Hepatoma derived growth factor binds DNA through the N-terminal PWWP domain

<p>Abstract</p> <p>Background</p> <p>Hepatoma Derived Growth Factor (HDGF) is a nuclear protein with nuclear targeting required for mitogenic activity. Recently we demonstrated that HDGF is a transcriptional repressor, but whether HDGF binds DNA, the specificity of DNA binding and what protein domain is required are still unknown. In this study, we aimed to identify if HDGF is a DNA binding protein, map the functional DNA binding domain and DNA binding element for HDGF.</p> <p>Results</p> <p>Using chromatin immunoprecipitation (ChIP) of human DNA, we isolated 10 DNA sequences sharing a conserved ~200 bp element. Homology analysis identified the binding sequences as a motif within the promoter of the SMYD1 gene, a HDGF target gene. Electrophoretic Mobility Shift Assays (EMSA) confirmed the binding of HDGF to this conserved sequence. As a result, an 80 bp conserved sequence located in the SMYD1 promoter bound GST-HDGF tightly. The binding core sequence for HDGF was narrowed down to 37 bp using a deletion mapping strategy from both the 5' and 3' ends. Moreover, ChIP and DNase I footprinting analysis revealed that HDGF binds this 80 bp DNA fragment specifically. Functionally overexpression of HDGF represses a reporter gene which is controlled by an SV-40 promoter containing the 80 bp DNA element. Using serial truncations of GST-HDGF, we mapped the DNA binding domain of HDGF to the N-terminal PWWP domain.</p> <p>Conclusion</p> <p>HDGF is a DNA binding protein, binds DNA specifically, and prefers a minimum of 37 bp long DNA fragment. The N-terminal PWWP domain of HDGF is required for DNA binding. HDGF exerts its transcription repressive effect through binding to a conserved DNA element in the promoter of target genes.</p

Can a circulating light beam produce a time machine?

In a recent paper, Mallett found a solution of the Einstein equations in which closed timelike curves (CTC's) are present in the empty space outside an infinitely long cylinder of light moving in circular paths around an axis. Here we show that, for physically realistic energy densities, the CTC's occur at distances from the axis greater than the radius of the visible universe by an immense factor. We then show that Mallett's solution has a curvature singularity on the axis, even in the case where the intensity of the light vanishes. Thus it is not the solution one would get by starting with Minkowski space and establishing a cylinder of light.Comment: 5 pages, RevTe

An Axial Time-of-flight Mass Spectrometer for Upper Atmospheric Measurements

As the “shoreline” of the Earth’s atmosphere, the mesosphere/lower thermosphere (MLT) region is home to many interesting and important phenomena, the most visible of which are the auroras. Geomagnetic storms, in addition to causing very intense auroral activity, also deposit large amounts of energy into the earth’s ionosphere. Recent analysis of data from the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument aboard the Thermosphere-Ionosphere-Mesosphere Energetics and Dynamics (TIMED) satellite suggests that 5.3μm emission from vibrationally excited NO is the main method of energy dissipation from energy deposited by geomagnetic storms. Additionally, NO+ has been shown to be the major contributor to geomagnetic storm induced 4.3μm nighttime emission. In order to better physically understand these two large sources of geomagnetic storm energy dissipation, a sounding rocket mission, ROCKet-borne Storm Energetics of Auroral Dosing in the E-region (ROCK-STEADE) is being proposed. The ROCK-STEADE instrument suite consists of several photometers, an interferometer, an IR spectrometer, and two time-of-flight mass spectrometers (TOFMS). The TOFMS will measure the ion and neutral compositions in the atmosphere as the sounding rocket travels through the MLT. Due to the use of microchannel plate (MCP) detectors in TOFMS, one of the major challenges to making measurements in the MLT is the high ambient pressure. Other challenges and sources of error and background include stray UV photons, scattering of gas molecules from the interior surfaces of the instrument, dissociation of molecules in the bow shock caused by the supersonic rocket flight, and reactive recombination at the surfaces of the instrument. Methods of dealing with these challenges include: • Recent advances in MCP technology allowing MCP operation into the mtorr range • Cooling the front surface of the TOFMS using liquid He to eliminate the bow shock (thus making possible the direct sampling of the ambient atmosphere) • Cryogenically cooling the interior of the instrument to eliminate scattering of gas from instrument walls and therefore also reducing the contribution of reactive recombination • Rigorous error analysis to account for the background contribution of stray U

Mitotic phosphorylation activates hepatoma-derived growth factor as a mitogen

<p>Abstract</p> <p>Background</p> <p>Hepatoma-derived growth factor (HDGF) is a nuclear protein that is a mitogen for a wide variety of cells. Mass spectrometry based methods have identified HDGF as a phosphoprotein without validation or a functional consequence of this post-translational modification.</p> <p>Results</p> <p>We found that HDGF in primary mouse aortic vascular smooth muscle cells (VSMC) was phosphorylated. Wild type HDGF was phosphorylated in asynchronous cells and substitution of S103, S165 and S202 to alanine each demonstrated a decrease in HDGF phosphorylation. A phospho-S103 HDGF specific antibody was developed and demonstrated mitosis-specific phosphorylation. HDGF-S103A was not mitogenic and FACS analysis demonstrated a G2/M arrest in HDGF-S103A expressing cells, whereas cells expressing HDGF-S103D showed cell cycle progression. Nocodazole arrest increased S103 phosphorylation from 1.6% to 29% (P = 0.037).</p> <p>Conclusions</p> <p>Thus, HDGF is a phosphoprotein and phosphorylation of S103 is mitosis related and required for its function as a mitogen. We speculate that cell cycle regulated phosphorylation of HDGF may play an important role in vascular cell proliferation.</p

Magnetic Fields from Phase Transitions

The generation of primordial magnetic fields from cosmological phase transitions is discussed, paying particular attention to the electroweak transition and to the various definitions of the `average' field that have been put forward. It is emphasised that only the volume average has dynamical significance as a seed for galactic dynamos. On rather general grounds of causality and energy conservation, it is shown that, in the absence of MHD effects that transfer power in the magnetic field from small to large scales, processes occurring at the electroweak transition cannot generate fields stronger than $10^{-20}$ Gauss on a scale of 0.5 Mpc. However, it is implausible that this upper bound could ever be reached, as it would require all the energy in the Universe to be turned into a magnetic field coherent at the horizon scale. Non-linear MHD effects seem therefore to be necessary if the electroweak transition is to create a primordial seed field.Comment: 6pp RevTeX. Correct finished version supplie

Bell Correlations and the Common Future

Reichenbach's principle states that in a causal structure, correlations of classical information can stem from a common cause in the common past or a direct influence from one of the events in correlation to the other. The difficulty of explaining Bell correlations through a mechanism in that spirit can be read as questioning either the principle or even its basis: causality. In the former case, the principle can be replaced by its quantum version, accepting as a common cause an entangled state, leaving the phenomenon as mysterious as ever on the classical level (on which, after all, it occurs). If, more radically, the causal structure is questioned in principle, closed space-time curves may become possible that, as is argued in the present note, can give rise to non-local correlations if to-be-correlated pieces of classical information meet in the common future --- which they need to if the correlation is to be detected in the first place. The result is a view resembling Brassard and Raymond-Robichaud's parallel-lives variant of Hermann's and Everett's relative-state formalism, avoiding "multiple realities."Comment: 8 pages, 5 figure

Candidate X-ray-Emitting OB Stars in the Carina Nebula Identified Via Infrared Spectral Energy Distributions

We report the results of a new survey of massive, OB stars throughout the Carina Nebula using the X-ray point source catalog provided by the Chandra Carina Complex Project (CCCP) in conjunction with infrared (IR) photometry from the Two Micron All-Sky Survey and the Spitzer Space Telescope Vela--Carina survey. Mid-IR photometry is relatively unaffected by extinction, hence it provides strong constraints on the luminosities of OB stars, assuming that their association with the Carina Nebula, and hence their distance, is confirmed. We fit model stellar atmospheres to the optical (UBV) and IR spectral energy distributions (SEDs) of 182 OB stars with known spectral types and measure the bolometric luminosity and extinction for each star. We find that the extinction law measured toward the OB stars has two components: Av=1--1.5 mag produced by foreground dust with a ratio of total-to-selective absorption Rv=3.1 plus a contribution from local dust with Rv>4.0 in the Carina molecular clouds that increases as Av increases. Using X-ray emission as a strong indicator of association with Carina, we identify 94 candidate OB stars with Lbol\geq10^4 Lsun by fitting their IR SEDs. If the candidate OB stars are eventually confirmed by follow-up spectroscopic observations, the number of cataloged OB stars in the Carina Nebula will increase by ~50%. Correcting for incompleteness due to OB stars falling below the Lbol cutoff or the CCCP detection limit, these results potentially double the size of the young massive stellar population.Comment: 19 pages, 8 figures, accepted for the ApJS Special Issue on the Chandra Carina Complex Project (CCCP), scheduled for publication in May 2011. All 16 CCCP Special Issue papers, including a version of this article with high-quality figures, are available at http://cochise.astro.psu.edu/Carina_public/special_issue.html (through 2011 at least

Averaged Methods for Vortex-String Evolution

We discuss friction-dominated vortex-string evolution using a new analytic model recently developed by the authors. By treating the average string velocity, as well as the characteristic lengthscale, as dynamical variables, we can provide a quantitative picture of the complete evolution of a vortex-string network. Previously known scaling laws are confirmed, and new quantitative predictions regarding loop production and evolution are made.Comment: REVTeX, 21 pages, 23 .eps files included. Submitted to Phys. Rev. B. Minor changes---but some key concepts clarifie

The PLATO Dome A Site-Testing Observatory : instrumentation and first results

The PLATeau Observatory (PLATO) is an automated self-powered astrophysical observatory that was deployed to Dome A, the highest point on the Antarctic plateau, in 2008 January. PLATO consists of a suite of site-testing instruments designed to quantify the benefits of the Dome A site for astronomy, and science instruments designed to take advantage of the unique observing conditions. Instruments include CSTAR, an array of optical telescopes for transient astronomy; Gattini, an instrument to measure the optical sky brightness and cloud cover statistics; DASLE, an experiment to measure the statistics of the meteorological conditions within the near-surface layer; Pre-HEAT, a submillimeter tipping radiometer measuring the atmospheric transmission and water vapor content and performing spectral line imaging of the Galactic plane; and Snodar, an acoustic radar designed to measure turbulence within the near-surface layer. PLATO has run completely unattended and collected data throughout the winter 2008 season. Here we present a detailed description of the PLATO instrument suite and preliminary results obtained from the first season of operation

Altered Tyrosine Phosphorylation of Cardiac Proteins Prompts Contractile Dysfunction in Hypertrophic Cardiomyopathy

Altered Serine/Threonine phosphorylation of the cardiac proteome is an established hallmark of heart failure (HF). However, the contribution of tyrosine phosphorylation to the pathogenesis of these diseases remains unclear. The cardiac proteome was explored by global mapping to discover and quantify site-specific tyrosine phosphorylation in two cardiac hypertrophic models; cardiac overexpression of ErbB2 (TgErbB2) and cardiac expression of a-Myosin heavy chain R403Q (R403Q-aMyHCTg) compared to control hearts. Phosphoproteomic changes found in R403Q-aMyHC Tg mice indicated EGFR1, Focal Adhesion, VEGF, ErbB signaling, and Chemokine signaling pathways activity were likely to be activated. On the other hand, TgErbB2 mice findings displayed significant overrepresentation of Right Ventricular Cardiomyopathy, Hypertrophic Cardiomyopathy (HCM), and dilated cardiomyopathy (DCM) KEGG Pathways. In silico kinase-substrate enrichment analysis (KSEA) highlighted a marked downregulation of canonical MAPK Pathway Activity downstream of k-Ras in TgErbB2 mice and activation of EGFR, PP2 inhibition of c-Src, and Hepatocyte growth factor stimulation. In vivo ErbB2 inhibition by AG-825 decreased cardiac fibrosis, cardiomyocyte disarray, and rescued contractile function on TgErbB2 mice. These results suggest that altered tyrosine phosphorylation may play a regulatory role in cardiac hypertrophic models, suggesting that tyrosine kinase inhibitors could be used therapeutically in Hypertrophic Cardiomyopathy