Microglial FABP4-UCP2 Axis Modulates Neuroinflammation and Cognitive Decline in Obese Mice

The microglial fatty-acid-binding protein 4-uncoupling protein 2 (FABP4-UCP2) axis is a key regulator of neuroinflammation in high-fat-diet (HFD)-fed animals, indicating a role for FABP4 in brain immune response. We hypothesized that the FABP4-UCP2 axis is involved in regulating diet-induced cognitive decline. We tested cognitive function in mice lacking microglial FABP4 (AKO mice). Fifteen-week-old male AKO and wild-type (WT) mice were maintained on 60% HFD or normal chow (NC) for 12 weeks. Body composition was measured using EchoMRI. Locomotor activity, working memory, and spatial memory were assessed using behavioral tests (open field, T-maze, and Barnes maze, respectively). Hippocampal microgliosis was assessed via immunohistochemical staining. An inflammatory cytokine panel was assayed using hippocampal tissue. Real-time RT-PCR was performed to measure microglial UCP2 mRNA expression. Our data support that loss of FABP4 prevents cognitive decline in vivo. HFD-fed WT mice exhibited impaired long- and short-term memory, in contrast with HFD-fed AKO mice. HFD-fed WT mice had an increase in hippocampal inflammatory cytokine expression (IFNγ, IL-1β, IL-5, IL-6, KC/GRO(CXCL1), IL-10, and TNFα) and microgliosis, and decreased microglial UCP2 expression. HFD-fed AKO mice had decreased hippocampal inflammatory cytokine expression and microgliosis and increased microglial UCP2 expression compared to HFD-fed WT mice. Collectively, our work supports the idea that the FABP4-UCP2 axis represents a potential therapeutic target in preventing diet-induced cognitive decline.     

The effect of inhibitors of platelet aggregation on the metabolism of platelet-activating factor (PAF) in washed rabbit platelets

The rabbit platelet metabolizes platelet-activating factor (PAF) intracellulary. PAF is deacetylated to produce lysoPAF which, in turn, can be acylated to produce 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine (alkylacyl GPC). Some PAF receptor antagonists have been shown to inhibit this metabolic conversion. In the present study we examined whether the PAF receptor antagonists SRI 63-441 and WEB 2086 would inhibit the metabolism of PAF by intact rabbit platelets. In addition, we examined whether iloprost, a stable analogue of prostaglandin I₂ (PGI₂), and a potent inhibitor of platelet activation induced by a range of agonists, would also inhibit PAF metabolism. We found that SRI 63-441 and WEB 2086 caused an almost complete inhibition of the conversion of PAF to alkylacyl GPC. Iloprost caused up to a 50% inhibition of PAF metabolism compared to antagonist-free controls. Iloprost (and PGI₂) is thought to inhibit platelet response by elevation of cAMP, while receptor antagonists act by blocking PAF binding to its receptor. Since iloprost caused partial inhibition of PAF metabolism, the results of this study suggest that inhibition of PAF metabolism does not occur solely due to competitive inhibition of PAF binding to its receptor. Based on a paper presented at the Third International Conference on Platelet Activating Factor and Structurally Related Alkyl Ether Lipids, Tokyo, Japan, May 1989.     

The viscosities of unbleached alkaline pulps. IV. The effect of alkali

Abstract

An equation has been developed to relate the viscosity of unbleached pulp to the residual alkali in the spent liquor, and the time-temperature profile of the cook (expressed as the G-factor). The equation is applicable to kraft, kraft-AQ and soda-AQ pulping and to a variety of wood species.     

Electrical Current Signatures of DNA Base Modifications in Single Molecules Immobilized in the α-Hemolysin Ion Channel

Nanopore technology holds high potential for next-generation DNA sequencing. This method operates by drawing an individual single-stranded DNA molecule through a nanoscale pore, while monitoring the current deflections that occur as the DNA passes through. Individual current levels for the four DNA nucleotides have been established by immobilization of an end biotinylated strand in the pore, in which the nucleotide of interest is suspended at the most sensitive region of the ion channel. Due to the inherent reactivity of DNA bases, many modified nucleotides in the genome exist as a result of oxidative and UV insults, among others. Herein, the current levels for common DNA damage lesions 8-oxo-7,8-dihydroguanine, spiroiminodihydantoin, guanidinohydantoin, uridine, abasic sites, thymine dimers, thymine glycol, and 5-iodocytosine were assessed through immobilization experiments. In some cases, the current difference between the damaged and canonical nucleotides was not well resolved; therefore, we took advantage of the chemical reactivity of the new functional groups present to make amine adducts that shifted the current levels outside the range of the native nucleotides. Among the adducts studied, only the 2-aminomethyl-18-crown-6 adduct was able to give a large current shift in the immobilization experiment, as well as being observed in a translocation experiment. The results show potential in providing current-level modulators for identification of some types of DNA damage. In principle, any DNA base modification that can be converted chemically or enzymatically into an abasic site could be identified in this way.     

Confocal Raman study of poly(ethylene terephthalate) fibres dyed in supercritical carbon dioxide: dye diffusion and polymer morphology

Confocal Raman microscopy (CRM) has been used to extract dye diffusion data from poly(ethylene terephthalate) (PET) fibres dyed with Disperse Yellow 23 under supercritical CO₂ conditions. Spectral information as a function of depth was measured in a non-destructive manner using dry and oil objectives in confocal Raman mode. Mapping along the radius of the fibre cross-section was performed and compared to the data from the confocal measurements. A significant dye concentration gradient has been observed along the line normal to the fibre surface which the data from the oil confocal measurements accurately describes to a depth of 45 μm. The effect of the supercritical CO₂ dyeing process on the fibre morphology has also been evaluated using CRM.     

Trans Fatty Acid Intakes and Food Sources in the U.S. Population: NHANES 1999–2002

Because of efforts to decrease trans fatty acids (TFA) in the food supply, intake should be assessed in the population to establish a baseline TFA intake. The 1999?C2002 National Health and Nutrition Examination Survey (NHANES) was used to identify a benchmark for TFA intake. TFA was estimated by mean, median, and quintile of intake, TFA intake data were weighted using the NHANES 4-year sample weights. The main outcome measures included TFA intake in grams per day and percentage of energy in the top 25 food sources of TFA. Data are reported for 16,669 individuals ??3 years of age. Median TFA intake was 2.3?% of calories (5?g/day) with 0.9?C4.5?% of energy (1.5?C13.1?g/day) over different quintiles of intake. Mean TFA intake was 2.5?% of energy (6.1?g/day). The range of TFA intake in the fifth quintile was very large, i.e., 3.5?C12.5?% of energy or 8.8?C92.4?g/day. Increasing quintiles of TFA intake were associated with increases in total fat (26.7?C37.6?% of energy), saturated fat (7.6?C10.5?% of energy), and calories (for those >20?years of age: 2,416?C2,583 for men and 1,679?C1,886 for women). Major food sources of dietary TFA were cakes, cookies, pies, and pastries. Based on current dietary guidance to consume as little industrial TFA as possible, much progress is needed to attain this goal, including food industry efforts to remove TFA from the food supply and educating the public about making healthy food choices.     

Controlling selectivity in catalysis: Selective greener oxidation of cyclohexene under microwave conditions

A smart and greener microwave approach to the selective oxidation of cyclohexene is reported whereby, depending on the reaction conditions, the epoxide (65% conversion, 75% selectivity), the enol (70% conversion, 80% selectivity) or the enone (>99% conversion, 89% selectivity) can be obtained in a short period of time ranging from 1 to 20 min. A cobalt-salen-SBA-15 material was employed as catalyst. The reported solventless microwave protocol was simple, greener and more efficient compared to any other reported cyclohexene oxidations.     

Commercial aircraft engine emissions characterization of in-use aircraft at Hartsfield-Jackson Atlanta International Airport

The emissions from in-use commercial aircraft engines have been analyzed for selected gas-phase species and particulate characteristics using continuous extractive sampling 1-2 min downwind from operational taxi- and runways at Hartsfield-Jackson Atlanta International Airport. Using the aircraft tail numbers, 376 plumes were associated with specific engine models. In general, for takeoff plumes, the measured NOx emission index is lower (approximately 18%) than that predicted by engine certification data corrected for ambient conditions. These results are an in-service observation of the practice of "reduced thrust takeoff". The CO emission index observed in ground idle plumes was greater (up to 100%) than predicted by engine certification data for the 7% thrust condition. Significant differences are observed in the emissions of black carbon and particle number among different engine models/technologies. The presence of a mode at approximately 65 nm (mobility diameter) associated with takeoff plumes and a smaller mode at approximately 25 nm associated with idle plumes has been observed. An anticorrelation between particle mass loading and particle number concentration is observed.     

Comparison of physician based reporting of tobacco attributable deaths and computer derived estimates of smoking attributable deaths, Oregon, 1989 to 1996

BACKGROUND: Tobacco use prevention programmes need accurate information about smoking related mortality. Beginning in 1989, Oregon began asking physicians to report on death certificates whether tobacco use contributed to the death. OBJECTIVE: To determine the long term comparability of this method of estimating tobacco attributable mortality to estimates of smoking attributable mortality derived from a computer model. DESIGN: For the period 1989 to 1996, we compared mortality resulting from tobacco use reported by Oregon physicians to estimates of smoking attributable deaths (SADs) derived by "Smoking attributable mortality, morbidity and economic costs" software version 3.0 (SAMMEC 3.0), a widely used software program that estimates SADs on the basis of smoking prevalence and relative risks of specific diseases among current and former smokers. MAIN OUTCOME MEASURES: Numbers of deaths, age, sex, and category of disease. RESULTS: Of 212, 448 Oregon deaths during 1989-1996, SAMMEC 3.0 estimated that 42, 778 (20.1%) were attributable to cigarette smoking. For the same 27 diagnoses, physicians reported that tobacco contributed to 42, 839 (20.2%) deaths-a cumulative difference of only 61 deaths over the eight year period. The age and sex distributions of tobacco and smoking attributable deaths reported by the two systems were also similar. By category of disease, the ratio of SAMMEC 3.0 estimates to physician reported deaths was 1.11 for neoplasms, 0.88 for heart disease, and 1.04 for respiratory disease. CONCLUSIONS: Physician reporting provides comparable estimates of smoking attributable mortality and can be a valuable source of data for communicating the risks of tobacco use to the public.     

SPATIAL AND TEMPORAL CHANGES IN TOTAL SUSPENDED SEDIMENT CONCENTRATIONS IN AN OXBOW LAKE AFTER IMPLEMENTING AGRICULTURAL LANDSCAPE MANAGEMENT PRACTICES

The Wolf–Broad oxbow lake (417 ha) was evaluated by the Mississippi Department of Environmental Quality and included on the Mississippi 303(d) list of impaired waterbodies for total suspended solids (TSS). A study was undertaken for 2 years to evaluate and document changes to TSS (mg L^?1) and overall lake turbidity (NTU) through best management practice implementation. These two objectives were analysed with routine monthly surface sampling events of turbidity (Eureka Manta 2, automated data sonde) as well as 20 random samples per sampling trip for TSS from June 2008 to June 2010. Results from a non‐parametric Kruskal–Wallis analysis indicated a significant month‐by‐year effect on turbidity and TSS (chi‐squared = 76.08, p = 0.001), but reach (chi‐squared = 2.45, p = 0.784) and depth by reach (chi‐squared = 2.44, p = 0.784) did not show significant effects on turbidity. There were no significant correlations between TSS concentrations and turbidity and 2 days and 7 days summed or mean rainfall for the duration of the evaluation. Spearman correlation analysis for TSS indicated significant correlations between TSS and mean two‐day (r² = 0.62, p = 0.002) and seven‐day (r² = 0.51, p = 0.014) wind speeds. All other variables used in the analysis did not show significant correlation with TSS ( p > 0.05). This suggests that wind conditions, rather than rainfall, predict the greatest variability in TSS and turbidity in Wolf Lake. These documented correlations between lake water column TSS, turbidity and wind highlight the difficulties of demonstrating success of management practices in the short temporal period between project initiation and completion. Unmanageable environmental conditions (wind speed and direction) and limited temporal monitoring scales (1 1/2 years post‐BMP implementation) limit the possibility of demonstrating successful water‐quality improvement within a 303(d) listed waterbody such as Wolf Lake. Copyright © 2011 John Wiley & Sons, Ltd.