Increasing evidence implicates oxidative stress as partially responsible for the neurodegenerative process of Alzheimer's disease (AD). Recent reports show an increased production of nitrotyrosine in ...AD brains, suggesting that peroxynitrite is produced in excess in this disease. Furthermore, incidence of cerebral amyloid angiopathy in AD cases is very frequent (83%), strongly suggesting a vascular component of AD pathogenesis. We have evaluated the hypothesis that peroxynitrite could be responsible for mediating the cytotoxicity and vasoactivity induced by the amyloid-beta1-40 (Abeta) peptide. Rat brain endothelial cells (RBE-4) appear to be sensitive to Abeta-induced toxicity but not to the cytotoxicity induced by peroxynitrite. Addition of Cu/Zn superoxide dismutase to cell culture media, which is only able to clear extracellular superoxide, was not effective in blocking Abeta-induced toxicity. However, we were able to partially block Abeta-induced cytotoxicity by using Mn(III)tetrakis(4-benzoic acid) porphyrin (MnTBAP) which dismutes superoxide intracellularily. Yet, MnTBAP was not able to prevent the vasoactivity triggered by Abeta. Moreover, addition of peroxynitrite to rat aortae did not modulate the vasotension induced by Abeta. We conclude that intracellular superoxide radicals may contribute to Abeta-induced cytotoxicity. Our results also indicate that peroxynitrite does not significantly contribute to Abeta-induced cytotoxicity in rat brain endothelial cells (RBE-4) or vasoactivity in rat aortae. These results suggest that therapeutic efforts aimed at removal of reactive oxygen species with SOD is unlikely to be beneficial for treatment of Abeta-induced endothelial dysfunction. However, compounds that clear free radicals intracellularly may well be beneficial.
Increasing evidence implicates oxidative stress as partially responsible for the neurodegenerative process of Alzheimer's disease (AD). Recent reports show an increased production of nitrotyrosine in ...AD brains, suggesting that peroxynitrite is produced in excess in this disease. Furthermore, incidence of cerebral amyloid angiopathy in AD cases is very frequent (83%), strongly suggesting a vascular component of AD pathogenesis. We have evaluated the hypothesis that peroxynitrite could be responsible for mediating the cytotoxicity and vasoactivity induced by the amyloid-β1–40(Aβ) peptide. Rat brain endothelial cells (RBE-4) appear to be sensitive to Aβ-induced toxicity but not to the cytotoxicity induced by peroxynitrite. Addition of Cu/Zn superoxide dismutase to cell culture media, which is only able to clear extracellular superoxide, was not effective in blocking Aβ-induced toxicity. However, we were able to partially block Aβ-induced cytotoxicity by using Mn(III)tetrakis(4-benzoic acid) porphyrin (MnTBAP) which dismutes superoxide intracellularily. Yet, MnTBAP was not able to prevent the vasoactivity triggered by Aβ. Moreover, addition of peroxynitrite to rat aortae did not modulate the vasotension induced by Aβ. We conclude that intracellular superoxide radicals may contribute to Aβ-induced cytotoxicity. Our results also indicate that peroxynitrite does not significantly contribute to Aβ-induced cytotoxicity in rat brain endothelial cells (RBE-4) or vasoactivity in rat aortae. These results suggest that therapeutic efforts aimed at removal of reactive oxygen species with SOD is unlikely to be beneficial for treatment of Aβ-induced endothelial dysfunction. However, compounds that clear free radicals intracellularly may well be beneficial.
β-Arrestins serve a dual regulatory role in the life cycle of G protein-coupled receptors such as the β 2 -adrenergic receptor. First, they mediate rapid desensitization by binding to G ...protein-coupled receptor kinase-phosphorylated
receptors. Second, they target the receptors for internalization into endosomal vesicles, wherein receptor dephosphorylation
and resensitization occur. Here we report that phosphorylation of a carboxyl-terminal serine (Ser-412) in β-arrestin1 regulates
its endocytotic but not its desensitization function. Cytoplasmic β-arrestin1 is constitutively phosphorylated and is recruited
to the plasma membrane by agonist stimulation of the receptors. At the plasma membrane, β-arrestin1 is rapidly dephosphorylated,
a process that is required for its clathrin binding and receptor endocytosis but not for its receptor binding and desensitization.
Once internalized, β-arrestin1 is rephosphorylated. Thus, as with the classical endocytic adaptor protein complex AP2, β-arrestin1
functions as a clathrin adaptor in receptor endocytosis which is regulated by dephosphorylation at the plasma membrane.
Since the launch of the Einstein X-ray Observatory in the 1970s, a number of broad absorption features have been reported in the X-ray spectra of BL Lac objects. These features are often interpreted ...as arising from high velocity outflows intrinsic to the BL Lac object, therefore providing important information about the inner environment around the central engine. However, such absorption features have not been observed more recently with high-resolution X-ray telescopes such as Chandra and XMM-Newton. In this paper, we report the detection of a transient X-ray absorption feature intrinsic to the BL Lac object H 2356-309 with the Chandra X-ray Telescope. This BL Lac object was observed during XMM cycle 7, Chandra cycle 8 and 10, as part of our campaign to investigate X-ray absorption produced by the warm-hot intergalactic medium (WHIM) residing in the foreground large scale superstructure. During one of the 80 ksec, Chandra cycle 10 observations, a transient absorption feature was detected at 3.3-sigma (or 99.9% confidence level, accounting for the number of trials), which we identify as the OVIII K-alpha line produced by an absorber intrinsic to the BL Lac object. None of the other 11 observations showed this line. We constrain the ionization parameter (25 <~ Xi <~ 40) and temperature (10^5 < T < 2.5 10^7 K) of the absorber. This absorber is likely produced by an outflow with a velocity up to 1,500 km/s. There is a suggestion of possible excess emission on the long-wavelength side of the absorption line; however, the derived properties of the emission material are very different from those of the absorption material, implying it is unlikely a typical P Cygni-type profile.
Cosmological simulations of galaxy clusters typically find that the weight of a cluster at a given radius is not balanced entirely by the thermal gas pressure of the hot ICM, with theoretical studies ...emphasizing the role of random turbulent motions to provide the necessary additional pressure support. Using a set of high-resolution, hydrodynamical simulations of galaxy clusters that include radiative cooling and star formation, we find instead that in the most relaxed clusters rotational support exceeds that from random turbulent motions for radii 0.1 - 0.5 r_500, and that the observed clusters are much rounder than the simulated, relaxed clusters within ~ 0.4 r_500. Moreover, while the observed clusters display an average ellipticity profile that does not vary significantly with radius, the ellipticity of the relaxed CDM clusters declines markedly with increasing radius, suggesting that the ICM of the observed clusters rotates less rapidly than that of the relaxed CDM clusters out to ~ 0.6 r_500. We also find the ellipticity profile of a simulated cluster without radiative cooling is in much better agreement with the observations, implying that over-cooling has a substantial impact on the gas dynamics and morphology out to larger radii than previously recognized. It also suggests that the 10%-20% systematic errors from non-thermal gas pressure support reported for simulated cluster masses, obtained from fitting simulated X-ray data over large radial ranges within r_500, may need to be revised downward. These results demonstrate the utility of X-ray ellipticity profiles as a probe of ICM rotation and over-cooling which should be used to constrain future cosmological cluster simulations.
In a previous paper we reported a 3-sigma detection of an absorption line from the Warm-Hot Intergalactic Medium (WHIM) using the Chandra and XMM X-ray grating spectra of the blazar H2356-309, the ...sight-line of which intercepts the Sculptor Wall, a large-scale superstructure of galaxies at z ~ 0.03. To verify our initial detection, we obtained a deep (500 ks), follow-up exposure of H2356-309 as part of the Cycle-10 Chandra Large Project Program. From a joint analysis of the Cycle-10 and previous (Cycle-8) Chandra grating data we detect the redshifted OVII WHIM line at a significance level of 3.4-sigma, a substantial improvement over the 1.7-sigma level reported previously when using only the Cycle-8 data. The significance increases to 4.0-sigma when the existing XMM grating data are included in the analysis, thus confirming at higher significance the existence of the line at the redshift of the Sculptor Wall with an equivalent width of 28.5+/-10.5 mA (90% confidence). We obtain a 90% lower limit on the OVII column density of 0.8 10^16 cm^-2 and a 90% upper limit on the Doppler-b parameter of 460 km/s. Assuming the absorber is uniformly distributed throughout the ~ 15 Mpc portion of the blazar's sight-line that intercepts the Sculptor Wall, that the OVII column density is ~ 2 10^16 cm^-2 (corresponding to b > 150 km/s where the inferred column density is only weakly dependent on b), and that the oxygen abundance is 0.1 solar, we estimate a baryon over-density of ~ 30 for the WHIM, which is consistent with the peak of the WHIM mass fraction predicted by cosmological simulations. The clear detection of OVII absorption in the Sculptor Wall demonstrates the viability of using current observatories to study WHIM in the X-ray absorption spectra of blazars behind known large-scale structures.
We present XMM RGS and Chandra LETG observations of the blazar, H 2356-309, located behind the Sculptor Wall, a large-scale galaxy structure expected to harbor high-density Warm-Hot Intergalactic ...Medium (WHIM). Our simultaneous analysis of the RGS and LETG spectra yields a 3-sigma detection of the crucial redshifted O vii K-alpha line with a column density (>~ 10^{16} cm^{-2}) consistent with similar large-scale structures produced in cosmological simulations. This represents the first detection of non-local WHIM from X-ray absorption studies where XMM and Chandra data are analyzed simultaneously and the absorber redshift is already known, thus providing robust evidence for the expected repository of the "missing baryons".
Reviews Nankervis, Max; Darville, Helen; Patrick, Colin ...
Journal of Australian Studies,
19/1/1/, Letnik:
20, Številka:
50-51
Book Review
Recenzirano
Jill Barnard, Jenny Keating, Plus Ca Change. The Sad History of The 'People's Playground', Albert Park. Chandos, Burwood, 1996, pp. 222, $25.
Peter Read, Returning to Nothing: the Meaning of Lost ...Places, Cambridge University Press, 1996, pp. xiv + 240, $29.95.
John Dargavel, Fashioning Australia's Forests, Oxford University Press, 1996, pp. xvi + 312, $39.95.
Steve Mullins, Torres Strait: A History of Colonial Occupation and Culture Contact 1864-1897, Central Queensland University Press, Rockhampton, 1995, pp. viii + 240, $19.95.
Lynnette Peel (ed), The Henty Journals. A Record of Farming, Whaling and Shipping in Portland Bay, 1834-1839, The Miegunyah Press, Melbourne, in association with The State Library of Victoria, 1996, pp. xi + 297, hardcover, $49.95.
Graham Seal, The Outlaw Legend: A Cultural Tradition in Britain, America and Australia, Cambridge University ress, Oakleigh, 1996, pp. xvi + 246, $90, hardback. $29.95, paperback.
Ken Stewart, (ed). The 1890s: Australian Literature and Literary Culture, University of Queensland Press, St. Lucia, 1996, xii + 379 pages, $26.95.
Lachlan Strahan, Australia's China: Changing Perceptions From The 1930s to the 1991s, Cambridge University Press, Cambridge, 1996, pp. 376, $34.95.
Jan Gothard (ed), Asian Orientations: Studies in Western Australian History, Centre for Western Australian History, University of Western Australia, No.16, 1995, pp. viii + 183, $15.
Sang Ye, The Year the Dragon Came, University of Queensland Press, St Lucia, 1996, pp. x + 204, $18.95.
D. O'Connor, No need to be afraid: Italian settlers in South Australia between 1839 and the Second World War, Wakefield Press, Kent Town (SA), 1996, pp. 283, $24.95.
Alan Powell, War by Stealth: Australians and the Allied Intelligence Bureau 1942-1945, Melbourne University Press, Melbourne, 1996, pp. xix + 403. $59.95.
Geoffrey Serle, Robin Boyd: A Life, Melbourne University Press, Melbourne, 1996, pp. 352, $29.95.
Shirley Fitzgerald and Garry Wotherspoon (eds), Minorities: Cultural Diversity in Sydney, State Library of New South Wales Press/Sydney History Group, Sydney, 1995, pp. 216, $24.95.
Neil Boyack, Simon Colvey, See Through, University of Queensland Press, St Lucia, 1996, pp. 250, $16.95.
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