166 research outputs found
Neprilysin Is Required for Angiotensin-(1-7)'s Ability to Enhance Insulin Secretion via Its Proteolytic Activity to Generate Angiotensin-(1-2)
Recent work has renewed interest in therapies targeting the renin-angiotensin system (RAS) to improve ÎČ-cell function in type 2 diabetes. Studies show that generation of angiotensin-(1â7) by ACE2 and its binding to the Mas receptor (MasR) improves glucose homeostasis, partly by enhancing glucose-stimulated insulin secretion (GSIS). Thus, islet ACE2 upregulation is viewed as a desirable therapeutic goal. Here, we show that, although endogenous islet ACE2 expression is sparse, its inhibition abrogates angiotensin-(1â7)âmediated GSIS. However, a more widely expressed islet peptidase, neprilysin, degrades angiotensin-(1â7) into several peptides. In neprilysin-deficient mouse islets, angiotensin-(1â7) and neprilysin-derived degradation products angiotensin-(1â4), angiotensin-(5â7), and angiotensin-(3â4) failed to enhance GSIS. Conversely, angiotensin-(1â2) enhanced GSIS in both neprilysin-deficient and wild-type islets. Rather than mediating this effect via activation of the G-proteinâcoupled receptor (GPCR) MasR, angiotensin-(1â2) was found to signal via another GPCR, namely GPCR family C group 6 member A (GPRC6A). In conclusion, in islets, intact angiotensin-(1â7) is not the primary mediator of beneficial effects ascribed to the ACE2/angiotensin-(1â7)/MasR axis. Our findings warrant caution for the concurrent use of angiotensin-(1â7) compounds and neprilysin inhibitors as therapies for diabetes
f(R) theories
Over the past decade, f(R) theories have been extensively studied as one of
the simplest modifications to General Relativity. In this article we review
various applications of f(R) theories to cosmology and gravity - such as
inflation, dark energy, local gravity constraints, cosmological perturbations,
and spherically symmetric solutions in weak and strong gravitational
backgrounds. We present a number of ways to distinguish those theories from
General Relativity observationally and experimentally. We also discuss the
extension to other modified gravity theories such as Brans-Dicke theory and
Gauss-Bonnet gravity, and address models that can satisfy both cosmological and
local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in
Relativity, Published version, Comments are welcom
Observation of an Exotic Baryon in Exclusive Photoproduction from the Deuteron
In an exclusive measurement of the reaction , a
narrow peak that can be attributed to an exotic baryon with strangeness
is seen in the invariant mass spectrum. The peak is at
GeV/c with a measured width of 0.021 GeV/c FWHM, which is largely
determined by experimental mass resolution. The statistical significance of the
peak is . The mass and width of the observed peak are
consistent with recent reports of a narrow baryon by other experimental
groups.Comment: 5 pages, 5 figure
Measurement of Beam-Spin Asymmetries for Deep Inelastic Electroproduction
We report the first evidence for a non-zero beam-spin azimuthal asymmetry in
the electroproduction of positive pions in the deep-inelastic region. Data have
been obtained using a polarized electron beam of 4.3 GeV with the CLAS detector
at the Thomas Jefferson National Accelerator Facility (JLab). The amplitude of
the modulation increases with the momentum of the pion relative to
the virtual photon, , with an average amplitude of for range.Comment: 5 pages, RevTEX4, 3 figures, 2 table
Measurement of the Polarized Structure Function for in the Resonance Region
The polarized longitudinal-transverse structure function
has been measured in the resonance region at and 0.65
GeV. Data for the reaction were taken at Jefferson Lab
with the CEBAF Large Acceptance Spectrometer (CLAS) using longitudinally
polarized electrons at an energy of 1.515 GeV. For the first time a complete
angular distribution was measured, permitting the separation of different
non-resonant amplitudes using a partial wave analysis. Comparison with previous
beam asymmetry measurements at MAMI indicate a deviation from the predicted
dependence of using recent phenomenological
models.Comment: 5 pages, LaTex, 4 eps figures: to be published in PRC/Rapid
Communications. Version 2 has revised Q^2 analysi
Two-Nucleon Momentum Distributions Measured in 3He(e,e'pp)n
We have measured the 3He(e,e'pp)n reaction at 2.2 GeV over a wide kinematic
range. The kinetic energy distribution for `fast' nucleons (p > 250 MeV/c)
peaks where two nucleons each have 20% or less, and the third nucleon has most
of the transferred energy. These fast pp and pn pairs are back-to-back with
little momentum along the three-momentum transfer, indicating that they are
spectators. Experimental and theoretical evidence indicates that we have
measured distorted two-nucleon momentum distributions by striking the third
nucleon and detecting the spectator correlated pair.Comment: 6 pages, 5 figures, submitted to PR
Survey of A_LT' asymmetries in semi-exclusive electron scattering on He4 and C12
Single spin azimuthal asymmetries A_LT' were measured at Jefferson Lab using
2.2 and 4.4 GeV longitudinally polarized electrons incident on He4 and C12
targets in the CLAS detector. A_LT' is related to the imaginary part of the
longitudinal-transverse interference and in quasifree nucleon knockout it
provides an unambiguous signature for final state interactions (FSI).
Experimental values of A_LT' were found to be below 5%, typically |A_LT'| < 3%
for data with good statistical precision. Optical Model in Eikonal
Approximation (OMEA) and Relativistic Multiple-Scattering Glauber Approximation
(RMSGA) calculations are shown to be consistent with the measured asymmetries.Comment: 9 pages, 5 figure
Onset of asymptotic scaling in deuteron photodisintegration
We investigate the transition from the nucleon-meson to quark-gluon
description of the strong interaction using the photon energy dependence of the
differential cross section for photon energies above 0.5 GeV and
center-of-mass proton angles between and . A possible
signature for this transition is the onset of cross section scaling
with the total energy squared, , at some proton transverse momentum, .
The results show that the scaling has been reached for proton transverse
momentum above about 1.1 GeV/c. This may indicate that the quark-gluon regime
is reached above this momentum.Comment: Accepted by PRL; 5 pages, 2 figure
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