Phosphorylation of the voltage-gated potassium channel Kv2.1 by AMP-activated protein kinase regulates membrane excitability

Firing of action potentials in excitable cells accelerates ATP turnover. The voltage-gated potassium channel Kv2.1 regulates action potential frequency in central neurons, whereas the ubiquitous cellular energy sensor AMP-activated protein kinase (AMPK) is activated by ATP depletion and protects cells by switching off energy-consuming processes. We show that treatment of HEK293 cells expressing Kv2.1 with the AMPK activator A-769662 caused hyperpolarizing shifts in the current-voltage relationship for channel activation and inactivation. We identified two sites (S440 and S537) directly phosphorylated on Kv2.1 by AMPK and, using phosphospecific antibodies and quantitative mass spectrometry, show that phosphorylation of both sites increased in A-769662-treated cells. Effects of A-769662 were abolished in cells expressing Kv2.1 with S440A but not with S537A substitutions, suggesting that phosphorylation of S440 was responsible for these effects. Identical shifts in voltage gating were observed after introducing into cells, via the patch pipette, recombinant AMPK rendered active but phosphatase-resistant by thiophosphorylation. Ionomycin caused changes in Kv2.1 gating very similar to those caused by A-769662 but acted via a different mechanism involving Kv2.1 dephosphorylation. In cultured rat hippocampal neurons, A-769662 caused hyperpolarizing shifts in voltage gating similar to those in HEK293 cells, effects that were abolished by intracellular dialysis with Kv2.1 antibodies. When active thiophosphorylated AMPK was introduced into cultured neurons via the patch pipette, a progressive, time-dependent decrease in the frequency of evoked action potentials was observed. Our results suggest that activation of AMPK in neurons during conditions of metabolic stress exerts a protective role by reducing neuronal excitability and thus conserving energy.

Phenolic acid intake, delivered via moderate champagne wine consumption, improves spatial working memory via the modulation of hippocampal and cortical protein expression/activation.

Aims: While much data exist for the effects of flavonoid-rich foods on spatial memory in rodents, there are no such data for foods/beverages predominantly containing hydroxycinnamates and phenolic acids. To address this, we investigated the effects of moderate Champagne wine intake, which is rich in these components, on spatial memory and related mechanisms relative to the alcohol- and energy-matched controls. Results: In contrast to the isocaloric and alcohol-matched controls, supplementation with Champagne wine (1.78 ml/kg BW, alcohol 12.5% vol.) for 6 weeks led to an improvement in spatial working memory in aged rodents. Targeted protein arrays indicated that these behavioral effects were paralleled by the differential expression of a number of hippocampal and cortical proteins (relative to the isocaloric control group), including those involved in signal transduction, neuroplasticity, apoptosis, and cell cycle regulation. Western immunoblotting confirmed the differential modulation of brain-derived neurotrophic factor, cAMP response-element-binding protein (CREB), p38, dystrophin, 2',3'-cyclic-nucleotide 3'-phosphodiesterase, mammalian target of rapamycin (mTOR), and Bcl-xL in response to Champagne supplementation compared to the control drink, and the modulation of mTOR, Bcl-xL, and CREB in response to alcohol supplementation. Innovation: Our data suggest that smaller phenolics such as gallic acid, protocatechuic acid, tyrosol, caftaric acid, and caffeic acid, in addition to flavonoids, are capable of exerting improvements in spatial memory via the modulation in hippocampal signaling and protein expression. Conclusion: Changes in spatial working memory induced by the Champagne supplementation are linked to the effects of absorbed phenolics on cytoskeletal proteins, neurotrophin expression, and the effects of alcohol on the regulation of apoptotic events in the hippocampus and cortex. Antioxid. Redox Signal. 00, 000-000.

The influence of nutritional supplement drinks on providing adequate calorie and protein intake in older adults with dementia

Objectives: Investigate the impact of the provision of ONS on protein and energy intake from food and ability to meet protein and calorie requirements in people with dementia. Design: After consent by proxy was obtained, participants took part in a cross over study comparing oral intake on an intervention day to an adjacent control day. Setting: The study occurred in Nursing homes and hspitalised settings. Participants: Older adults with dementia over the age of 65 were recruited. 26 participants (aged 83.9+/-8.4 years, MMSE 13.08+/-8.13) took part. Intervention (if any): On the intervention day nutritional supplement drinks were provided three times. Each drink provided 283.3+/-41.8 Kcal of energy and 13.8+/-4.7g of protein. Supplements were removed approximately 1 hour before meals were served and weighed waste (g) was obtained. Measurements: Intake of food consumed was determined on intervention and control days using the quartile method (none, quarter, half, three quarters, all) for each meal component. Results: More people achieved their energy and protein requirements with the supplement drink intervention with no sufficient impact on habitual food consumption. Conclusion: Findings from these 26 participants with dementia indicate that supplement drinks may be beneficial in reducing the prevalence of malnutrition within teh group as more people meet their nutritional requirements. As the provision of supplement drinks is also demonstrated to have an additive effect to consumption of habitual foods, these can be used alongside other measures to also improve oral intake.

Unique structural properties associated with mouse prion Δ105-125 protein

Murine prion protein deleted for residues 105-125 is intrinsically neurotoxic and mediates a TSE-like phenotype in transgenic mice. Equivalent and overlapping deletions were expressed in E.coli, purified and analyzed. Among mutants spanning the region 95-135, a construct lacking solely residues 105-125 had distinct properties when compared with the full-length prion protein 23-231 or other deletions. This distinction was also apparent followed expression in eukaryotic cells. Unlike the full-length protein, all deletion mutants failed to bind to synthetic membranes in vitro. These data suggest a novel structure for the 105-125 deleted variant that may relate to its biological properties

Energy and pitch-angle dispersions of LLBL/cusp ions seen at middle altitudes: predictions by the open magnetosphere model

Numerical simulations are presented of the ion distribution functions seen by middle-altitude spacecraft in the low-latitude boundary layer (LLBL) and cusp regions when reconnection is, or has recently been, taking place at the equatorial magnetopause. From the evolution of the distribution function with time elapsed since the field line was opened, both the observed energy/observation-time and pitch-angle/energy dispersions are well reproduced. Distribution functions showing a mixture of magnetosheath and magnetospheric ions, often thought to be a signature of the LLBL, are found on newly opened field lines as a natural consequence of the magnetopause effects on the ions and their flight times. In addition, it is shown that the extent of the source region of the magnetosheath ions that are detected by a satellite is a function of the sensitivity of the ion instrument . If the instrument one-count level is high (and/or solar-wind densities are low), the cusp ion precipitation detected comes from a localised region of the mid-latitude magnetopause (around the magnetic cusp), even though the reconnection takes place at the equatorial magnetopause. However, if the instrument sensitivity is high enough, then ions injected from a large segment of the dayside magnetosphere (in the relevant hemisphere) will be detected in the cusp. Ion precipitation classed as LLBL is shown to arise from the low-latitude magnetopause, irrespective of the instrument sensitivity. Adoption of threshold flux definitions has the same effect as instrument sensitivity in artificially restricting the apparent source region.

The geomagnetic mass spectrometer— mass and energy dispersions of ionospheric ion flows into the magnetosphere

NASA's Dynamics Explorer (DE) mission was designed to study the coupling between the Earth's magnetosphere, ionosphere and neutral thermosphere1. One area of major interest is the outflow of ionospheric plasma into the magnetosphere, the scale and significance of which is only now becoming apparent with the advent of mass-resolving, low-energy ion detectors. Here we compare observations of ion flows in the polar magnetosphere, made by the retarding ion mass spectrometer (RIMS)2 on DE1, with those made simultaneously in the topside ionosphere by the ion drift meter (IDM)3 on the lower-altitude DE2 spacecraft. The results show the dayside auroral ionosphere to be a significant and highly persistent source of plasma for the magnetosphere. The upwelling ionospheric ions are spatially dispersed, according to both their energy and mass, by the combined actions of the geomagnetic field and the dawn-to-dusk convection electric field, in an effect analogous to the operation of an ion mass spectrometer.

Associations between FTO genotype and total energy and macronutrients intake: a systematic review and meta-analysis

Risk variants of the fat-mass and obesity-associated (FTO) gene have been associated with increased obesity. However, the evidence for associations between FTO genotype and macronutrients intake has not been reviewed systematically. Our aim was to evaluate potential associations between FTO genotype and intakes of total energy, fat, carbohydrate and protein. We undertook a systematic literature search in Medline, Scopus, EMBASE and Cochrane of associations between macronutrients intake and FTO genotype in adults. Beta coefficients and confidence intervals were used for per-allele comparisons. Random-effects models assessed the pooled effect sizes. We identified 56 eligible studies reporting on 213 173 adults. For each copy of the FTO risk allele, individuals reported 6.46 kcal/day (95% CI: 10.76, 2.16) lower total energy intake (P=0.003). Total fat (P=0.028) and protein (P=0.006), but not carbohydrate intakes, were higher in those carrying the FTO risk allele. After adjustment for body weight, total energy intakes remained significantly lower in individuals with the FTO risk genotype (P=0.028). The FTO risk allele is associated with a lower reported total energy intake and with altered patterns of macronutrients intake. Although significant, these differences are small and further research is needed to determine whether the associations are independent of dietary misreporting.

Combining satellite observations and reanalysis energy transports to estimate global net surface energy fluxes 1985-2012

Two methods are developed to estimate net surface energy fluxes based upon satellite-based reconstructions of radiative fluxes at the top of atmosphere and the atmospheric energy tendencies and transports from the ERA-Interim reanalysis. Method 1 applies the mass adjusted energy divergence from ERA-Interim while method 2 estimates energy divergence based upon the net energy difference at the top of atmosphere and the surface from ERA-Interim. To optimise the surface flux and its variability over ocean, the divergences over land are constrained to match the monthly area mean surface net energy flux variability derived from a simple relationship between the surface net energy flux and the surface temperature change. The energy divergences over the oceans are then adjusted to remove an unphysical residual global mean atmospheric energy divergence. The estimated net surface energy fluxes are compared with other data sets from reanalysis and atmospheric model simulations. The spatial correlation coefficients of multi-annual means between the estimations made here and other data sets are all around 0.9. There are good agreements in area mean anomaly variability over the global ocean, but discrepancies in the trend over the eastern Pacific are apparent.

Effect of maternal protein restriction during pregnancy and postweaning high-fat feeding of diet-induced thermogenesis in adult mouse offspring

Purpose Prenatal undernutrition followed by postweaning feeding of a high-fat diet results in obesity in the adult offspring. In this study, we investigated whether diet-induced thermogenesis is altered as a result of such nutritional mismatch. Methods Female MF-1 mice were fed a normal protein (NP, 18 % casein) or a protein-restricted (PR, 9 % casein) diet throughout pregnancy and lactation. After weaning, male offspring of both groups were fed either a high-fat diet (HF; 45 % kcal fat) or standard chow (C, 7 % kcal fat) to generate the NP/C, NP/HF, PR/C and PR/HF adult offspring groups (n = 7–11 per group). Results PR/C and NP/C offspring have similar body weights at 30 weeks of age. Postweaning HF feeding resulted in significantly heavier NP/HF offspring (P < 0.01), but not in PR/HF offspring, compared with their chow-fed counterparts. However, the PR/HF offspring exhibited greater adiposity (P < 0.01) v the NP/HF group. The NP/HF offspring had increased energy expenditure and increased mRNA expression of uncoupling protein-1 and β-3 adrenergic receptor in the interscapular brown adipose tissue (iBAT) compared with the NP/C mice (both at P < 0.01). No such differences in energy expenditure and iBAT gene expression were observed between the PR/HF and PR/C offspring. Conclusions These data suggest that a mismatch between maternal diet during pregnancy and lactation, and the postweaning diet of the offspring, can attenuate diet-induced thermogenesis in the iBAT, resulting in the development of obesity in adulthood.

Decoupling of building energy use and climate

Energy use intensity (EUI) and climate have a well documented correlation, which is generally applied in building energy management. Green buildings have sought to greatly reduce energy consumption and a number of examples are documented in the literature. A sample of high performance buildings constructed in a variety of global locations is analyzed here, and provides evidence that measures to reduce energy consumption have reduced EUI to the point where its correlation with heating degree days is no longer apparent. This result suggests that end-user behaviour is the next major hurdle in lowering the energy consumption of greener buildings.

Energy compensation following consumption of sugar-reduced products: a randomized controlled trial

PURPOSE: Consumption of sugar-reformulated products (commercially available foods and beverages that have been reduced in sugar content through reformulation) is a potential strategy for lowering sugar intake at a population level. The impact of sugar-reformulated products on body weight, energy balance (EB) dynamics and cardiovascular disease risk indicators has yet to be established. The REFORMulated foods (REFORM) study examined the impact of an 8-week sugar-reformulated product exchange on body weight, EB dynamics, blood pressure, arterial stiffness, glycemia and lipemia. METHODS: A randomized, controlled, double-blind, crossover dietary intervention study was performed with fifty healthy normal to overweight men and women (age 32.0 ± 9.8 year, BMI 23.5 ± 3.0 kg/m2) who were randomly assigned to consume either regular sugar or sugar-reduced foods and beverages for 8 weeks, separated by 4-week washout period. Body weight, energy intake (EI), energy expenditure and vascular markers were assessed at baseline and after both interventions. RESULTS: We found that carbohydrate (P < 0.001), total sugars (P < 0.001) and non-milk extrinsic sugars (P < 0.001) (% EI) were lower, whereas fat (P = 0.001) and protein (P = 0.038) intakes (% EI) were higher on the sugar-reduced than the regular diet. No effects on body weight, blood pressure, arterial stiffness, fasting glycemia or lipemia were observed. CONCLUSIONS: Consumption of sugar-reduced products, as part of a blinded dietary exchange for an 8-week period, resulted in a significant reduction in sugar intake. Body weight did not change significantly, which we propose was due to energy compensation.

Equations to predict methane emissions from cows fed at maintenance energy level in pasture-based systems

Ruminant production is a vital part of food industry but it raises environmental concerns, partly due to the associated methane outputs. Efficient methane mitigation and estimation of emissions from ruminants requires accurate prediction tools. Equations recommended by international organizations or scientific studies have been developed with animals fed conserved forages and concentrates and may be used with caution for grazing cattle. The aim of the current study was to develop prediction equations with animals fed fresh grass in order to be more suitable to pasture-based systems and for animals at lower feeding levels. A study with 25 nonpregnant nonlactating cows fed solely fresh-cut grass at maintenance energy level was performed over two consecutive grazing seasons. Grass of broad feeding quality, due to contrasting harvest dates, maturity, fertilisation and grass varieties, from eight swards was offered. Cows were offered the experimental diets for at least 2 weeks before housed in calorimetric chambers over 3 consecutive days with feed intake measurements and total urine and faeces collections performed daily. Methane emissions were measured over the last 2 days. Prediction models were developed from 100 3-day averaged records. Internal validation of these equations, and those recommended in literature, was performed. The existing in greenhouse gas inventories models under-estimated methane emissions from animals fed fresh-cut grass at maintenance while the new models, using the same predictors, improved prediction accuracy. Error in methane outputs prediction was decreased when grass nutrient, metabolisable energy and digestible organic matter concentrations were added as predictors to equations already containing dry matter or energy intakes, possibly because they explain feed digestibility and the type of energy-supplying nutrients more efficiently. Predictions based on readily available farm-level data, such as liveweight and grass nutrient concentrations were also generated and performed satisfactorily. New models may be recommended for predictions of methane emissions from grazing cattle at maintenance or low feeding levels.

Influence of thermoplastic extrusion on the nutritive value of bovine rumen protein

This Study investigated the impact of thermoplastic extrusion on the nutritive quality of bovine rumen protein. Proximal composition, amino acid profile and in vivo true protein digestibility among rats were determined in raw (RBR) and extruded (EBR) rumen. Raw and extruded bovine rumen presented high percentages of protein (more than 95% on dry basis). Neither raw nor extruded proteins had any limiting amino acid, and the RBR and EBR amino acid scores were, respectively, 1.28 (leucine) and 1.25 (methionine plus cystine). Extrusion reduced significantly true protein digestibility from 97.7% to 93.1% (p < 0.001), but protein digestibility-corrected amino acid scores for both proteins (RBR and EBR) were 100%. Animal growth presented comparable profiles using raw and extruded rumen. In conclusion, thermoplastic extrusion did not affect the protein quality of bovine rumen, and this does not hinder the use of this material as a food ingredient. (C) 2009 Elsevier Ltd. Ail rights reserved.

Amaranth protein presents cholesterol-lowering effect

This study describes amaranth`s protein cholesterol-lowering effect and investigates its mechanisms hypercholesterolaemia was induced in male hamsters through diet rich in casein (300 g/kg diet) containing regular levels of cholesterol (0.5 kg/g) fed during 3 weeks. Animals were divided into three groups and fed ad libitum diets for 4 weeks containing as the sole source of protein: casein (control), amaranth protein isolate or, casein + amaranth protein isolate. Plasma concentrations of cholesterol and triacylglycerols were measured at four different points: at the beginning of the study. after hypercholesterolaemia was induced, in the first week and then at the end of the experimental diet period. The reduction of the total plasma cholesterol concentration at the end of experimental period for animals fed on diets containing amaranth protein isolate pure and with casein were 27% (P < 0.05) and 48% (P < 0.05). respectively, being the non-HDL fractions the most affected. Digestibility of protein as well as excretion of cholesterol and bile acid, were investigated as the possible mechanisms for this significant hypocholesterolaemic effect. Cholesterol excretion was related to the hypocholesterolaemia but could not explain all the observed reduction. Our findings suggest that amaranth protein has a metabolic effect on endogenous cholesterol metabolism. (C) 2009 Elsevier Ltd. All rights reserved.

Cholesterol-Lowering Properties of Whole Cowpea Seed and Its Protein Isolate in Hamsters

Hypercholesterolemic hamsters were fed for 4 wk on diets rich in saturated fatty acids and cholesterol, differing only in protein source (20%): casein (control group, HC), whole cowpea seed (HWS), and cowpea protein isolate (HPI). Hamsters fed on HWS and HPI presented significant reductions in plasma total cholesterol and non-HDL cholesterol. HPI and HC presented similar protein digestibility, which were significantly higher than that of HWS. Animals fed on HWS presented significantly higher levels of bile acids and cholesterol in feces than did the animals fed on casein or HPI diets. Histological analyses of the liver showed that HC diet resulted in steatosis widely distributed throughout the hepatic lobule, while HWS and HPI diets promoted reductions in liver steatosis. The effectiveness of HWS for modulating lipid metabolism was greater than that of HPI, as measured by plasma cholesterol reduction and liver steatosis.