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The role of dyslipidemia in the development of retinal dysfunction remains poorly understood. Using an animal model of diet-induced obesity/pre-type 2 diabetes, we investigated molecular defects in the retina arising from consumption of a diet high in saturated fats and sugars ( i.e., a Western diet). We found that feeding mice a Western diet increased the abundance of retinal sphingolipids, attenuated protein kinase B (Akt) phosphorylation, enhanced JNK activation, and increased retinal cell death. When we used palmitate or C6-ceramide (Cer) to assess sphingolipid-mediated signaling in cultured murine and human cells, we observed similar effects on Akt, JNK, and cell death. Furthermore, both Western diet and C6-Cer exposure enhanced expression of the stress-response protein regulated in development and DNA damage response 1 (REDD1) and loss of REDD1 increased C6-Cer-induced JNK activation and cell death. Exogenous REDD1 expression repressed JNK-mediated phosphorylation in cultured cells. We found that thioredoxin-interacting protein (TXNIP) expression was elevated in REDD1-deficient cell lines and C6-Cer promoted TXNIP expression in both wild-type and REDD1-deficient cells. Likewise, TXNIP knockdown attenuated JNK activation and caspase 3 cleavage after either C6-Cer exposure or REDD1 deletion. The results support a model wherein Cer-induced REDD1 expression attenuates TXNIP-dependent JNK activation and retinal cell death.-Dai, W., Miller, W. P., Toro, A. L., Black, A. J., Dierschke, S. K., Feehan, R. P., Kimball, S. R., Dennis, M. D. Deletion of the stress-response protein REDD1 promotes ceramide-induced retinal cell death and JNK activation.

The direct synthesis of lower olefins via the Fischer-Tropsch reaction (FTO) has been performed over a series of Fe-MnOx/SiO2 catalysts. The addition of MnOx could improve the dispersion of iron species, and promote the reduction of iron oxide during the activation and subsequent carburization. Moreover, the results of characterization demonstrated that MnOx could enhance the surface basicity of the catalysts due to electronic effects and promote the formation of iron carbides. For the first time, the intrinsic power-law kinetics for FTO was obtained for both Fe20/SiO2 and Fe20-Mn1/SiO2 catalysts. Kinetic parameters and structure characterizations indicated that MnOx could facilitate the CO dissociation on the catalyst surface, thus enhancing the adsorption strength and capacity of surface carbonaceous intermediates. The weak hydrogenation of carbonaceous species would boost the selectivities toward lower olefins. Finally, a plausible mechanism for FTO, involving the promotional effects of MnOx on Fe, has been proposed. © 2017 American Institute of Chemical Engineers AIChE J, 63: 4451–4464, 2017

Soil water is very important in hilly areas with thin soil layers and deep groundwater tables, such as the karst peak-cluster region of Southwest China. An investigation into soil water movement can provide insights into management of shallow water resources and soil nutrients, as well as prevention of groundwater pollution. In this study, O-18 and H-2 tracers were used to trace soil water movement in planar soil mass type microhabitats in the middle part of a steep hillslope covered by grasses in a karst peak-cluster region of China. From May 2008 to July 2009, samples of precipitation and two types of soil water, which had different integrated degrees of mobility and were of different depth intervals or depths, were collected. The hydrogeochemical characteristics were compared between precipitation and soil water, and these data were applied in convolution-based lumped parameter models. Our results indicated that vertical piston flow, rather than lateral flow along the soil-bedrock interface, played an important role in soil water percolation at least in the upper soil layer approximately 7cm over the permeable bedrock. The mixing effect and preferential flow might also play a role in soil water percolation. In general, the evaporation effect on soil water was weak except for the uppermost 10cm soil matrix water during winter. The lower limits of mean transit time of soil matrix flow passing through 5, 15, 25, 35, and 41.5cm depths were 4.81, 7.70, 16.19, 21.85, and 27.44days, respectively. Our study demonstrated the crucial functions of the soil reservoir in regulating the water cycle and could provide guidance on conservation of soil water and hydrological studies. The applied method was proved to be a suitable approach for investigating soil water movement on a monthly scale.

Increasing atmospheric reactive nitrogen (N) deposition due to human activities could change N cycling in terrestrial ecosystems. However, the differences between the fates of deposited NH4+ and NO3- are still not fully understood. Here we investigated the fates of deposited NH4+ and NO3- respectively via the application of 15NH4NO3 and NH415NO3 in a temperate forest ecosystem. Results showed that at 410 days after tracer application, most 15NH4+ was immobilized in litter layer (50 ± 2%), while a considerable amount of 15NO3- penetrated into 0-5 cm mineral soil (42 ± 2%), indicating that litter layer and 0-5 cm mineral soil were the major N sinks of NH4+ and NO3-, respectively. Broad-leaved trees assimilated more 15N under NH415NO3 treatment compared to under 15NH4NO3 treatment, indicating their preference for NO3--N. At 410 days after tracer application, 16 ± 4% added 15N was found in aboveground biomass under 15NO3- treatment, which was twice more than that under 15NH4+ treatment (6 ± 1%). At the same time, approximately 80% added 15N was recovered in soil and plants under both treatments, which suggested that this forest had high potential for retention of deposited N. These results provided evidence that there were great differences between the fates of deposited NH4+ and NO3-, which could help us better understand the mechanisms and capability of forest ecosystems as a sink of reactive nitrogen. This article is protected by copyright. All rights reserved.

Rho-kinase dimerization is essential for its kinase activity and biological function; disruption of the dimerization has recently been established as a new and promising therapeutics strategy for cerebrovascular malformation (CM). Based on Rho-kinase dimer crystal structure we herein combined in silico analysis and in vitro assay to rationally derive self-inhibitory peptides from the dimerization interface. Three peptides namely Hlp1, Hlp2 and Hlp3 were successfully designed that have potential capability to rebind at the dimerization domain of Rho-kinase. Molecular dynamics (MD) simulations revealed that these peptides are helically structured when bound to Rho-kinase, but exhibit partially intrinsic disorder in unbound state. Binding free energy (BFE) analysis suggested that the peptides have a satisfactory energetic profile to interact with Rho-kinase. The computational findings were then substantiated by fluorescence anisotropy assays, conforming that the helical peptides can bind tightly to Rho-kinase with affinity KD at micromolar level. These designed peptides are considered as lead molecular entities that can be further modified and optimized to obtain more potent peptidomimetics as self-competitors to disrupt Rho-kinase dimerization in CM.

By using operando Raman spectroscopy (ORS), we investigated the panoramic structure evolution of an iron oxide (a-Fe2O3) catalyst, which is used for the production of olefins via Fischer–Tropsch (FTO). During activation in different atmospheres and reaction at 260 8C and 3.0 MPa, a-Fe2O3 was only partially transformed into g-Fe2O3 by H2 pretreatment; meanwhile, a transformation of a-Fe2O3!g-Fe2O3!Fe3O4!Fe5C2 was observed in both CO and syngas (H2/CO). Combining with other techniques such as XRD, TEM, XPS and TPSR, we reveal that assembles of various iron oxides (g-Fe2O3, Fe3O4, Fe carbide, and their combinations) are responsible for FTO. Especially, the preliminary relationship of catalyst structure and performance relating to the production of olefins directly from syngas was established. Such a study is critical for further understanding of the FTO reaction and other catalytic reactions.

The multi-objective land allocation problem is to optimize the selection of land for different uses based on a set of decision objectives. For most applications, a geographical information system (GIS) is either absent or loosely coupled through file exchange. In this article the evolutionary algorithm (EA), a heuristic solution method for optimization problems, is integrated with a raster GIS to form a spatial decision support system (SDSS) for multi-objective conservation reserve design. The SDSS effectively combines the functions of a GIS for data management, analysis, and visualization, with the optimization capability of the EA; and provides a uniform way to solve conservation reserve design problems with different types of constraints and objectives. The SDSS is demonstrated through application to the creation of conservation reserves in Bolivia to protect 17 endemic mammals.

In response to cellular insult, several pathways can be activated, including necrosis, apoptosis, and autophagy. Because glucocorticoids (GCs) have been shown to induce both osteocyte apoptosis and autophagy, we sought to determine whether osteocyte cell fate in the presence of GCs was dose dependent by performing in vivo and in vitro studies. Male Swiss-Webster mice were treated with slow-release prednisolone pellets at 1.4, 2.8, and 5.6 mg/kg/d for 28 d. An osteocyte cell line, MLO-Y4 cells, was treated with various doses of dexamethasone. We found that GC treatments dose dependently decreased activation of antioxidant-, autophagy-, and antiapoptosis-focused RT-PCR gene pathways in mouse cortical bone. The activation of antioxidant genes was correlated with autophagy gene expression after the GC treatments. The presence of osteocyte autophagy, as detected by immunostaining for LC3, increased ∼50% at the distal femur cortical bone region but not at trabecular bone region at the 1.4 and 2.8 mg/kg/d GC dose levels. The number of apoptotic osteocytes was increased at the cortical bone region by ∼40% initially observed at the 2.8 mg/kg/d dose level. In addition, the presence of the osteocyte autophagy was associated with an increased protein level of cathepsin K in vitro after the GC treatments. In summary, we found that GC treatment dose-dependently decreased antioxidant gene expression, with lower GC doses activating autophagy, whereas a higher dose increased apoptosis. These data suggest that autophagy may provide a mechanism for osteocytes to survive the stress after GC exposure and provide further insight into how GCs alter bone cell fate.—Jia, J., Yao, W., Guan, M., Dai, W., Shahnazari, M., Kar, R., Bonewald, L., Jiang, J. X., Lane, N. E. Glucocorticoid dose determines osteocyte cell fate.