Mixed muscle and hepatic derived plasma protein metabolism is differentially regulated in older and younger men following resistance exercise

We sought to determine whether exercise-induced muscle protein turnover alters the subsequent production of hepatically derived acute-phase plasma proteins, and whether age affects how these proteins are regulated. We measured arteriovenous (a-v) balance and the synthesis of mixed muscle protein, albumin (A) and fibrinogen (F) before exercise (REST) and from the beginning of exercise to 10, 60, and 180 min following a single bout of moderate-intensity leg extension exercise (POST-EX) in postabsorptive untrained older (n = 6) and younger (n = 6) men using L-[ring-2H5]phenylalanine (Phe). Subjects performed 6 sets of 8 repetitions of leg extension at 80% of their 1-RM (one-repetition maximum). All data are presented as the difference from REST (Delta from REST at 10, 60, and 180 min POST-EX). Mixed muscle fractional synthesis rate (FSR-M) increased significantly from the beginning of exercise until 10 min POST-EX in the older men (DeltaFSR-M: 0.044%/h), whereas FSR-M in the younger men was not elevated until 180 min POST-EX (DeltaFSR-M: 0.030%/h). FSR-A and FSR-F increased at all POST-EX periods in the older men (DeltaFSR-A = 10 min: 1.90%/day; 60 min: 2.72%/day; 180 min: 2.78%/day; DeltaFSR-F = 10 min: 1.00%/day; 60 min: 3.01%/day; 180 min: 3.73%/day). No change occurred in FSR-A in the younger men, but FSR-F was elevated from the beginning of exercise until 10 and 180 min POST-EX (10 min: 3.07%/day and 180 min: 3.96%/day). Net balance of Phe was positive in the older men in the immediate POST-EX period. Our data indicate that mixed muscle and hepatic derived protein synthesis is differentially regulated in younger and older men in response to a single bout of moderate-intensity leg extension exercise. Moreover, our data suggest that with age may come a greater need to salvage or make available amino acids from exercise-induced muscle protein breakdown to mount an acute-phase response.     

PPARα is essential for retinal lipid metabolism and neuronal survival

Background

Peroxisome proliferator activated receptor-alpha (PPARα) is a ubiquitously expressed nuclear receptor. The role of endogenous PPARα in retinal neuronal homeostasis is unknown. Retinal photoreceptors are the highest energy-consuming cells in the body, requiring abundant energy substrates. PPARα is a known regulator of lipid metabolism, and we hypothesized that it may regulate lipid use for oxidative phosphorylation in energetically demanding retinal neurons.

Results

We found that endogenous PPARα is essential for the maintenance and survival of retinal neurons, with Pparα ^-/- mice developing retinal degeneration first detected at 8 weeks of age. Using extracellular flux analysis, we identified that PPARα mediates retinal utilization of lipids as an energy substrate, and that ablation of PPARα ultimately results in retinal bioenergetic deficiency and neurodegeneration. This may be due to PPARα regulation of lipid transporters, which facilitate the internalization of fatty acids into cell membranes and mitochondria for oxidation and ATP production.

Conclusion

We identify an endogenous role for PPARα in retinal neuronal survival and lipid metabolism, and furthermore underscore the importance of fatty acid oxidation in photoreceptor survival. We also suggest PPARα as a putative therapeutic target for age-related macular degeneration, which may be due in part to decreased mitochondrial efficiency and subsequent energetic deficits.

     

Dda helicase tightly couples translocation on single-stranded DNA to unwinding of duplex DNA: Dda is an optimally active helicase

Helicases utilize the energy of ATP hydrolysis to unwind double-stranded DNA while translocating on the DNA. Mechanisms for melting the duplex have been characterized as active or passive, depending on whether the enzyme actively separates the base pairs or simply sequesters single-stranded DNA (ssDNA) that forms due to thermal fraying. Here, we show that Dda translocates unidirectionally on ssDNA at the same rate at which it unwinds double-stranded DNA in both ensemble and single-molecule experiments. Further, the unwinding rate is largely insensitive to the duplex stability and to the applied force. Thus, Dda transduces all of its translocase activity into DNA unwinding activity so that the rate of unwinding is limited by the rate of translocation and that the enzyme actively separates the duplex. Active and passive helicases have been characterized by dividing the velocity of DNA unwinding in base pairs per second (V_un) by the velocity of translocation on ssDNA in nucleotides per second (V_trans). If the resulting fraction is 0.25, then a helicase is considered to be at the lower end of the “active” range. In the case of Dda, the average DNA unwinding velocity was 257 ± 42 bp/s, and the average translocation velocity was 267 ± 15 nt/s. The V_un/V_trans value of 0.96 places Dda in a unique category of being an essentially “perfectly” active helicase.     

Dissolved phosphorus concentrations and sediment interactions in effluent–dominated Ozark streams

Phosphorus (P) loads from point sources have a significant influence on dissolved P concentrations in streams and sediment-water column dynamics. The goal of this study was to quantify dissolved P concentrations and sediment-P interactions in Ozark (USA) headwater streams with high point source P loads. Specifically, the objectives were to: (1) compare soluble reactive P (SRP) upstream and downstream from wastewater treatment plant (WWTP) effluent discharges; (2) examine longitudinal gradients in SRP downstream from WWTPs; (3) evaluate the effect of WTTP P inputs on sediment-water column P equilibrium and sediment exchangeable P. Water and sediment samples were collected, extracted and analyzed from July 2002 through June 2003 at these Ozark streams. Mean SRP concentrations in the select Ozark streams were significantly greater downstream from effluent discharges (0.08–2.10 mg L⁻¹) compared to upstream (0.02–0.12 mg L⁻¹). Effluent discharge from the WWTPs increased equilibrium concentrations between stream sediments and the water column; mean sediment equilibrium P concentration (EPC₀) was between 0.01–0.07 mg L⁻¹ upstream from WWTP and the increase downstream was proportional to that observed in water column SRP. Sediment exchangeable P (EXP) was greater downstream from the effluent discharges (0.3–6.8 mg kg⁻¹) compared to upstream (0.03–1.4 mg kg⁻¹), representing a substantial transient storage of P inputs from WWTPs. Furthermore, P was generally not retained in these stream reaches when dilution was considered using a hydrologic tracer and was released in one stream reach where effluent P concentrations decreased over the study period. Thus, the effect of the WWTPs was profound in these streams increasing water column and sediment-bound P, and also reducing the ability of these stream reaches to retain P. In P-enriched streams, effluent P discharges likely regulate sediment and aqueous phase P equilibrium and sediment bioavailable P, not the sediments.     

Genetic relationships among three chlorophyll-deficient mutants in peanut,Arachis hypogaea L.

Summary The genetic relationships of three chlorophyll-deficient mutant peanuts, lutescens (lu), aureus (au), and virescent (v) were studied under field and greenhouse conditions. The F₁ plants from crosses between these mutants produced phenotypically normal green. In F₂, aureus X virescent segregated 675 normal green : 225 virescent : 45 aureus : 15 virescent aureus : 64 seedling lethal, and lutescens X virescent segregated 45 normal green : 15 virescent : 3 lutescens : 1 seedling lethal. (Lutescens peanuts were seedling lethal in the field.) As previously reported, the F₂ of aureus X lutescens gave 225 normal green : 15 aureus :15 lutescens : 1 seedling lethal. The three chlorophyll-deficient factors (au, lu, and v) show independent inheritance. The recessive combinations from the parental types between aureus and virescent and between aureus and lutescens would produce plants with a combination of their respective parental characteristics, but the recessive combination between lutescens and virescent was nearly albino. The v-au and lu-au seedlings have a longer life span than the v-lu seedling has. The genotypes for the three mutants are tentatively identified as lutescens VV Au ₁ Au ₁ Au ₂ Au ₂ lu ₁ lu ₁ lu ₂ lu ₂ L ₁ L ₁ L ₂ L ₂, aureus VV au₁au₁ au₂au₂ Lu₁Lu₁ Lu₂Lu₂ L₁L₁ l₂l₂, and virescent vv Au₁Au₁ Au₂Au₂ lu₁lu₁ Lu₂Lu₂ l₁l₁ L₂L₂.     

An ecological risk assessment paradigm using the Spatially Integrated model for Phosphorus Loading and Erosion (SIMPLE)

Ecological risk assessments provide a probabilitistic approach to analyzing and predicting ecosystem responses to stress. We are evaluating the relationship between nonpoint source (NPS) phosphorus loading and the trophic status of the aquatic ecosystem. We are using SIMPLE (the Spatially Integrated Model for Phosphorus Loading and Erosion) to identify probable phosphorus sources in a watershed, simulate the phosphorus loading to streams, and analyze the relationships between input variables and their ecological impact. The objective of this paper is to describe a risk-based paradigm using SIMPLE to characterize the probability of exceeding a critical phosphorus loading to a lotic ecosystem. We have characterized the risk of exceeding a threshold loading of 0.5 kilogram total phosphorus per hectare per year from a 2238 hectare watershed. Two-hundred-fifty random SIMPLE simulations were performed to estimate annual total phosphorus, dissolved phosphorus, and sediment-bound phosphorus loading to a lotic ecosystem from the watershed. Simulation results were analyzed statistically to determine the probabilities of exceeding the critical loadings. Based on the current land use practices in the Battle Creek watershed, the probability of exceeding the total phosphorus critical loading rate of 0.5 kg/ha/yr was approximately 11 percent, or one year in nine the total annual loading will exceed the critical loading rate. The 95 percent confidence intervals for the total phosphorus loading occurring on average once in nine years were relatively close (0.45 to 0.60 kg/ha/yr), assuming the only variability from year to year was due to natural variability in weather.