297 research outputs found
Stimulation of G proteincoupled bile acid receptor enhances vascular endothelial barrier function via activation of protein kinase A and Rac1
ABSTRACT Bile acids are end products of cholesterol metabolism, and they constantly exist at high concentrations in the blood. Since vascular endothelial cells express G protein-coupled bile acid receptor (GPBAR), bile acids potentially modulate endothelial function. Here, we investigated whether and how GPBAR agonism affects endothelial barrier function. In bovine aortic endothelial cells (BAECs), treatment with a GPBAR agonist, taurolithocholic acid (TLCA) increased the transendothelial electrical resistance. In addition, TLCA suppressed the thrombin-induced dextran infiltration through the endothelial monolayer. Knockdown of GPBAR abolished the inhibitory effect of TLCA on hyperpermeability. These results indicate that stimulation of GPBAR enhances endothelial barrier function. TLCA increased intracellular cAMP production in BAECs. Inhibition of protein kinase A (PKA) or Rac1 significantly attenuated the TLCA-induced endothelial barrier protection. TLCA induced cortical actin polymerization, which was attenuated by a Rac1 inhibitor. In vivo, local administration of TLCA into the mouse ear significantly inhibited vascular leakage and edema formation induced by croton oil or vascular endothelial growth factor. These results indicate that stimulation of GPBAR enhances endothelial barrier function by cAMP/PKA/Rac1-dependent cytoskeletal rearrangement
Synergistic Formation of Radicals by Irradiation with Both Vacuum Ultraviolet and Atomic Hydrogen: A Real-Time In Situ Electron Spin Resonance Study
We report on the surface modification of polytetrafluoroethylene (PTFE) as an
example of soft- and bio-materials that occur under plasma discharge by
kinetics analysis of radical formation using in situ real-time electron spin
resonance (ESR) measurements. During irradiation with hydrogen plasma,
simultaneous measurements of the gas-phase ESR signals of atomic hydrogen and
the carbon dangling bond (C-DB) on PTFE were performed. Dynamic changes of the
C-DB density were observed in real time, where the rate of density change was
accelerated during initial irradiation and then became constant over time. It
is noteworthy that C-DBs were formed synergistically by irradiation with both
vacuum ultraviolet (VUV) and atomic hydrogen. The in situ real-time ESR
technique is useful to elucidate synergistic roles during plasma surface
modification.Comment: 14 pages, 4 figure
New Modularity of DAP-Kinases: Alternative Splicing of the DRP-1 Gene Produces a ZIPk-Like Isoform
DRP-1 and ZIPk are two members of the Death Associated Protein Ser/Thr Kinase
(DAP-kinase) family, which function in different settings of cell death
including autophagy. DAP kinases are very similar in their catalytic domains but
differ substantially in their extra-catalytic domains. This difference is
crucial for the significantly different modes of regulation and function among
DAP kinases. Here we report the identification of a novel alternatively spliced
kinase isoform of the DRP-1 gene, termed DRP-1β. The
alternative splicing event replaces the whole extra catalytic domain of DRP-1
with a single coding exon that is closely related to the sequence of the extra
catalytic domain of ZIPk. As a consequence, DRP-1β lacks the calmodulin
regulatory domain of DRP-1, and instead contains a leucine zipper-like motif
similar to the protein binding region of ZIPk. Several functional assays proved
that this new isoform retained the biochemical and cellular properties that are
common to DRP-1 and ZIPk, including myosin light chain phosphorylation, and
activation of membrane blebbing and autophagy. In addition, DRP-1β also
acquired binding to the ATF4 transcription factor, a feature characteristic of
ZIPk but not DRP-1. Thus, a splicing event of the DRP-1 produces a ZIPk like
isoform. DRP-1β is highly conserved in evolution, present in all known
vertebrate DRP-1 loci. We detected the corresponding mRNA and
protein in embryonic mouse brains and in human embryonic stem cells thus
confirming the in vivo utilization of this isoform. The
discovery of module conservation within the DAPk family members illustrates a
parsimonious way to increase the functional complexity within protein families.
It also provides crucial data for modeling the expansion and evolution of DAP
kinase proteins within vertebrates, suggesting that DRP-1 and ZIPk most likely
evolved from their ancient ancestor gene DAPk by two gene duplication events
that occurred close to the emergence of vertebrates
Effects of mouse utricle stromal tissues on hair cell induction from induced pluripotent stem cells
The Maternal-Effect Gene cellular island Encodes Aurora B Kinase and Is Essential for Furrow Formation in the Early Zebrafish Embryo
Females homozygous for a mutation in cellular island (cei) produce embryos with defects in cytokinesis during early development. Analysis of the cytoskeletal events associated with furrow formation reveal that these defects include a general delay in furrow initiation as well as a complete failure to form furrow-associated structures in distal regions of the blastodisc. A linkage mapping-based candidate gene approach, including transgenic rescue, shows that cei encodes the zebrafish Aurora B kinase homologue. Genetic complementation analysis between the cei mutation and aurB zygotic lethal mutations corroborate gene assignment and reveal a complex nature of the maternal-effect cei allele, which appears to preferentially affect a function important for cytokinesis in the early blastomeres. Surprisingly, in cei mutant embryos a short yet otherwise normal furrow forms in the center of the blastodisc. Furrow formation is absent throughout the width of the blastodisc in cei mutant embryos additionally mutant for futile cycle, which lack a spindle apparatus, showing that the residual furrow signal present in cei mutants is derived from the mitotic spindle. Our analysis suggests that partially redundant signals derived from the spindle and astral apparatus mediate furrow formation in medial and distal regions of the early embryonic blastomeres, respectively, possibly as a spatial specialization to achieve furrow formation in these large cells. In addition, our data also suggest a role for Cei/AurB function in the reorganization of the furrow-associated microtubules in both early cleavage- and somite-stage embryos. In accordance with the requirement for cei/aurB in furrow induction in the early cleavage embryo, germ plasm recruitment to the forming furrow is also affected in embryos lacking normal cei/aurB function
J/psi suppression at forward rapidity in Au+Au collisions at sqrt(s_NN)=39 and 62.4 GeV
We present measurements of the J/psi invariant yields in sqrt(s_NN)=39 and
62.4 GeV Au+Au collisions at forward rapidity (1.2<|y|<2.2). Invariant yields
are presented as a function of both collision centrality and transverse
momentum. Nuclear modifications are obtained for central relative to peripheral
Au+Au collisions (R_CP) and for various centrality selections in Au+Au relative
to scaled p+p cross sections obtained from other measurements (R_AA). The
observed suppression patterns at 39 and 62.4 GeV are quite similar to those
previously measured at 200 GeV. This similar suppression presents a challenge
to theoretical models that contain various competing mechanisms with different
energy dependencies, some of which cause suppression and others enhancement.Comment: 365 authors, 10 pages, 11 figures, 4 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
Establishment of a new human osteosarcoma cell line, UTOS-1: cytogenetic characterization by array comparative genomic hybridization
The cytogenetic characteristics of osteosarcoma (OS) remain controversial. The establishment of a new human OS cell line may improve the characterization. We report the establishment of a new human osteosarcoma cell line, UTOS-1, from a typical osteoblastic OS of an 18-year-old man. Cultured UTOS-1 cells are spindle-shaped, and have been maintained in vitro for over 50 passages in more than 2 years. Xenografted UTOS-1 cells exhibit features typical of OS, such as production of osteoid or immature bone matrix, and proliferation potency in vivo. UTOS-1 also exhibit morphological and immunohistochemical characteristics typical of osteoblastic OS. Chromosomal analysis by G-band show 73~85 chromosomes with complicated translocations. Array CGH show frequent gains at locus DAB2 at chromosome 5q13, CCND2 at 12p13, MDM2 at 12q14.3-q15, FLI and TOP3A at 17p11.2-p12 and OCRL1 at Xq25, and show frequent losses at HTR1B at 6q13, D6S268 at 6q16.3-q21, SHGC17327 at 18ptel, and STK6 at 20q13.2-q13.3. The UTOS-1 cell line may prove useful for biologic and molecular pathogenetic investigations of human OS
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 higher cumulants of net-charge multiplicity distributions in AuAu collisions at GeV
We report the measurement of cumulants () of the net-charge
distributions measured within pseudorapidity () in AuAu
collisions at GeV with the PHENIX experiment at the
Relativistic Heavy Ion Collider. The ratios of cumulants (e.g. ,
) of the net-charge distributions, which can be related to volume
independent susceptibility ratios, are studied as a function of centrality and
energy. These quantities are important to understand the quantum-chromodynamics
phase diagram and possible existence of a critical end point. The measured
values are very well described by expectation from negative binomial
distributions. We do not observe any nonmonotonic behavior in the ratios of the
cumulants as a function of collision energy. The measured values of and can be directly compared to lattice
quantum-chromodynamics calculations and thus allow extraction of both the
chemical freeze-out temperature and the baryon chemical potential at each
center-of-mass energy.Comment: 512 authors, 8 pages, 4 figures, 1 table. v2 is version accepted for
publication in Phys. Rev. C as a Rapid Communication. 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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