Considerable evidence suggests that the time of day at which calories are consumed markedly impacts body weight gain and adiposity. However, a precise quantification of energy balance parameters ...during controlled animal studies enforcing time-of-day-restricted feeding is currently lacking in the absence of direct human interaction.
The purpose of the present study was therefore to quantify the effects of restricted feeding during the light (sleep)-phase in a fully-automated, computer-controlled comprehensive laboratory animal monitoring system (CLAMS) designed to modulate food access in a time-of-day-dependent manner. Energy balance, gene expression (within metabolically relevant tissues), humoral factors and body weight were assessed.
We report that relative to mice fed only during the dark (active)-phase, light (sleep)-phase fed mice: (1) consume a large meal upon initiation of food availability; (2) consume greater total calories per day; (3) exhibit a higher respiratory exchange ratio (indicative of decreased reliance on lipid/fatty acid oxidation); (4) exhibit tissue-specific alterations in the phases and amplitudes of circadian clock and metabolic genes in metabolically active tissues (greatest phase differences observed in the liver and diminution of amplitudes in epididymal fat, gastrocnemius muscle and heart); (5) exhibit diminished amplitude in humoral factor diurnal variations (for example, corticosterone); and (6) exhibit greater weight gain within 9 days of restricted feeding.
Collectively, these data suggest that weight gain following light (sleep)-phase restricted feeding is associated with significant alterations in energy balance, as well as dyssynchrony between metabolically active organs.
Variation in platelet reactivity contributes to disorders of hemostasis and thrombosis, but the molecular mechanisms are not well understood.
To discover associations between interindividual platelet ...variability and the responsible platelet genes, and to begin to define the molecular mechanisms altering platelet gene expression.
Two hundred and eighty-eight healthy subjects were phenotyped for platelet responsiveness. Platelet RNA from subjects demonstrating hyperreactivity (n=18) and hyporeactivity (n=11) was used to screen the human transcriptome.
Distinctly different mRNA profiles were observed between subjects with differing platelet reactivity. Increased levels of mRNA for VAMP8/endobrevin, a critical v-SNARE involved in platelet granule secretion, were associated with platelet hyperreactivity (Q=0.0275). Validation studies of microarray results showed 4.8-fold higher mean VAMP8 mRNA levels in hyperreactive than hyporeactive platelets (P=0.0023). VAMP8 protein levels varied 13-fold among platelets from these normal subjects, and were 2.5-fold higher in hyperreactive platelets (P=0.05). Among our cohort of 288 subjects, a VAMP8 single-nucleotide polymorphism (rs1010) was associated with platelet reactivity in an age-dependent manner (P<0.003). MicroRNA-96 was predicted to bind to the 3'-untranslated regionof VAMP8 mRNA and was detected in platelets. Overexpression of microRNA-96 in VAMP8-expressing cell lines caused a dose-dependent decrease in VAMP8 protein and mRNA, suggesting a role in VAMP8 mRNA degradation.
These findings support a role for VAMP8/endobrevin in the heterogeneity of platelet reactivity, and suggest a role for microRNA-96 in the regulation of VAMP8 expression.
Background: Excess caloric intake is strongly associated with the development of increased adiposity, glucose intolerance, insulin resistance, dyslipidemia, and hyperleptinemia (that is the ...cardiometabolic syndrome). Research efforts have focused attention primarily on the quality (that is nutritional content) and/or quantity of ingested calories as potential causes for diet-induced pathology. Despite growing acceptance that biological rhythms profoundly influence energy homeostasis, little is known regarding how the timing of nutrient ingestion influences development of common metabolic diseases. Objective: To test the hypothesis that the time of day at which dietary fat is consumed significantly influences multiple cardiometabolic syndrome parameters. Results: We report that mice fed either low- or high-fat diets in a contiguous manner during the 12 h awake/active period adjust both food intake and energy expenditure appropriately, such that metabolic parameters are maintained within a normal physiologic range. In contrast, fluctuation in dietary composition during the active period (as occurs in human beings) markedly influences whole body metabolic homeostasis. Mice fed a high-fat meal at the beginning of the active period retain metabolic flexibility in response to dietary challenges later in the active period (as revealed by indirect calorimetry). Conversely, consumption of high-fat meal at the end of the active phase leads to increased weight gain, adiposity, glucose intolerance, hyperinsulinemia, hypertriglyceridemia, and hyperleptinemia (that is cardiometabolic syndrome) in mice. The latter perturbations in energy/metabolic homeostasis are independent of daily total or fat-derived calories. Conclusions: The time of day at which carbohydrate versus fat is consumed markedly influences multiple cardiometabolic syndrome parameters.
Physical activity and exercise play critical roles in energy balance. While many interventions targeted at increasing physical activity have demonstrated efficacy in promoting weight loss or ...maintenance in the short term, long term adherence to such programmes is not frequently observed. Numerous factors have been examined for their ability to predict and/or influence physical activity and exercise adherence. Although physical activity has been demonstrated to have a strong genetic component in both animals and humans, few studies have examined the association between genetic variation and exercise adherence. In this review, we provide a detailed overview of the non‐genetic and genetic predictors of physical activity and adherence to exercise. In addition, we report the results of analysis of 26 single nucleotide polymorphisms in six candidate genes examined for association to exercise adherence, duration, intensity and total exercise dose in young adults from the Training Interventions and Genetics of Exercise Response (TIGER) Study. Based on both animal and human research, neural signalling and pleasure/reward systems in the brain may drive in large part the propensity to be physically active and to adhere to an exercise programme. Adherence/compliance research in other fields may inform future investigation of the genetics of exercise adherence.
Summary
Obesity is one of the most profound public health problems today, and simplistic explanations based on excessive nutritional consumption or lack of physical activity are inadequate to account ...for this dramatic and literal growth in our world population. Recent reports have suggested that disruptions in sleep patterns, often linked to our ‘24‐h’ lifestyle, are associated with increased body fat and altered metabolism, although the cause–effect relationship for these associations has yet to be elucidated. Abnormal sleep/wake patterns likely alter intracellular circadian clocks, which are molecular mechanisms that enable the cell/tissue/organism to anticipate diurnal variations in its environment. The environment may include circulating levels of nutrients (e.g. glucose, fatty acids and triglycerides) and various hormones (e.g. insulin, glucocorticoids). As such, alterations in this molecular mechanism, in particular within the adipocyte, likely induce metabolic changes that may potentiate disrupted metabolism, adipose accumulation and/or obesity. Although diurnal variations in adipokines and adipose tissue metabolism have been observed, little is known regarding the molecular mechanisms that influence these events.
NASA's New Horizons spacecraft has revealed the complex geology of Pluto and Charon. Pluto's encounter hemisphere shows ongoing surface geological activity centered on a vast basin containing a thick ...layer of volatile ices that appears to be involved in convection and advection, with a crater retention age no greater than ~10 million years. Surrounding terrains show active glacial flow, apparent transport and rotation of large buoyant water-ice crustal blocks, and pitting, the latter likely caused by sublimation erosion and/or collapse. More enigmatic features include tall mounds with central depressions that are conceivably cryovolcanic and ridges with complex bladed textures. Pluto also has ancient cratered terrains up to ~4 billion years old that are extensionally faulted and extensively mantled and perhaps eroded by glacial or other processes. Charon does not appear to be currently active, but experienced major extensional tectonism and resurfacing (probably cryovolcanic) nearly 4 billion years ago. Impact crater populations on Pluto and Charon are not consistent with the steepest impactor size-frequency distributions proposed for the Kuiper belt.
We investigate the single-photon double ionization of helium at photon energies of 440 and 800 eV. We observe doubly charged ions with close to zero momentum corresponding to electrons emitted back ...to back with equal energy. These slow ions are the unique fingerprint of an elusive quasifree photon double ionization mechanism predicted by Amusia et al. nearly four decades ago J. Phys. B 8, 1248 (1975). It results from the nondipole part of the electromagnetic interaction. Our experimental data are supported by calculations performed using the convergent close-coupling and time-dependent close-coupling methods.
Hyperacute kidney rejection is unusual in crossmatch positive recipients of simultaneous liver–kidney transplants (SLKT). However, recent data suggest that these patients remain at risk for ...antibody‐mediated kidney rejection. To further investigate the risk associated with donor‐specific alloantibodies (DSA) in SLKT, we studied 86 consecutive SLKT patients with an available pre‐SLKT serum sample. Serum samples were analyzed in a blinded fashion for HLA DSA using single antigen beads (median florescence intensity ≥ 2,000 = positive). Post‐SLKT samples were analyzed when available (76%). Thirty patients had preformed DSA, and nine developed de novo DSA. Preformed class I DSA did not change the risk of rejection, patient or allograft survival. In contrast, preformed class II DSA was associated with a markedly increased risk of renal antibody mediated rejection (AMR) (p = 0.006), liver allograft rejection (p = 0.002), patient death (p = 0.02), liver allograft loss (p = 0.02) and renal allograft loss (p = 0.045). Multivariable modeling showed class II DSA (preformed or de novo) to be an independent predictor of patient death (HR = 2.2; p = 0.043) and liver allograft loss (HR = 2.2; p = 0.044). These data warrant reconsideration of the approach to DSA in SLKT.
Preformed class II, but not class I, donor‐specifi c alloantibodies are associated with an increased risk of renal antibody‐mediated rejection, liver allograft rejection, patient death, liver allograft loss, and renal allograft loss in recipients of simultaneous liver—kidney transplants.
The Pluto system was recently explored by NASA's New Horizons spacecraft, making closest approach on 14 July 2015. Pluto's surface displays diverse landforms, terrain ages, albedos, colors, and ...composition gradients. Evidence is found for a water-ice crust, geologically young surface units, surface ice convection, wind streaks, volatile transport, and glacial flow. Pluto's atmosphere is highly extended, with trace hydrocarbons, a global haze layer, and a surface pressure near 10 microbars. Pluto's diverse surface geology and long-term activity raise fundamental questions about how small planets remain active many billions of years after formation. Pluto's large moon Charon displays tectonics and evidence for a heterogeneous crustal composition; its north pole displays puzzling dark terrain. Small satellites Hydra and Nix have higher albedos than expected.
PDF
