Identification of Enolase as the Target of 2-Aminothiazoles in Mycobacterium tuberculosis

Tuberculosis is a massive global burden and Mycobacterium tuberculosis is increasingly resistant to first- and second-line drugs. There is an acute need for new anti-mycobacterial drugs with novel targets. We previously evaluated a series of 2-aminothiazoles with activity against Mycobacterium tuberculosis. In this study, we identify the glycolytic enzyme enolase as the target of these molecules using pull down studies. We demonstrate that modulation of the level of enolase expression affects sensitivity to 2-aminothiazoles; increased expression leads to resistance while decreased protein levels increase sensitivity. Exposure to 2-aminothiazoles results in increased levels of metabolites preceding the action of enolase in the glycolytic pathway and decreased ATP levels. We demonstrate that 2-aminothiazoles inhibit the activity of the human α-enolase, which could also account for the cytotoxicity of some of those molecules. If selectivity for the bacterial enzyme over the human enzyme could be achieved, enolase would represent an attractive target for M. tuberculosis drug discovery and development efforts

TNOs are cool: a survey of the transneptunian region

Over one thousand objects have so far been discovered orbiting beyond Neptune. These trans-Neptunian objects (TNOs) represent the primitive remnants of the planetesimal disk from which the planets formed and are perhaps analogous to the unseen dust parent-bodies in debris disks observed around other main-sequence stars. The dynamical and physical properties of these bodies provide unique and important constraints on formation and evolution models of the Solar System. While the dynamical architecture in this region (also known as the Kuiper Belt) is becoming relatively clear, the physical properties of the objects are still largely unexplored. In particular, fundamental parameters such as size, albedo, density and thermal properties are difficult to measure. Measurements of thermal emission, which peaks at far-IR wavelengths, offer the best means available to determine the physical properties. While Spitzer has provided some results, notably revealing a large albedo diversity in this population, the increased sensitivity of Herschel and its superior wavelength coverage should permit profound advances in the field. Within our accepted project we propose to perform radiometric measurements of 139 objects, including 25 known multiple systems. When combined with measurements of the dust population beyond Neptune (e.g. from the New Horizons mission to Pluto), our results will provide a benchmark for understanding the Solar debris disk, and extra-solar ones as well

VIDEO: Session III, Part 1: Looking Forward

VIDEO: SESSION III, PART 1: Looking Forward 8:00 a.m. - 8:30 a.m. Setting the Stage: Moving Beyond the Basin Study: Brad Udall, Director, Getches-Wilkinson Center 8:30 a.m. - 9:00 a.m. Interim Guidelines (and What Happens Below 1025’): Pat Mulroy, General Manager, Southern Nevada Water Authority 9:00 a.m. - 9:20 a.m. Respondent: Barton “Buzz” Thompson, Professor, Stanford University 9:20 a.m. - 9:50 a.m. The (Ongoing) Evolution of Lower Basin Water Banking: Tanya Trujillo, Executive Director, Colorado River Board of California 9:50 a.m. - 10:20 a.m. Next Up: Upper Basin Water Banks: Eric Kuhn, General Manager, Colorado River Water Conservation Distric

VIDEO: Session III, Part 1: Looking Forward

VIDEO: SESSION III, PART 1: Looking Forward 8:00 a.m. - 8:30 a.m. Setting the Stage: Moving Beyond the Basin Study: Brad Udall, Director, Getches-Wilkinson Center 8:30 a.m. - 9:00 a.m. Interim Guidelines (and What Happens Below 1025’): Pat Mulroy, General Manager, Southern Nevada Water Authority 9:00 a.m. - 9:20 a.m. Respondent: Barton “Buzz” Thompson, Professor, Stanford University 9:20 a.m. - 9:50 a.m. The (Ongoing) Evolution of Lower Basin Water Banking: Tanya Trujillo, Executive Director, Colorado River Board of California 9:50 a.m. - 10:20 a.m. Next Up: Upper Basin Water Banks: Eric Kuhn, General Manager, Colorado River Water Conservation Distric

VIDEO: Session 1: The State of the River: New and Evolving Agreements in the Basin, Panel B: Indian Water Rights Settlements and Panel C: U.S.-Mexico Negotiations

VIDEO: 1:00 p.m. - 3:00 p.m. SESSION 1: The State of the River Panel B: Indian Water Rights Settlements Panelists: Tanya Trujillo, Counsel, Senate Energy & Natural Resources Committee; Katie Yellowhorse Gilbert, former Navajo Nation Water Commissioner Panel C: U.S.-Mexico Negotiations Panelists: Mario López Pérez, Engineering and Technical Standards Manager, National Water Commission of Mexico; Steve Fitten, Chief Counsel, International Boundary Waters Commission; Jennifer Gimbel, Colorado Water Conservation Boar

VIDEO: Session IV: The Big Picture

VIDEO: SESSION IV: The Big Picture 1:30 p.m. - 2:00 p.m. Restoring the Health of the River: Jack Schmidt, Chief, USGS Grand Canyon Monitoring and Research Center 2:00 p.m. - 2:30 p.m. Reckoning Arizona v. California with the Colorado River Compact: Jason Robison, Professor, University of Wyoming 2:30 p.m. - 4:00 p.m. Tying it All Together: Final Observations: Eric Kuhn, General Manager, Colorado River Water Conservation District Tanya Trujillo, Executive Director, Colorado River Board of California Pat Mulroy, General Manager, Southern Nevada Water Authority Jim Lochhead, CEO/Manager, Denver Water Sandy Fabritz-Whitney, Director, Arizona Department of Water Resource

VIDEO: Session IV: The Big Picture

VIDEO: SESSION IV: The Big Picture 1:30 p.m. - 2:00 p.m. Restoring the Health of the River: Jack Schmidt, Chief, USGS Grand Canyon Monitoring and Research Center 2:00 p.m. - 2:30 p.m. Reckoning Arizona v. California with the Colorado River Compact: Jason Robison, Professor, University of Wyoming 2:30 p.m. - 4:00 p.m. Tying it All Together: Final Observations: Eric Kuhn, General Manager, Colorado River Water Conservation District Tanya Trujillo, Executive Director, Colorado River Board of California Pat Mulroy, General Manager, Southern Nevada Water Authority Jim Lochhead, CEO/Manager, Denver Water Sandy Fabritz-Whitney, Director, Arizona Department of Water Resource