Defect-enhanced energy storage
Dielectric capacitors are vital components of electronics and power systems. The thin-film materials of which capacitors are composed are usually optimized by changing ...the material composition. However, Kim
et al.
found that postprocessing an already effective thin-film dielectric by high-energy ion bombardment further improved the material because of the introduction of specific types of defects that ultimately improved the energy storage performance. The results suggest that postprocessing may be important for developing the next generation of capacitors.
Science
, this issue p.
81
High-energy ion bombardment considerably improves the dielectric properties of a relaxor ferroelectric thin film.
Dielectric capacitors can store and release electric energy at ultrafast rates and are extensively studied for applications in electronics and electric power systems. Among various candidates, thin films based on relaxor ferroelectrics, a special kind of ferroelectric with nanometer-sized domains, have attracted special attention because of their high energy densities and efficiencies. We show that high-energy ion bombardment improves the energy storage performance of relaxor ferroelectric thin films. Intrinsic point defects created by ion bombardment reduce leakage, delay low-field polarization saturation, enhance high-field polarizability, and improve breakdown strength. We demonstrate energy storage densities as high as ~133 joules per cubic centimeter with efficiencies exceeding 75%. Deterministic control of defects by means of postsynthesis processing methods such as ion bombardment can be used to overcome the trade-off between high polarizability and breakdown strength.
Engineering mammalian cells to carry out sophisticated and customizable genetic programs requires a toolkit of multiple orthogonal and well-characterized transcription factors (TFs). To address this ...need, we develop the COmposable Mammalian Elements of Transcription (COMET)-an ensemble of TFs and promoters that enable the design and tuning of gene expression to an extent not, to the best of our knowledge, previously possible. COMET currently comprises 44 activating and 12 inhibitory zinc-finger TFs and 83 cognate promoters, combined in a framework that readily accommodates new parts. This system can tune gene expression over three orders of magnitude, provides chemically inducible control of TF activity, and enables single-layer Boolean logic. We also develop a mathematical model that provides mechanistic insights into COMET performance characteristics. Altogether, COMET enables the design and construction of customizable genetic programs in mammalian cells.
Glycine N-methyltransferase (GNMT) is the most abundant liver methyltransferase regulating the availability of the biological methyl donor, S-adenosylmethionine (SAM). Moreover, GNMT has been ...identified to be down-regulated in hepatocellular carcinoma (HCC). Despite its role in regulating SAM levels and association of its down-regulation with liver tumorigenesis, the impact of reduced GNMT on metabolic reprogramming before the manifestation of HCC has not been investigated in detail. Herein, we used 2H/13C metabolic flux analysis in conscious, unrestrained mice to test the hypothesis that the absence of GNMT causes metabolic reprogramming. GNMT-null (KO) mice displayed a reduction in blood glucose that was associated with a decline in both hepatic glycogenolysis and gluconeogenesis. The reduced gluconeogenesis was due to a decrease in liver gluconeogenic precursors, citric acid cycle fluxes, and anaplerosis and cataplerosis. A concurrent elevation in both hepatic SAM and metabolites of SAM utilization pathways was observed in the KO mice. Specifically, the increase in metabolites of SAM utilization pathways indicated that hepatic polyamine synthesis and catabolism, transsulfuration, and de novo lipogenesis pathways were increased in the KO mice. Of note, these pathways utilize substrates that could otherwise be used for gluconeogenesis. Also, this metabolic reprogramming occurs before the well-documented appearance of HCC in GNMT-null mice. Together, these results indicate that GNMT deletion promotes a metabolic shift whereby nutrients are channeled away from glucose formation toward pathways that utilize the elevated SAM.
Glucagon's effect on liver protein metabolism in vivo Kraft, Guillaume; Coate, Katie C; Winnick, Jason J ...
American journal of physiology: endocrinology and metabolism,
09/2017, Letnik:
313, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The postprandial state is characterized by a storage of nutrients in the liver, muscle, and adipose tissue for later utilization. In the case of a protein-rich meal, amino acids (AA) stimulate ...glucagon secretion by the α-cell. The aim of the present study was to determine the impact of the rise in glucagon on AA metabolism, particularly in the liver. We used a conscious catheterized dog model to recreate a postprandial condition using a pancreatic clamp. Portal infusions of glucose, AA, and insulin were used to achieve postprandial levels, while portal glucagon infusion was either maintained at the basal level or increased by three-fold. The high glucagon infusion reduced the increase in arterial AA concentrations compared with the basal glucagon level (-23%,
< 0.05). In the presence of high glucagon, liver AA metabolism shifted toward a more catabolic state with less protein synthesis (-36%) and increased urea production (+52%). Net hepatic glucose uptake was reduced modestly (-35%), and AA were preferentially used in gluconeogenesis, leading to lower glycogen synthesis (-54%). The phosphorylation of AMPK was increased by the high glucagon infusion (+40%), and this could be responsible for increasing the expression of genes related to pathways producing energy and lowering those involved in energy consumption. In conclusion, the rise in glucagon associated with a protein-rich meal promotes a catabolic utilization of AA in the liver, thereby, opposing the storage of AA in proteins.
Abstract
Background
Dementia is an increasingly important public health problem with various risk factors. Respiratory function, measured via peak expiratory flow (PEF), may be a modifiable dementia ...risk factor.
Methods
We investigated the association between PEF and incident dementia in 5 935 older adults from the National Health and Aging Trends Study (NHATS) from 2011 to 2014. Baseline PEF, expressed as a standardized residual (SR) percentile, was analyzed as a predictor of incident dementia using discrete-time proportional hazards models, while controlling for several health and sociodemographic covariates.
Results
After 14 332 person-years of follow-up, 9.0% (N = 536) had incident cases of dementia. Compared to the lowest PEF category (SR-percentile < 10%), the highest PEF category (SR-percentile ≥ 80%) had 49% lower risk of incident dementia (hazard ratio HR = 0.51; 95% confidence interval CI; 0.37, 0.71), and the second highest PEF category (SR-percentile 50%–80%) had 25% lower risk of incident dementia (HR = 0.75; 95% CI 0.56, 1.00). A sensitivity analysis using multiple imputation to account for missing PEF measurements yielded similar associations with incident dementia.
Conclusion
These associations suggest a dose–dependent relationship such that higher PEF categories were more protective against incident dementia. PEF may be considered as an easily administered, low-cost measure of respiratory function and a potentially modifiable dementia risk factor. Improving PEF may reduce dementia risk through vascular mechanisms, such as increased brain oxygenation. Future research should explore potential causal pathways between PEF and dementia.
Pathologies including diabetes and conditions such as exercise place an unusual demand on liver energy metabolism, and this demand induces a state of energy discharge. Hepatic AMP-activated protein ...kinase (AMPK) has been proposed to inhibit anabolic processes such as gluconeogenesis in response to cellular energy stress. However, both AMPK activation and glucose release from the liver are increased during exercise. Here, we sought to test the role of hepatic AMPK in the regulation of in vivo glucose-producing and citric acid cycle–related fluxes during an acute bout of muscular work. We used 2H/13C metabolic flux analysis to quantify intermediary metabolism fluxes in both sedentary and treadmill-running mice. Additionally, liver-specific AMPK α1 and α2 subunit KO and WT mice were utilized. Exercise caused an increase in endogenous glucose production, glycogenolysis, and gluconeogenesis from phosphoenolpyruvate. Citric acid cycle fluxes, pyruvate cycling, anaplerosis, and cataplerosis were also elevated during this exercise. Sedentary nutrient fluxes in the postabsorptive state were comparable for the WT and KO mice. However, the increment in the endogenous rate of glucose appearance during exercise was blunted in the KO mice because of a diminished glycogenolytic flux. This lower rate of glycogenolysis was associated with lower hepatic glycogen content before the onset of exercise and prompted a reduction in arterial glucose during exercise. These results indicate that liver AMPKα1α2 is required for maintaining glucose homeostasis during an acute bout of exercise.
Multiferroic BiFeO3 (BFO) films with spontaneously formed periodic stripe domains can generate above-gap open circuit voltages under visible light illumination; nevertheless the underlying mechanism ...behind this intriguing optoelectronic response has not been understood to date. Here, we make contact-free measurements of light-induced currents in epitaxial BFO films via detecting terahertz radiation emanated by these currents, enabling a direct probe of the intrinsic charge separation mechanisms along with quantitative measurements of the current amplitudes and their directions. In the periodic stripe samples, we find that the net photocurrent is dominated by the charge separation across the domain walls, whereas in the monodomain samples the photovoltaic response arises from a bulk shift current associated with the non-centrosymmetry of the crystal. The peak current amplitude driven by the charge separation at the domain walls is found to be 2 orders of magnitude higher than the bulk shift current response, indicating the prominent role of domain walls acting as nanoscale junctions to efficiently separate photogenerated charges in the stripe domain BFO films. These findings show that domain-wall-engineered BFO thin films offer exciting prospects for ferroelectric-based optoelectronics, as well as bias-free strong terahertz emitters.
AMPK is an energy sensor that protects cellular energy state by attenuating anabolic and promoting catabolic processes. AMPK signaling is purported to regulate hepatic gluconeogenesis and substrate ...oxidation; coordination of these processes is vital during nutrient deprivation or pathogenic during overnutrition. Here we directly test hepatic AMPK function in regulating metabolic fluxes that converge to produce glucose and energy in vivo. Flux analysis was applied in mice with a liver-specific deletion of AMPK (L-KO) or floxed control littermates to assess rates of hepatic glucose producing and citric acid cycle (CAC) fluxes. Fluxes were assessed in short and long term fasted mice; the latter condition is a nutrient stressor that increases liver AMP/ATP. The flux circuit connecting anaplerosis with gluconeogenesis from the CAC was unaffected by hepatic AMPK deletion in short and long term fasting. Nevertheless, depletion of hepatic ATP was exacerbated in L-KO mice, corresponding to a relative elevation in citrate synthase flux and accumulation of branched-chain amino acid-related metabolites. L-KO mice also had a physiological reduction in flux from glycogen to G6P. These results demonstrate AMPK is unnecessary for maintaining gluconeogenic flux from the CAC yet is critical for stabilizing liver energy state during nutrient deprivation.
Objective. Walking is a key component of daily-life mobility. We examined associations between laboratory-measured gait quality and daily-life mobility through Actigraphy and Global Positioning ...System (GPS). We also assessed the relationship between two modalities of daily-life mobility i.e., Actigraphy and GPS. Methods . In community-dwelling older adults (N = 121, age = 77±5 years, 70% female, 90% white), we obtained gait quality from a 4-m instrumented walkway (gait speed, walk-ratio, variability) and accelerometry during 6-Minute Walk (adaptability, similarity, smoothness, power, and regularity). Physical activity measures of step-count and intensity were captured from an Actigraph. Time out-of-home, vehicular time, activity-space, and circularity were quantified using GPS. Partial Spearman correlations between laboratory gait quality and daily-life mobility were calculated. Linear regression was used to model step-count as a function of gait quality. ANCOVA and Tukey analysis compared GPS measures across activity groups high, medium, low based on step-count. Age, BMI, and sex were used as covariates. Results . Greater gait speed, adaptability, smoothness, power, and lower regularity were associated with higher step-counts (0.20<|ρ p |<0.26, p<.05 ). Age(β = -0.37), BMI(β = -0.30), speed(β = 0.14), adaptability(β = 0.20), and power(β = 0.18), explained 41.2% variance in step-count. Gait characteristics were not related to GPS measures. Participants with high (>4800 steps) compared to low activity (steps<3100) spent more time out-of-home (23 vs 15%), more vehicular travel (66 vs 38 minutes), and larger activity-space (5.18 vs 1.88 km 2 ), all p<.05 . Conclusions . Gait quality beyond speed contributes to physical activity. Physical activity and GPS-derived measures capture distinct aspects of daily-life mobility. Wearable-derived measures should be considered in gait and mobility-related interventions.
The importance of hypothalamic insulin action to the regulation of hepatic glucose metabolism in the presence of a normal liver/brain insulin ratio (3:1) is unknown. Thus, we assessed the role of ...central insulin action in the response of the liver to normal physiologic hyperinsulinemia over 4 h. Using a pancreatic clamp, hepatic portal vein insulin delivery was increased three- or eightfold in the conscious dog. Insulin action was studied in the presence or absence of intracerebroventricularly mediated blockade of hypothalamic insulin action. Euglycemia was maintained, and glucagon was clamped at basal. Both the molecular and metabolic aspects of insulin action were assessed. Blockade of hypothalamic insulin signaling did not alter the insulin-mediated suppression of hepatic gluconeogenic gene transcription but blunted the induction of glucokinase gene transcription and completely blocked the inhibition of glycogen synthase kinase-3β gene transcription. Thus, central and peripheral insulin action combined to control some, but not other, hepatic enzyme programs. Nevertheless, inhibition of hypothalamic insulin action did not alter the effects of the hormone on hepatic glucose flux (production or uptake). These data indicate that brain insulin action is not a determinant of the rapid (<4 h) inhibition of hepatic glucose metabolism caused by normal physiologic hyperinsulinemia in this large animal model.
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