191 research outputs found
The pro-neurotrophin receptor sortilin is a major neuronal apolipoprotein E receptor for catabolism of amyloid-β peptide in the brain
Apolipoprotein E (APOE) is the major risk factor for sporadic Alzheimer's disease. Among other functions, APOE is proposed to sequester neurotoxic amyloid-{beta} (A{beta}) peptides in the brain, delivering them to cellular catabolism via neuronal APOE receptors. Still, the receptors involved in this process remain controversial. Here, we identified the pro-neurotrophin receptor sortilin as major endocytic pathway for clearance of APOE/A{beata} complexes in neurons. Sortilin binds APOE with high affinity. Lack of receptor expression in mice results in accumulation of APOE and of A{beta} in the brain and in aggravated plaque burden. Also, primary neurons lacking sortilin exhibit significantly impaired uptake of APOE/A{beta} complexes despite proper expression of other APOE receptors. Despite higher than normal brain APOE levels, sortilin-deficient animals display anomalies in brain lipid metabolism (e.g., accumulation of sulfatides) seen in APOE-deficient mice, indicating functional deficiency in cellular APOE uptake pathways. Together, our findings identified sortilin as an essential neuronal pathway for APOE-containing lipoproteins in vivo and suggest an intriguing link between A{beta} catabolism and pro-neurotrophin signaling converging on this receptor
Measuring the Weak Phase gamma in Color Allowed B->DKpi Decays
We present a method to measure the weak phase gamma in the three-body decay
of charged B mesons to the final states D K pi0. These decays are mediated by
interfering amplitudes which are color-allowed and hence relatively large. As a
result, large CP violation effects that could be observed with high statistical
significance are possible. In addition, the three-body decay helps resolve
discrete ambiguities that are usually present in measurements of the weak
phase. The experimental implications of conducting these measurements with
three-body decays are discussed, and the sensitivity of the method is evaluated
using a simulation.Comment: 18 pages, LaTex, 15 eps and ps figure
Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy
We review HB stars in a broad astrophysical context, including both variable
and non-variable stars. A reassessment of the Oosterhoff dichotomy is
presented, which provides unprecedented detail regarding its origin and
systematics. We show that the Oosterhoff dichotomy and the distribution of
globular clusters (GCs) in the HB morphology-metallicity plane both exclude,
with high statistical significance, the possibility that the Galactic halo may
have formed from the accretion of dwarf galaxies resembling present-day Milky
Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the
second-parameter problem is presented. A technique is proposed to estimate the
HB types of extragalactic GCs on the basis of integrated far-UV photometry. The
relationship between the absolute V magnitude of the HB at the RR Lyrae level
and metallicity, as obtained on the basis of trigonometric parallax
measurements for the star RR Lyrae, is also revisited, giving a distance
modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are
studied. Finally, the conductive opacities used in evolutionary calculations of
low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and
Space Scienc
Comprehensive lung injury pathology induced by mTOR inhibitors
Molecular Targets in Oncology[Abstract] Interstitial lung disease is a rare side effect of temsirolimus treatment in renal cancer patients. Pulmonary fibrosis is characterised by the accumulation of extracellular matrix collagen, fibroblast proliferation and migration, and loss of alveolar gas exchange units. Previous studies of pulmonary fibrosis have mainly focused on the fibro-proliferative process in the lungs. However, the molecular mechanism by which sirolimus promotes lung fibrosis remains elusive. Here, we propose an overall cascade hypothesis of interstitial lung diseases that represents a common, partly underlying synergism among them as well as the lung pathogenesis side effects of mammalian target of rapamycin inhibitors
A search for the decay
We search for the rare flavor-changing neutral-current decay in a data sample of 82 fb collected with the {\sl BABAR}
detector at the PEP-II B-factory. Signal events are selected by examining the
properties of the system recoiling against either a reconstructed hadronic or
semileptonic charged-B decay. Using these two independent samples we obtain a
combined limit of
at the 90% confidence level. In addition, by selecting for pions rather than
kaons, we obtain a limit of using only the hadronic B reconstruction method.Comment: 7 pages, 8 postscript figures, submitted to Phys. Rev. Let
High-reflectivity broadband distributed Bragg reflector lattice matched to ZnTe
We report on the realization of a high quality distributed Bragg reflector
with both high and low refractive index layers lattice matched to ZnTe. Our
structure is grown by molecular beam epitaxy and is based on binary compounds
only. The high refractive index layer is made of ZnTe, while the low index
material is made of a short period triple superlattice containing MgSe, MgTe,
and ZnTe. The high refractive index step of Delta_n=0.5 in the structure
results in a broad stopband and the reflectivity coefficient exceeding 99% for
only 15 Bragg pairs.Comment: 4 pages, 3 figure
EuFeAs under high pressure: an antiferromagnetic bulk superconductor
We report the ac magnetic susceptibility and resistivity
measurements of EuFeAs under high pressure . By observing nearly
100% superconducting shielding and zero resistivity at = 28 kbar, we
establish that -induced superconductivity occurs at ~30 K in
EuFeAs. shows an anomalous nearly linear temperature dependence
from room temperature down to at the same . indicates that
an antiferromagnetic order of Eu moments with ~20 K persists
in the superconducting phase. The temperature dependence of the upper critical
field is also determined.Comment: To appear in J. Phys. Soc. Jpn., Vol. 78 No.
Measurement of the electron energy spectrum and its moments in inclusive B -> Xe nu decays
We report a measurement of the inclusive electron energy spectrum for semileptonic decays of B mesons in a data sample of 52 million Y(4S)-->B(B) over bar decays collected with the BABAR detector at the PEP-II asymmetric-energy B-meson factory at SLAC. We determine the branching fraction, first, second, and third moments of the spectrum for lower cutoffs on the electron energy between 0.6 and 1.5 GeV. We measure the partial branching fraction to be B(B-->Xenu,E-e>0.6 GeV)=[10.36+/-0.06(stat.)+/-0.23(sys.)]%
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