Resolved Debris Discs Around A Stars in the Herschel DEBRIS Survey

The majority of debris discs discovered so far have only been detected through infrared excess emission above stellar photospheres. While disc properties can be inferred from unresolved photometry alone under various assumptions for the physical properties of dust grains, there is a degeneracy between disc radius and dust temperature that depends on the grain size distribution and optical properties. By resolving the disc we can measure the actual location of the dust. The launch of Herschel, with an angular resolution superior to previous far-infrared telescopes, allows us to spatially resolve more discs and locate the dust directly. Here we present the nine resolved discs around A stars between 20 and 40 pc observed by the DEBRIS survey. We use these data to investigate the disc radii by fitting narrow ring models to images at 70, 100 and 160 {\mu}m and by fitting blackbodies to full spectral energy distributions. We do this with the aim of finding an improved way of estimating disc radii for unresolved systems. The ratio between the resolved and blackbody radii varies between 1 and 2.5. This ratio is inversely correlated with luminosity and any remaining discrepancies are most likely explained by differences to the minimum size of grain in the size distribution or differences in composition. We find that three of the systems are well fit by a narrow ring, two systems are borderline cases and the other four likely require wider or multiple rings to fully explain the observations, reflecting the diversity of planetary systems.Comment: 19 pages, 13 figures, 6 tables. Accepted for publication in MNRA

The debris disk around gamma Doradus resolved with Herschel

We present observations of the debris disk around gamma Doradus, an F1V star, from the Herschel Key Programme DEBRIS (Disc Emission via Bias-free Reconnaissance in the Infrared/Submillimetre). The disk is well-resolved at 70, 100 and 160 micron, resolved along its major axis at 250 micron, detected but not resolved at 350 micron, and confused with a background source at 500 micron. It is one of our best resolved targets and we find it to have a radially broad dust distribution. The modelling of the resolved images cannot distinguish between two configurations: an arrangement of a warm inner ring at several AU (best-fit 4 AU) and a cool outer belt extending from ~55 to 400 AU or an arrangement of two cool, narrow rings at ~70 AU and ~190 AU. This suggests that any configuration between these two is also possible. Both models have a total fractional luminosity of ~10^{-5} and are consistent with the disk being aligned with the stellar equator. The inner edge of either possible configuration suggests that the most likely region to find planets in this system would be within ~55 AU of the star. A transient event is not needed to explain the warm dust's fractional luminosity.Comment: 12 pages, 6 figures, accepted for publication in Ap

Hepatic Endothelial CCL25 Mediates the Recruitment of CCR9+ Gut-homing Lymphocytes to the Liver in Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC), a chronic inflammatory liver disease characterized by progressive bile duct destruction, develops as an extra-intestinal complication of inflammatory bowel disease (IBD) (Chapman, R.W. 1991. Gut. 32:1433–1435). However, the liver and bowel inflammation are rarely concomitant, and PSC can develop in patients whose colons have been removed previously. We hypothesized that PSC is mediated by long-lived memory T cells originally activated in the gut, but able to mediate extra-intestinal inflammation in the absence of active IBD (Grant, A.J., P.F. Lalor, M. Salmi, S. Jalkanen, and D.H. Adams. 2002. Lancet. 359:150–157). In support of this, we show that liver-infiltrating lymphocytes in PSC include mucosal T cells recruited to the liver by aberrant expression of the gut-specific chemokine CCL25 that activates α4β7 binding to mucosal addressin cell adhesion molecule 1 on the hepatic endothelium. This is the first demonstration in humans that T cells activated in the gut can be recruited to an extra-intestinal site of disease and provides a paradigm to explain the pathogenesis of extra-intestinal complications of IBD

Huntingtin-mediated axonal transport requires arginine methylation by PRMT6

The huntingtin (HTT) protein transports various organelles, including vesicles containing neurotrophic factors, from embryonic development throughout life. To better understand how HTT mediates axonal transport and why this function is disrupted in Huntington's disease (HD), we study vesicle-associated HTT and find that it is dimethylated at a highly conserved arginine residue (R118) by the protein arginine methyltransferase 6 (PRMT6). Without R118 methylation, HTT associates less with vesicles, anterograde trafficking is diminished, and neuronal death ensues—very similar to what occurs in HD. Inhibiting PRMT6 in HD cells and neurons exacerbates mutant HTT (mHTT) toxicity and impairs axonal trafficking, whereas overexpressing PRMT6 restores axonal transport and neuronal viability, except in the presence of a methylation-defective variant of mHTT. In HD flies, overexpressing PRMT6 rescues axonal defects and eclosion. Arginine methylation thus regulates HTT-mediated vesicular transport along the axon, and increasing HTT methylation could be of therapeutic interest for HD.Telethon-Italy and Autonomous Province of Trento (TCP12013 to M.P.); Association Française contre les Myopathies (AFM-22221 to M.P. and M.B.); PRIN-MUR (2017F2A2C5 to M.P.); National Institutes of Health (1R21NS111768-01 to M.P. and U.B.P.); PROGRAM RARE DISEASES CNCCS-Scarl-Pomezia (M.P.); FONDAZIONE AIRC-Italy (24423 to M.P.); Alzheimer Trento Onlus with the legato Baldrachi (M.B.); the Agence Nationale de la Recherche (ANR-15-JPWG-0003-05 JPND CIRCPROT and ANR-18-CE16-0009-01 AXYON to F.S.) and the Spanish Ministry of Science, Innovation and Universities (RTI2018-096322-B-I00 MCIU/AEI/FEDER-UE to J.J.L.

HST NIR Snapshot Survey of 3CR Radio Source Counterparts II: An Atlas and Inventory of the Host Galaxies, Mergers and Companions

We present the second part of an H-band (1.6 microns) atlas of z<0.3 3CR radio galaxies, using the Hubble Space Telescope Near Infrared Camera and Multi-Object Spectrometer (HST NICMOS2). We present new imaging for 21 recently acquired sources, and host galaxy modeling for the full sample of 101 (including 11 archival) -- an 87% completion rate. Two different modeling techniques are applied, following those adopted by the galaxy morphology and the quasar host galaxy communities. Results are compared, and found to be in excellent agreement, although the former breaks down in the case of strongly nucleated sources. Companion sources are tabulated, and the presence of mergers, tidal features, dust disks and jets are catalogued. The tables form a catalogue for those interested in the structural and morphological dust-free host galaxy properties of the 3CR sample, and for comparison with morphological studies of quiescent galaxies and quasar host galaxies. Host galaxy masses are estimated, and found to typically lie at around 2*10^11 solar masses. In general, the population is found to be consistent with the local population of quiescent elliptical galaxies, but with a longer tail to low Sersic index, mainly consisting of low-redshift (z<0.1) and low-radio-power (FR I) sources. A few unusually disky FR II host galaxies are picked out for further discussion. Nearby external sources are identified in the majority of our images, many of which we argue are likely to be companion galaxies or merger remnants. The reduced NICMOS data are now publicly available from our website (http://archive.stsci.edu/prepds/3cr/)Comment: ApJS, 177, 148: Final version; includes revised figures 1, 15b, and section 7.5 (and other minor changes from editing process. 65 pages, inc. 17 figure

Exo-zodi Modeling for the Large Binocular Telescope Interferometer

Habitable zone dust levels are a key unknown that must be understood to ensure the success of future space missions to image Earth analogs around nearby stars. Current detection limits are several orders of magnitude above the level of the solar system's zodiacal cloud, so characterization of the brightness distribution of exo-zodi down to much fainter levels is needed. To this end, the Large Binocular Telescope Interferometer (LBTI) will detect thermal emission from habitable zone exo-zodi a few times brighter than solar system levels. Here we present a modeling framework for interpreting LBTI observations, which yields dust levels from detections and upper limits that are then converted into predictions and upper limits for the scattered light surface brightness. We apply this model to the HOSTS survey sample of nearby stars; assuming a null depth uncertainty of 10^(–4) the LBTI will be sensitive to dust a few times above the solar system level around Sun-like stars, and to even lower dust levels for more massive stars

Roles for H2A.Z and Its Acetylation in GAL1 Transcription and Gene Induction, but Not GAL1-Transcriptional Memory

H2A.Z does not appear to have a role in GAL1 transcriptional memory, but it does have both acetylation-dependent and acetylation-independent roles in GAL1 induction and expression

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Changes in brain glutamate on switching to clozapine in treatment-resistant schizophrenia

It has been suggested that the antipsychotic clozapine may modulate brain glutamate, and that this effect could contribute to its efficacy in treatment-resistant schizophrenia (TRS). The aim of this study was to examine the effects of clozapine on brain glutamate in TRS longitudinally. This study examined individuals with TRS before and 12 weeks after switching from a non-clozapine antipsychotic to treatment with clozapine as part of their normal clinical care. Proton magnetic resonance spectroscopy (1H-MRS) measured concentrations, corrected for voxel tissue content, of glutamate (Glucorr), and glutamate plus glutamine (Glxcorr) in the anterior cingulate cortex (ACC) and right caudate nucleus. Symptoms were monitored using the Positive and Negative Syndrome Scale (PANSS). Of 37 recruited patients (27 men, 39.30 years old, 84% clozapine naïve), 25 completed 1H-MRS at both timepoints. 12 weeks of clozapine was associated with a longitudinal reduction in Glucorr in the caudate (n = 23, F = 7.61 P =. 01) but not in the ACC (n = 24, F = 0.02, P =. 59). Percentage reduction in caudate Glucorr was positively correlated with percentage improvement in symptoms (total PANSS score, n = 23, r =. 42, P =. 04). These findings indicate that reductions in glutamate in the caudate nucleus may contribute to symptomatic improvement during the first months of clozapine treatment

Single cell derived mRNA signals across human kidney tumors.

Funder: Department of HealthTumor cells may share some patterns of gene expression with their cell of origin, providing clues into the differentiation state and origin of cancer. Here, we study the differentiation state and cellular origin of 1300 childhood and adult kidney tumors. Using single cell mRNA reference maps of normal tissues, we quantify reference "cellular signals" in each tumor. Quantifying global differentiation, we find that childhood tumors exhibit fetal cellular signals, replacing the presumption of "fetalness" with a quantitative measure of immaturity. By contrast, in adult cancers our assessment refutes the suggestion of dedifferentiation towards a fetal state in most cases. We find an intimate connection between developmental mesenchymal populations and childhood renal tumors. We demonstrate the diagnostic potential of our approach with a case study of a cryptic renal tumor. Our findings provide a cellular definition of human renal tumors through an approach that is broadly applicable to human cancer