ALMA Reveals the Molecular Medium Fueling the Nearest Nuclear Starburst

We use ALMA to derive the mass, length, and time scales associated with the nuclear starburst in NGC 253. This region forms ~2 M_sun/yr of stars and resembles other starbursts in scaling relations, with star formation consuming the gas reservoir 10 times faster than in galaxy disks. We present observations of CO, the high effective density transitions HCN(1-0), HCO+(1-0), CS(2-1), and their isotopologues. We identify ten clouds that appear as peaks in line emission and enhancements in the HCN-to-CO ratio. These clouds are massive (~10^7 M_sun) structures with sizes (~30 pc) similar to GMCs in other systems. Compared to disk galaxy GMCs, they show high line widths (~20-40 km/s) given their size, with implied Mach numbers ~90. The clouds also show high surface (~6,000 M_sun/pc^2) and volume densities (n_H2~2,000 cm^-3). Given these, self-gravity can explain the line widths. This short free fall time (~0.7 Myr) helps explain the more efficient star formation in NGC 253. We also consider the starburst region as a whole. The geometry is confused by the high inclination, but simple models support a non-axisymmetric, bar-like geometry with a compact, clumpy region of high gas density embedded in an extended CO distribution. Even for the whole region, the surface density still exceeds that of a disk galaxy GMC. The orbital time (~10 Myr), disk free fall time (<~ 3 Myr), and disk crossing time (<~ 3 Myr) are each much shorter than in a normal spiral galaxy disk. Some but not all aspects of the structure correspond to predictions from assuming vertical dynamical equilibrium or a marginally stable rotating disk. Finally, the CO-to-H2 conversion factor implied by our cloud calculations is approximately Galactic, contrasting with results showing a low value for the whole starburst region. The contrast provides resolved support for the idea of mixed molecular ISM phases in starburst galaxies.Comment: Accepted for publication in the Astrophysical Journal. 31 pages, 16 Figure

Chromosome 10q26-driven age-related macular degeneration is associated with reduced levels of HTRA1 in human retinal pigment epithelium

Genome-wide association studies have identified the chromosome 10q26 (Chr10) locus, which contains the age-related maculopathy susceptibility 2 (ARMS2) and high temperature requirement A serine peptidase 1 (HTRA1) genes, as the strongest genetic risk factor for age-related macular degeneration (AMD) [L.G. Fritsche et al., Annu. Rev. Genomics Hum. Genet. 15, 151–171, (2014)]. To date, it has been difficult to assign causality to any specific single nucleotide polymorphism (SNP), haplotype, or gene within this region because of high linkage disequilibrium among the disease-associated variants [J. Jakobsdottir et al. Am. J. Hum. Genet. 77, 389–407 (2005); A. Rivera et al. Hum. Mol. Genet. 14, 3227–3236 (2005)]. Here, we show that HTRA1 messenger RNA (mRNA) is reduced in retinal pigment epithelium (RPE) but not in neural retina or choroid tissues derived from human donors with homozygous risk at the 10q26 locus. This tissue-specific decrease is mediated by the presence of a noncoding, cis-regulatory element overlapping the ARMS2 intron, which contains a potential Lhx2 transcription factor binding site that is disrupted by risk variant rs36212733. HtrA1 protein increases with age in the RPE–Bruch’s membrane (BM) interface in Chr10 nonrisk donors but fails to increase in donors with homozygous risk at the 10q26 locus. We propose that HtrA1, an extracellular chaperone and serine protease, functions to maintain the optimal integrity of the RPE–BM interface during the aging process and that reduced expression of HTRA1 mRNA and protein in Chr10 risk donors impairs this protective function, leading to increased risk of AMD pathogenesis. HtrA1 augmentation, not inhibition, in high-risk patients should be considered as a potential therapy for AMD

Examination of the association of sex and race/ethnicity with appearance concerns: A Scleroderma Patient-centered Intervention Network (SPIN) cohort study

Objective: Appearance concerns are common in systemic sclerosis (SSc) and have been linked to younger age and more severe disease. No study has examined their association with sex or race/ethnicity. Methods: SSc patients were sampled from the Scleroderma Patient-centered Intervention Network Cohort. Presence of appearance concerns was assessed with a single item, and medical and sociodemographic information were collected. Results: Of 644 patients, appearance concerns were present in 72%, including 421 of 565 women (75%), 42 of 79 men (53%), 392 of 550 patients who identified as White (71%), 35 of 41 who identified as Black (85%), and 36 of 53 who identified as another race/ethnicity (68%). In multivariate analysis, women had significantly greater odds of reporting appearance concerns than men (odds ratio (OR)=2.97, 95% confidence interval (CI)=1.78-4.95,

Dense Molecular Gas Tracers in the Outflow of the Starburst Galaxy NGC 253

We present a detailed study of a molecular outflow feature in the nearby starburst galaxy NGC 253 using ALMA. We find that this feature is clearly associated with the edge of NGC 253's prominent ionized outflow, has a projected length of ~300 pc, with a width of ~50 pc, and a velocity dispersion of ~40 km s^(−1), which is consistent with an ejection from the disk about 1 Myr ago. The kinematics of the molecular gas in this feature can be interpreted (albeit not uniquely) as accelerating at a rate of 1 km s^(−1) pc^(−1). In this scenario, the gas is approaching an escape velocity at the last measured point. Strikingly, bright tracers of dense molecular gas (HCN, CN, HCO^+, CS) are also detected in the molecular outflow: we measure an HCN(1–0)/CO(1–0) line ratio of ~1/10 in the outflow, similar to that in the central starburst region of NGC 253 and other starburst galaxies. By contrast, the HCN/CO line ratio in the NGC 253 disk is significantly lower (~1/30), similar to other nearby galaxy disks. This strongly suggests that the streamer gas originates from the starburst, and that its physical state does not change significantly over timescales of ~1 Myr during its entrainment in the outflow. Simple calculations indicate that radiation pressure is not the main mechanism for driving the outflow. The presence of such dense material in molecular outflows needs to be accounted for in simulations of galactic outflows

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment