotating disk electrodes (RDEs). We also investigated cerium ammonium nitrate (CAN), which has an exceptionally high potential for reduction. Of the oxidants studied, CAN offers the best immediate advantage, but MnO4 ?, though requiring development efforts, shows the most long-term promise for high-power fuel cells. © 2011 American Chemical Society.

Booth J.G.,Cornell University | Eilertson K.E.,Cornell University | Olinares P.D.B.,Baker Laboratory | Olinares P.D.B.,Cornell University | Yu H.,Cornell University
Molecular and Cellular Proteomics | Year: 2011

Recent developments in mass-spectrometry-based shotgun proteomics, especially methods using spectral counting, have enabled large-scale identification and differential profiling of complex proteomes. Most such proteomic studies are interested in identifying proteins, the abundance of which is different under various conditions. Several quantitative methods have recently been proposed and implemented for this purpose. Building on some techniques that are now widely accepted in the microarray literature, we developed and implemented a new method using a Bayesian model to calculate posterior probabilities of differential abundance for thousands of proteins in a given experiment simultaneously. Our Bayesian model is shown to deliver uniformly superior performance when compared with several existing methods. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

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