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We explore the fundamental relations governing the radial and vertical velocity dispersions of stars in the Milky Way, from combined studies of complementary surveys including GALAH, LAMOST, APOGEE, the NASA Kepler and K2 missions, and Gaia DR2. We find that different stellar samples, even though they target different tracer populations and employ a variety of age estimation techniques, follow the same set of fundamental relations. We provide the clearest evidence to date that, in addition to the well-known dependence on stellar age, the velocity dispersions of stars depend on orbital angular momentum Lz, metallicity, and height above the plane |z|, and are well described by a multiplicatively separable functional form. The dispersions have a power-law dependence on age with exponents of 0.441 ± 0.007 and 0.251 ± 0.006 for σz and σR, respectively, and the power law is valid even for the oldest stars. For the solar neighbourhood stars, the apparent break in the power law for older stars, as seen in previous studies, is due to the anticorrelation of Lz with age. The dispersions decrease with increasing Lz until we reach the Sun's orbital angular momentum, after which σz increases (implying flaring in the outer disc) while σR flattens. For a given age, the dispersions increase with decreasing metallicity, suggesting that the dispersions increase with birth radius. The dispersions also increase linearly with |z|. The same set of relations that work in the solar neighbourhood also work for stars between 3 < R/kpc < 20. Finally, the high-[α/Fe] stars follow the same relations as the low-[α/Fe] stars.

Asteroseismology is a promising tool to study Galactic structure and evolution because it can probe the ages of stars. Earlier attempts comparing seismic data from the Kepler satellite with predictions from Galaxy models found that the models predicted more low-mass stars compared to the observed distribution of masses. It was unclear if the mismatch was due to inaccuracies in the Galactic models, or the unknown aspects of the selection function of the stars. Using new data from the K2 mission, which has a well-defined selection function, we find that an old metal-poor thick disc, as used in previous Galactic models, is incompatible with the asteroseismic information. We use an importance-sampling framework, which takes the selection function into account, to fit for the metallicities of a population synthesis model using spectroscopic data. We show that spectroscopic measurements of [Fe/H] and [α/Fe] elemental abundances from the GALAH survey indicate a mean metallicity of log (Z/Z☉) = −0.16 for the thick disc. Here Z is the effective solar-scaled metallicity, which is a function of [Fe/H] and [α/Fe]. With the revised disc metallicities, for the first time, the theoretically predicted distribution of seismic masses show excellent agreement with the observed distribution of masses. This indirectly verifies that the asteroseismic mass scaling relation is good to within five per cent. Assuming the asteroseismic scaling relations are correct, we estimate the mean age of the thick disc to be about 10 Gyr, in agreement with the traditional idea of an old α-enhanced thick disc.

We use the second data releases of the European Space AgencyGaia astrometric survey and the high-resolution Galactic Archaeology with HERMES (GALAH) spectroscopic survey to analyse the structure of our Galaxy's disc components. With GALAH, we separate the α-rich and α-poor discs (with respect to Fe), which are superposed in both position and velocity space, and examine their distributions in action space. We study the distribution of stars in the zVz phase plane, for both Vφ and VR, and recover the remarkable 'phase spiral' discovered by Gaia. We identify the anticipated quadrupole signature in zVz of a tilted velocity ellipsoid for stars above and below the Galactic plane. By connecting our work with earlier studies, we show that the phase spiral is likely to extend well beyond the narrow solar neighbourhood cylinder in which it was found. The phase spiral is a signature of corrugated waves that propagate through the disc, and the associated non-equilibrium phase mixing. The radially asymmetric distribution of stars involved in the phase spiral reveals that the corrugation, which is mostly confined to the α-poor disc, grows in z-amplitude with increasing radius. We present new simulations of tidal disturbance of the Galactic disc by the Sagittarius (Sgr) dwarf. The effect on the zVz phase plane lasts ≥2Gyr, but a subsequent disc crossing wipes out the coherent structure. We find that the phase spiral was excited ≤0.5 Gyr ago by an object like Sgr with total mass ∼3 × 1010 M⊙ (stripped down from ∼5 × 1010 M⊙ when it first entered the halo) passing through the plane.

The overlap between the spectroscopic Galactic Archaeology with HERMES (GALAH) survey and Gaia provides a high-dimensional chemodynamical space of unprecedented size. We present a first analysis of a subset of this overlap, of 7066 dwarf, turn-off, and sub-giant stars. These stars have spectra from the GALAH survey and high parallax precision from the Gaia DR1 Tycho-Gaia Astrometric Solution. We investigate correlations between chemical compositions, ages, and kinematics for this sample. Stellar parameters and elemental abundances are derived from the GALAH spectra with the spectral synthesis code SPECTROSCOPY MADE EASY. We determine kinematics and dynamics, including action angles, from the Gaia astrometry and GALAH radial velocities. Stellar masses and ages are determined with Bayesian isochrone matching, using our derived stellar parameters and absolute magnitudes. We report measurements of Li, C, O, Na, Mg, Al, Si, K, Ca, Sc, Ti, V, Cr, Mn, Co, Ni, Cu, Zn, Y, as well as Ba and we note that we have employed non-LTE calculations for Li, O, Al, and Fe. We show that the use of astrometric and photometric data improves the accuracy of the derived spectroscopic parameters, especially log g. Focusing our investigation on the correlations between stellar age, iron abundance [Fe/H], and mean alpha-enhancement [α/Fe] of the magnitude-selected sample, we recover the result that stars of the high-α sequence are typically older than stars in the low-α sequence, the latter spanning iron abundances of -0.7 < [Fe/H] < +0.5. While these two sequences become indistinguishable in [α/Fe] vs. [Fe/H] at the metal-rich regime, we find that age can be used to separate stars from the extended high-α and the low-α sequence even in this regime. When dissecting the sample by stellar age, we find that the old stars (>8 Gyr) have lower angular momenta Lz than the Sun, which implies that they are on eccentric orbits and originate from the inner disc. Contrary to some previous smaller scale st

The Galactic Archaeology with HERMES (GALAH) survey is a large-scale stellar spectroscopic survey of theMilkyWay, designed to deliver complementary chemical information to a large number of stars covered by the Gaia mission. We present the GALAH second public data release (GALAH DR2) containing 342 682 stars. For these stars, the GALAH collaboration provides stellar parameters and abundances for up to 23 elements to the community. Here we present the target selection, observation, data reduction, and detailed explanation of how the spectra were analysed to estimate stellar parameters and element abundances. For the stellar analysis, we have used a multistep approach. We use the physics-driven spectrum synthesis of Spectroscopy Made Easy (SME) to derive stellar labels (Teff, logg, [Fe/H], [X/Fe], vmic, vsin i, AKS) for a representative training set of stars. This information is then propagated to the whole sample with the data-driven method of The Cannon. Special care has been exercised in the spectral synthesis to only consider spectral lines that have reliable atomic input data and are little affected by blending lines. Departures from local thermodynamic equilibrium (LTE) are considered for several key elements, including Li, O, Na, Mg, Al, Si, and Fe, using 1D MARCS stellar atmosphere models. Validation tests including repeat observations, Gaia benchmark stars, open and globular clusters, and K2 asteroseismic targets lend confidence to our methods and results. Combining the GALAH DR2 catalogue with the kinematic information from Gaia will enable a wide range of Galactic Archaeology studies, with unprecedented detail, dimensionality, and scope.

To further its pathogenesis, S. Typhimurium delivers effector proteins into host cells, including the novel E3 ubiquitin ligase (NEL) effector SspH2. Using model systems in a cross-kingdom approach we gained further insight into the molecular function of this effector. Here, we show that SspH2 modulates innate immunity in both mammalian and plant cells. In mammalian cell culture, SspH2 significantly enhanced Nod1-mediated IL-8 secretion when transiently expressed or bacterially delivered. In addition, SspH2 also enhanced an Rx-dependent hypersensitive response in planta. In both of these nucleotide-binding leucine rich repeat receptor (NLR) model systems, SspH2-mediated phenotypes required its catalytic E3 ubiquitin ligase activity and interaction with the conserved host protein SGT1. SGT1 has an essential cell cycle function and an additional function as an NLR co-chaperone in animal and plant cells. Interaction between SspH2 and SGT1 was restricted to SGT1 proteins that have NLR co-chaperone function and accordingly, SspH2 did not affect SGT1 cell cycle functions. Mechanistic studies revealed that SspH2 interacted with, and ubiquitinated Nod1 and could induce Nod1 activity in an agonist-independent manner if catalytically active. Interestingly, SspH2 in vitro ubiquitination activity and protein stability were enhanced by SGT1. Overall, this work adds to our understanding of the sophisticated mechanisms used by bacterial effectors to co-opt host pathways by demonstrating that SspH2 can subvert immune responses by selectively exploiting the functions of a conserved host co-chaperone.

Huntington's disease is an inherited and incurable neurodegenerative disorder caused by an abnormal polyglutamine (polyQ) expansion in huntingtin (encoded by HTT). PolyQ length determines disease onset and severity, with a longer expansion causing earlier onset. The mechanisms of mutant huntingtin-mediated neurotoxicity remain unclear; however, mitochondrial dysfunction is a key event in Huntington's disease pathogenesis. Here we tested whether mutant huntingtin impairs the mitochondrial fission-fusion balance and thereby causes neuronal injury. We show that mutant huntingtin triggers mitochondrial fragmentation in rat neurons and fibroblasts of individuals with Huntington's disease in vitro and in a mouse model of Huntington's disease in vivo before the presence of neurological deficits and huntingtin aggregates. Mutant huntingtin abnormally interacts with the mitochondrial fission GTPase dynamin-related protein-1 (DRP1) in mice and humans with Huntington's disease, which, in turn, stimulates its enzymatic activity. Mutant huntingtin-mediated mitochondrial fragmentation, defects in anterograde and retrograde mitochondrial transport and neuronal cell death are all rescued by reducing DRP1 GTPase activity with the dominant-negative DRP1 K38A mutant. Thus, DRP1 might represent a new therapeutic target to combat neurodegeneration in Huntington's disease.

Our recent analyses of the cholesterol biosynthetic pathway in Huntington's disease (HD) cells, in the R6/2 huntingtin-fragment mouse model of HD as well as in human tissues have provided the first evidence of altered activity of this pathway in genetically identifiable HD samples. Here we report that these changes also occur in the full-length-huntingtin YAC128 (yeast artificial chromosome) mouse model, which shows a consistent reduction in the activity or levels of multiple components of the cholesterogenic pathway. We also show that this phenotype is progressive and is specific for the brain region most affected in HD. Mice over-expressing the wild-type protein with 18 CAG (YAC18 mice) show the opposite phenotype with higher activity of the cholesterol biosynthetic pathway compared with littermate mice. Finally, we report that plasma levels of cholesterol, its precursors and its brain-derived catabolite 24-S-hydroxycholesterol in YAC mice mirror brain biosynthetic levels supporting further investigation of their potential as peripheral biomarkers in HD. S-hydroxycholesterol in YAC mice mirror brain biosynthetic levels supporting further investigation of their potential as peripheral biomarkers in HD.