148 research outputs found
MicroRNA-143 activation regulates smooth muscle and endothelial cell crosstalk in pulmonary arterial hypertension
Rationale: The pathogenesis of PAH remains unclear. The four microRNAs representing the miR-143 and miR-145 stem loops are genomically clustered.
Objective: To elucidate the transcriptional regulation of the miR-143/145 cluster, and the role of miR-143 in PAH.
Methods and Results: We identified the promoter region that regulates miR-143/145 miRNA expression in pulmonary artery smooth muscle cells (PASMCs). We mapped PAH-related signalling pathways, including estrogens receptor (ER), liver X factor/retinoic X receptor (LXR/RXR), TGF-β (Smads), and hypoxia (HRE) that regulated levels of all pri-miR stem loop transcription and resulting miRNA expression. We observed that miR-143-3p is selectively upregulated compared to miR-143-5p during PASMC migration. Modulation of miR-143 in PASMCs significantly altered cell migration and apoptosis. In addition, we found high abundance of miR-143-3p in PASMCs-derived exosomes. Using assays with pulmonary arterial endothelial cells (PAECs) we demonstrated a paracrine pro-migratory and pro-angiogenic effect of miR-143-3p enriched exosomes from PASMC. Quantitative PCR and in situ hybridisation showed elevated expression of miR-143 in calf models of PAH as well as in samples from PAH patients. Moreover, in contrast to our previous findings that had not supported a therapeutic role in vivo, we now demonstrate a protective role for miR-143 in experimental PH in vivo in miR-143-/- and antimiR143-3p-treated mice exposed to chronic hypoxia in both preventative and reversal settings.
Conclusions: MiR-143-3p modulated both cellular and exosome-mediated responses in pulmonary vascular cells, while inhibition of miR-143-3p blocked experimental PH. Taken together these findings confirm an important role for the miR-143/145 cluster in PAH pathobiology
Severe Acute Respiratory Syndrome–associated Coronavirus Infection
Whether severe acute respiratory syndrome–associated coronavirus (SARS-CoV) infection can be asymptomatic is unclear. We examined the seroprevalence of SARS-CoV among 674 healthcare workers from a hospital in which a SARS outbreak had occurred. A total of 353 (52%) experienced mild self-limiting illnesses, and 321 (48%) were asymptomatic throughout the course of these observations. None of these healthcare workers had antibody to SARS CoV, indicating that subclinical or mild infection attributable to SARS CoV in adults is rare
Upsilon (1S+2S+3S) production in d+Au and p+p collisions at sqrt(s_NN)=200 GeV and cold-nuclear matter effects
The three Upsilon states, Upsilon(1S+2S+3S), are measured in d+Au and p+p
collisions at sqrt(s_NN)=200 GeV and rapidities 1.2<|y|<2.2 by the PHENIX
experiment at the Relativistic Heavy-Ion Collider. Cross sections for the
inclusive Upsilon(1S+2S+3S) production are obtained. The inclusive yields per
binary collision for d+Au collisions relative to those in p+p collisions
(R_dAu) are found to be 0.62 +/- 0.26 (stat) +/- 0.13 (syst) in the gold-going
direction and 0.91 +/- 0.33 (stat) +/- 0.16 (syst) in the deuteron-going
direction. The measured results are compared to a nuclear-shadowing model,
EPS09 [JHEP 04, 065 (2009)], combined with a final-state breakup cross section,
sigma_br, and compared to lower energy p+A results. We also compare the results
to the PHENIX J/psi results [Phys. Rev. Lett. 107, 142301 (2011)]. The rapidity
dependence of the observed Upsilon suppression is consistent with lower energy
p+A measurements.Comment: 495 authors, 11 pages, 9 figures, 5 tables. Submitted to 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 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
Double Spin Asymmetry of Electrons from Heavy Flavor Decays in p+p Collisions at sqrt(s)=200 GeV
We report on the first measurement of double-spin asymmetry, A_LL, of
electrons from the decays of hadrons containing heavy flavor in longitudinally
polarized p+p collisions at sqrt(s)=200 GeV for p_T= 0.5 to 3.0 GeV/c. The
asymmetry was measured at mid-rapidity (|eta|<0.35) with the PHENIX detector at
the Relativistic Heavy Ion Collider. The measured asymmetries are consistent
with zero within the statistical errors. We obtained a constraint for the
polarized gluon distribution in the proton of |Delta g/g(log{_10}x=
-1.6^+0.5_-0.4, {mu}=m_T^c)|^2 < 0.033 (1 sigma), based on a leading-order
perturbative-quantum-chromodynamics model, using the measured asymmetry.Comment: 385 authors, 17 pages, 15 figures, 5 tables. Submitted to 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
Measurement of long-range angular correlation and quadrupole anisotropy of pions and (anti)protons in central Au collisions at =200 GeV
We present azimuthal angular correlations between charged hadrons and energy
deposited in calorimeter towers in central Au and minimum bias
collisions at GeV. The charged hadron is measured at
midrapidity , and the energy is measured at large rapidity
(, Au-going direction). An enhanced near-side angular
correlation across 2.75 is observed in Au collisions.
Using the event plane method applied to the Au-going energy distribution, we
extract the anisotropy strength for inclusive charged hadrons at
midrapidity up to GeV/. We also present the measurement of
for identified and (anti)protons in central Au collisions,
and observe a mass-ordering pattern similar to that seen in heavy ion
collisions. These results are compared with viscous hydrodynamic calculations
and measurements from Pb at TeV. The magnitude of
the mass-ordering in Au is found to be smaller than that in Pb
collisions, which may indicate smaller radial flow in lower energy Au
collisions.Comment: 424 authors, 8 pages, and 4 figures. v2 is version accepted for
publication in Phys. Rev. Lett. Published version will be at
http://www.phenix.bnl.gov/phenix/WWW/info/pp1/161/ Plain text data tables
will be at http://www.phenix.bnl.gov/papers.htm
Cold-nuclear-matter effects on heavy-quark production at forward and backward rapidity in d+Au collisions at sqrt(s_NN)=200 GeV
The PHENIX experiment has measured open heavy-flavor production via
semileptonic decay muons over the transverse momentum range 1 < pT < 6 GeV/c at
forward and backward rapidity (1.4 < |y| < 2.0) in d+Au and p+p collisions at
?sNN = 200 GeV. In central d+Au collisions an enhancement (suppression) of
heavy-flavor muon production is observed at backward (forward) rapidity
relative to the yield in p+p collisions scaled by the number of binary
collisions. Modification of the gluon density distribution in the Au nucleus
contributes in terms of anti-shadowing enhancement and shadowing suppression;
however, the enhancement seen at backward rapidity exceeds expectations from
this effect alone. These results, implying an important role for additional
cold nuclear matter effects, serves as a key baseline for heavy-quark
measurements in A+A collisions and in constraining the magnitude of charmonia
breakup effects at the Relativistic Heavy Ion Collider and the Large Hadron
Collider.Comment: 424 authors, 69 insitutions, 8 pages, 4 figures. Submitted to
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
A Large Population Histology Study Showing the Lack of Association between ALT Elevation and Significant Fibrosis in Chronic Hepatitis B
OBJECTIVE: We determined the association between various clinical parameters and significant liver injury in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. METHODS: From 1994 to 2008, liver biopsy was performed on 319 treatment-naive CHB patients. Histologic assessment was based on the Knodell histologic activity index for necroinflammation and the Ishak fibrosis staging for fibrosis. RESULTS: 211 HBeAg-positive and 108 HBeAg-negative patients were recruited, with a median age of 31 and 46 years respectively. 9 out of 40 (22.5%) HBeAg-positive patients with normal ALT had significant histologic abnormalities (necroinflammation grading >/= 7 or fibrosis score >/= 3). There was a significant difference in fibrosis scores among HBeAg-positive patients with an ALT level within the Prati criteria (30 U/L for men, 19 U/L for women) and patients with a normal ALT but exceeding the Prati criteria (p = 0.024). Age, aspartate aminotransferase and platelet count were independent predictors of significant fibrosis in HBeAg-positive patients with an elevated ALT by multivariate analysis (p = 0.007, 0.047 and 0.045 respectively). HBV DNA and platelet count were predictors of significant fibrosis in HBeAg-negative disease (p = 0.020 and 0.015 respectively). An elevated ALT was not predictive of significant fibrosis for HBeAg-positive (p = 0.345) and -negative (p = 0.544) disease. There was no significant difference in fibrosis staging among ALT 1-2 x upper limit of normal (ULN) and > x 2 ULN for both HBeAg-positive (p = 0.098) and -negative (p = 0.838) disease. CONCLUSION: An elevated ALT does not accurately predict significant liver injury. Decisions on commencing antiviral therapy should not be heavily based on a particular ALT threshold.published_or_final_versio
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