Role of Age in Mitochondrial Susceptibility to 1,3-Dinitrobenzene-Induced Neurotoxicity.

The prevalence of neurodegenerative disease is projected to increase in proportion to the doubling of older Americans over the coming decades. While age is the principle epidemiologic factor, it is likely that the development of these complex neuropathological entities is multifactorial and reflects the accumulation of chemical, physical and/or biological insults to the CNS. The Superfund chemical, 1,3-Dinitrobenzene (DNB), is an industrial intermediate in the production of dyes, plastics, and explosives. DNB selectively targets astrocytes in brainstem nuclei innervated by the 8th cranial nerve. The toxicity of DNB has been previously linked to dysfunction in astrocyte mitochondria. This study focuses on the susceptibility of key mitochondrial proteins to selective and specific oxidation following exposure to DNB in vitro and in vivo. Using an immortalized cortical astrocyte culture, passage number provided a useful surrogate for age in vitro. In a co-culture system containing immortalized astrocytes and primary neurons, low passage immortalized astrocytes are able to protect neurons in DNB exposure (whereas high passage immortalized astrocytes are not); additionally, low passage immortalized astrocytes are better able to survive DNB exposure in co-culture than high passage immortalized astrocytes. Additionally, in vivo data shows that proteins in older mitochondria are more susceptible to oxidation by DNB than the ones from young organelles, and mitochondria-related proteins are more highly expressed in young control animals than in older animals (both control and DNB-exposed). This data suggests that aging increases mitochondrial susceptibility to DNB-induced neurotoxicity. Using a high throughput proteomic approach with subsequent pathway analysis, it was determined that cation transmembrane transporter, nucleoside-triphosphatase, pyrophosphatase, and hydrolase activity pathways are selectively vulnerable to oxidation in older mitochondria. These results provide compelling evidence that environmental chemicals such as DNB may aid in the acceleration of injury to specific brain regions by inducing oxidation of sensitive mitochondrial proteins.PhDToxicologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/108896/1/lauramau_1.pd

Discovery of A Very Bright, Strongly-Lensed z=2 Galaxy in the SDSS DR5

We report on the discovery of a very bright z = 2.00 star-forming galaxy that is strongly lensed by a foreground z=0.422 luminous red galaxy (LRG). This system was found in a systematic search for bright arcs lensed by LRGs and brightest cluster galaxies in the Sloan Digital Sky Survey Data Release 5 sample. Follow-up observations on the Subaru 8.2m telescope on Mauna Kea and the Astrophysical Research Consortium 3.5m telescope at Apache Point Observatory confirmed the lensing nature of this system. A simple lens model for the system, assuming a singular isothermal ellipsoid mass distribution, yields an Einstein radius of 3.82 +/- 0.03 arcsec or 14.8 +/- 0.1 kpc/h at the lens redshift. The total projected mass enclosed within the Einstein radius is 2.10 +/- 0.03 x 10^12 M_sun/h, and the magnification factor for the source galaxy is 27 +/- 1. Combining the lens model with our gVriz photometry, we find an (unlensed) star formation rate for the source galaxy of 32 M_sun/h / yr, adopting a fiducial constant star formation rate model with an age of 100 Myr and E(B-V) = 0.25. With an apparent magnitude of r = 19.9, this system is among the very brightest lensed z >= 2 galaxies, and provides an excellent opportunity to pursue detailed studies of the physical properties of an individual high-redshift star-forming galaxy.Comment: 31 pages, 12 figures, 4 tables, submitted to Ap

Chronic alcohol exposure alters circulating insulin and ghrelin levels: role of ghrelin in hepatic steatosis

Fatty liver is the earliest response of the liver to excessive ethanol consumption. Central in the development of alcoholic steatosis is increased mobilization of nonesterified free fatty acids (NEFAs) to the liver from the adipose tissue. In this study, we hypothesized that ethanol-induced increase in ghrelin by impairing insulin secretion, could be responsible for the altered lipid metabolism observed in adipose and liver tissue. Male Wistar rats were fed for 5–8 wk with control or ethanol Lieber-DeCarli diet, followed by biochemical analyses in serum and liver tissues. In addition, in vitro studies were conducted on pancreatic islets isolated from experimental rats. We found that ethanol increased serum ghrelin and decreased serum insulin levels in both fed and fasting conditions. These results were corroborated by our observations of a significant accumulation of insulin in pancreatic islets of ethanol-fed rats, indicating that its secretion was impaired. Furthermore, ethanol-induced reduction in circulating insulin was associated with lower adipose weight and increased NEFA levels observed in these rats. Additionally, we found that increased concentration of serum ghrelin was due to increased synthesis and maturation in the stomach of the ethanol-fed rats. We also report that in addition to its effect on the pancreas, ghrelin can also directly act on hepatocytes via the ghrelin receptors and promote fat accumulation. In conclusion, alcohol-induced elevation of circulating ghrelin levels impairs insulin secretion. Consequently, reduced circulating insulin levels likely contribute to increased free fatty acid mobilization from adipose tissue to liver, thereby contributing to hepatic steatosis

Chronic alcohol exposure alters circulating insulin and ghrelin levels: role of ghrelin in hepatic steatosis

Fatty liver is the earliest response of the liver to excessive ethanol consumption. Central in the development of alcoholic steatosis is increased mobilization of nonesterified free fatty acids (NEFAs) to the liver from the adipose tissue. In this study, we hypothesized that ethanol-induced increase in ghrelin by impairing insulin secretion, could be responsible for the altered lipid metabolism observed in adipose and liver tissue. Male Wistar rats were fed for 5–8 wk with control or ethanol Lieber-DeCarli diet, followed by biochemical analyses in serum and liver tissues. In addition, in vitro studies were conducted on pancreatic islets isolated from experimental rats. We found that ethanol increased serum ghrelin and decreased serum insulin levels in both fed and fasting conditions. These results were corroborated by our observations of a significant accumulation of insulin in pancreatic islets of ethanol-fed rats, indicating that its secretion was impaired. Furthermore, ethanol-induced reduction in circulating insulin was associated with lower adipose weight and increased NEFA levels observed in these rats. Additionally, we found that increased concentration of serum ghrelin was due to increased synthesis and maturation in the stomach of the ethanol-fed rats. We also report that in addition to its effect on the pancreas, ghrelin can also directly act on hepatocytes via the ghrelin receptors and promote fat accumulation. In conclusion, alcohol-induced elevation of circulating ghrelin levels impairs insulin secretion. Consequently, reduced circulating insulin levels likely contribute to increased free fatty acid mobilization from adipose tissue to liver, thereby contributing to hepatic steatosis

Morphological Description of Telaepolella tubasferens n. g., n. sp., Isolate ATCC© 50593™, a Filose Amoeba in the Gracilipodida, Amoebozoa

We describe the amoeboid isolate ATCC© 50593™ as a new taxon, Telaepolella tubasferens n. gen. n. sp. This multinucleated amoeba has filose pseudopods and is superficially similar to members of the vampyrellids (Rhizaria) such as Arachnula impatiens Cienkowski, 1876, which was the original identification upon deposition. However, previous multigene analyses place this taxon within the Gracilipodida Lahr and Katz 2011 in the Amoebozoa. Here, we document the morphology of this organism at multiple life history stages and describe data underlying the description as a new taxon. We demonstrate that T. tubaspherens is distinct from Arachnula and other rhizarians (Theratromyxa, Leptophrys) in a suite of morphological characters such as general body shape, relative size of pseudopods, distinction of ecto- and endoplasmic regions, and visibility of nuclei in non-stained cells (an important diagnostic character). Although Amoebozoa taxa generally have lobose pseudopods, genera in Gracilipodida such as Flamella and Filamoeba as well as several organisms previously classified as protosteloid amoebae (e.g. schizoplasmodiis, cavosteliids and Stemonitales) present filose pseudopodia. Thus, classification of amoeboid organisms merely by filose-lobose distinction must be reconsidered