Metatranscriptomics analysis reveals a novel transcriptional and translational landscape during Middle East respiratory syndrome coronavirus infection

Among all RNA viruses, coronavirus RNA transcription is the most complex and involves a process termed “discontinuous transcription” that results in the production of a set of 3′-nested, co-terminal genomic and subgenomic RNAs during infection. While the expression of the classic canonical set of subgenomic RNAs depends on the recognition of a 6- to 7-nt transcription regulatory core sequence (TRS), here, we use deep sequence and metagenomics analysis strategies and show that the coronavirus transcriptome is even more vast and more complex than previously appreciated and involves the production of leader-containing transcripts that have canonical and noncanonical leader-body junctions. Moreover, by ribosome protection and proteomics analyses, we show that both positive- and negative-sense transcripts are translationally active. The data support the hypothesis that the coronavirus proteome is much vaster than previously noted in the literature

Volume I. Introduction to DUNE

The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay—these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. This TDR is intended to justify the technical choices for the far detector that flow down from the high-level physics goals through requirements at all levels of the Project. Volume I contains an executive summary that introduces the DUNE science program, the far detector and the strategy for its modular designs, and the organization and management of the Project. The remainder of Volume I provides more detail on the science program that drives the choice of detector technologies and on the technologies themselves. It also introduces the designs for the DUNE near detector and the DUNE computing model, for which DUNE is planning design reports. Volume II of this TDR describes DUNE\u27s physics program in detail. Volume III describes the technical coordination required for the far detector design, construction, installation, and integration, and its organizational structure. Volume IV describes the single-phase far detector technology. A planned Volume V will describe the dual-phase technology

Deep Underground Neutrino Experiment (DUNE), far detector technical design report, volume III: DUNE far detector technical coordination

The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay—these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. Volume III of this TDR describes how the activities required to design, construct, fabricate, install, and commission the DUNE far detector modules are organized and managed. This volume details the organizational structures that will carry out and/or oversee the planned far detector activities safely, successfully, on time, and on budget. It presents overviews of the facilities, supporting infrastructure, and detectors for context, and it outlines the project-related functions and methodologies used by the DUNE technical coordination organization, focusing on the areas of integration engineering, technical reviews, quality assurance and control, and safety oversight. Because of its more advanced stage of development, functional examples presented in this volume focus primarily on the single-phase (SP) detector module

Timing of syenite-charnockite magmatism and ruby- and sapphire metamorphism in the Mogok valley region, Myanmar

We thank the Oxford–Burma Aung San Suu Kyi trust for funding research and fieldwork visits to Myanmarfor MS,NG and LR. Geochronology was funded by UCSB and NSF grants EAR-1348003and EAR-1551054.The Mogok metamorphic belt (MMB) extends for over 1,000 km along central Burma from the Andaman Sea to the East Himalayan syntaxis and represents exhumed lower and middle crustal metamorphic rocks of the Sibumasu plate. In the Mogok valley region, the MMB consists of regional high‐grade marbles containing calcite + phlogopite + spinel + apatite ± diopside ± olivine and hosts world class ruby and sapphire gemstones. The coarse‐grained marbles have been intruded by orthopyroxene‐ and clinopyroxene‐bearing charnockite‐syenite sheet‐like intrusions that have skarns around the margins. Syenites range from hornblende‐ to quartz‐bearing and frequently show layering that could be a primary igneous texture or a later metamorphic overprint. Calc‐silicate skarns contain both rubies and blue sapphires with large biotites. Rubies occur in marbles with scapolite, phlogopite, graphite, occasional diopside, and blue apatite. Both marbles and syenites have been intruded by the Miocene Kabaing garnet‐muscovite‐biotite peraluminous leucogranite. New mapping and structural observations combined with U‐Th‐Pb zircon, monazite, and titanite geochronology from syenites, charnockites, leucogranites, meta‐rhyolite‐tuffs, and skarns have revealed a complex multiphase igneous and metamorphic history for the MMB. U‐Pb zircon ages of the charnockite‐syenites fall into three categories, Jurassic (170–168 Ma), latest Cretaceous to early Paleocene (~68‐63 Ma), and late Eocene–Oligocene (44–21 Ma). New ages from five samples suggest that metamorphism in the presence of garnet and melt occurred between ~45 and 24 Ma. U‐Pb titanite ages from the ruby marbles and meta‐skarns at Le Oo mine in the Mogok valley are 21 Ma, similar to titanite ages from an adjacent syenite (22 Ma). U‐Th‐Pb dating shows that all the metamorphic ages are Late Cretaceous–early Miocene and related to the India‐Sibumasu collision.Publisher PDFPeer reviewe

Receptor tyrosine kinase-G-protein coupled receptor complex signaling in mammalian cells

Recent evidence suggests that signals transmitted by receptor tyrosine kinases (RTK) and G-protein coupled receptors (GPCR) are integrated to promote efficient growth factor stimulation of cellular responses (Waters et al., 2004). The important feature of this model is that agents that disrupt GPCR function (e.g. pertussis toxin (PTX) and the C-terminal tail of GRK2, which sequesters Gbg subunits) block the growth factor-stimulated activation of various effector modules, such as p42/p44 mitogen activated protein kinase (p42/p44 MAPK) (Luttrell et al., 1995; Fedorov et al., 1998; Conway et al., 1999; Alderton et al., 2001; Waters et al., 2003). This invokes a role for GPCR and places the G-protein down-stream from the RTK. There is now a body of evidence which supports this type of model in mammalian cells. For instance, the IGF-1 and FGF receptors use the G-protein, Gi to stimulate activation of p42/p44 MAPK in fibroblasts and skeletal muscle, respectively (Luttrell et al., 1995; Fedorov et al., 1998). We have also reported that the platelet derived growth factor (PDGF)-induced activation of c-Src and p42/p44 MAPK can be reduced by PTX and CT-GRK2 in airway smooth muscle (ASM) cells and HEK 293 cells (Conway et al., 1999; Alderton et al., 2001; Waters et al., 2003) and that the overexpression of Gia2 enhances the stimulation of p42/p44 MAPK by PDGF, associated with a PDGFb receptor kinase-catalyzed tyrosine phosphorylation of Gia2 (Alderton et al., 2001). The tyrosine phosphorylation of endogenous Gia2 might prevent reformation of the inactive Gabg complex, thereby prolonging the lifetime of active G-protein subunits, including Gbg. The integrative signal mechanism is distinct from the transactivation of RTK by GPCR agonists, which involves stimulation of the tyrosine phosphorylation of the RTK