140 research outputs found
ALMA follows streaming of dense gas down to 40 pc from the supermassive black hole in NGC1097
We present a kinematic analysis of the dense molecular gas in the central 200
parsecs of the nearby galaxy NGC1097, based on Cycle 0 observations with the
Atacama Large Millimeter/sub-millimeter Array (ALMA). We use the HCN(4-3) line
to trace the densest interstellar molecular gas, and quantify its kinematics,
and estimate an inflow rate for the molecular gas. We find a striking
similarity between the ALMA kinematic data and the analytic spiral inflow model
that we have previously constructed based on ionized gas velocity fields on
larger scales. We are able to follow dense gas streaming down to 40 pc distance
from the supermassive black hole in this Seyfert 1 galaxy. In order to fulfill
marginal stability, we deduce that the dense gas is confined to a very thin
disc, and we derive a dense gas inflow rate of 0.09 Msun/yr at 40 pc radius.
Combined with previous values from the Ha and CO gas, we calculate a combined
molecular and ionized gas inflow rate of 0.2 Msun/yr at 40 pc distance from the
central supermassive black hole of NGC1097.Comment: Accepted for Publication in the ApJ Letter
Submillimeter ALMA Observations of the Dense Gas in the Low-Luminosity Type-1 Active Nucleus of NGC 1097
We present the first 100 pc scale view of the dense molecular gas in the
central ~ 1.3 kpc region of the type-1 Seyfert NGC 1097 traced by HCN (J=4-3)
and HCO+ (J=4-3) lines afforded with ALMA band 7. This galaxy shows significant
HCN enhancement with respect to HCO+ and CO in the low-J transitions, which
seems to be a common characteristic in AGN environments. Using the ALMA data,
we study the characteristics of the dense gas around this AGN and search for
the mechanism of HCN enhancement. We find a high HCN (J=4-3) to HCO+ (J=4-3)
line ratio in the nucleus. The upper limit of the brightness temperature ratio
of HCN (v2=1^{1f}, J=4-3) to HCN (J=4-3) is 0.08, which indicates that IR
pumping does not significantly affect the pure rotational population in this
nucleus. We also find a higher HCN (J=4-3) to CS (J=7-6) line ratio in NGC 1097
than in starburst galaxies, which is more than 12.7 on the brightness
temperature scale. Combined from similar observations from other galaxies, we
tentatively suggest that this ratio appears to be higher in AGN-host galaxies
than in pure starburst ones similar to the widely used HCN to HCO+ ratio. LTE
and non-LTE modeling of the observed HCN and HCO+ lines using J=4-3 and 1-0
data from ALMA, and J=3-2 data from SMA, reveals a high HCN to HCO+ abundance
ratio (5 < [HCN]/[HCO+] < 20: non-LTE analysis) in the nucleus, and that the
high-J lines (J=4-3 and 3-2) are emitted from dense (10^{4.5} < n_H2 [/cc] <
10^6), hot (70 < Tkin [K] < 550) regions. Finally we propose that the high
temperature chemistry is more plausible to explain the observed enhanced HCN
emission in NGC 1097 than the pure gas phase PDR/XDR chemistry.Comment: 28 pages, 17 figures, 10 tables. Accepted to PAS
Biparatopic sybodies neutralize SARS-CoV-2 variants of concern and mitigate drug resistance
The ongoing COVID-19 pandemic represents an unprecedented global health crisis. Here, we report the identification of a synthetic nanobody (sybody) pair, Sb#15 and Sb#68, that can bind simultaneously to the SARS-CoV-2 spike RBD and efficiently neutralize pseudotyped and live viruses by interfering with ACE2 interaction. Cryo-EM confirms that Sb#15 and Sb#68 engage two spatially discrete epitopes, influencing rational design of bispecific and tri-bispecific fusion constructs that exhibit up to 100- and 1,000-fold increase in neutralization potency, respectively. Cryo-EM of the sybody-spike complex additionally reveals a novel up-out RBD conformation. While resistant viruses emerge rapidly in the presence of single binders, no escape variants are observed in the presence of the bispecific sybody. The multivalent bispecific constructs further increase the neutralization potency against globally circulating SARS-CoV-2 variants of concern. Our study illustrates the power of multivalency and biparatopic nanobody fusions for the potential development of therapeutic strategies that mitigate the emergence of new SARS-CoV-2 escape mutants
The state of the Martian climate
60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes
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
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 Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
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
Public awareness of the link between alcohol and cancer in England in 2015: A population-based survey
Background: Public knowledge of the association between alcohol and cancer is reported to be low. We
aimed to provide up-to-date evidence for England regarding awareness of the link between alcohol and
different cancers and to determine whether awareness differs by demographic characteristics, alcohol use,
and geographic region.
Methods: A representative sample of 2100 adults completed an online survey in July 2015. Respondents were
asked to identify which health outcomes, including specific cancers, may be caused by alcohol consumption.
Logistic regressions explored whether demographic, alcohol use, and geographic characteristics predicted
correctly identifying alcohol-related cancer risk.
Results: Unprompted, 12.9% of respondents identified cancer as a potential health outcome of alcohol
consumption. This rose to 47% when prompted (compared to 95% for liver disease and 73% for heart
disease). Knowledge of the link between alcohol and specific cancers varied between 18% (breast) and 80%
(liver). Respondents identified the following cancers as alcohol-related where no such evidence exists: bladder
(54%), brain (32%), ovarian (17%). Significant predictors of awareness of the link between alcohol and cancer
were being female, more highly educated, and living in North-East England.
Conclusion: There is generally low awareness of the relationship between alcohol consumption and cancer,
particularly breast cancer. Greater awareness of the relationship between alcohol and breast cancer in NorthEast
England, where a mass media campaign highlighted this relationship, suggests that population awareness
can be influenced by social marketing
TRPM7 kinase activity is essential for T cell colonization and alloreactivity in the gut
The melastatin-like transient-receptor-potential-7 protein (TRPM7), harbouring a cation channel and a serine/threonine kinase, has been implicated in thymopoiesis and cytokine expression. Here we show, by analysing TRPM7 kinase-dead mutant (Trpm7 R/R) mice, that the enzymatic activity of the receptor is not essential for thymopoiesis, but is required for CD103 transcription and gut-homing of intra-epithelial lymphocytes. Defective T cell gut colonization reduces MHCII expression in intestinal epithelial cells. Mechanistically, TRPM7 kinase activity controls TGF-β-induced CD103 expression and pro-inflammatory T helper 17, but not regulatory T, cell differentiation by modulating SMAD2. Notably, we find that the TRPM7 kinase activity promotes gut colonization by alloreactive T cells in acute graft-versus-host disease. Thus, our results unravel a function of TRPM7 kinase in T cell activity and suggest a therapeutic potential of kinase inhibitors in averting acute graft-versus-host disease
- …