Central glucose sensing and the control of energy homeostasis

Glucose is an important signal that regulates glucose and energy homeostasis but its precise physiological role and signaling mechanism in the brain are still uncompletely understood. Over the recent years we have investigated the possibility that central glucose sensing may share functional similarities with glucose sensing by pancreatic beta-cells, in particular a requirement for the expression of the glucose transporter Glut2. Using mice with genetic inactivation of Glut2, but rescued pancreatic beta-cell function by transgenic expression of a glucose transporter, we have established that extrapancreatic glucose sensors are involved: i) in the control of glucagon secretion in response to hypoglycemia, ii) in the control of feeding and iii) of energy expenditure. We have more recently shown that central Glut2-dependent glucose sensors are involved in the regulation of NPY and POMC expression by arcuate nucleus neurons and that the sensitivity to leptin of these neurons is enhanced by Glut2-dependent glucose sensors. Using mice with genetic tagging of Glut2-expressing cells, we determined that the NPY and POMC neurons did not express Glut2 but were connected to Glut2 expressing neurons located most probably outside of the arcuate nucleus. We are now defining the electrophysiological behavior of these Glut2 expressing neurons. Our data provide an initial map of glucose sensing neurons expressing Glut2 and link these neurons with the control of specific physiological function.

Use of phycoerythrin and allophycocyanin for fluorescence resonance energy transfer analyzed by flow cytometry: advantages and limitations.

BACKGROUND: This study validates the use of phycoerythrin (PE) and allophycocyanin (APC) for fluorescence energy transfer (FRET) analyzed by flow cytometry. METHODS: FRET was detected when a pair of antibody conjugates directed against two noncompetitive epitopes on the same CD8alpha chain was used. FRET was also detected between antibody conjugate pairs specific for the two chains of the heterodimeric alpha (4)beta(1) integrin. Similarly, the association of T-cell receptor (TCR) with a soluble antigen ligand was detected by FRET when anti-TCR antibody and MHC class I/peptide complexes (<<tetramers>>) were used. RESULTS: FRET efficiency was always less than 10%, probably because of steric effects associated with the size and structure of PE and APC. Some suggestions are given to take into account this and other effects (e.g., donor and acceptor concentrations) for a better interpretation of FRET results obtained with this pair of fluorochromes. CONCLUSIONS: We conclude that FRET assays can be carried out easily with commercially available antibodies and flow cytometers to study arrays of multimolecular complexes.

The psychosocial difficulties in brain disorders that explain short term changes in health outcomes.

BACKGROUND: This study identifies a set of psychosocial difficulties that are associated with short term changes in health outcomes across a heterogeneous set of brain disorders, neurological and psychiatric. METHODS: Longitudinal observational study over approximately 12 weeks with three time points of assessment and 741 patients with depression, bipolar disorders, multiple sclerosis, parkinson's disease, migraine, traumatic brain injury and stroke. The data on disability was collected with the checklist of the International Classification of Functioning, Disability and Health. The selected health outcomes were the Short Form 36 and the World Health Organization Disability Assessment Schedule. Multilevel models for change were applied controlling for age, gender and disease severity. RESULTS: The psychosocial difficulties that explain the variability and change over time of the selected health outcomes were energy and drive, sleep, and emotional functions, and a broad range of activities and participation domains, such as solving problems, conversation, areas of mobility and self-care, relationships, community life and recreation and leisure. CONCLUSIONS: Our findings are of interest to researchers and clinicians for interventions and health systems planning as they show that in addition to difficulties that are diagnostic criteria of these disorders, there are other difficulties that explain small changes in health outcomes over short periods of time.

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.

Energy relaxation in nonlinear one-dimensional lattices

We study energy relaxation in thermalized one-dimensional nonlinear arrays of the Fermi-Pasta-Ulam type. The ends of the thermalized systems are placed in contact with a zero-temperature reservoir via damping forces. Harmonic arrays relax by sequential phonon decay into the cold reservoir, the lower-frequency modes relaxing first. The relaxation pathway for purely anharmonic arrays involves the degradation of higher-energy nonlinear modes into lower-energy ones. The lowest-energy modes are absorbed by the cold reservoir, but a small amount of energy is persistently left behind in the array in the form of almost stationary low-frequency localized modes. Arrays with interactions that contain both a harmonic and an anharmonic contribution exhibit behavior that involves the interplay of phonon modes and breather modes. At long times relaxation is extremely slow due to the spontaneous appearance and persistence of energetic high-frequency stationary breathers. Breather behavior is further ascertained by explicitly injecting a localized excitation into the thermalized arrays and observing the relaxation behavior.

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.

Iowa's Renewable Energy and Infrastructure Impacts, TR-593, 2010

The federal government is aggressively promoting biofuels as an answer to global climate change and dependence on imported sources of energy. Iowa has quickly become a leader in the bioeconomy and wind energy production, but meeting the United States Department of Energy’s goal having 20% of U.S. transportation fuels come from biologically based sources by 2030 will require a dramatic increase in ethanol and biodiesel production and distribution. At the same time, much of Iowa’s rural transportation infrastructure is near or beyond its original design life. As Iowa’s rural roadway structures, pavements, and unpaved roadways become structurally deficient or functionally obsolete, public sector maintenance and rehabilitation costs rapidly increase. More importantly, costs to move all farm products will rapidly increase if infrastructure components are allowed to fail; longer hauls, slower turnaround times, and smaller loads result. When these results occur on a large scale, Iowa will start to lose its economic competitive edge in the rapidly developing bioeconomy. The primary objective of this study was to document the current physical and fiscal impacts of Iowa’s existing biofuels and wind power industries. A four-county cluster in north-central Iowa and a two-county cluster in southeast Iowa were identified through a local agency survey as having a large number of diverse facilities and were selected for the traffic and physical impact analysis. The research team investigated the large truck traffic patterns on Iowa’s secondary and local roads from 2002 to 2008 and associated those with the pavement condition and county maintenance expenditures. The impacts were quantified to the extent possible and visualized using geographic information system (GIS) tools. In addition, a traffic and fiscal assessment tool was developed to understand the impact of the development of the biofuels on Iowa’s secondary road system. Recommended changes in public policies relating to the local government and to the administration of those policies included standardizing the reporting and format of all county expenditures, conducting regular pavement evaluations on a county’s system, cooperating and communicating with cities (adjacent to a plant site), considering utilization of tax increment financing (TIF) districts as a short-term tool to produce revenues, and considering alternative ways to tax the industry.

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.

Dynamic Modelling of Material Flows and Sustainable Resource Use: Case Studies in Regional Metabolism and Space Life Support Systems

Sustainable resource use is one of the most important environmental issues of our times. It is closely related to discussions on the 'peaking' of various natural resources serving as energy sources, agricultural nutrients, or metals indispensable in high-technology applications. Although the peaking theory remains controversial, it is commonly recognized that a more sustainable use of resources would alleviate negative environmental impacts related to resource use. In this thesis, sustainable resource use is analysed from a practical standpoint, through several different case studies. Four of these case studies relate to resource metabolism in the Canton of Geneva in Switzerland: the aim was to model the evolution of chosen resource stocks and flows in the coming decades. The studied resources were copper (a bulk metal), phosphorus (a vital agricultural nutrient), and wood (a renewable resource). In addition, the case of lithium (a critical metal) was analysed briefly in a qualitative manner and in an electric mobility perspective. In addition to the Geneva case studies, this thesis includes a case study on the sustainability of space life support systems. Space life support systems are systems whose aim is to provide the crew of a spacecraft with the necessary metabolic consumables over the course of a mission. Sustainability was again analysed from a resource use perspective. In this case study, the functioning of two different types of life support systems, ARES and BIORAT, were evaluated and compared; these systems represent, respectively, physico-chemical and biological life support systems. Space life support systems could in fact be used as a kind of 'laboratory of sustainability' given that they represent closed and relatively simple systems compared to complex and open terrestrial systems such as the Canton of Geneva. The chosen analysis method used in the Geneva case studies was dynamic material flow analysis: dynamic material flow models were constructed for the resources copper, phosphorus, and wood. Besides a baseline scenario, various alternative scenarios (notably involving increased recycling) were also examined. In the case of space life support systems, the methodology of material flow analysis was also employed, but as the data available on the dynamic behaviour of the systems was insufficient, only static simulations could be performed. The results of the case studies in the Canton of Geneva show the following: were resource use to follow population growth, resource consumption would be multiplied by nearly 1.2 by 2030 and by 1.5 by 2080. A complete transition to electric mobility would be expected to only slightly (+5%) increase the copper consumption per capita while the lithium demand in cars would increase 350 fold. For example, phosphorus imports could be decreased by recycling sewage sludge or human urine; however, the health and environmental impacts of these options have yet to be studied. Increasing the wood production in the Canton would not significantly decrease the dependence on wood imports as the Canton's production represents only 5% of total consumption. In the comparison of space life support systems ARES and BIORAT, BIORAT outperforms ARES in resource use but not in energy use. However, as the systems are dimensioned very differently, it remains questionable whether they can be compared outright. In conclusion, the use of dynamic material flow analysis can provide useful information for policy makers and strategic decision-making; however, uncertainty in reference data greatly influences the precision of the results. Space life support systems constitute an extreme case of resource-using systems; nevertheless, it is not clear how their example could be of immediate use to terrestrial systems.