1,151 research outputs found
Generation of Active Protein Phosphatase 2A Is Coupled to Holoenzyme Assembly
Protein phosphatase 2A (PP2A) is a prime example of the multisubunit architecture of protein serine/threonine phosphatases. Until substrate-specific PP2A holoenzymes assemble, a constitutively active, but nonspecific, catalytic C subunit would constitute a risk to the cell. While it has been assumed that the severe proliferation impairment of yeast lacking the structural PP2A subunit, TPD3, is due to the unrestricted activity of the C subunit, we recently obtained evidence for the existence of the C subunit in a low-activity conformation that requires the RRD/PTPA proteins for the switch into the active conformation. To study whether and how maturation of the C subunit is coupled with holoenzyme assembly, we analyzed PP2A biogenesis in yeast. Here we show that the generation of the catalytically active C subunit depends on the physical and functional interaction between RRD2 and the structural subunit, TPD3. The phenotype of the tpd3Δ strain is therefore caused by impaired, rather than increased, PP2A activity. TPD3/RRD2-dependent C subunit maturation is under the surveillance of the PP2A methylesterase, PPE1, which upon malfunction of PP2A biogenesis, prevents premature generation of the active C subunit and holoenzyme assembly by counteracting the untimely methylation of the C subunit. We propose a novel model of PP2A biogenesis in which a tightly controlled activation cascade protects cells from untargeted activity of the free catalytic PP2A subunit
Hilbert--Schmidt volume of the set of mixed quantum states
We compute the volume of the convex N^2-1 dimensional set M_N of density
matrices of size N with respect to the Hilbert-Schmidt measure. The hyper--area
of the boundary of this set is also found and its ratio to the volume provides
an information about the complex structure of M_N. Similar investigations are
also performed for the smaller set of all real density matrices. As an
intermediate step we analyze volumes of the unitary and orthogonal groups and
of the flag manifolds.Comment: 13 revtex pages, ver 3: minor improvement
A new measurement of antineutrino oscillation with the full detector configuration at Daya Bay
We report a new measurement of electron antineutrino disappearance using the
fully-constructed Daya Bay Reactor Neutrino Experiment. The final two of eight
antineutrino detectors were installed in the summer of 2012. Including the 404
days of data collected from October 2012 to November 2013 resulted in a total
exposure of 6.910 GW-ton-days, a 3.6 times increase over
our previous results. Improvements in energy calibration limited variations
between detectors to 0.2%. Removal of six Am-C radioactive
calibration sources reduced the background by a factor of two for the detectors
in the experimental hall furthest from the reactors. Direct prediction of the
antineutrino signal in the far detectors based on the measurements in the near
detectors explicitly minimized the dependence of the measurement on models of
reactor antineutrino emission. The uncertainties in our estimates of
and were halved as a result of these
improvements. Analysis of the relative antineutrino rates and energy spectra
between detectors gave and eV in the three-neutrino
framework.Comment: Updated to match final published versio
Recommended from our members
BioTIME: A database of biodiversity time series for the Anthropocene.
MotivationThe BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community-led open-source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene.Main types of variables includedThe database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record.Spatial location and grainBioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km2 (158 cm2) to 100 km2 (1,000,000,000,000 cm2).Time period and grainBioTIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year.Major taxa and level of measurementBioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates.Software format.csv and .SQL
Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis
Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis
- …