Modeling the Neuroprotective Role of Enhanced Astrocyte Mitochondrial Metabolism during Stroke

AbstractA mathematical model that integrates the dynamics of cell membrane potential, ion homeostasis, cell volume, mitochondrial ATP production, mitochondrial and endoplasmic reticulum Ca2+ handling, IP3 production, and GTP-binding protein-coupled receptor signaling was developed. Simulations with this model support recent experimental data showing a protective effect of stimulating an astrocytic GTP-binding protein-coupled receptor (P2Y1Rs) following cerebral ischemic stroke. The model was analyzed to better understand the mathematical behavior of the equations and to provide insights into the underlying biological data. This approach yielded explicit formulas determining how changes in IP3-mediated Ca2+ release, under varying conditions of oxygen and the energy substrate pyruvate, affected mitochondrial ATP production, and was utilized to predict rate-limiting variables in P2Y1R-enhanced astrocyte protection after cerebral ischemic stroke

The Antennae Galaxies (NGC 4038/4039) Revisited: ACS and NICMOS Observations of a Prototypical Merger

The ACS and NICMOS have been used to obtain new HST images of NGC 4038/4039 ("The Antennae"). These new observations allow us to better differentiate compact star clusters from individual stars, based on both size and color. We use this ability to extend the cluster luminosity function by approximately two magnitudes over our previous WFPC2 results, and find that it continues as a single power law, dN/dL propto L^alpha with alpha=-2.13+/-0.07, down to the observational limit of Mv~-7. Similarly, the mass function is a single power law dN/dM propto M^beta with beta=-2.10+/-0.20 for clusters with ages t<3x10^8 yr, corresponding to lower mass limits that range from 10^4 to 10^5 Msun, depending on the age range of the subsample. Hence the power law indices for the luminosity and mass functions are essentially the same. The luminosity function for intermediate-age clusters (i.e., ~100-300 Myr old objects found in the loops, tails, and outer areas) shows no bend or turnover down to Mv~-6, consistent with relaxation-driven cluster disruption models which predict the turnover should not be observed until Mv~-4. An analysis of individual ~0.5-kpc sized areas over diverse environments shows good agreement between values of alpha and beta, similar to the results for the total population of clusters in the system. Several of the areas studied show evidence for age gradients, with somewhat older clusters appearing to have triggered the formation of younger clusters. The area around Knot B is a particularly interesting example, with an ~10-50 Myr old cluster of estimated mass ~10^6 Msun having apparently triggered the formation of several younger, more massive (up to 5x10^6 Msun) clusters along a dust lane.Comment: 84 pages, 9 tables, 31 figures; ApJ accepte

Theory and laboratory astrophysics

Science opportunities in the 1990's are discussed. Topics covered include the large scale structure of the universe, galaxies, stars, star formation and the interstellar medium, high energy astrophysics, and the solar system. Laboratory astrophysics in the 1990's is briefly surveyed, covering such topics as molecular, atomic, optical, nuclear and optical physics. Funding recommendations are given for the National Science Foundation, NASA, and the Department of Energy. Recommendations for laboratory astrophysics research are given

The Morphological Diversities Among Star-forming Galaxies at High Redshifts in the Great Observatories Origins Deep Survey (GOODS)

We have used the HST/ACS images to identify 4700 Lyman break galaxies (LBGs) in GOODS. We present the results from a parametric analysis of the 2-D surface brightness profiles, for 1333 LBGs at z > 2.5 with rest-frame UV(1600 Angstrom) AB magnitude < -20.5. Based on the Sersic index, n, which measures the profile shape, we find that about 40% of LBGs at z=3 have light profiles close to exponential, and only 30% have the high concentrations seen for spheroids. About 30% of LBGs appear to have multiple cores or disturbed morphologies suggestive of close pairs or on-going mergers. The fraction of spheroid-like (n > 2.5) LBGs decreases by about 15% from z = 5 to 3. A comparison of LBGs with the starburst galaxies at z = 1.2, shows that the fraction of spheroid-like profiles is about 20% higher among LBGs. The ellipticity distribution for LBGs exhibits a pronounced skew towards high ellipticities (> 0.5), which cannot be explained by morphologies similar to the local disks and spheroids viewed at random orientations. The peak of the distribution evolves toward lower ellipticities, from 0.7 at z = 4 to 0.5 at z = 3. At z = 1.2 the distribution is relatively flat as seen among the present-day galaxies. The dominance of elongated morphologies among LBGs suggests that in a significant fraction of them we may be witnessing star-formation in clumps along gas-rich filaments, or the earliest gas-rich bars that encompass essentially the entire visible galaxy. Similar features are found to be ubiquitous in hydrodynamical simulations in which galaxy formation at high redshifts occurs in filamentary inflows of dynamically cold gas within the dark matter halos, and involves gas- rich mergers.Comment: Accepted for publication in the Astrophysical Journal (10 October, 2006 issue), 15 pages + 12 JPEG figure

Post-prandial hyperlipidaemia results in systemic nitrosative stress and impaired cerebrovascular function in the aged

Post-prandial hyperlipidaemia (PPH) acutely impairs systemic vascular endothelial function, potentially attributable to a free radical-mediated reduction in vascular nitric oxide (NO) bioavailability (oxidative-nitrosative stress). However, it remains to be determined whether this extends to the cerebrovasculature. To examine this, 38 (19 young (≤35 years) and 19 aged (≥60 years)) healthy males were recruited. Cerebrovascular function (middle cerebral artery velocity, MCAv) and cerebrovascular reactivity to hypercapnea (CVRCO2Hyper) and hypocapnea (CVRCO2Hypo) were determined via trans-cranial Doppler ultrasound and capnography. Venous blood samples were obtained for the assessment of triglycerides (photometry), glucose (photometry), insulin (radioimmunoassay), ascorbate free radical (A•-, electron paramagnetic resonance spectroscopy) and nitrite (NO2 -, ozone-based chemiluminescence) in the fasted state prior to and 4 h following consumption of a standardized high-fat meal (1362 kcal; 130 g of fat). Circulating triglycerides, glucose and insulin increased in both groups following the high-fat meal (P &lt; 0.05), with triglycerides increasing by 1.37 ± 1.09 mmol/l in the young and 1.54 ± 1.00 mmol/l in the aged (P &lt; 0.05). This resulted in an increased systemic formation of free radicals in the young (P &lt; 0.05) but not the aged (P &gt; 0.05) and corresponding reduction in NO2 - in both groups (P &lt; 0.05). While the meal had no effect on MCAv in either age group, CVRCO2Hyper was selectively impaired in the aged (P &lt; 0.05). These findings indicate that PPH causes acute cerebrovascular dysfunction in the aged subsequent to systemic nitrosative stress