Studying U.S. Music in the Twenty-First Century

Musi

Inwardly rectifying potassium channels (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

The 2TM domain family of K channels are also known as the inward-rectifier K channel family. This family includes the strong inward-rectifier K channels (Kir2.x) that are constitutively active, the G-protein-activated inward-rectifier K channels (Kir3.x) and the ATP-sensitive K channels (Kir6.x, which combine with sulphonylurea receptors (SUR1-3)). The pore-forming α subunits form tetramers, and heteromeric channels may be formed within subfamilies (e.g. Kir3.2 with Kir3.3)

Inwardly rectifying potassium channels (KIR) in GtoPdb v.2021.3

The 2TM domain family of K channels are also known as the inward-rectifier K channel family. This family includes the strong inward-rectifier K channels (Kir2.x) that are constitutively active, the G-protein-activated inward-rectifier K channels (Kir3.x) and the ATP-sensitive K channels (Kir6.x, which combine with sulphonylurea receptors (SUR1-3)). The pore-forming α subunits form tetramers, and heteromeric channels may be formed within subfamilies (e.g. Kir3.2 with Kir3.3)

Epidermal Growth Factor Receptor and PTEN Modulate Tissue Factor Expression in Glioblastoma through JunD/Activator Protein-1 Transcriptional Activity

Hypoxia and necrosis are fundamental features of glioblastoma (GBM) and their emergence is critical for the rapid biological progression of this fatal tumor; yet, underlying mechanisms are poorly understood. We have suggested that vaso-occlusion following intravascular thrombosis could initiate or propagate hypoxia and necrosis in GBM. Tissue factor (TF), the main cellular initiator of coagulation, is overexpressed in GBMs and likely favors a thrombotic microenvironment. Epidermal growth factor receptor (EGFR) amplification and PTEN loss are two common genetic alterations seen in GBM but not in lower-grade astrocytomas that could be responsible for TF up-regulation. The most frequent EGFR mutation in GBM involves deletion of exons 2 to 7, resulting in the expression of a constitutively active receptor, EGFRvIII. Here, we show that overexpression of EGFR or EGFRvIII in human glioma cells causes increased basal TF expression and that stimulation of EGFR by its ligand, EGF, leads to a marked dose-dependent up-regulation of TF. In all cases, increased TF expression led to accelerated plasma coagulation in vitro. EGFR-mediated TF expression depended most strongly on activator protein-1 (AP-1) transcriptional activity and was associated with c-Jun NH2-terminal kinase (JNK) and JunD activation. Restoration of PTEN expression in PTEN-deficient GBM cells diminished EGFR-induced TF expression by inhibiting JunD/AP-1 transcriptional activity. PTEN mediated this effect by antagonizing phosphatidylinositol 3-kinase activity, which in turn attenuated both Akt and JNK activities. These mechanisms are likely at work in vivo, as EGFR expression was highly correlated with TF expression in human high-grade astrocytoma specimens

The Second-generation z (Redshift) and Early Universe Spectrometer. I. First-light Observation of a Highly Lensed Local-ulirg Analog at High-z

We recently commissioned our new spectrometer, the second-generation z(Redshift) and Early Universe Spectrometer (ZEUS-2) on the Atacama Pathfinder Experiment telescope. ZEUS-2 is a submillimeter grating spectrometer optimized for detecting the faint and broad lines from distant galaxies that are redshifted into the telluric windows from 200 to 850 μm. It uses a focal plane array of transition-edge sensed bolometers, the first use of these arrays for astrophysical spectroscopy. ZEUS-2 promises to be an important tool for studying galaxies in the years to come because of its synergy with Atacama Large Millimeter Array and its capabilities in the short submillimeter windows that are unique in the post-Herschel era. Here, we report on our first detection of the [C II] 158 μm line with ZEUS-2. We detect the line at z ~ 1.8 from H-ATLAS J091043.1–000322 with a line flux of (6.44 ± 0.42) × 10^(–18) W m^(–2). Combined with its far-IR luminosity and a new Herschel-PACS detection of the [O I] 63 μm line, we model the line emission as coming from a photo-dissociation region with far-ultraviolet radiation field, G ~ 2 × 10^4 G_0, gas density, n ~ 1 × 10^3 cm^(–3) and size between ~0.4 and 1 kpc. On the basis of this model, we conclude that H-ATLAS J091043.1–000322 is a high-redshift analog of a local ultra-luminous IR galaxy; i.e., it is likely the site of a compact starburst caused by a major merger. Further identification of these merging systems is important for constraining galaxy formation and evolution models

The Second-Generation \u3cem\u3ez\u3c/em\u3e (Redshift) and Early Universe Spectrometer. I. First-Light Observation of a Highly Lensed Local Ulirg Analog at High-\u3cem\u3ez\u3c/em\u3e

We recently commissioned our new spectrometer, the second-generation z(Redshift) and Early Universe Spectrometer (ZEUS-2) on the Atacama Pathfinder Experiment telescope. ZEUS-2 is a submillimeter grating spectrometer optimized for detecting the faint and broad lines from distant galaxies that are redshifted into the telluric windows from 200 to 850 μm. It uses a focal plane array of transition-edge sensed bolometers, the first use of these arrays for astrophysical spectroscopy. ZEUS-2 promises to be an important tool for studying galaxies in the years to come because of its synergy with Atacama Large Millimeter Array and its capabilities in the short submillimeter windows that are unique in the post-Herschel era. Here, we report on our first detection of the [C II] 158 μm line with ZEUS-2. We detect the line at z ~ 1.8 from H-ATLAS J091043.1–000322 with a line flux of (6.44 ± 0.42) × 10–18 W m–2. Combined with its far-IR luminosity and a new Herschel-PACS detection of the [O I] 63 μm line, we model the line emission as coming from a photo-dissociation region with far-ultraviolet radiation field, G ~ 2 × 104 G 0, gas density, n ~ 1 × 103 cm–3 and size between ~0.4 and 1 kpc. On the basis of this model, we conclude that H-ATLAS J091043.1–000322 is a high-redshift analog of a local ultra-luminous IR galaxy; i.e., it is likely the site of a compact starburst caused by a major merger. Further identification of these merging systems is important for constraining galaxy formation and evolution models

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

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