Role of vitamin E in glutathione-induced oxidant stress: methemoglobin, lipid peroxidation, and hemolysis.

Red blood cells (RBC) from normal and vitamin E-deficient rats were incubated in a hypertonic solution of reduced glutathione adjusted to pH 8. Methemoglobin formation occurred in intact RBC from both normal and vitamin E-deficient rats. Hemolysis was significantly greater in RBC from vitamin E-deficient rats. Experiments with catalase, superoxide dismutase, and methional showed that H(2)O(2) was the primary extracellular source of oxidant stress. Extracellular superoxide and hydroxyl radical were not involved in oxidant stress. Experiments with dimethyl sulfoxide showed that intracellular hydroxyl radical, generated from H(2)O(2), was the hemolytic agent. Neither methemoglobin formation nor lipid peroxidation involved hydroxyl radical. Indeed, lipid peroxidation and hemolysis in RBC from vitamin E-deficient rats were concurrent rather than consecutive events. Phase contrast microscopy showed that rigid, crenated RBC with a precipitate around the interior periphery formed during glutathione-induced oxidant stress. The precipitate dissolved slowly as the crenated RBC were converted to smooth ghosts. It appeared that protein precipitates involving mixed disulfide bonds were reduced and solubilized when extracellular glutathione penetrated the ruptured cell. Comparisons between normal RBC and vitamin E-deficient RBC suggest that vitamin E has little effect on the inward diffusion of extra-cellular H(2)O(2). Vitamin E apparently interacts with different oxidant species derived from intracellular H(2)O(2) in preventing lipid peroxidation and the sulfhydryl group oxidation leading to hemolysis.     

Effects of glycine hydroxamate, carbon dioxide, and oxygen on photorespiratory carbon and nitrogen metabolism in spinach mesophyll cells

The effects of added glycine hydroxamate on the photosynthetic incorporation of ¹⁴CO₂ into metabolites by isolated mesophyll cells of spinach (Spinacia oleracea L.) was investigated under conditions favorable to photorespiratory (PR) metabolism (0.04% CO₂ and 20% O₂) and under conditions leading to nonphotorespiratory (NPR) metabolism (0.2% CO₂ and 2.7% O₂). Glycine hydroxamate (GH) is a competitive inhibitor of the photorespiratory conversion of glycine to serine, CO₂ and NH₄⁺. During PR fixation, addition of the inhibitor increased glycine and decreased glutamine labeling. In contrast, labeling of glycine decreased under NPR conditions. This suggests that when the rate of glycolate synthesis is slow, the primary route of glycine synthesis is through serine rather than from glycolate. GH addition increased serine labeling under PR conditions but not under NPR conditions. This increase in serine labeling at a time when glycine to serine conversion is partially blocked by the inhibitor may be due to serine accumulation via the “reverse” flow of photorespiration from 3-P-glycerate to hydroxypyruvate when glycine levels are high. GH increased glyoxylate and decreased glycolate labeling. These observations are discussed with respect to possible glyoxylate feedback inhibition of photorespiration.     

Diaminothiazoles Modify Tau Phosphorylation and Improve the Tauopathy in Mouse Models

Although Tau accumulation is a feature of several neurodegenerative conditions, treatment options for these conditions are nonexistent. Targeting Tau kinases represents a potential therapeutic approach. Small molecules in the diaminothiazole class are potent Tau kinase inhibitors that target CDK5 and GSK3β. Lead compounds from the series have IC₅₀ values toward CDK5/p25 and GSK3β in the low nanomolar range and no observed toxicity in the therapeutic dose range. Neuronal protective effects and decreased PHF-1 immunoreactivity were observed in two animal models, 3×Tg-AD and CK-p25. Treatment nearly eliminated Sarkosyl-insoluble Tau with the most prominent effect on the phosphorylation at Ser-404. Treatment also induced the recovery of memory in a fear conditioning assay. Given the contribution of both CDK5/p25 and GSK3β to Tau phosphorylation, effective treatment of tauopathies may require dual kinase targeting.     

Fertility following fixed-time AI or insemination at observed estrus in Ovsynch and Heatsynch programs in lactating dairy cows

The objective of this study was to compare the conception rate for fixed-timed artificial insemination (FTAI) and observed heat artificial insemination (HAI) prior to the scheduled FTAI in Ovsynch and Heatsynch synchronization protocols. In Experiment 1, lactating dairy cows (n=535) received two set-up injections of 25mg prostaglandin F(2alpha) (PGF(2alpha)) i.m., 14 days apart starting at 36+/-3 days in milk (DIM). Cows were blocked by parity and were randomly allocated to either Ovsynch or Heatsynch groups. All cows received 100 microg of GnRH i.m. 14 days after the second set-up injection of PGF(2alpha), followed by a third injection of 25mg PGF(2alpha) i.m., 7 days later. In the Ovsynch group, HAI cows (n=29) were bred on standing estrus after the third PGF(2alpha) before the scheduled second GnRH, whereas FTAI cows (n=218) that were not observed in estrus, received a second injection of 100 microg of GnRH i.m., 48 h after the third PGF(2alpha) and received TAI 8 h after the second GnRH. In the Heatsynch group, all cows (n=288) received 0.5 mg of estradiol cypionate (ECP) 24 h after third PGF(2alpha) and HAI cows (n=172) were bred on standing estrus and FTAI cows (n=116) that were not observed in estrus, received TAI 72 h after the third PGF(2alpha). In Experiment 2, repeat breeder cows (n=186) were randomly assigned to either Ovsynch or Heatsynch groups. The FTAI and HAI cows were inseminated similar to Experiment 1. All cows were observed for estrus three times daily. The associations with the conception rate were modeled with logistic regression separately for Experiments 1 and 2. Of all the variables included in the model in Experiment 1, type of AI (HAI versus FTAI, P=0.0003) and parity (primiparous versus multiparous, P=0.05) influenced the first service conception rate. Over-all conception rate and first service conception rate for HAI cows were higher compared to FTAI cows (33.8% versus 21.3%, and 35.3% versus 21.0%; P=0.001). In the Heatsynch group, cows that received HAI had significantly higher over-all conception rate and first service conception rate compared to FTAI (35.2% versus 17.3% and 36.0% versus 15.5%; P=0.0001). The conception rates in repeat breeder cows for HAI and FTAI (30.1% versus 22.3%) were not different (P>0.1). In conclusion, it was recommended to include AI at observed estrus and fixed-time AI for cows not observed in estrus in order to improve the conception rate in synchronization protocols.     

Interannual variability of Aureococcus anophagefferens in Quantuck Bay, Long Island: natural test of the DON hypothesis

This study examined benthic and pelagic rate processes from the perspective of benthic dissolved organic matter (DOM) and its possible role in Aureococcus anophagefferens population dynamics. Sampling was conducted in Quantuck Bay, Long Island, New York, at three times in the summer of 2000 and two times in the summer of 2001. A. anophagefferens exhibited a large bloom between the May and July 2000 sample periods, but a smaller bloom was captured in the September 2000 sampling. Densities throughout 2001 were significantly lower than during 2000. There were few differences in most parameters measured between years, but the largest difference was the seasonal increase in both particulate (POM) and dissolved organic matter (DOM) during 2000 that was not observed during 2001. In particular, DOP accumulated the most, followed by DON and DOC, which resulted in significant seasonal decreases in the C:N:P ratios of the DOM pools. On the contrary, changes in elemental ratios of POM were not observed. The seasonal accumulation of DON appeared to be driven largely (50%) by the flux of DON from the benthos in 2000, but during 2001, all measured DON fluxes were into the sediment from the water column. This is consistent with the lack of accumulation during this year. There was little evidence for changes in microzooplankton grazing pressure between 2000 and 2001, and therefore the accumulation of DON and DOP during 2000 could have provided a competitive advantage to A. anophagefferens over other picoalgal species (e.g., Synechococcus) resulting in the significant blooms observed in 2000.     

Expression of the bilateral deficit during reflexively evoked contractions.

During maximal contractions, the sum of forces exerted by homonymous muscles unilaterally is typically larger than the sum of forces exerted by the same muscles bilaterally. This phenomenon is known as the bilateral deficit (BLD), and it is suggested that this deficit is due to neural inhibition. It remains unclear, however, whether such inhibition is mediated by supraspinal mechanisms or by reflex pathways at the level of spinal cord. To further study the origin of likely neural influences, we tested for the presence of BLD under the condition of reflexive force generation. Force output and integrated electromyogram (iEMG) (quadriceps femoris) were measured in 17 male participants after initiation of the myotatic patellar reflex under unilateral and bilateral conditions. A significant BLD of 9.26 +/- 1.19 (P = 0.004) and 16.76 +/- 4.69% (P = 0.001) was found for force and iEMG, respectively. However, because similar findings were not evident during maximal isometric knee extensions, it is difficult to predict the contribution of a spinal mechanism to the BLD under the condition of maximal voluntary activation.     

A Geographic Mosaic of Climate Change Impacts on Terrestrial Vegetation: Which Areas Are Most at Risk?

Changes in climate projected for the 21^st century are expected to trigger widespread and pervasive biotic impacts. Forecasting these changes and their implications for ecosystem services is a major research goal. Much of the research on biotic responses to climate change has focused on either projected shifts in individual species distributions or broad-scale changes in biome distributions. Here, we introduce a novel application of multinomial logistic regression as a powerful approach to model vegetation distributions and potential responses to 21^st century climate change. We modeled the distribution of 22 major vegetation types, most defined by a single dominant woody species, across the San Francisco Bay Area. Predictor variables included climate and topographic variables. The novel aspect of our model is the output: a vector of relative probabilities for each vegetation type in each location within the study domain. The model was then projected for 54 future climate scenarios, spanning a representative range of temperature and precipitation projections from the CMIP3 and CMIP5 ensembles. We found that sensitivity of vegetation to climate change is highly heterogeneous across the region. Surprisingly, sensitivity to climate change is higher closer to the coast, on lower insolation, north-facing slopes and in areas of higher precipitation. While such sites may provide refugia for mesic and cool-adapted vegetation in the face of a warming climate, the model suggests they will still be highly dynamic and relatively sensitive to climate-driven vegetation transitions. The greater sensitivity of moist and low insolation sites is an unexpected outcome that challenges views on the location and stability of climate refugia. Projections provide a foundation for conservation planning and land management, and highlight the need for a greater understanding of the mechanisms and time scales of potential climate-driven vegetation transitions.     

Brittle ductile transition in carbon nanotube bundles

The superior strength and stiffness of carbon nanotubes (CNTs) make them attractive for many structural applications. Although the strength and stiffness of CNTs are extremely high, fibres of aligned CNTs have been found to date to be far weaker than the constituent CNTs. The intermolecular interactions between the CNTs in the fibres are governed by weak van der Waals forces, resulting in slippage between CNTs which occurs at tensions well below the breaking strength of the CNTs. Both theoretical and experimental studies show that by introducing chemical bonds between the CNTs increases load transfer and prevents the CNTs from slipping.