TBK1 Limits mTORC1 by Promoting Phosphorylation of Raptor Ser877

While best known for its role in the innate immune system, the TANK-binding kinase 1 (TBK1) is now known to play a role in modulating cellular growth and autophagy. One of the major ways that TBK1 accomplishes this task is by modulating the mechanistic Target of Rapamycin (mTOR), a master regulator that when activated promotes cell growth and inhibits autophagy. However, whether TBK1 promotes or inhibits mTOR activity is highly cell type and context dependent. To further understand the mechanism whereby TBK1 regulates mTOR, we tested the hypothesis that TBK1 phosphorylates a key component of the mTOR complex 1 (mTORC1), Raptor. Using kinase assays coupled with mass spectrometry, we mapped the position of the TBK1 dependent phosphorylation sites on Raptor in vitro. Among the sites identified in vitro, we found that TBK1 promotes Raptor Ser877 phosphorylation in cells both basally and in response to pathogen-associated molecules known to induce TBK1 activity. The levels of Raptor Ser877 phosphorylation were inversely correlated with the levels of mTOR activity. Expression of a mutant Raptor that could not be phosphorylated at Ser877 led to an increase in mTORC1 activity. We conclude that TBK1 limits mTORC1 activity by promoting Raptor Ser877 phosphorylation

Nearby early-type galaxies with ionized gas. The UV emission from GALEX observations

We present GALEX far-ultraviolet (FUV, $\lambda_{eff}$=1538 \AA) and near-ultraviolet (NUV, $\lambda_{eff}$=2316 \AA) surface photometry of 40 early-type galaxies (ETGs) selected from a wider sample of 65 nearby ETGs showing emission lines in their optical spectra. We derive FUV and NUV surface brightness profiles, (FUV-NUV) colour profiles and D$_{25}$ integrated magnitudes. We extend the photometric study to the optical {\it r} band from SDSS imaging for 14 of these ETGs. In general, the (FUV-NUV) radial colour profiles become redder with galactocentric distance in both rejuvenated ($\leq 4$ Gyr) and old ETGs. Colour profiles of NGC 1533, NGC 2962, NGC 2974, NGC 3489, and IC 5063 show rings and/or arm-like structures, bluer than the body of the galaxy, suggesting the presence of recent star formation. Although seven of our ETGs show shell systems in their optical image, only NGC 7135 displays shells in the UV bands. We characterize the UV and optical surface brightness profiles, along the major axis, using a Sersic law. The Sersic law exponent, $n$, varies from 1 to 16 in the UV bands. S0 galaxies tend to have lower values of $n$ ($\leq5$). The Sersic law exponent $n=4$ seems to be a watershed: ETGs with $n>4$ tend to have [$\alpha$/Fe] greater than 0.15, implying a short star-formation time scale. We find a significant correlation between the FUV$-$NUV colour and central velocity dispersions $\sigma$, with the UV colours getting bluer at larger $\sigma$. This trend is likely driven by a combined effect of `downsizing' and of the mass-metallicity relation.Comment: Accepted for publication in MNRAS, 33 pages, 7 figure

Allan Sandage and the Cosmic Expansion

This is an account of Allan Sandage's work on (1) The character of the expansion field. For many years he has been the strongest defender of an expanding Universe. He later explained the CMB dipole by a local velocity of 220 +/- 50 km/s toward the Virgo cluster and by a bulk motion of the Local supercluster (extending out to ~3500 km/s) of 450-500 km/s toward an apex at l=275, b=12. Allowing for these streaming velocities he found linear expansion to hold down to local scales (~300 km/s). (2) The calibration of the Hubble constant. Probing different methods he finally adopted - from Cepheid-calibrated SNe Ia and from independent RR Lyr-calibrated TRGBs - H_0 = 62.3 +/- 1.3 +/- 5.0 km/s/Mpc.Comment: 12 pages, 11 figures, 1 table, Submitted to Astrophysics and Space Science, Special Issue on the Fundamental Cosmic Distance Scale in the Gaia Er

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele