On the Usage of Recalibrated Radiance in Reanalysis Experiments

Usage of re-calibrated data in reanalysis systems are quite common due to their uniform and continuous data distribution. Recalibrated radiosonde temperature and SSU radiances have already shown positive impact in MERRA and MERRA2 reanalyses. In this study recalibrated AMSU-A radiances are used to study sudden degradation of observation statistics which are noticed with the introduction of new AMSU-A radiances in MERRA2. In particular, the analysis temperature in the upper stratosphere showed large variability due to lack of viable observation at that height in the atmosphere. Our results show that the re-calibrated AMSU-A radiance in a system similar to MERRA2 is capable of mitigating the problem

Behavioral Characterization of GCLM-Knockout Mice, a Model for Enhanced Susceptibility to Oxidative Stress

Glutathione (GSH) is a major player in cellular defense against oxidative stress. Deletion of the modifier subunit of glutamate cysteine ligase (GCLM), the first and the rate-limiting enzyme in the synthesis of GSH, leads to significantly lower GSH levels in all tissues including the brain. GCLM-knockout (Gclm−/−) mice may thus represent a model for compromised response to oxidative stress amenable to in vitro and in vivo investigations. In order to determine whether the diminished GSH content would by itself cause behavioral alterations, a series of behavioral tests were carried out comparing young adult Gclm−/− with wild-type mice. Tests included the rotarod, acoustic startle reflex and prepulse inhibition of the startle reflex, open field behavior, and the platform reversal variant of the Morris Water Maze. Results showed no differences between Gclm−/− and wild-type mice in any of the neurobehavioral tests. However, more subtle alterations, or changes which may appear as animals age, cannot be excluded

Glutamate Cysteine Ligase Modifier Subunit (Gclm) Null Mice Have Increased Ovarian Oxidative Stress and Accelerated Age-Related Ovarian Failure.

Glutathione (GSH) is the one of the most abundant intracellular antioxidants. Mice lacking the modifier subunit of glutamate cysteine ligase (Gclm), the rate-limiting enzyme in GSH synthesis, have decreased GSH. Our prior work showed that GSH plays antiapoptotic roles in ovarian follicles. We hypothesized that Gclm(-/-) mice have accelerated ovarian aging due to ovarian oxidative stress. We found significantly decreased ovarian GSH concentrations and oxidized GSH/oxidized glutathione redox potential in Gclm(-/-) vs Gclm(+/+) ovaries. Prepubertal Gclm(-/-) and Gclm(+/+) mice had similar numbers of ovarian follicles, and as expected, the total number of ovarian follicles declined with age in both genotypes. However, the rate of decline in follicles was significantly more rapid in Gclm(-/-) mice, and this was driven by accelerated declines in primordial follicles, which constitute the ovarian reserve. We found significantly increased 4-hydroxynonenal immunostaining (oxidative lipid damage marker) and significantly increased nitrotyrosine immunostaining (oxidative protein damage marker) in prepubertal and adult Gclm(-/-) ovaries compared with controls. The percentage of small ovarian follicles with increased granulosa cell proliferation was significantly higher in prepubertal and 2-month-old Gclm(-/-) vs Gclm(+/+) ovaries, indicating accelerated recruitment of primordial follicles into the growing pool. The percentages of growing follicles with apoptotic granulosa cells were increased in young adult ovaries. Our results demonstrate increased ovarian oxidative stress and oxidative damage in young Gclm(-/-) mice, associated with an accelerated decline in ovarian follicles that appears to be mediated by increased recruitment of follicles into the growing pool, followed by apoptosis at later stages of follicular development

Acetaminophen-induced liver damage in mice is associated with gender-specific adduction of peroxiredoxin-6

The mechanism by which acetaminophen (APAP) causes liver damage evokes many aspects drug metabolism, oxidative chemistry, and genetic-predisposition. In this study, we leverage the relative resistance of female C57BL/6 mice to APAP-induced liver damage (AILD) compared to male C57BL/6 mice in order to identify the cause(s) of sensitivity. Furthermore, we use mice that are either heterozygous (HZ) or null (KO) for glutamate cysteine ligase modifier subunit (Gclm), in order to titrate the toxicity relative to wild-type (WT) mice. Gclm is important for efficient de novo synthesis of glutathione (GSH). APAP (300 mg/kg, ip) or saline was administered and mice were collected at 0, 0.5, 1, 2, 6, 12, and 24 h. Male mice showed marked elevation in serum alanine aminotransferase by 6 h. In contrast, female WT and HZ mice showed minimal toxicity at all time points. Female KO mice, however, showed AILD comparable to male mice. Genotype-matched male and female mice showed comparable APAP–protein adducts, with Gclm KO mice sustaining significantly greater adducts. ATP was depleted in mice showing toxicity, suggesting impaired mitochondria function. Indeed, peroxiredoxin-6, a GSH-dependent peroxiredoxin, was preferentially adducted by APAP in mitochondria of male mice but rarely adducted in female mice. These results support parallel mechanisms of toxicity where APAP adduction of peroxiredoxin-6 and sustained GSH depletion results in the collapse of mitochondria function and hepatocyte death. We conclude that adduction of peroxiredoxin-6 sensitizes male C57BL/6 mice to toxicity by acetaminophen