Role of CYP2B6 in Perfluorooctanesulfonic Acid (PFOS)-Induced Toxicity and Non Alcoholic Fatty Liver Disease (NAFLD)

Perfluorooctanesulfonic acid (PFOS) is a persistent, toxic fluorosurfactant foam used in firefighting foams, textiles, and other industrial products. Human CYP2B6 is predominantly expressed in the liver and responsible for metabolizing xeno- and endobiotics. CYP2B is induced by PFOS and high-fat diets in rodents and therefore it was hypothesized that CYP2B contributed to PFOS-induced steatosis. Cyp2b-9/10/13-null (Cyp2b-null) and humanized CYP2B6-Tg (hCYP2B6-Tg) mice were treated with PFOS (0, 1, or 10 mg/kg/day) by oral gavage in mice fed either a typical chow diet (ND) or a high-fat diet (HFD). Our studies show human CYP2B6 is also inducible in vivo by PFOS. In addition, three ND-fed hCYP2B6-Tg female mice treated with 10 mg/kg/day PFOS died during the exposure period. Similarly treated HFD-fed mice did not die. Interestingly, hCYP2B6-Tg mice retained significantly more PFOS in the serum and liver than Cyp2b-null mice presumably leading to the observed toxicity. Serum PFOS retention was significantly reduced in the HFD-fed hCYP2B6-Tg mice, which is the opposite trend observed in HFD-fed Cyp2b-null mice. Hepatotoxicity biomarkers, ALT and ALP, were higher in PFOS-treated mice and lowered by a HFD. However, PFOS combined with a HFD exacerbated hepatic lipid accumulation in all mice, especially in the hCYP2B6-Tg mice with significant disruption of key lipid metabolism genes such as Srebp1, Pparg, and Cpt1a. In conclusion, CYP2B6 is induced by PFOS and protects from PFOS-mediated steatosis in ND-fed mice; however, it’s presence increases hepatic triglyceride content in HFD-PFOS co-treated mice and increases toxicity in ND-fed mice

Public knowledge about polar regions increases while concerns remain unchanged

The authors of this brief conduct the first comparative analysis of the polar questions that were part of the National Opinion Research Center\u27s 2006 and 2010 General Social Survey. Developed by scientists at the National Science Foundation\u27s Office of Polar Programs, these questions covered topics such as climate change, melting ice and rising sea levels, and species extinction. The authors report that the public\u27s knowledge about the north and south polar regions significantly improved between 2006 and 2010--before and after the International Polar Year. In addition, respondents who know more about science in general, and polar facts specifically, tend to be more concerned about polar changes. More knowledgeable respondents also tend to favor reserving the Antarctic for science, rather than opening it for commercial development

Arctic–CHAMP: A program to study Arctic hydrology and its role in global change

The Arctic constitutes a unique and important environment that is central to the dynamics and evolution of the Earth system. The Arctic water cycle, which controls countless physical, chemical, and biotic processes, is also unique and important. These processes, in turn, regulate the climate, habitat, and natural resources that are of great importance to both native and industrial societies. Comprehensive understanding of water cycling across the Arctic and its linkage to global biogeophysical dynamics is a scientific as well as strategic policy imperative

Arctic–CHAMP: A program to study Arctic hydrology and its role in global change

The Arctic constitutes a unique and important environment that is central to the dynamics and evolution of the Earth system. The Arctic water cycle, which controls countless physical, chemical, and biotic processes, is also unique and important. These processes, in turn, regulate the climate, habitat, and natural resources that are of great importance to both native and industrial societies. Comprehensive understanding of water cycling across the Arctic and its linkage to global biogeophysical dynamics is a scientific as well as strategic policy imperative

Molecular brakes regulating mTORC1 activation in skeletal muscle following synergist ablation

The goal of the current work was to profile positive (mTORC1 activation, autocrine/paracrine growth factors) and negative [AMPK, unfolded protein response (UPR)] pathways that might regulate overload-induced mTORC1 (mTOR complex 1) activation with the hypothesis that a number of negative regulators of mTORC1 will be engaged during a supraphysiological model of hypertrophy. To achieve this, mTORC1- IRS-1/2 signaling, BiP/CHOP/IRE1, and AMPK activation were determined in rat plantaris muscle following synergist ablation (SA). SA resulted in significant increases in muscle mass of 4% per day throughout the 21 days of the experiment. The expression of the insulin-like growth factors (IGF) were high throughout the 21st day of overload. However, IGF signaling was limited, since IRS-1 and -2 were undetectable in the overloaded muscle from day 3 to day 9. The decreases in IRS-1/2 protein were paralleled by increases in GRB10 Ser501/503 and S6K1 Thr389 phosphorylation, two mTORC1 targets that can destabilize IRS proteins. PKB Ser473 phosphorylation was higher from 3– 6 days, and this was associated with increased TSC2 Thr939 phosphorylation. The phosphorylation of TSC2 Thr1345 (an AMPK site) was also elevated, whereas phosphorylation at the other PKB site, Thr1462, was unchanged at 6 days. In agreement with the phosphorylation of Thr1345, SA led to activation of AMPK1 during the initial growth phase, lasting the first 9 days before returning to baseline by day 12. The UPR markers CHOP and BiP were elevated over the first 12 days following ablation, whereas IRE1 levels decreased. These data suggest that during supraphysiological muscle loading at least three potential molecular brakes engage to downregulate mTORC1. m

Improving the repeatability and reproducibility of belt fit measurement with 6YO and 10YO ATDs

In previous work, researchers at the University of Michigan Transportation Research Institute (UMTRI) developed a method for quantifying the belt fit provided by belt-positioning boosters by measuring the belt location relative to the six- and ten-year-old Hybrid-III dummies. In another study, the torso and lap belt scores obtained by this method were found to be closely related to the belt fit obtained by similar-size children across a wide range of booster and belt conditions. The Insurance Institute for Highway Safety (IIHS) adapted the UMTRI procedure to develop a rating system for booster belt fit, but adoption by other labs has been slowed by difficulty in obtaining repeatable results. The current study was undertaken to improve the repeatability and reproducibility across operators of the procedure. The modifications made by IIHS were studied and most incorporated, and a number of other issues were examined through pilot testing. A revised version of the procedure was tested with repeated measurements by three operators in six boosters. The results were analyzed to quantify the variance associated with the operators, the installation of the booster and dummy, and the routing of the belt. The results show that trained operators can perform the procedure with minimal systematic bias across boosters. The variability within booster varies considerably, with some boosters producing higher precision measurements due to the design of their belt-routing features. For any particular booster, the booster and dummy installation process accounts for about half the variability in the belt fit scores with the remainder due to variability in the belt routing and other measurement variability. Based on these findings, multiple measurements of belt fit in each booster are recommended to establish the desired level of confidence in the true belt fit. Straightforward statistical methods involving confidence intervals are recommended for establishing objective test methods. More testing will be needed to determine the reproducibility of the method across laboratories.National Highway Traffic Safety Administrationhttp://deepblue.lib.umich.edu/bitstream/2027.42/89866/1/102812.pd

Road-Edge Effects on Herpetofauna in a Lowland Amazonian Rainforest

The impact of roads on the flora and fauna of Neotropical rainforest is perhaps the single biggest driver of habitat modification and population declines in these ecosystems. We investigated the road-edge effect of a low-use dirt road on amphibian and reptile abundance, diversity, and composition within adjacent lowland Amazonian rainforest at San José de Payamino, Ecuador. The road has been closed to vehicle traffic since its construction in 2010. Thus, effects from vehicle mortality, vehicle-related pollution, and road noise were not confounding factors. Herpetofauna were surveyed using both visual encounter surveys and drift fences with pitfall and funnel traps at varying distances from the road. Structural and microclimate features of the forest were measured at each sampling distance. Several habitat variables were found to differ at intermediate and interior sampling distances from the road compared to forest edge conditions, suggesting the road-edge effect began to attenuate by the intermediate sampling distance. However, the edge effect on amphibians and reptiles appeared to extend 100 m from the road edge, as abundance and diversity were significantly greater at the interior forest compared to the forest edge. Additionally, assemblage composition as well as the hierarchical position of species shifted between sampling distances. Habitat predictor models indicate that amphibian abundance was best predicted by vine abundance, while both vine and mature tree abundance were the best predictors for species richness and diversity. Overall, and contrary to what might otherwise be expected, our results demonstrate that small, little-used road disturbances can nonetheless have profound impacts on wildlife

Electropolymerized Layersas Selective Membranesin First Generation Uric Acid Biosensors

Electropolymerized films that can serve as semi-permeable membranes and provide selectivity within a xerogel-based, 1stgeneration biosensor assembly are explored in this study. Layered biosensing schemes of this nature rely primarily upon an electropolymerized ad-layer to supplement the xerogel and provide effective selectivity for detection of a targeted analyte. While effective electropolymers have been established for glucose sensing, the adaptation of the strategy to other analytes of clinical importance hinges upon the systematic evaluation of electropolymerized films to identify a selective film. Uric acid is a key species in the diagnosis/monitoring of a number of diseases and conditions. An effective uric acid biosensor, exhibiting high selectivity against common interferent species while maintaining uric acid sensitivity across physiologically relevant concentrations, would represent significant sensor development. Cyclic voltammetry allows for initial electropolymerization as well as the verification of polymer-modified electrodes. By forming electropolymerized films at glassy carbon electrodes, the sensitivity and permeability index toward uric acid and other interferents is readily measured via amperometric current responses. Of the significant number of polymer films examined in the study, only those films formed from luminol/aniline and luminol/Nafion mixtures showed positive selectivity coefficients for uric acid when incorporated into the layered xerogel schemes. The use of these specific mixed polymer films within the biosensing scheme resulted in well-defined amperometric responses to uric acid, linear calibration curves across clinically relevant uric acid concentrations, and effective selectivity for uric acid with discrimination against all major interferents except acetaminophen. The demonstrated and systematic evaluation of a specifically selective electropolymerized film is an important advancement for uric acid biosensor development as well as further adaptation of biosensing strategies involving polymer interfaces to other targeted analytes

Rapid prototype feasibility testing with simulation: Improvements and updates to the Taiwanese “aerosol box”

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Determining the probability of cyanobacterial blooms: the application of Bayesian networks in multiple lake systems

A Bayesian network model was developed to assess the combined influence of nutrient conditions and climate on the occurrence of cyanobacterial blooms within lakes of diverse hydrology and nutrient supply. Physicochemical, biological, and meteorological observations were collated from 20 lakes located at different latitudes and characterized by a range of sizes and trophic states. Using these data, we built a Bayesian network to (1) analyze the sensitivity of cyanobacterial bloom development to different environmental factors and (2) determine the probability that cyanobacterial blooms would occur. Blooms were classified in three categories of hazard (low, moderate, and high) based on cell abundances. The most important factors determining cyanobacterial bloom occurrence were water temperature, nutrient availability, and the ratio of mixing depth to euphotic depth. The probability of cyanobacterial blooms was evaluated under different combinations of total phosphorus and water temperature. The Bayesian network was then applied to quantify the probability of blooms under a future climate warming scenario. The probability of the "high hazardous" category of cyanobacterial blooms increased 5% in response to either an increase in water temperature of 0.8°C (initial water temperature above 24°C) or an increase in total phosphorus from 0.01 mg/L to 0.02 mg/L. Mesotrophic lakes were particularly vulnerable to warming. Reducing nutrient concentrations counteracts the increased cyanobacterial risk associated with higher temperatures