Tissue-resident memory T cells orchestrate tumour-immune equilibrium

The immune system can prevent tumour development by engaging in a process termed cancer immunosurveillance, during which immune cells such as T cells restrict tumour growth either by completely eradicating cancer cells in a process of ‘elimination’ or by suppressing cancer cell outgrowth by establishing a state of tumour-immune ‘equilibrium’. Most cancers develop within epithelial layers of tissues but circulating T cells are largely excluded from these epithelial tissue compartments in the absence of infection or overt inflammation. In contrast, CD8+ tissue-resident memory T (TRM) cells reside permanently within epithelial layers of peripheral tissues without recirculating in blood. Accumulating evidence suggests that TRM cells are found in diverse human solid cancers where they correlate with improved prognosis and can protect against tumour challenge in mice. However, the mechanisms through which these cells mediate cancer protection are poorly understood. In our recent study (Park SL et al, Nature 565(7739), 2019) we developed a melanoma model that allowed us to identify a critical role for TRM cells in the establishment and maintenance of tumour-immune equilibrium in skin. Our findings provide insight into the immune cell populations important for maintaining long-term tumour dormancy in peripheral tissues and imply that targeting TRM cells may serve as a novel cancer treatment strategy

The Black Hole in NGC 3379: A Comparison of Gas and Stellar Dynamical Mass Measurements with HST and Integral-Field Data

We combine Hubble Space Telescope spectroscopy and ground-based integral-field data from the SAURON and OASIS instruments to study the central black hole in the nearby elliptical galaxy NGC 3379. From these data, we obtain kinematics of both the stars and the nuclear gaseous component. Axisymmetric three-integral models of the stellar kinematics find a black hole of mass 1.4 (+2.6 / -1.0) x 10^8 M_sun (3 sigma errors). These models also probe the velocity distribution in the immediate vicinity of the black hole and reveal a nearly isotropic velocity distribution throughout the galaxy and down to the black hole sphere of influence R_BH. The morphology of the nuclear gas disc suggests that it is not in the equatorial plane; however the core of NGC 3379 is nearly spherical. Inclined thin-disc models of the gas find a nominal black hole of mass 2.0 (+/- 0.1) x 10^8 M_sun (3 sigma errors), but the model is a poor fit to the kinematics. The data are better fit by introducing a twist in the gas kinematics (with the black hole mass assumed to be 2.0 x 10^8 M_sun), although the constraints on the nature and shape of this perturbation are insufficient for more detailed modelling. Given the apparent regularity of the gas disc's appearance, the presence of such strong non-circular motion indicates that caution must be used when measuring black hole masses with gas dynamical methods alone.Comment: 22 pages, 19 figures. Accepted for publication in MNRAS. A version with full resolution figures is available at http://astro.berkeley.edu/~shapiro/Papers/shapiro2006_N3379.pd

A search for massive UCDs in the Centaurus Galaxy Cluster

We recently initiated a search for ultra-compact dwarf galaxies (UCDs) in the Centaurus galaxy cluster (Mieske et al. 2007), resulting in the discovery of 27 compact objects with -12.2<M_V<-10.9 mag. Our overall survey completeness was 15-20% within 120 kpc projected clustercentric distance. In order to better constrain the luminosity distribution of the brightest UCDs in Centaurus, we continue our search by substantially improving our survey completeness specifically in the regime M_V<-12 mag (V_0<21.3 mag). Using VIMOS at the VLT, we obtain low-resolution spectra of 400 compact objects with 19.3<V_0<21.3 mag (-14<M_V<-12 mag at the Centaurus distance) in the central 25' of the Centaurus cluster, which corresponds to a projected radius of ~150 kpc. Our survey yields complete area coverage within ~120 kpc. For 94% of the sources included in the masks we successfully measure a redshift. Due to incompleteness in the slit assignment, our final completeness in the area surveyed is 52%. Among our targets we find three new UCDs in the magnitude range -12.2<M_V<-12 mag, hence at the faint limit of our survey. One of them is covered by archival HST WFPC2 imaging, yielding a size estimate of r_h <= 8-9 pc. At 95% confidence we can reject the hypothesis that in the area surveyed there are more than 2 massive UCDs with M_V<-12.2 mag and r_eff <=70 pc. Our survey hence confirms the extreme rareness of massive UCDs. We find that the radial distributions of Centaurus and Fornax UCDs with respect to their host clusters' centers agree within the 2 sigma level.Comment: 9 pages, 7 figures, accepted as Research Note for A&

Distinct APC subtypes drive spatially segregated CD4+ and CD8+ T-Cell effector activity during skin infection with HSV-1

Efficient infection control requires potent T-cell responses at sites of pathogen replication. However, the regulation of T-cell effector function in situ remains poorly understood. Here, we show key differences in the regulation of effector activity between CD4+ and CD8+ T-cells during skin infection with HSV-1. IFN-γ-producing CD4+ T cells disseminated widely throughout the skin and draining lymph nodes (LN), clearly exceeding the epithelial distribution of infectious virus. By contrast, IFN-γ-producing CD8+ T cells were only found within the infected epidermal layer of the skin and associated hair follicles. Mechanistically, while various subsets of lymphoid- and skin-derived dendritic cells (DC) elicited IFN-γ production by CD4+ T cells, CD8+ T cells responded exclusively to infected epidermal cells directly presenting viral antigen. Notably, uninfected cross-presenting DCs from both skin and LNs failed to trigger IFN-γ production by CD8+ T-cells. Thus, we describe a previously unappreciated complexity in the regulation of CD4+ and CD8+ T-cell effector activity that is subset-specific, microanatomically distinct and involves largely non-overlapping types of antigen-presenting cells (APC).The work was funded by grant (APP628423 and APP1059514) and fellowship support from the National Health and Medical Research Council Australia (NHMRC)and the Australian Research Council (ARC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The globular cluster system of NGC 1399. III. VLT spectroscopy and database

Radial velocities of 468 globular clusters around NGC 1399, the central galaxy in the Fornax cluster, have been obtained with FORS2 and the Mask Exchange Unit (MXU) at the ESO Very Large Telescope. This is the largest sample of globular cluster velocities around any galaxy obtained so far. The mean velocity uncertainty is 50 km s-1. This data sample is accurate and large enough to be used in studies of the mass distribution of NGC 1399 and the properties of its globular cluster system. Here we describe the observations and the reduction procedure, and we discuss the uncertainties of the resulting velocities. The complete sample of cluster velocities that is used in a dynamical study of NGC 1399 is tabulated. A subsample is compared with previously published values.Facultad de Ciencias Astronómicas y Geofísica

Using Dark Energy Explorers and Machine Learning to Enhance the Hobby-Eberly Telescope Dark Energy Experiment

We present analysis using a citizen science campaign to improve the cosmological measures from the Hobby-Eberly Telescope Dark Energy Experiment (HETDEX). The goal of HETDEX is to measure the Hubble expansion rate, $H(z)$, and angular diameter distance, $D_A(z)$, at $z =$ 2.4, each to percent-level accuracy. This accuracy is determined primarily from the total number of detected Lyman-$\alpha$ emitters (LAEs), the false positive rate due to noise, and the contamination due to [O II] emitting galaxies. This paper presents the citizen science project, Dark Energy Explorers, with the goal of increasing the number of LAEs, decreasing the number of false positives due to noise and the [O II] galaxies. Initial analysis shows that citizen science is an efficient and effective tool for classification most accurately done by the human eye, especially in combination with unsupervised machine learning. Three aspects from the citizen science campaign that have the most impact are 1) identifying individual problems with detections, 2) providing a clean sample with 100% visual identification above a signal-to-noise cut, and 3) providing labels for machine learning efforts. Since the end of 2022, Dark Energy Explorers has collected over three and a half million classifications by 11,000 volunteers in over 85 different countries around the world. By incorporating the results of the Dark Energy Explorers we expect to improve the accuracy on the $D_A(z)$ and $H(z)$ parameters at $z =$ 2.4 by 10 - 30%. While the primary goal is to improve on HETDEX, Dark Energy Explorers has already proven to be a uniquely powerful tool for science advancement and increasing accessibility to science worldwide.Comment: 14 pages, 6 figures, accepted for publication in The Astrophysical Journa

Evolution of chemical abundances in Seyfert galaxies

We computed the chemical evolution of spiral bulges hosting Seyfert nuclei, based on updated chemical and spectro-photometrical evolution models for the bulge of our Galaxy, made predictions about other quantities measured in Seyferts, and modeled the photometry of local bulges. The chemical evolution model contains detailed calculations of the Galactic potential and of the feedback from the central supermassive black hole, and the spectro-photometric model covers a wide range of stellar ages and metallicities. We followed the evolution of bulges in the mass range 10^9 - 10^{11} Msun by scaling the star formation efficiency and the bulge scalelength as in the inverse-wind scenario for elliptical galaxies, and considering an Eddington limited accretion onto the central supermassive black hole. We successfully reproduced the observed black hole-host bulge mass relation. The observed nuclear bolometric luminosity is reproduced only at high redshift or for the most massive bulges; in the other cases, at z = 0 a rejuvenation mechanism is necessary. The black hole feedback is in most cases not significant in triggering the galactic wind. The observed high star formation rates and metal overabundances are easily achieved, as well as the constancy of chemical abundances with redshift and the bulge present-day colours. Those results are not affected if we vary the index of the stellar IMF from x=0.95 to x=1.35; a steeper IMF is instead required in order to reproduce the colour-magnitude relation and the present K-band luminosity of the bulge.Comment: 17 pages, 15 figures, 3 tables, accepted for publication in A&

Enhanced Star Formation in Narrow Line Seyfert 1 AGN revealed by Spitzer

We present new low resolution Spitzer mid-infrared spectroscopy of a sample of 20 ROSAT selected local Narrow Line Seyfert 1 galaxies (NLS1s). We detect strong AGN continuum in all and clear PAH emission in 70% of the sources. The 6.2 micron PAH luminosity spans three orders of magnitudes, from ~10^(39) erg/s to ~10^(42) erg/s providing strong evidence for intense ongoing star formation in the circumnuclear regions of these sources. Using the IRS/Spitzer archive we gather a large number of additional NLS1s and their broad line counterparts (BLS1s) and constructed NLS1 and BLS1 sub-samples to compare them in various ways. The comparison shows a clear separation according to FWHM(H_beta) such that objects with narrower broad H_beta lines are the strongest PAH emitters. We test this division in various ways trying to remove biases due to luminosity and aperture size. Specifically, we find that star formation activity around NLS1 AGN is larger than around BLS1 of the same AGN luminosity. The above result seems to hold over the entire range of distance and luminosity. Moreover the star formation rate is higher in low black hole mass and high L/L_Edd systems indicating that black hole growth and star formation are occurring simultaneously.Comment: 30 pages, 11 figures, 4 tables. Now accepted in MNRA

SDSS J1254+0846: A Binary Quasar Caught in the Act of Merging

We present the first luminous, spatially resolved binary quasar that clearly inhabits an ongoing galaxy merger. SDSS J125455.09+084653.9 and SDSS J125454.87+084652.1 (SDSS J1254+0846 hereafter) are two luminous z=0.44 radio quiet quasars, with a radial velocity difference of just 215 km/s, separated on the sky by 21 kpc in a disturbed host galaxy merger showing obvious tidal tails. The pair was targeted as part of a complete sample of binary quasar candidates with small transverse separations drawn from SDSS DR6 photometry. We present follow-up optical imaging which shows broad, symmetrical tidal arm features spanning some 75 kpc at the quasars' redshift. Numerical modeling suggests that the system consists of two massive disk galaxies prograde to their mutual orbit, caught during the first passage of an active merger. This demonstrates rapid black hole growth during the early stages of a merger between galaxies with pre-existing bulges. Neither of the two luminous nuclei show significant instrinsic absorption by gas or dust in our optical or X-ray observations, illustrating that not all merging quasars will be in an obscured, ultraluminous phase. We find that the Eddington ratio for the fainter component B is rather normal, while for the A component L/LEdd is quite (>3sigma) high compared to quasars of similar luminosity and redshift, possibly evidence for strong merger-triggered accretion. More such mergers should be identifiable at higher redshifts using binary quasars as tracers.Comment: 15 pages, 5 figures, accepted to the Astrophysical Journal for the February 2010 - 20 v710 issue. Latest version corrects author lis

Determination of masses of the central black holes in NGC524 and NGC2549 using Laser Guide Star Adaptive Optics

[abridged] We present observations of NGC524 and NGC2549 with LGS AO obtained at GEMINI North telescope using the NIFS IFU in the K band. The purpose of these observations, together with previously obtained observations with the SAURON IFU, is to determine the masses (Mbh) of the supermassive black holes (SMBH). The targeted galaxies were chosen to have central light profiles showing a core (NGC524) and a cusp (NGC2549), to probe the feasibility of using the galaxy centre as the NGS required for LGS AO. We employ an innovative `open loop' technique. The data have spatial resolution of 0.23" and 0.17" FWHM, showing that high quality LGS AO observations of these objects are possible. We construct axisymmetric three-integral dynamical models which are constrained with both the NIFS and SAURON data. The best fitting models yield Mbh=(8.3 +2.7 -1.3) x 10^8 Msun for NGC524 and Mbh=(1.4 +0.2 -1.3) x 10^7 Msun for NGC2549 (all errors are at the 3 sigma CL). We demonstrate that the wide-field SAURON data play a crucial role in the M/L determination increasing the accuracy of M/L by a factor of at least 5, and constraining the upper limits on Mbh. The NIFS data are crucial in constraining the lower limits of Mbh and in combination with the large scale data reducing the uncertainty by a factor of 2 or more. We find that the orbital structure of NGC524 shows significant tangential anisotropy, while at larger radii both galaxies are consistent with having almost perfectly oblate velocity ellipsoids. Tangential anisotropy in NGC524 coincides with the size of SMBH sphere of influence and the core region in the light profile. We test the accuracy to which Mbh can be measured using seeings obtained from typical LGS AO observations, and conclude that for a typical conditions and Mbh the expected uncertainty is of the order of 50%.Comment: 19 pages, 14 figure