Experimental reductions in subdaily flow fluctuations increased gross primary productivity for 425 river kilometers downstream.

Aquatic primary production is the foundation of many river food webs. Dams change the physical template of rivers, often driving food webs toward greater reliance on aquatic primary production. Nonetheless, the effects of regulated flow regimes on primary production are poorly understood. Load following is a common dam flow management strategy that involves subdaily changes in water releases proportional to fluctuations in electrical power demand. This flow regime causes an artificial tide, wetting and drying channel margins and altering river depth and water clarity, all processes that are likely to affect primary production. In collaboration with dam operators, we designed an experimental flow regime whose goal was to mitigate negative effects of load following on ecosystem processes. The experimental flow contrasted steady-low flows on weekends with load following flows on weekdays. Here, we quantify the effect of this experimental flow on springtime gross primary production (GPP) 90-to-425 km downstream of Glen Canyon Dam on the Colorado River, AZ, USA. GPP during steady-low flows was 41% higher than during load following flows, mostly owing to nonlinear reductions in sediment-driven turbidity. The experimental flow increased weekly GPP even after controlling for variation in weekly mean discharge, demonstrating a negative effect of load following on GPP. We estimate that this environmental flow increased springtime carbon fixation by 0.27 g C m-2 d-1, which is ecologically meaningful considering median C fixation in 356 US rivers of 0.44 g C m-2 d-1 and the fact that native fish populations in this river are food-limited.

A need for speed in Bayesian population models: a practical guide to marginalizing and recovering discrete latent states.

Bayesian population models can be exceedingly slow due, in part, to the choice to simulate discrete latent states. Here, we discuss an alternative approach to discrete latent states, marginalization, that forms the basis of maximum likelihood population models and is much faster. Our manuscript has two goals: (1) to introduce readers unfamiliar with marginalization to the concept and provide worked examples and (2) to address topics associated with marginalization that have not been previously synthesized and are relevant to both Bayesian and maximum likelihood models. We begin by explaining marginalization using a Cormack-Jolly-Seber model. Next, we apply marginalization to multistate capture-recapture, community occupancy, and integrated population models and briefly discuss random effects, priors, and pseudo-R2 . Then, we focus on recovery of discrete latent states, defining different types of conditional probabilities and showing how quantities such as population abundance or species richness can be estimated in marginalized code. Last, we show that occupancy and site-abundance models with auto-covariates can be fit with marginalized code with minimal impact on parameter estimates. Marginalized code was anywhere from five to >1,000 times faster than discrete code and differences in inferences were minimal. Discrete latent states and fully conditional approaches provide the best estimates of conditional probabilities for a given site or individual. However, estimates for parameters and derived quantities such as species richness and abundance are minimally affected by marginalization. In the case of abundance, marginalized code is both quicker and has lower bias than an N-augmentation approach. Understanding how marginalization works shrinks the divide between Bayesian and maximum likelihood approaches to population models. Some models that have only been presented in a Bayesian framework can easily be fit in maximum likelihood. On the other hand, factors such as informative priors, random effects, or pseudo-R2 values may motivate a Bayesian approach in some applications. An understanding of marginalization allows users to minimize the speed that is sacrificed when switching from a maximum likelihood approach. Widespread application of marginalization in Bayesian population models will facilitate more thorough simulation studies, comparisons of alternative model structures, and faster learning.

Phenotypic Alteration of Hepatocytes in Non-Alcoholic Fatty Liver Disease.

Non-Alcoholic Fatty Liver Disease (NAFLD) has been recognized as the most common liver disorder in developed countries. NAFLD progresses from fat accumulation in hepatocytes to steatohepatitis to further stages of fibrosis and cirrhosis. Simple steatosis, i.e. fat deposition in the liver, is considered benign and gives way to non-alcoholic steatohepatitis (NASH) with a higher probability of progressing to cirrhosis, and liver-related mortality. Evidence has been found that this progression has been associated with marked alterations in hepatocyte histology and a shift in marker expression of healthy hepatocytes including increased expression of peroxisome proliferator-activated receptor gamma (PPARγ), adipocyte protein (aP2), CD36, interleukin-6 (IL-6), interleukin-18 (IL-18) and adiponectin. This progression shares much in common with the obesity phenotype, which involves a transformation of adipocytes from small, healthy cells to large, dysfunctional ones that contribute to redox imbalance and the progression of metabolic syndrome. Further, activation of Src/ERK signaling via the sodium potassium adenosine triphosphatase (Na/K-ATPase) α-1 subunit in impaired hepatocytes may contribute to redox imbalance, exacerbating the progression of NAFLD. This review hypothesizes that an adipogenic transformation of hepatocytes propagates redox imbalance and that the processes occurring in adipogenesis become activated in fat-laden hepatocytes in liver, thereby driving progression to NAFLD. Further, this review discusses therapeutic interventions to reverse NAFLD including the thiazolidinediones (TZDs) and a variety of antioxidant species. The peptide, pNaKtide, which is an antagonist of Na/K-ATPase signaling, is also proposed as a potential pharmacologic option for reducing reactive oxygen species (ROS) and reversing NAFLD by inhibiting the Na/K-ATPase-modulated ROS amplification loop.

Corrigendum: Attenuation of Na/K-ATPase Mediated Oxidant Amplification with pNaKtide Ameliorates Experimental Uremic Cardiomyopathy.

This corrects the article DOI: 10.1038/srep34592.

Attenuation of Na/K-ATPase Mediated Oxidant Amplification with pNaKtide Ameliorates Experimental Uremic Cardiomyopathy.

We have previously reported that the sodium potassium adenosine triphosphatase (Na/K-ATPase) can effect the amplification of reactive oxygen species. In this study, we examined whether attenuation of oxidant stress by antagonism of Na/K-ATPase oxidant amplification might ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy (PNx). PNx induced the development of cardiac morphological and biochemical changes consistent with human uremic cardiomyopathy. Both inhibition of Na/K-ATPase oxidant amplification with pNaKtide and induction of heme oxygenase-1 (HO-1) with cobalt protoporphyrin (CoPP) markedly attenuated the development of phenotypical features of uremic cardiomyopathy. In a reversal study, administration of pNaKtide after the induction of uremic cardiomyopathy reversed many of the phenotypical features. Attenuation of Na/K-ATPase oxidant amplification may be a potential strategy for clinical therapy of this disorder.

Lipopolysaccharide increases Na(+),K(+)-pump, but not ENaC, expression in guinea-pig airway epithelium.

Earlier, we found in functional experiments that lipopolysaccharide (LPS; 4mg/kg; i.p.) hyperpolarized the epithelium by stimulating the transepithelial transport of Na(+) in guinea-pig tracheal epithelium. Epithelial sodium channel (ENaC) activity and Na(+),K(+)-pump activity were increased. In this study, we hypothesized that LPS increases the expression of ENaC and the Na(+),K(+)-pump in the epithelium and investigated the levels of transcription and protein abundance. Using qPCR, the effects of LPS on the transcription of αENaC, α(1) Na(+),K(+)-pump, COX-2, eNOS, iNOS, IL-1ß, and TNF-α were measured at 3 and 18h. In the epithelium, LPS increased the transcription of COX-2, IL-1ß, and, to a nonsignificant extent, TNF-α at 3h, but not at 18h. In alveolar macrophages, TNF-α, and, to a nonsignificant extent, COX-2 and IL-1ß were up-regulated at 3h, but not at 18h. Even though LPS stimulated the transcription of some genes, αENaC and α(1) Na(+),K(+)-ATPase transcription were not affected. The expressions of α-, ß-, and γ-ENaC and α(1) Na(+),K(+)-pump from the tracheal epithelium and kidney cortex/medulla were investigated by western blotting. All three ENaC subunits were detected as cleavage fragments, yet LPS had no effect on their expression. LPS increased the expression of the α(1) subunit and the α(1), α(2), and α(3) subunits, collectively, of the Na(+),K(+)-pump. Taken together, these data indicate that LPS increases Na(+) transport downstream of the genetic level, in part, by stimulating the expression of the Na(+),K(+)-pump.

Lipopolysaccharide hyperpolarizes guinea pig airway epithelium by increasing the activities of the epithelial Na(+) channel and the Na(+)-K(+) pump.

Earlier, we found that systemic administration of lipopolysaccharide (LPS; 4 mg/kg) hyperpolarized the transepithelial potential difference (V(t)) of tracheal epithelium in the isolated, perfused trachea (IPT) of the guinea pig 18 h after injection. As well, LPS increased the hyperpolarization component of the response to basolateral methacholine, and potentiated the epithelium-derived relaxing factor-mediated relaxation responses to hyperosmolar solutions applied to the apical membrane. We hypothesized that LPS stimulates the transepithelial movement of Na(+) via the epithelial sodium channel (ENaC)/Na(+)-K(+) pump axis, leading to hyperpolarization of V(t). LPS increased the V(t)-depolarizing response to amiloride (10 µM), i.e., offset the effect of LPS, indicating that Na(+) transport activity was increased. The functional activity of ENaC was measured in the IPT after short-circuiting the Na(+)-K(+) pump with basolateral amphotericin B (7.5 µM). LPS had no effect on the hyperpolarization response to apical trypsin (100 U/ml) in the Ussing chamber, indicating that channel-activating proteases are not involved in the LPS-induced activation of ENaC. To assess Na(+)-K(+) pump activity in the IPT, ENaC was short-circuited with apical amphotericin B. The greater V(t) in the presence of amphotericin B in tracheas from LPS-treated animals compared with controls revealed that LPS increased Na(+)-K(+) pump activity. This finding was confirmed in the Ussing chamber by inhibiting the Na(+)-K(+) pump via extracellular K(+) removal, loading the epithelium with Na(+), and observing a greater hyperpolarization response to K(+) restoration. Together, the findings of this study reveal that LPS hyperpolarizes the airway epithelium by increasing the activities of ENaC and the Na(+)-K(+) pump.

Experimental validation of a target method for balancing exhaust ventilation duct systems with dampers.

This study tested the "Target Method" for adjusting ventilation systems. The Target Method is based on target hood static pressures (SPh(target)) computed in a manner designed to take into account the estimated effects of dampers on the fan, the order of damper adjustments, and the ratio of the prebalancing branch airflows to their goals. It is aimed at achieving a desired relative distribution of airflows even if the fan output is far from ideal. The method assumes the fan output will be adjusted after the dampers are adjusted. The method is expected to produce lower fan pressure requirements than some commonly used methods. The method was tested on a working seven-branch, full-sized exhaust ventilation system in the West Virginia University Exposure Assessment Laboratory. Two radically different target distributions were tested with two replications apiece. Both target distributions of airflows were substantially different from the initial distribution, providing a high degree of challenge to the methodology. For each distribution, SPh(target) values were computed for the first round of adjustments. Each damper was adjusted until the observed value of the hood static pressure was nearly equal to that damper's computed SPh(target) value for that distribution. Each of the other branch dampers was adjusted similarly in turn. After the first round of adjustments, the median ratio of SPh to SPh(target) provided the targets for the partial second round of adjustments. Twenty-point Pitot traverses were used to determine the airflow in each branch duct both before and after employing the adjustment method, providing the basis to determine the success in reaching each of the two desired distributions. The percentage of excess airflow (assuming ideal adjustment of the fan speed) was below 2.2% for all experimental trials. An unpublished study by Vivek Balasubramanian showed that excess airflow was 4.8% to 8.5% in the same experimental system after two full rounds of adjustment using the customary Target Method. Under poor measurement conditions, the greater uncertainty of pressure measurements would likely produce somewhat higher excess airflows.