Fourier transform convolution integrals applied to generalized Born molecular volume.

Generalized Born methods are currently among the solvation models most commonly used for biological applications. We reformulate the generalized Born molecular volume method initially described by (Lee et al, 2003, J Phys Chem, 116, 10606; Lee et al, 2003, J Comp Chem, 24, 1348) using fast Fourier transform convolution integrals. Changes in the initial method are discussed and analyzed. Finally, the method is extensively checked with snapshots from common molecular modeling applications: binding free energy computations and docking. Biologically relevant test systems are chosen, including 855-36091 atoms. It is clearly demonstrated that, precision-wise, the proposed method performs as good as the original, and could better benefit from hardware accelerated boards.

Direct numerical simulations of interface dynamics to link capillary pressure and total surface energy

The flow of two immiscible fluids through a porous medium depends on the complex interplay between gravity, capillarity, and viscous forces. The interaction between these forces and the geometry of the medium gives rise to a variety of complex flow regimes that are difficult to describe using continuum models. Although a number of pore-scale models have been employed, a careful investigation of the macroscopic effects of pore-scale processes requires methods based on conservation principles in order to reduce the number of modeling assumptions. In this work we perform direct numerical simulations of drainage by solving Navier-Stokes equations in the pore space and employing the Volume Of Fluid (VOF) method to track the evolution of the fluid-fluid interface. After demonstrating that the method is able to deal with large viscosity contrasts and model the transition from stable flow to viscous fingering, we focus on the macroscopic capillary pressure and we compare different definitions of this quantity under quasi-static and dynamic conditions. We show that the difference between the intrinsic phase-average pressures, which is commonly used as definition of Darcy-scale capillary pressure, is subject to several limitations and it is not accurate in presence of viscous effects or trapping. In contrast, a definition based on the variation of the total surface energy provides an accurate estimate of the macroscopic capillary pressure. This definition, which links the capillary pressure to its physical origin, allows a better separation of viscous effects and does not depend on the presence of trapped fluid clusters.

Dynamic models of energy allocation and investment

In dynamic models of energy allocation, assimilated energy is allocated to reproduction, somatic growth, maintenance or storage, and the allocation pattern can change with age. The expected evolutionary outcome is an optimal allocation pattern, but this depends on the environment experienced during the evolutionary process and on the fitness costs and benefits incurred by allocating resources in different ways. Here we review existing treatments which encompass some of the possibilities as regards constant or variable environments and their predictability or unpredictability, and the ways in which production rates and mortality rates depend on body size and composition and age and on the pattern of energy allocation. The optimal policy is to allocate resources where selection pressures are highest, and simultaneous allocation to several body subsystems and reproduction can be optimal if these pressures are equal. This may explain balanced growth commonly observed during ontogeny. Growth ceases at maturity in many models; factors favouring growth after maturity include non-linear trade-offs, variable season length, and production and mortality rates both increasing (or decreasing) functions of body size. We cannot yet say whether these are sufficient to account for the many known cases of growth after maturity and not all reasonable models have yet been explored. Factors favouring storage are also reviewed.

Verbal labels selectively bias brain responses to high-energy foods.

The influence of external factors on food preferences and choices is poorly understood. Knowing which and how food-external cues impact the sensory processing and cognitive valuation of food would provide a strong benefit toward a more integrative understanding of food intake behavior and potential means of interfering with deviant eating patterns to avoid detrimental health consequences for individuals in the long run. We investigated whether written labels with positive and negative (as opposed to 'neutral') valence differentially modulate the spatio-temporal brain dynamics in response to the subsequent viewing of high- and low-energetic food images. Electrical neuroimaging analyses were applied to visual evoked potentials (VEPs) from 20 normal-weight participants. VEPs and source estimations in response to high- and low- energy foods were differentially affected by the valence of preceding word labels over the ~260-300 ms post-stimulus period. These effects were only observed when high-energy foods were preceded by labels with positive valence. Neural sources in occipital as well as posterior, frontal, insular and cingulate regions were down-regulated. These findings favor cognitive-affective influences especially on the visual responses to high-energetic food cues, potentially indicating decreases in cognitive control and goal-adaptive behavior. Inverse correlations between insular activity and effectiveness in food classification further indicate that this down-regulation directly impacts food-related behavior.

Evidence of energy sparing in Gambian women during pregnancy: a longitudinal study using whole-body calorimetry.

Components of daily energy expenditure were measured serially by whole-body calorimetry in Gambian women before pregnancy and at 6, 12, 18, 24, 30, and 36 wk gestation. Weight gain was (mean +/- SD) 6.8 +/- 2.8 kg, fat deposition was 2.0 +/- 2.5 kg and lean tissue deposition was 5.0 +/- 2.5 kg. Basal metabolic rate (BMR) was depressed during the first 18 wk of gestation, causing total cumulative maintenance costs by week 36 to be 8.4 MJ. Individual responses to pregnancy correlated with changes in body mass (36 wk: delta BMR vs delta weight; r = 0.60, P < 0.01 delta BMR vs delta LBM; r = 0.62, P < 0.01). There was no significant increase in the cost of treadmill exercise (0% slope: F = 0.71, P = 0.64; 5% slope: F = 1.97, P = 0.10), 24-h energy expenditure (F = 0.72, P = 0.64), activity or diet-induced thermogenesis (F = 1.02, P = 0.43), during pregnancy in spite of body weight gain. Total metabolic costs over 36 wk were 144 MJ (fetus 43 MJ, fat deposition 92 MJ, cumulative maintenance costs 8.4 MJ). These were far lower than reported for well-nourished Western populations.

Transepidermal water loss and resting energy expenditure in preterm infants.

Skin water loss of preterm infants, nursed naked in incubators under thermoneutral conditions, was assessed by a method based on the measurement of water vapor pressure gradient close to the skin surface. The corresponding skin evaporative heat loss was calculated using an energy equivalent of 0.58 kcal/g water vaporised. During the first 5 weeks of life, 128 sets of measurements were made on 56 infants whose gestational age ranged from 28 to 37 weeks. In the first week of life, infants of less than 30 weeks of gestation had substantially higher transepidermal water loss (TEWL) and skin evaporative heat loss (skin EHL) (41.5 +/- 11.5 g/kg X day TEWL; 24.1 +/- 6.5 kcal/kg X day skin EHL) than infants of 34 weeks and greater (11.1 +/- 4.1 g/kg X day; 6.4 +/- 2.4 kcal/kg X day). Infants of 30-33 weeks of gestation had intermediate values (22.4 +/- 7.6 g/kg X day; 13 +/- 4.4 kcal/kg X day). From the third week of life on, TEWL was similar for all preterm infants, i.e. 14.2 +/- 2.6 to 12.7 +/- 1.9 g/kg X day and corresponds to skin EHL of 8.2 +/- 1.5 to 7.4 +/- 1.1 kcal/kg X day. There was a significant inverse relationship between gestational age and TEWL and also between postnatal age and TEWL. In an additional group of 7 preterm infants (30-34 weeks of gestation, mean postnatal age of 21 +/- 9 days) transepidermal water loss and energy expenditure were measured simultaneously. The skin evaporative heat loss (8.8 +/- 2.5 kcal/kg X day) accounted for 17 +/- 5% of energy expenditure (53.3 +/- 4.1 kcal/kg X day). This study emphasizes that in infants of less than 30 weeks of gestation, the transepidermal water loss is of great importance and makes a major contribution to water and heat balances.

Effects of mental stress on insulin-mediated glucose metabolism and energy expenditure in lean and obese women.

The effects of the sympathetic activation elicited by a mental stress on insulin sensitivity and energy expenditure (VO(2)) were studied in 11 lean and 8 obese women during a hyperinsulinemic-euglycemic clamp. Six lean women were restudied under nonselective beta-adrenergic blockade with propranolol to determine the role of beta-adrenoceptors in the metabolic response to mental stress. In lean women, mental stress increased VO(2) by 20%, whole body glucose utilization ([6,6-(2)H(2)]glucose) by 34%, and cardiac index (thoracic bioimpedance) by 25%, whereas systemic vascular resistance decreased by 24%. In obese women, mental stress increased energy expenditure as in lean subjects, but it neither stimulated glucose uptake nor decreased systemic vascular resistance. In the six lean women who were restudied under propranolol, the rise in VO(2), glucose uptake, and cardiac output and the decrease in systemic vascular resistance during mental stress were all abolished. It is concluded that 1) in lean subjects, mental stress stimulates glucose uptake and energy expenditure and produces vasodilation; activation of beta-adrenoceptors is involved in these responses; and 2) in obese patients, the effects of mental stress on glucose uptake and systemic vascular resistance, but not on energy expenditure, are blunted.

Energy gap in the aetiology of body weight gain and obesity: a challenging concept with a complex evaluation and pitfalls.

The concept of energy gap(s) is useful for understanding the consequence of a small daily, weekly, or monthly positive energy balance and the inconspicuous shift in weight gain ultimately leading to overweight and obesity. Energy gap is a dynamic concept: an initial positive energy gap incurred via an increase in energy intake (or a decrease in physical activity) is not constant, may fade out with time if the initial conditions are maintained, and depends on the 'efficiency' with which the readjustment of the energy imbalance gap occurs with time. The metabolic response to an energy imbalance gap and the magnitude of the energy gap(s) can be estimated by at least two methods, i.e. i) assessment by longitudinal overfeeding studies, imposing (by design) an initial positive energy imbalance gap; ii) retrospective assessment based on epidemiological surveys, whereby the accumulated endogenous energy storage per unit of time is calculated from the change in body weight and body composition. In order to illustrate the difficulty of accurately assessing an energy gap we have used, as an illustrative example, a recent epidemiological study which tracked changes in total energy intake (estimated by gross food availability) and body weight over 3 decades in the US, combined with total energy expenditure prediction from body weight using doubly labelled water data. At the population level, the study attempted to assess the cause of the energy gap purported to be entirely due to increased food intake. Based on an estimate of change in energy intake judged to be more reliable (i.e. in the same study population) and together with calculations of simple energetic indices, our analysis suggests that conclusions about the fundamental causes of obesity development in a population (excess intake vs. low physical activity or both) is clouded by a high level of uncertainty.

Prolonged but not short negative energy condition restored corticoadrenal leptin sensitivity in the hypothalamic obese rat.

BACKGROUND/AIM: We have reported that neonatal treatment with monosodium L-glutamate (MSG), which causes damage to the arcuate nucleus, leads to severe hyperleptinemia and reduced adrenal leptin receptor (ob-Rb) expression in adulthood. As a result, rats given MSG neonatally display corticoadrenal leptin-resistance, a defect that is overridden by normalization of corticoadrenal hyperfunction. The aim of the present study was to determine whether negative energy conditions could correct corticoadrenal cell dysfunction in rats given MSG neonatally. METHODS: Normal (CTR) and MSG-treated female rats were subjected to food removal for 1-5 days, or prolonged (24-61 days) food restriction (FR). Plasma levels of several biomarkers and in vitro corticoadrenal function were evaluated following starvation or FR. RESULTS: Fasting for 1-5 days reduced plasma leptin levels in CTR and MSG rats, compared to levels in the respective groups fed ad libitum(p < 0.05), but adrenal leptin-resistance was unchanged. With prolonged FR, isolated adrenal cells from MSG rats became sensitive to leptin, which lowered ACTH-induced glucocorticoid release. This restoration of leptin response was associated with normalization of adrenal ob-Rb gene expression. CONCLUSION: Dietary restriction in some leptin-resistant obese phenotypes may normalize adrenocortical function.

Energy metabolism during the postexercise recovery in man.

In order to explore the magnitude and duration of the long-term residual effect of physical exercise, a mixed meal (55% CHO, 27% fat and 18% protein) was given to 10 young male volunteers on two occasions: after a 4-h resting period, and on the next day, 30 min after completion of a 3-h exercise at 50% VO2max. Energy expenditure and substrate utilization were determined by indirect calorimetry for 17 h after meal ingestion. The fuel mix oxidized after the meal was characterized by a greater contribution of lipid oxidation to total energy expenditure when the meal was ingested during the post-exercise period as compared with the meal ingested without previous exercise. During the night following the exercise, the stimulation of energy expenditure observed during the early recovery period gradually faded out. However, resting energy expenditure measured the next morning was significantly higher (+4.7%) than that measured without previous exercise. It is concluded that intense exercise stimulates both energy expenditure and lipid oxidation for a prolonged period.

The kinetic parameters and energy cost of the Hsp70 chaperone as a polypeptide unfoldase.

Hsp70-Hsp40-NEF and possibly Hsp100 are the only known molecular chaperones that can use the energy of ATP to convert stably pre-aggregated polypeptides into natively refolded proteins. However, the kinetic parameters and ATP costs have remained elusive because refolding reactions have only been successful with a molar excess of chaperones over their polypeptide substrates. Here we describe a stable, misfolded luciferase species that can be efficiently renatured by substoichiometric amounts of bacterial Hsp70-Hsp40-NEF. The reactivation rates increased with substrate concentration and followed saturation kinetics, thus allowing the determination of apparent V(max)' and K(m)' values for a chaperone-mediated renaturation reaction for the first time. Under the in vitro conditions used, one Hsp70 molecule consumed five ATPs to effectively unfold a single misfolded protein into an intermediate that, upon chaperone dissociation, spontaneously refolded to the native state, a process with an ATP cost a thousand times lower than expected for protein degradation and resynthesis.