1,469 research outputs found
Inhibition of the tyrosine phosphatase SHP-2 suppresses angiogenesis in vitro and in vivo
Endothelial cell survival is indispensable to maintain endothelial integrity and initiate new vessel formation. We investigated the role of SHP-2 in endothelial cell survival and angiogenesis in vitro as well as in vivo. SHP-2 function in cultured human umbilical vein and human dermal microvascular endothelial cells was inhibited by either silencing the protein expression with antisense-oligodesoxynucleotides or treatment with a pharmacological inhibitor (PtpI IV). SHP-2 inhibition impaired capillary-like structure formation (p < 0.01; n = 8) in vitro as well as new vessel growth ex vivo (p < 0.05; n = 10) and in vivo in the chicken chorioallantoic membrane (p < 0.01, n = 4). Additionally, SHP-2 knock-down abrogated fibroblast growth factor 2 (FGF-2)-dependent endothelial proliferation measured by MTT reduction ( p ! 0.01; n = 12). The inhibitory effect of SHP-2 knock-down on vessel growth was mediated by increased endothelial apoptosis ( annexin V staining, p ! 0.05, n = 9), which was associated with reduced FGF-2-induced phosphorylation of phosphatidylinositol 3-kinase (PI3-K), Akt and extracellular regulated kinase 1/2 (ERK1/2) and involved diminished ERK1/2 phosphorylation after PI3-K inhibition (n=3). These results suggest that SHP-2 regulates endothelial cell survival through PI3-K-Akt and mitogen-activated protein kinase pathways thereby strongly affecting new vessel formation. Thus, SHP-2 exhibits a pivotal role in angiogenesis and may represent an interesting target for therapeutic approaches controlling vessel growth. Copyright (C) 2007 S. Karger AG, Basel
Cosmic ray diffusion near the Bohm limit in the Cassiopeia A supernova remnant
Supernova remnants (SNRs) are believed to be the primary location of the
acceleration of Galactic cosmic rays, via diffusive shock (Fermi) acceleration.
Despite considerable theoretical work the precise details are still unknown, in
part because of the difficulty in directly observing nucleons that are
accelerated to TeV energies in, and affect the structure of, the SNR shocks.
However, for the last ten years, X-ray observatories ASCA, and more recently
Chandra, XMM-Newton, and Suzaku have made it possible to image the synchrotron
emission at keV energies produced by cosmic-ray electrons accelerated in the
SNR shocks. In this article, we describe a spatially-resolved spectroscopic
analysis of Chandra observations of the Galactic SNR Cassiopeia A to map the
cutoff frequencies of electrons accelerated in the forward shock. We set upper
limits on the electron diffusion coefficient and find locations where particles
appear to be accelerated nearly as fast as theoretically possible (the Bohm
limit).Comment: 18 pages, 5 figures. Accepted for publication in Nature Physics (DOI
below), final version available week of August 28, 2006 at
http://www.nature.com/nphy
When a 520 million-year-old Chengjiang fossil meets a modern micro-CT - a case study
The 520 million-year-old Chengjiang biota of China (UNESCO World Heritage) presents the earliest known evidence of the so-called Cambrian Explosion. Studies, however, have mainly been limited to the information exposed on the surface of the slabs. Thus far, structures preserved inside the slabs were accessed by careful removal of the matrix, in many cases with the unfortunate sacrifice of some "less important" structures, which destroys elements of exceptionally preserved specimens. Here, we show for the first time that microtomography (micro-CT) can reveal structures situated inside a Chengjiang fossil slab without causing any damage. In the present study a trilobitomorph arthropod (Xandarella spectaculum) can be reliably identified only with the application of micro-CT. We propose that this technique is an important tool for studying three-dimensionally preserved Chengjiang fossils and, most likely, also those from other biota with a comparable type of preservation, specifically similar iron concentrations
GLAST: Understanding the High Energy Gamma-Ray Sky
We discuss the ability of the GLAST Large Area Telescope (LAT) to identify,
resolve, and study the high energy gamma-ray sky. Compared to previous
instruments the telescope will have greatly improved sensitivity and ability to
localize gamma-ray point sources. The ability to resolve the location and
identity of EGRET unidentified sources is described. We summarize the current
knowledge of the high energy gamma-ray sky and discuss the astrophysics of
known and some prospective classes of gamma-ray emitters. In addition, we also
describe the potential of GLAST to resolve old puzzles and to discover new
classes of sources.Comment: To appear in Cosmic Gamma Ray Sources, Kluwer ASSL Series, Edited by
K.S. Cheng and G.E. Romer
The First Molecular Phylogeny of Strepsiptera (Insecta) Reveals an Early Burst of Molecular Evolution Correlated with the Transition to Endoparasitism
A comprehensive model of evolution requires an understanding of the relationship between selection at the molecular and phenotypic level. We investigate this in Strepsiptera, an order of endoparasitic insects whose evolutionary biology is poorly studied. We present the first molecular phylogeny of Strepsiptera, and use this as a framework to investigate the association between parasitism and molecular evolution. We find evidence of a significant burst in the rate of molecular evolution in the early history of Strepsiptera. The evolution of morphological traits linked to parasitism is significantly correlated with the pattern in molecular rate. The correlated burst in genotypic-phenotypic evolution precedes the main phase of strepsipteran diversification, which is characterised by the return to a low and even molecular rate, and a period of relative morphological stability. These findings suggest that the transition to endoparasitism led to relaxation of selective constraint in the strepsipteran genome. Our results indicate that a parasitic lifestyle can affect the rate of molecular evolution, although other causal life-history traits correlated with parasitism may also play an important role
Study of the reaction e^{+}e^{-} -->J/psi\pi^{+}\pi^{-} via initial-state radiation at BaBar
We study the process with
initial-state-radiation events produced at the PEP-II asymmetric-energy
collider. The data were recorded with the BaBar detector at center-of-mass
energies 10.58 and 10.54 GeV, and correspond to an integrated luminosity of 454
. We investigate the mass
distribution in the region from 3.5 to 5.5 . Below 3.7
the signal dominates, and above 4
there is a significant peak due to the Y(4260). A fit to
the data in the range 3.74 -- 5.50 yields a mass value
(stat) (syst) and a width value (stat)(syst) for this state. We do not
confirm the report from the Belle collaboration of a broad structure at 4.01
. In addition, we investigate the system
which results from Y(4260) decay
Coronary collaterals and risk for restenosis after percutaneous coronary interventions: a meta-analysis
<p>Abstract</p> <p>Background</p> <p>The benefit of the coronary collateral circulation (natural bypass network) on survival is well established. However, data derived from smaller studies indicates that coronary collaterals may increase the risk for restenosis after percutaneous coronary interventions. The purpose of this systematic review and meta-analysis of observational studies was to explore the impact of the collateral circulation on the risk for restenosis.</p> <p>Methods</p> <p>We searched the MEDLINE, EMBASE and ISI Web of Science databases (2001 to 15 July 2011). Random effects models were used to calculate summary risk ratios (RR) for restenosis. The primary endpoint was angiographic restenosis > 50%.</p> <p>Results</p> <p>A total of 7 studies enrolling 1,425 subjects were integrated in this analysis. On average across studies, the presence of a good collateralization was predictive for restenosis (risk ratio (RR) 1.40 (95% CI 1.09 to 1.80); <it>P </it>= 0.009). This risk ratio was consistent in the subgroup analyses where collateralization was assessed with intracoronary pressure measurements (RR 1.37 (95% CI 1.03 to 1.83); <it>P </it>= 0.038) versus visual assessment (RR 1.41 (95% CI 1.00 to 1.99); <it>P </it>= 0.049). For the subgroup of patients with stable coronary artery disease (CAD), the RR for restenosis with 'good collaterals' was 1.64 (95% CI 1.14 to 2.35) compared to 'poor collaterals' (<it>P </it>= 0.008). For patients with acute myocardial infarction, however, the RR for restenosis with 'good collateralization' was only 1.23 (95% CI 0.89 to 1.69); <it>P </it>= 0.212.</p> <p>Conclusions</p> <p>The risk of restenosis after percutaneous coronary intervention (PCI) is increased in patients with good coronary collateralization. Assessment of the coronary collateral circulation before PCI may be useful for risk stratification and for the choice of antiproliferative measures (drug-eluting stent instead bare-metal stent, cilostazol).</p
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