Regulation of Dopamine Release by CASK-β Modulates Locomotor Initiation in Drosophila melanogaster

CASK is an evolutionarily conserved scaffolding protein that has roles in many cell types. In Drosophila, loss of the entire CASK gene or just the CASK- transcript causes a complex set of adult locomotor defects. In this study, we show that the motor initiation component of this phenotype is due to loss of CASK- in dopaminergic neurons and can be specifically rescued by expression of CASK- within this subset of neurons. Functional imaging demonstrates that mutation of CASK- disrupts coupling of neuronal activity to vesicle fusion. Consistent with this, locomotor initiation can be rescued by artificially driving activity in dopaminergic neurons. The molecular mechanism underlying this role of CASK- in dopaminergic neurons involves interaction with Hsc70-4, a molecular chaperone previously shown to regulate calcium-dependent vesicle fusion. These data suggest that there is a novel CASK- -dependent regulatory complex in dopaminergic neurons that serves to link activity and neurotransmitter release.Fil: Slawson, Justin B. Brandeis University; Estados UnidosFil: Kuklin, Elena A. Brandeis University; Estados UnidosFil: Mukherjee, Konark. Brandeis University; Estados UnidosFil: Pírez, Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina. Brandeis University; Estados UnidosFil: Donelson, Nathan C. Brandeis University; Estados UnidosFil: Griffith, Leslie C. Brandeis University; Estados Unido

SN 2008S: A Cool Super-Eddington Wind in a Supernova Impostor

We present visual-wavelength photometry and spectroscopy of supernova SN2008S. Based on the low peak luminosity for a SN of M_R = -13.9 mag, photometric and spectral evolution unlike that of low-luminosity SNe, a late-time decline rate slower than 56Co decay, and slow outflow speeds of 600-1000 km/s, we conclude that SN2008S is not a true core-collapse SN and is probably not an electron-capture SN. Instead, we show that SN2008S more closely resembles a "SN impostor" event like SN1997bs, analogous to the giant eruptions of LBVs. Its total radiated energy was 1e47.8 ergs, and it may have ejected 0.05-0.2 Msun in the event. We discover an uncanny similarity between the spectrum of SN 2008S and that of the Galactic hypergiant IRC+10420, which is dominated by narrow H-alpha, [Ca II], and Ca II emission lines formed in an opaque wind. We propose a scenario where the vastly super-Eddington wind of SN2008S partly fails because of reduced opacity due to recombination, as suggested for IRC+10420. The range of initial masses susceptible to eruptive LBV-like mass loss was known to extend down to 20-25 Msun, but estimates for the progenitor of SN2008S (and the similar NGC300 transient) may extend this range to around 15 Msun. As such, SN2008S may have implications for the progenitor of SN1987A.Comment: 4.5 pages, 2 figs, ApJ Letters accepted, figs and text significantly revised, fig1 in colo

Performance of a prototype atomic clock based on lin||lin coherent population trapping resonances in Rb atomic vapor

We report on the performance of the first table-top prototype atomic clock based on coherent population trapping (CPT) resonances with parallel linearly polarized optical fields (lin||lin configuration). Our apparatus uses a vertical cavity surface emitting laser (VCSEL) tuned to the D1 line of 87Rb with current modulation at the 87Rb hyperfine frequency. We demonstrate cancellation of the first-order light shift by proper choice of rf modulation power, and further improve our prototype clock stability by optimizing the parameters of the microwave lock loop. Operating in these optimal conditions, we measured a short-term fractional frequency stability (Allan deviation) 2*10^{-11} tau^{-1/2} for observation times 1s<tau< 20s. This value is limited by large VCSEL phase noise and environmental temperature fluctuation. Further improvements in frequency stability should be possible with an apparatus designed as a dedicated lin||lin CPT resonance clock with environmental impacts minimized.Comment: 6 pages, 8 fugure

Presidential Debate

What issues will be driving college students to and (potentially) away from the polls this Fall? Dr. Nathan Griffith will moderate a student debate and, time permitting, a discussion focusing on this year’s presidential election

Democracy by Dostoyevskii: Morality and Civility in Politics

In The Brothers Karamazov, Fyodor Dostoyevskii presents two tales, each of which has a lesson to teach about the role of morality and civility in politics. The first, and most well-known of these, is Ivan’s tale of the Grand Inquisitor; the second is Alexei’s recording of the life story of Elder Zosima. This presentation will explore how these tales illustrate the importance of morality and civility in politics, especially as presented in Tocqueville’s Democracy in America and Niebuhr’s The Children of Light and the Children of Darkness

Propulsion Control Technology Development Needs to Address NASA Aeronautics Research Mission Goals for Thrusts 3a and 4

The Commercial Aero-Propulsion Control Working Group (CAPCWG), consisting of propulsion control technology leads from The Boeing Company, GE Aviation, Honeywell, Pratt & Whitney, Rolls-Royce, and NASA (National Aeronautics and Space Administration) Glenn Research Center, has been working together over the past year to identify propulsion control technology areas of common interest that we believe are critical to achieving the challenging NASA Aeronautics Research goals for Thrust 3a: Ultra-Efficient Commercial Vehicles - Subsonic Transports, and Thrust 4: Transition to Alternative Propulsion and Energy. This paper describes the various propulsion control technology development areas identified by CAPCWG as most critical for NASA to invest in. For Thrust 3a these are: i) Integrated On-Board Model Based Engine Control and Health Management; ii) Flexible and Modular Networked Control Hardware and Software Architecture; iii) Intelligent Air/Fuel Control for Low Emissions Combustion; and iv) Active Clearance Control. For Thrust 4a, the focus is on Hybrid Electric Propulsion (HEP) for single aisle commercial aircraft. The specific technology development areas include: i) Integrated Power and Propulsion System Dynamic Modeling for Control; ii) Control Architectures for HEP; iii) HEP Control Verification and Validation; and iv) Engine/Airplane Control Integration. For each of the technology areas, the discussion includes: problem to be solved and how it relates to NASA goals, and the challenges to be addressed in reducing risk

A Study of the Diverse T Dwarf Population Revealed by WISE

We report the discovery of 87 new T dwarfs uncovered with the Wide-field Infrared Survey Explorer (WISE) and three brown dwarfs with extremely red near-infrared colors that exhibit characteristics of both L and T dwarfs. Two of the new T dwarfs are likely binaries with L7+/-1 primaries and mid-type T secondaries. In addition, our follow-up program has confirmed 10 previously identified T dwarfs and four photometrically-selected L and T dwarf candidates in the literature. This sample, along with the previous WISE discoveries, triples the number of known brown dwarfs with spectral types later than T5. Using the WISE All-Sky Source Catalog we present updated color-color and color-type diagrams for all the WISE-discovered T and Y dwarfs. Near-infrared spectra of the new discoveries are presented, along with spectral classifications. To accommodate later T dwarfs we have modified the integrated flux method of determining spectral indices to instead use the median flux. Furthermore, a newly defined J-narrow index differentiates the early-type Y dwarfs from late-type T dwarfs based on the J-band continuum slope. The K/J indices for this expanded sample show that 32% of late-type T dwarfs have suppressed K-band flux and are blue relative to the spectral standards, while only 11% are redder than the standards. Comparison of the Y/J and K/J index to models suggests diverse atmospheric conditions and supports the possible re-emergence of clouds after the L/T transition. We also discuss peculiar brown dwarfs and candidates that were found not to be substellar, including two Young Stellar Objects and two Active Galactic Nuclei. The coolest WISE-discovered brown dwarfs are the closest of their type and will remain the only sample of their kind for many years to come.Comment: Accepted to ApJS on 15 January 2013; 99 pages in preprint format, 30 figures, 12 table

SciClone: Inferring clonal architecture and tracking the spatial and temporal patterns of tumor evolution

The sensitivity of massively-parallel sequencing has confirmed that most cancers are oligoclonal, with subpopulations of neoplastic cells harboring distinct mutations. A fine resolution view of this clonal architecture provides insight into tumor heterogeneity, evolution, and treatment response, all of which may have clinical implications. Single tumor analysis already contributes to understanding these phenomena. However, cryptic subclones are frequently revealed by additional patient samples (e.g., collected at relapse or following treatment), indicating that accurately characterizing a tumor requires analyzing multiple samples from the same patient. To address this need, we present SciClone, a computational method that identifies the number and genetic composition of subclones by analyzing the variant allele frequencies of somatic mutations. We use it to detect subclones in acute myeloid leukemia and breast cancer samples that, though present at disease onset, are not evident from a single primary tumor sample. By doing so, we can track tumor evolution and identify the spatial origins of cells resisting therapy

A type I IFN-dependent DNA damage response regulates the genetic program and inflammasome activation in macrophages

Macrophages produce genotoxic agents, such as reactive oxygen and nitrogen species, that kill invading pathogens. Here we show that these agents activate the DNA damage response (DDR) kinases ATM and DNA-PKcs through the generation of double stranded breaks (DSBs) in murine macrophage genomic DNA. In contrast to other cell types, initiation of this DDR depends on signaling from the type I interferon receptor. Once activated, ATM and DNA-PKcs regulate a genetic program with diverse immune functions and promote inflammasome activation and the production of IL-1β and IL-18. Indeed, following infection with Listeria monocytogenes, DNA-PKcs-deficient murine macrophages produce reduced levels of IL-18 and are unable to optimally stimulate IFN-γ production by NK cells. Thus, genomic DNA DSBs act as signaling intermediates in murine macrophages, regulating innate immune responses through the initiation of a type I IFN-dependent DDR.</jats:p