155 research outputs found
A long non-coding RNA protects the heart from pathological hypertrophy
The role of long noncoding RNA (lncRNA) in adult hearts is unknownalso unclear is how lncRNA modulates nucleosome remodeling. An estimated 70% of mouse genes undergo antisense transcription, including myosin heavy chain 7 (Myh7) that encodes molecular motor proteins for heart contraction. Here, we identify a cluster of lncRNA transcripts from Myh7 loci and show a new lncRNA–chromatin mechanism for heart failure. In mice, these transcripts, which we named Myosin Heavy Chain Associated RNA Transcripts (MyHEART or Mhrt), are cardiac-specific and abundant in adult hearts. Pathological stress activates the Brg1-Hdac-Parp chromatin repressor complex to inhibit Mhrt transcription in the heart. Such stress-induced Mhrt repression is essential for cardiomyopathy to develop: restoring Mhrt to the pre-stress level protects the heart from hypertrophy and failure. Mhrt antagonizes the function of Brg1, a chromatin-remodeling factor that is activated by stress to trigger aberrant gene expression and cardiac myopathy. Mhrt prevents Brg1 from recognizing its genomic DNA targets, thus inhibiting chromatin targeting and gene regulation by Brg1. Mhrt binds to the helicase domain of Brg1, and this domain is crucial for tethering Brg1 to chromatinized DNA targets. Brg1 helicase has dual nucleic acid-binding specificities: it is capable of binding lncRNA (Mhrt) and chromatinized—but not naked—DNA. This dual-binding feature of helicase enables a competitive inhibition mechanism by which Mhrt sequesters Brg1 from its genomic DNA targets to prevent chromatin remodeling. A Mhrt-Brg1 feedback circuit is thus crucial for heart function. Human MHRT also originates from MYH7 loci and is repressed in various types of myopathic hearts, suggesting a conserved lncRNA mechanism in human cardiomyopathy. Our studies identify the first cardioprotective lncRNA, define a new targeting mechanism for ATP-dependent chromatin-remodeling factors, and establish a new paradigm for lncRNA–chromatin interaction
Experimentally constrained rates and implications for the process
The -ray strength function and the nuclear level density of
Ho have been extracted using the Oslo method from a
Ho experiment carried out at the Oslo
Cyclotron Laboratory. The level density displays a shape that is compatible
with %can be approximated with the constant temperature model in the
quasicontinuum, while the strength function shows structures indicating the
presence of both a scissors and a pygmy dipole resonance. Using our present
results as well as data from a previous
Ho experiment, the
and MACS uncertainties
have been constrained. The possible influence of the low-lying, long-lived
6~keV isomer Ho in the process is investigated in the context of a
2~, [Fe/H]=-0.5 AGB star. We show that the newly obtained
MACS affects the final Ho abundance, while
the MACS only impacts the enrichment of
Er to a limited degree due to the relatively rapid decay of
the thermalized Ho at typical -process temperatures.Comment: 11 pages, submitted to Physical Reviews
Science Impacts of the SPHEREx All-Sky Optical to Near-Infrared Spectral Survey: Report of a Community Workshop Examining Extragalactic, Galactic, Stellar and Planetary Science
SPHEREx is a proposed SMEX mission selected for Phase A. SPHEREx will carry
out the first all-sky spectral survey and provide for every 6.2" pixel a
spectra between 0.75 and 4.18 m [with R41.4] and 4.18 and 5.00
m [with R135]. The SPHEREx team has proposed three specific science
investigations to be carried out with this unique data set: cosmic inflation,
interstellar and circumstellar ices, and the extra-galactic background light.
It is readily apparent, however, that many other questions in astrophysics and
planetary sciences could be addressed with the SPHEREx data. The SPHEREx team
convened a community workshop in February 2016, with the intent of enlisting
the aid of a larger group of scientists in defining these questions. This paper
summarizes the rich and varied menu of investigations that was laid out. It
includes studies of the composition of main belt and Trojan/Greek asteroids;
mapping the zodiacal light with unprecedented spatial and spectral resolution;
identifying and studying very low-metallicity stars; improving stellar
parameters in order to better characterize transiting exoplanets; studying
aliphatic and aromatic carbon-bearing molecules in the interstellar medium;
mapping star formation rates in nearby galaxies; determining the redshift of
clusters of galaxies; identifying high redshift quasars over the full sky; and
providing a NIR spectrum for most eROSITA X-ray sources. All of these
investigations, and others not listed here, can be carried out with the nominal
all-sky spectra to be produced by SPHEREx. In addition, the workshop defined
enhanced data products and user tools which would facilitate some of these
scientific studies. Finally, the workshop noted the high degrees of synergy
between SPHEREx and a number of other current or forthcoming programs,
including JWST, WFIRST, Euclid, GAIA, K2/Kepler, TESS, eROSITA and LSST.Comment: Report of the First SPHEREx Community Workshop,
http://spherex.caltech.edu/Workshop.html , 84 pages, 28 figure
Cross-National Differences in Victimization : Disentangling the Impact of Composition and Context
Varying rates of criminal victimization across countries are assumed to be the outcome of countrylevel structural constraints that determine the supply ofmotivated o¡enders, as well as the differential composition within countries of suitable targets and capable guardianship. However, previous empirical tests of these ‘compositional’ and ‘contextual’ explanations of cross-national di¡erences
have been performed upon macro-level crime data due to the unavailability of comparable individual-level data across countries. This limitation has had two important consequences for cross-national crime research. First, micro-/meso-level mechanisms underlying cross-national differences cannot be truly inferred from macro-level data. Secondly, the e¡ects of contextual measures (e.g. income inequality) on crime are uncontrolled for compositional heterogeneity. In this
paper, these limitations are overcome by analysing individual-level victimization data across 18 countries from the International CrimeVictims Survey. Results from multi-level analyses on theft and violent victimization indicate that the national level of income inequality is positively related to risk, independent of compositional (i.e. micro- and meso-level) di¡erences. Furthermore, crossnational variation in victimization rates is not only shaped by di¡erences in national context, but
also by varying composition. More speci¢cally, countries had higher crime rates the more they consisted of urban residents and regions with lowaverage social cohesion.
Electromagnetic Wave Theory and Applications
Contains table of contents for Section 3 and reports on seven research projects.Joint Services Electronics Program Contract DAAL03-89-C-0001National Science Foundation Contract ECS 86-20029Schlumberger- Doll ResearchU.S. Army Research Office Contract DAAL03 88-K-0057National Aeronautics and Space Administration Contract NAGW-1617U.S. Navy - Office of Naval Research Contract N00014-89-J-1107National Aeronautics and Space Administration Contract NAGW-1272National Aeronautics and Space Administration Contract 958461Simulation Technologies Contract DAAH01-87-C-0679U.S. Army Corp of Engineers Contract DACA39-87-K-0022WaveTracer, Inc.U.S. Navy - Office of Naval Research Contract N00014-89-J-1019U.S. Air Force Systems - Electronic Systems Division Contract F19628-88-K-0013Digital Equipment CorporationInternational Business Machines CorporationU.S. Department of Transportation Contract DTRS-57-88-C-0007
Electromagnetic Wave Theory and Applications
Contains table of contents for Section 3, reports on four research projects and a list of publications.National Aeronautics and Space Administration Grant NAGW-1617National Aeronautics and Space Administration Agreement 958461National Aeronautics and Space Administration Grant NAGW-1272U.S. Army Corp of Engineers Contract DACA39-87-K-0022U.S. Navy - Office of Naval Research Grant N00014-89-J-1107U.S. Navy - Office of Naval Research Grant N00014-92-J-1616Digital Equipment CorporationJoint Services Electronics Program Contract DAAL03-92-C-0001U.S. Navy - Office of Naval Research Grant N00014-90-J-1002U.S. Navy - Office of Naval Research Grant N00014-89-J-1019U.S. Department of Transportation Agreement DTRS-57-88-C-00078TTD13U.S. Department of Transportation Agreement DTRS-57-88-C-00078TTD30U.S. Department of Transportation Agreement DTRS-57-92-C-00054TTD1DARPA/Consortium for Superconducting Electronics Contract MDA972-90-C-0021National Science Foundation Fellowship MIP 88-5876
Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels
Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets
The JCMT BISTRO Survey: Studying the Complex Magnetic Field of L43
We present observations of polarized dust emission at 850 μm from the L43 molecular cloud, which sits in the Ophiuchus cloud complex. The data were taken using SCUBA-2/POL-2 on the James Clerk Maxwell Telescope as a part of the BISTRO large program. L43 is a dense (NH 10
22 2 ~ –1023 cm−2) complex molecular cloud with a submillimeter-bright starless core and two protostellar sources. There appears to be an evolutionary gradient along the isolated filament that L43 is embedded within, with the most evolved source closest to the Sco OB2 association. One of the protostars drives a CO outflow that has created a cavity to the southeast. We see a magnetic field that appears to be aligned with the cavity walls of the outflow, suggesting interaction with the outflow. We also find a magnetic field strength of up to ∼160 ± 30 μG in the main starless core and up to ∼90 ± 40 μG in the more diffuse, extended region. These field strengths give magnetically super- and subcritical values, respectively, and both are found to be roughly trans-Alfvénic. We also present a new method of data reduction for these denser but fainter objects like starless cores
Filamentary Network and Magnetic Field Structures Revealed with BISTRO in the High-Mass Star-Forming Region NGC2264 : Global Properties and Local Magnetogravitational Configurations
We report 850 m continuum polarization observations toward the
filamentary high-mass star-forming region NGC 2264, taken as part of the
B-fields In STar forming Regions Observations (BISTRO) large program on the
James Clerk Maxwell Telescope (JCMT). These data reveal a well-structured
non-uniform magnetic field in the NGC 2264C and 2264D regions with a prevailing
orientation around 30 deg from north to east. Field strengths estimates and a
virial analysis for the major clumps indicate that NGC 2264C is globally
dominated by gravity while in 2264D magnetic, gravitational, and kinetic
energies are roughly balanced. We present an analysis scheme that utilizes the
locally resolved magnetic field structures, together with the locally measured
gravitational vector field and the extracted filamentary network. From this, we
infer statistical trends showing that this network consists of two main groups
of filaments oriented approximately perpendicular to one another. Additionally,
gravity shows one dominating converging direction that is roughly perpendicular
to one of the filament orientations, which is suggestive of mass accretion
along this direction. Beyond these statistical trends, we identify two types of
filaments. The type-I filament is perpendicular to the magnetic field with
local gravity transitioning from parallel to perpendicular to the magnetic
field from the outside to the filament ridge. The type-II filament is parallel
to the magnetic field and local gravity. We interpret these two types of
filaments as originating from the competition between radial collapsing, driven
by filament self-gravity, and the longitudinal collapsing, driven by the
region's global gravity.Comment: Accepted for publication in the Astrophysical Journal. 43 pages, 32
figures, and 4 tables (including Appendix
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