THE ROLE OF P53 IN OXIDATIVE STRESS AND POLYGLUTAMINE NEUROTOXICITY

Polyglutamine expansion disorders are progressive neurodegenerative diseasesthat are caused by the pathological expansion of polyglutamine repeats. Huntington\u27sdisease (HD) is a polyglutamine disorder caused by the expansion of an existingpolyglutamine tract in a novel protein, Huntingtin (Htt). Oxidative stress has beenimplicated in the neural dysfunction observed in multiple neurodegenerative conditionsincluding HD. The tumor suppressor p53 is a multifunctional protein that has roles inthe cell cycle, apoptosis and neurodevelopment. The role of p53 in HD-associatedneurodegeneration has been studied but not fully elucidated, nor has the role of p53 inoxidative stress toxicity been fully elucidated.Here I present work that demonstrates polyglutamine expansion inducedalterations to p53 stability, localization, and activity. The transcriptional activity of p53was found to have a role in oxidative stress mediated as well as polyglutaminemediated neurotoxicity in vitro. The expression of p53 was also altered in vivo in amouse model of HD as well as in HD brain.Taken together, these data demonstrate a role for p53 in polyglutamine and oxidativestress toxicity

Reconciling Greed and Altruism in the Open Source Community

Adam Smith observed in The Theory of Moral Sentiments, that people pursue wealth not to to supply the necessities of nature but in order to procure superfluities that satisfy a basic psychological need to be thought of well by others (Smith, 62). It is not wealth that men desire, but the consideration and good opinion that wait upon riches . We know that there is some truth to this statement, as even a cursory glance at metrics representing standards of living show them increasing 1 or 2% each year since they were first measured (in terms of GDP per capita, Tables A-1 c and A-1 d). Yet there is something in human beings that drive us to possess non-physical items not necessary for survival in endless quantities. As an example, the market for virtual goods (fake items sold in online virtual worlds) is estimated to grow to become a 2.5 billion dollar market by 2013

Intrinsic Absorption with the Far Ultraviolet Spectroscopic Explorer

We present a survey of 72 Seyfert galaxies and quasars observed by the Far Ultraviolet Spectroscopic Explorer (FUSE). Our survey is the largest to date searching for intrinsic UV absorption with high spectral resolution, and is the first step toward a more comprehensive study of intrinsic absorption in low-redshift AGN. We have determined that 72 of 253 available active galactic nuclei (AGN) are viable targets for detection of intrinsic absorption lines. We examined these spectra for signs of intrinsic absorption in the O VI doublet (lambda lamdba 1031.9, 1037.6) and Lyman beta (lambda 1025.7). The fraction of Seyfert 1 galaxies and low-redshift quasars at z\u3c0.15 that show evidence of intrinsic UV absorption is ~50, which is slightly lower than Crenshaw et al. found (60%) based on a smaller sample of C IV absorption in Seyfert 1 galaxies observed with the Hubble Space Telescope (HST). The intrinsic absorption lines are mostly blueshifted with respect to the rest frame of the galaxy, indicating outflow of ionized gas from the AGN. With this new fraction we find a global covering factor of the absorbing gas with respect to the central nucleus of ~0.4. We also provide a deeper analysis of the intrinsic absorption features we found in 35 objects. We have characterized the relation between luminosity and velocity, and examined the relationships between equivalent width, full width at half maximum, velocity and continuum flux. The luminosity/velocity correlation has been explored previously by Laor & Brandt (2002), but at a significantly higher redshift and heavily weighted by Broad Absorption Line quasars. Our survey is for lower redshift and lower luminosity objects, mostly Seyfert galaxies. We have also explored each object with multiple observations for variablity in each of the aforementioned quantities and characterized the variation of equivalent width with continuum flux. Variability for low-z AGN has been seen in the past. In our survey, we find that variability of O VI (lambda lambda 1032, 1038) is less common than for the UV doublets of C IV and N V seen at longer wavelengths, because the O VI absorption is usually saturated. Lyman beta absorption variability is more frequent. In the target-by-target examination we find that Broad Absorption Line (BAL) features and Narrow Absorption Line (NAL) features are related, in that they follow a single relationship between the maximum outflow velocity and the AGN luminosity, and both can be exhibited in similar luminosity objects. IRAS F22456-5125 is one particular Seyfert galaxy that we have selected for modelling due to its interesting assortment of intrinsic absorption lines. It shows a system of five individual kinematic components of absorption features in both O VI lines and in several of the Lyman series lines. We find that each of the components are relatively simple to model and appear to be weak in the X-ray

A 10 kpc Scale Seyfert Galaxy Outflow: HST/COS Observations of IRAS F22456-5125

We present analysis of the UV-spectrum of the low-z AGN IRAS-F22456-5125 obtained with the Cosmic Origins Spectrograph on board the Hubble Space Telescope. The spectrum reveals six main kinematic components, spanning a range of velocities of up to 800 km s-1, which for the first time are observed in troughs associated with CII, CIV, NV, SiII, SiIII, SiIV and SIV. We also obtain data on the OVI troughs, which we compare to those available from an earlier FUSE epoch. Column densities measured from these ions allow us to derive a well-constrained photoionization solution for each outflow component. Two of these kinematic components show troughs associated with transitions from excited states of SiII\ and CII. The number density inferred from these troughs, in combination with the deduced ioinization parameter, allows us to determine the distance to these outflow components from the central source. We find these components to be at a distance of ~ 10 kpc. The distances and the number densities derived are consistent with the outflow being part of a galactic wind.Comment: 52 pages, 15 figures, accepted for publication in ApJ March 25, 201

Effects of Equilenin on the Embryological Development of the Zebra Fish, Brachydanio Rerio (Hamilton)

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Distance to Multiple Kinematic Components of Quasar Outflows: VLT Observations of QSO 2359-1241 and SDSS J0318-0600

Using high resolution VLT spectra, we study the multi-component outflow systems of two quasars exhibiting intrinsic Fe II absorption (QSO 2359-1241 and SDSS J0318-0600). From the extracted ionic column densities and using photoionization modeling we determine the gas density, total column density, and ionization parameter for several of the components. For each object the largest column density component is also the densest, and all other components have densities of roughly 1/4 of that of the main component. We demonstrate that all the absorbers lie roughly at the same distance from the source. Further, we calculate the total kinetic luminosities and mass outflow rates of all components and show that these quantities are dominated by the main absorption component.Comment: 27 pages, 5 figure

BAL Outflow Contribution to AGN Feedback: Frequency of S iv Outflows in the SDSS

We present a study of Broad Absorption Line (BAL) quasar outflows that show S IV ?1063 and S IV* ?1073 troughs. The fractional abundance of S IV and C IV peak at similar value of the ionization parameter, implying that they arise from the same physical component of the outflow. Detection of the S IV* troughs will allow us to determine the distance to this gas with higher resolution and higher signal-to-noise spectra, therefore providing the distance and energetics of the ubiquitous C IV BAL outflows. In our bright sample of 156 SDSS quasars 14% show C IV and 1.9% S IV troughs, which is consistent with a fainter magnitude sample with twice as many objects. One object in the fainter sample shows evidence of a broad S IV trough without any significant trough present from the excited state line, which implies that this outflow could be at a distance of several kpc. Given the fractions of C IV and S IV, we establish firm limits on the global covering factor on S IV that ranges from 2.8% to 21% (allowing for the k-correction). Comparison of the expected optical depth for these ions with their detected percentage suggests that these species arise from common outflows with a covering factor closer to the latter.Comment: Published in ApJ (2012 ApJ, 750, 143