Riding the DUBway: regulation of protein trafficking by deubiquitylating enzymes

Ubiquitylation is a key regulator of protein trafficking, and much about the functions of ubiquitin ligases, which add ubiquitin to substrates in this regulation, has recently come to light. However, a clear understanding of ubiquitin-dependent protein localization cannot be achieved without knowledge of the role of deubiquitylating enzymes (DUBs). DUBs, by definition, function downstream in ubiquitin pathways and, as such, have the potential to be the final editors of protein ubiquitylation status, thus determining substrate fate. This paper assimilates the current evidence concerning the substrates and activities of DUBs that regulate protein trafficking

Allowable Trajectory Variations for Space Shuttle Orbiter Entry-Aeroheating CFD

Reynolds-number criteria are developed for acceptable variations in Space Shuttle Orbiter entry trajectories for use in computational aeroheating analyses. The criteria determine if an existing computational fluid dynamics solution for a particular trajectory can be extrapolated to a different trajectory. The criteria development begins by estimating uncertainties for seventeen types of computational aeroheating data, such as boundary layer thickness, at exact trajectory conditions. For each type of datum, the allowable uncertainty contribution due to trajectory variation is set to be half of the value of the estimated exact-trajectory uncertainty. Then, for the twelve highest-priority datum types, Reynolds-number relations between trajectory variation and output uncertainty are determined. From these relations the criteria are established for the maximum allowable trajectory variations. The most restrictive criterion allows a 25% variation in Reynolds number at constant Mach number between trajectories

The Shape of LITTLE THINGS Dwarf Galaxies DDO 46 and DDO 168: Understanding the stellar and gas kinematics

We present the stellar and gas kinematics of DDO 46 and DDO 168 from the LITTLE THINGS survey and determine their respective Vmax/sigma_z,0 values. We used the KPNO's 4-meter telescope with the Echelle spectrograph as a long-slit spectrograph. We acquired spectra of DDO 168 along four position angles by placing the slit over the morphological major and minor axes and two intermediate position angles. However, due to poor weather conditions during our observing run for DDO 46, we were able to extract only one useful data point from the morphological major axis. We determined a central stellar velocity dispersion perpendicular to the disk, sigma_z,0, of 13.5+/-8 km/s for DDO 46 and of 10.7+/-2.9 km/s for DDO 168. We then derived the maximum rotation speed in both galaxies using the LITTLE THINGS HI data. We separated bulk motions from non-circular motions using a double Gaussian decomposition technique and applied a tilted-ring model to the bulk velocity field. We corrected the observed HI rotation speeds for asymmetric drift and found a maximum velocity, Vmax, of 77.4 +/- 3.7 and 67.4 +/- 4.0 km/s for DDO 46 and DDO 168, respectively. Thus, we derived a kinematic measure, Vmax/sigma_z,0, of 5.7 +/- 0.6 for DDO 46 and 6.3 +/- 0.3 for DDO 168. Comparing these values to ones determined for spiral galaxies, we find that DDO 46 and DDO 168 have Vmax/sigma_z,0 values indicative of thin disks, which is in contrast to minor-to-major axis ratio studies

Similar Progression of Morphological and Metabolic Phenotype in R6/2 Mice with Different CAG Repeats Revealed by In Vivo Magnetic Resonance Imaging and Spectroscopy.

BACKGROUND: Huntington's disease (HD) is caused by an unstable polyglutamine (CAG) repeat in the HD gene, whereby a CAG repeat length greater than ∼36 leads to the disease. In HD patients, longer repeats correlate with more severe disease and earlier death. This is also seen in R6/2 mice carrying repeat lengths up to ∼200. Paradoxically, R6/2 mice with repeat lengths >300 have a less aggressive phenotype and longer lifespan than those with shorter repeats. The mechanism underlying this phenomenon is unknown. OBJECTIVE: To investigate the consequences of longer repeat lengths on structural changes in the brains of R6/2 mice, especially with regard to progressive atrophy. METHODS: We used longitudinal in vivo magnetic resonance imaging (MRI) and spectroscopy (MRS) to compare pathological changes in two strains of R6/2 mice, one with a rapidly progressing disease (250 CAG repeats), and the other with a less aggressive phenotype (350 CAG repeats). RESULTS: We found significant progressive brain atrophy in both 250 and 350 CAG repeat mice, as well as changes in metabolites (glutamine/glutamate, choline and aspartate). Although similar in magnitude, atrophy in the brains of 350 CAG R6/2 mice progressed more slowly than that seen in 250 CAG mice, in line with the milder phenotype and longer lifespan. Interestingly, significant atrophy was detectable in 350 CAG mice as early as 8-12 weeks of age, although behavioural abnormalities in these mice are not apparent before 25-30 weeks. This finding fits well with human data from the PREDICT-HD and TRACK-HD project, where reductions in brain volume were found 10 years in advance of the onset of symptoms. CONCLUSIONS: The similar brain atrophy with a mismatch between onset of brain atrophy and behavioural phenotype in HD mice with 350 repeats will make this mouse particularly useful for modelling early stages of HD pathology.This project was funded by a grant from CHDI Inc.This is the author accepted manuscript. The final version is available from IOS Press at https://doi.org/10.3233/JHD-160208

Report of the panel on volcanology, section 4

Two primary goals are identified as focal to NASA's research efforts in volcanology during the 1990s: to understand the eruption of lavas, gases, and aerosols from volcanoes, the dispersal of these materials on the Earth's surface and through the atmosphere, and the effects of these eruptions on the climate and environment; and to understand the physical processes that lead to the initiation of volcanic activity, that influence the styles of volcanic eruptions, and that dictate the morphology and evolution of volcanic landforms. Strategy and data requirements as well as research efforts are discussed

Reparametrising the Skyrme Model using the Lithium-6 Nucleus

The minimal energy B=6 solution of the Skyrme model is a static soliton with $D_{4d}$ symmetry. The symmetries of the solution imply that the quantum numbers of the ground state are the same as those of the Lithium-6 nucleus. This identification is considered further by obtaining expressions for the mean charge radius and quadrupole moment, dependent only on the Skyrme model parameters $e$ (a dimensionless constant) and $F_\pi$ (the pion decay constant). The optimal values of these parameters have often been deliberated upon, and we propose, for $B>2$, changing them from those which are most commonly accepted. We obtain specific values for these parameters for B=6, by matching with properties of the Lithium-6 nucleus. We find further support for the new values by reconsidering the $\alpha$-particle and deuteron as quantized B=4 and B=2 Skyrmions.Comment: 18 page

Computational Aeroheating Predictions for X-34

Radiative equilibrium surface temperatures, heating rates, streamlines, surface pressures, and flow-field features as predicted by the Langley Aerothermodynamic Upwind Relaxation Algorithm (Laura) are presented for the X-34 Technology Demonstrator. Results for two trajectory points corresponding to entry peak heating and two control surface deflections are discussed. This data is also discussed in context of Thermal Protection System (TPS) design issues. The work presented in this report is part of a larger effort to define the X-34 aerothermal environment, including the application of engineering codes and wind-tunnel studies