562 research outputs found
Towards Retinoid Therapy for Alzheimer’s Disease
Alzheimer’s disease(AD) is associated with a variety of pathophysiological features, including amyloid plaques, inflammation, immunological changes, cell death and regeneration processes, altered neurotransmission, and age-related changes. Retinoic acid receptors (RARs) and retinoids are relevant to all of these. Here we review the pathology, pharmacology, and biochemistry of AD in relation to RARs and retinoids, and we suggest that retinoids are candidate drugs for treatment of AD
Tumor Suppressor p53 Functions as a Negative Regulator in IgE-Mediated Mast Cell Activation
Mast cells are known to play a pivotal role in allergic diseases such as allergic rhinitis, asthma, and atopic dermatitis by releasing granules containing histamine, LTC4, and other preformed chemical mediators. Previous reports have demonstrated that IKK2 (also called IKKβ), a central intracellular component of NF-κB activation pathways, plays a critical role in IgE-mediated degranulation of mast cells and anaphylaxis in mice. In this study, we show that protein levels of tumor suppressor p53 are up-regulated upon IgE-mediated activation in mast cells and lack of p53 results in enhanced responses in both early and late phase anaphylaxis. p53 inhibits not only the catalytic activity of IKK2 presumably through the modulation of glycosylation but also p65 (RelA)-mediated transactivation. Our findings are the first to demonstrate that p53 functions as a negative regulator in mast cells
Glucocorticoid-induced TNF receptor-triggered T cells are key modulators for survival/death of neural stem/progenitor cells induced by ischemic stroke
Increasing evidences show that immune response affects the reparative mechanisms in injured brain. Recently, we have demonstrated that CD4+T cells serve as negative modulators in neurogenesis after stroke, but the mechanistic detail remains unclear. Glucocorticoid-induced tumor necrosis factor (TNF) receptor (GITR), a multifaceted regulator of immunity belonging to the TNF receptor superfamily, is expressed on activated CD4+T cells. Herein, we show, by using a murine model of cortical infarction, that GITR triggering on CD4+T cells increases poststroke inflammation and decreases the number of neural stem/progenitor cells induced by ischemia (iNSPCs). CD4+GITR+T cells were preferentially accumulated at the postischemic cortex, and mice treated with GITR-stimulating antibody augmented poststroke inflammatory responses with enhanced apoptosis of iNSPCs. In contrast, blocking the GITR–GITR ligand (GITRL) interaction by GITR–Fc fusion protein abrogated inflammation and suppressed apoptosis of iNSPCs. Moreover, GITR-stimulated T cells caused apoptosis of the iNSPCs, and administration of GITR-stimulated T cells to poststroke severe combined immunodeficient mice significantly reduced iNSPC number compared with that of non-stimulated T cells. These observations indicate that among the CD4+T cells, GITR+CD4+T cells are major deteriorating modulators of poststroke neurogenesis. This suggests that blockade of the GITR–GITRL interaction may be a novel immune-based therapy in stroke
Transverse energy production and charged-particle multiplicity at midrapidity in various systems from to 200 GeV
Measurements of midrapidity charged particle multiplicity distributions,
, and midrapidity transverse-energy distributions,
, are presented for a variety of collision systems and energies.
Included are distributions for AuAu collisions at ,
130, 62.4, 39, 27, 19.6, 14.5, and 7.7 GeV, CuCu collisions at
and 62.4 GeV, CuAu collisions at
GeV, UU collisions at GeV,
Au collisions at GeV, HeAu collisions at
GeV, and collisions at
GeV. Centrality-dependent distributions at midrapidity are presented in terms
of the number of nucleon participants, , and the number of
constituent quark participants, . For all collisions
down to GeV, it is observed that the midrapidity data
are better described by scaling with than scaling with . Also presented are estimates of the Bjorken energy density,
, and the ratio of to ,
the latter of which is seen to be constant as a function of centrality for all
systems.Comment: 706 authors, 32 pages, 20 figures, 34 tables, 2004, 2005, 2008, 2010,
2011, and 2012 data. v2 is version accepted for publication in Phys. Rev.
Measurements of elliptic and triangular flow in high-multiplicity HeAu collisions at GeV
We present the first measurement of elliptic () and triangular ()
flow in high-multiplicity HeAu collisions at
GeV. Two-particle correlations, where the particles have a large separation in
pseudorapidity, are compared in HeAu and in collisions and
indicate that collective effects dominate the second and third Fourier
components for the correlations observed in the HeAu system. The
collective behavior is quantified in terms of elliptic and triangular
anisotropy coefficients measured with respect to their corresponding
event planes. The values are comparable to those previously measured in
Au collisions at the same nucleon-nucleon center-of-mass energy.
Comparison with various theoretical predictions are made, including to models
where the hot spots created by the impact of the three He nucleons on the
Au nucleus expand hydrodynamically to generate the triangular flow. The
agreement of these models with data may indicate the formation of low-viscosity
quark-gluon plasma even in these small collision systems.Comment: 630 authors, 9 pages, 4 figures, 2 tables. v2 is the version accepted
for publication by Physical Review Letters. Plain text data tables for the
points plotted in figures for this and previous PHENIX publications are (or
will be) publicly available at http://www.phenix.bnl.gov/papers.htm
L\'evy-stable two-pion Bose-Einstein correlations in GeV AuAu collisions
We present a detailed measurement of charged two-pion correlation functions
in 0%-30% centrality GeV AuAu collisions by the
PHENIX experiment at the Relativistic Heavy Ion Collider. The data are well
described by Bose-Einstein correlation functions stemming from L\'evy-stable
source distributions. Using a fine transverse momentum binning, we extract the
correlation strength parameter , the L\'evy index of stability
and the L\'evy length scale parameter as a function of average
transverse mass of the pair . We find that the positively and the
negatively charged pion pairs yield consistent results, and their correlation
functions are represented, within uncertainties, by the same L\'evy-stable
source functions. The measurements indicate a decrease of the
strength of the correlations at low . The L\'evy length scale parameter
decreases with increasing , following a hydrodynamically
predicted type of scaling behavior. The values of the L\'evy index of stability
are found to be significantly lower than the Gaussian case of
, but also significantly larger than the conjectured value that may
characterize the critical point of a second-order quark-hadron phase
transition.Comment: 448 authors, 25 pages, 11 figures, 4 tables, 2010 data. v2 is version
accepted for publication in Phys. Rev. C. Plain text data tables for the
points plotted in figures for this and previous PHENIX publications are (or
will be) publicly available at http://www.phenix.bnl.gov/papers.htm
Measurements of double-helicity asymmetries in inclusive production in longitudinally polarized collisions at GeV
We report the double helicity asymmetry, , in inclusive
production at forward rapidity as a function of transverse momentum
and rapidity . The data analyzed were taken during
GeV longitudinally polarized collisions at the Relativistic Heavy Ion
Collider (RHIC) in the 2013 run using the PHENIX detector. At this collision
energy, particles are predominantly produced through gluon-gluon
scatterings, thus is sensitive to the gluon polarization
inside the proton. We measured by detecting the decay
daughter muon pairs within the PHENIX muon spectrometers in the
rapidity range . In this kinematic range, we measured the
to be ~(stat)~~(syst). The
can be expressed to be proportional to the product of the
gluon polarization distributions at two distinct ranges of Bjorken : one at
moderate range where recent RHIC data of jet and
double helicity spin asymmetries have shown evidence for significant gluon
polarization, and the other one covering the poorly known small- region . Thus our new results could be used to further
constrain the gluon polarization for .Comment: 335 authors, 10 pages, 4 figures, 3 tables, 2013 data. Version
accepted for publication by Phys. Rev. D. Plain text data tables for the
points plotted in figures for this and previous PHENIX publications are (or
will be) publicly available at http://www.phenix.bnl.gov/papers.htm
Cross Section and Transverse Single-Spin Asymmetry of Mesons in Collisions at GeV at Forward Rapidity
We present a measurement of the cross section and transverse single-spin
asymmetry () for mesons at large pseudorapidity from
~GeV collisions. The measured cross section for
~GeV/ and is well described by a
next-to-leading-order perturbative-quantum-chromodynamics calculation. The
asymmetries have been measured as a function of Feynman- () from
, as well as transverse momentum () from
~GeV/. The asymmetry averaged over positive is
. The results are consistent with prior
transverse single-spin measurements of forward and mesons at
various energies in overlapping ranges. Comparison of different particle
species can help to determine the origin of the large observed asymmetries in
collisions.Comment: 484 authors, 13 pages, 11 figures, 4 tables, 2008 data. v2 is version
accepted by Phys. Rev. D. Plain text data tables for the points plotted in
figures for this and previous PHENIX publications are (or will be)publicly
available at http://www.phenix.bnl.gov/papers.htm
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