Exome sequencing identifies CTSK mutations in patients originally diagnosed as intermediate osteopetrosis.

Autosomal Recessive Osteopetrosis is a genetic disorder characterized by increased bone density due to lack of resorption by the osteoclasts. Genetic studies have widely unraveled the molecular basis of the most severe forms, while cases of intermediate severity are more difficult to characterize, probably because of a large heterogeneity. Here, we describe the use of exome sequencing in the molecular diagnosis of 2 siblings initially thought to be affected by "intermediate osteopetrosis", which identified a homozygous mutation in the CTSK gene. Prompted by this finding, we tested by Sanger sequencing 25 additional patients addressed to us for recessive osteopetrosis and found CTSK mutations in 4 of them. In retrospect, their clinical and radiographic features were found to be compatible with, but not typical for, Pycnodysostosis. We sought to identify modifier genes that might have played a role in the clinical manifestation of the disease in these patients, but our results were not informative. In conclusion, we underline the difficulties of differential diagnosis in some patients whose clinical appearance does not fit the classical malignant or benign picture and recommend that CTSK gene be included in the molecular diagnosis of high bone density conditions.

Determinants of brain cell metabolic phenotypes and energy substrate utilization unraveled with a modeling approach.

Although all brain cells bear in principle a comparable potential in terms of energetics, in reality they exhibit different metabolic profiles. The specific biochemical characteristics explaining such disparities and their relative importance are largely unknown. Using a modeling approach, we show that modifying the kinetic parameters of pyruvate dehydrogenase and mitochondrial NADH shuttling within a realistic interval can yield a striking switch in lactate flux direction. In this context, cells having essentially an oxidative profile exhibit pronounced extracellular lactate uptake and consumption. However, they can be turned into cells with prominent aerobic glycolysis by selectively reducing the aforementioned parameters. In the case of primarily oxidative cells, we also examined the role of glycolysis and lactate transport in providing pyruvate to mitochondria in order to sustain oxidative phosphorylation. The results show that changes in lactate transport capacity and extracellular lactate concentration within the range described experimentally can sustain enhanced oxidative metabolism upon activation. Such a demonstration provides key elements to understand why certain brain cell types constitutively adopt a particular metabolic profile and how specific features can be altered under different physiological and pathological conditions in order to face evolving energy demands.

Effect of weight loss on resting energy expenditure in obese prepubertal children.

To assess the effect of weight loss on resting metabolic rate (RMR), the energy expenditure of eight obese prepubertal children (age 9 +/- 1 years; weight 48.7 +/- 9.1 kg; BMI 25.3 +/- 3.9) and of 14 age-matched children of normal body weight (age 9 +/- 1 years; weight 28.8 +/- 5.6 kg; BMI 16.5 +/- 1.7) was measured by indirect calorimetry. The obese children were reinvestigated after a mean weight loss of 5.4 +/- 1.2 kg induced by a six-months mixed hypocaloric diet. Before slimming, the obese group showed a higher daily energy intake than the control group (10.40 +/- 3.45 MJ/day vs 7.97 +/- 2.02 MJ/day respectively; P less than 0.05) but a similar value was observed per unit fat-free mass (FFM) (0.315 +/- 0.032 MJ/kgFFM/day vs 0.329 +/- 0.041 MJ/kgFFM/day respectively). The average RMR of the obese children was greater than that of the control group (5217 +/- 531 kJ/day vs 4477 +/- 506 kJ/day) but similar after adjusting for FFM (4728 +/- 3102 kJ/day vs 4899 +/- 3102 kJ/day). Weight loss resulted in a reduction in RMR (5217 +/- 531 kJ/day vs 4874 +/- 820 kJ/day), each kg of weight loss being accompanied by a decrease of RMR of 64 kJ (15.3 kcal) per day. The changes in RMR induced by weight loss paralleled the changes in FFM. No difference was found in average RQ in obese children vs controls (0.85 +/- 0.03 vs 0.87 +/- 0.03 respectively) and in the obese children before and after weight loss (0.87 +/- 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Increasing lactate turnover rate during exercise by means of altitude training and fructose ingestion : effects on substrate metabolism and endurance performance

Summary : With regard to exercise metabolism, lactate was long considered as a dead-end waste product responsible for muscle fatigue and a limiting factor for motor performance. However, a large body of evidence clearly indicates that lactate is an energy efficient metabolite able to link the glycolytic pathway with aerobic metabolism and has endocrine-like actions, rather than to be a dead-end waste product. Lactate metabolism is also known to be quickly upregulated by regular endurance training and is thought to be related to exercise performance. However, to what extent its modulation can increase exercise performance in already endurance-trained subjects is unknown. The general hypothesis of this work was therefore that increasing either lactate metabolic clearance rate or lactate availability could, in turn, increase endurance performance. The first study (Study I) aimed at increasing the lactate clearance rate by means of assumed interaction effects of endurance training and hypoxia on lactate metabolism and endurance performance. Although this study did not demonstrate any interaction of training and hypoxia on both lactate metabolism and endurance performance, a significant deleterious effect of endurance training in hypoxia was shown on glucose homeostasis. The methods used to determine lactate kinetics during exercise exhibited some limitations, and the second study did delineate some of the issues raised (Study 2). The third study (Study 3) investigated the metabolic and performance effects of increasing plasma lactate production and availability during prolonged exercise in the fed state. A nutritional intervention was used for this purpose: part of glucose feedings ingested during the control condition was substituted by fructose. The results of this study showed a significant increase of lactate turnover rate, quantified the metabolic fate of fructose; and demonstrated a significant decrease of lipid oxidation and glycogen breakdown. In contrast, endurance performance appeared to be unmodified by this dietary intervention, being at odds with recent reports. Altogether the results of this thesis suggest that in endurance athletes the relationship between endurance performance and lactate turnover rate remains unclear. Nonetheless, the result of the present study raises questions and opens perspectives on the rationale of using hypoxia as a therapeutic aid for the treatment of insulin resistance. Moreover, the results of the second study open perspectives on the role of lactate as an intermediate metabolite and its modulatory effects on substrate metabolism during exercise. Additionally it is suggested that the simple nutritional intervention used in the third study can be of interest in the investigation on the aforementioned roles of lactate. Résumé : Lorsque le lactate est évoqué en rapport avec l'exercice, il est souvent considéré comme un déchet métabolique responsable de l'acidose métabolique, de la fatigue musculaire ou encore comme un facteur limitant de la performance. Or la littérature montre clairement que le lactate se révèle être plutôt un métabolite utilisé efficacement par de nombreux tissus par les voies oxydatives et, ainsi, il peut être considéré comme un lien entre le métabolisme glycolytique et le métabolisme oxydatif. De plus on lui prête des propriétés endocrines. Il est connu que l'entraînement d'endurance accroît rapidement le métabolisme du lactate, et il est suggéré que la performance d'endurance est liée à son métabolisme. Toutefois la relation entre le taux de renouvellement du lactate et la performance d'endurance est peu claire, et, de même, de quelle manière la modulation de son métabolisme peut influencer cette dernière. Le but de cette thèse était en conséquence d'investiguer de quelle manière et à quel degré l'augmentation du métabolisme du lactate, par l'augmentation de sa clearance et de son turnover, pouvait à son tour améliorer la performance d'endurance de sujets entraînés. L'objectif de la première étude a été d'augmenter la clearance du lactate par le biais d'un entraînement en conditions hypoxiques chez des cyclistes d'endurance. Basé sur la littérature scientifique existante, on a fait l'hypothèse que l'entraînement d'endurance et l'hypoxie exerceraient un effet synergétique sur le métabolisme du lactate et sur la performance, ce qui permettrait de montrer des relations entre performance et métabolisme du lactate. Les résultats de cette étude n'ont montré aucun effet synergique sur la performance ou le métabolisme du lactate. Toutefois, un effet délétère sur le métabolisme du glucose a été démontré. Quelques limitations de la méthode employée pour la mesure du métabolisme du lactate ont été soulevées, et partiellement résolues dans la seconde étude de ce travail, qui avait pour but d'évaluer la sensibilité du modèle pharmacodynamique utilisé pour le calcul du turnover du lactate. La troisième étude a investigué l'effet d'une augmentation de la lactatémie sur le métabolisme des substrats et sur la performance par une intervention nutritionnelle substituant une partie de glucose ingéré pendant l'exercice par du fructose. Les résultats montrent que les composants dynamiques du métabolisme du lactate sont significativement augmentés en présence de fructose, et que les oxydations de graisse et de glycogène sont significativement diminuées. Toutefois aucun effet sur la performance n'a été démontré. Les résultats de ces études montrent que la relation entre le métabolisme du lactate et la performance reste peu claire. Les résultats délétères de la première étude laissent envisager des pistes de travail, étant donné que l'entraînement en hypoxie est considéré comme outil thérapeutique dans le traitement de pathologies liées à la résistance à l'insuline. De plus les résultats de la troisième étude ouvrent des perspectives de travail quant au rôle du lactate comme intermédiaire métabolique durant l'exercice ainsi que sur ses effets directs sur le métabolisme. Ils suggèrent de plus que la manipulation nutritionnelle simple qui a été utilisée se révèle être un outil prometteur dans l'étude des rôles et effets métaboliques que peut revêtir le lactate durant l'exercice.

Development of a microprocessor controlled energy harvester using a Peltier element

Nowadays it is necessary to research other types of energy alternatives and find the way to supply and save the energy we waste. The aim of the project consist of programming a microprocessor to measure if an oven radiates heat to the exterior, for the measure It is used a Peltier element that generates a voltage depending of the temperature difference between the oven and the air of the place where the oven is situated; The energy generated by the oven will be recollected in a condensor. A sensor will be used to know the exact measure. The second part of the project the main propose, is the development of a harvester. The microprocessor will use the voltage produced by the Peltier element to supply the electricity that it needs to work. A low power circuit and the appropriate software are needed to save the voltage generated.

Energy investment in gynes of the Argentine ant Iridomyrmex humilis (Mayr) in relation to the mode of colony founding in ants (Hymenoptera, Formicidae)

The increase in weight, fat and energy content of queens was studied in Iridomyrmex humilis (Mayr) in relation to the mode of colony founding in ants. The increase in energy content of gynes during the time between emergence and mating reaches only 80% in this species in which queens found colonies with the help of workers (dependent mode), whereas it can reach 470% in species in which queens found colonies without the help of workers (independent mode). These results are discussed with regard to the investment in energy required by each mode of colony founding.

Improving energy access in rural sub-Saharan Africa

XVII Convocatòria d’ajuts a accions de cooperació - 2009GRECDH – UPC. Improving Energy Access In Rural sub- Saharan Africa. O-006/09. Informe

An approach to costs and energy consumption in private urban Spanish Mediterranean landscapes from a simplified model in sprinkle irrigation

The number of private gardens has increased in recent years, creating a more pleasant urban model, but not without having an environmental impact, including increased energy consumption, which is the focus of this study. The estimation of costs and energy consumption for the generic typology of private urban gardens is based on two simplifying assumptions: square geometry with surface areas from 25 to 500 m2 and hydraulic design with a single pipe. In total, eight sprinkler models have been considered, along with their possible working pressures, and 31 pumping units grouped into 5 series that adequately cover the range of required flow rates and pressures, resultin in 495 hydraulic designs repeated for two climatically different locations in the Spanish Mediterranean area (Girona and Elche). Mean total irrigation costs for the locality with lower water needs (Girona) and greater needs (Elche) were € 2,974 ha-¹ yr-¹ and € 3,383 ha-¹ yr-¹, respectively. Energy costs accounted for 11.4% of the total cost for the first location, and 23.0% for the second. While a suitable choice of the hydraulic elements of the setup is essential, as it may provide average energy savings of 77%, due to the low energy cost in relation to the cost of installation, the potential energy savings do not constitute a significant incentive for the irrigation system design. The low efficiency of the pumping units used in this type of garden is the biggest obstacle and constraint to achieving a high quality energy solution

Microquasars as high energy gamma-ray sources

Galactic microquasars are certainly one of the most recent additions to the field of high energy astrophysics and have attracted increasing interest over the last decade. However, the high energy part of the spectrum of microquasars is the most poorly known, mainly due the lack of sensitive instrumentation in the past. Microquasars are now primary targets for all of the observatories working in the X-ray and gamma-ray domains. They also appear as the possible counterparts for some of the unidentified sources of high-energy gamma-rays detected by the experiment EGRET on board the satellite COMPTON-GRO. This paper provides a general review of the main observational results obtained up to now as well as a summary of the scenarios for production of high-energy gamma-rays at the present moment.

High-energy gamma-ray emission from microquasars: LS 5039 and LS I+61303

The possible associations between the microquasars LS 5039 and LS I +61 303 and the EGRET sources 3EG J1824-1514 and 3EG J0241+6103 suggest that microquasars could also be sources of high-energy gamma-rays. In this work, we present a detailed numerical inverse Compton (IC) model, based on a microquasar scenario, that reproduces the high-energy gamma-ray spectra and variability observed by EGRET for the mentioned sources. Our model considers a population of relativistic electrons entrained in a cylindrical inhomogeneous jet that interact through IC scattering with both the radiation and the magnetic fields.

Search for very high energy gamma-ray emission from pulsar-pulsar wind nebula systems with the MAGIC telescope

The MAGIC collaboration has searched for high-energy gamma-ray emission of some of the most promising pulsar candidates above an energy threshold of 50 GeV, an energy not reachable up to now by other ground-based instruments. Neither pulsed nor steady gamma-ray emission has been observed at energies of 100 GeV from the classical radio pulsars PSR J0205+6449 and PSR J2229+6114 (and their nebulae 3C58 and Boomerang, respectively) and the millisecond pulsar PSR J0218+4232. Here, we present the flux upper limits for these sources and discuss their implications in the context of current model predictions.

Variable Very-High-Energy Gamma-Ray Emission from the Microquasar LS I +61 303

Microquasars are binary star systems with relativistic radio-emitting jets. They are potential sources of cosmic rays and can be used to elucidate the physics of relativistic jets. We report the detection of variable gamma-ray emission above 100 gigaelectron volts from the microquasar LS I 61 + 303. Six orbital cycles were recorded. Several detections occur at a similar orbital phase, which suggests that the emission is periodic. The strongest gamma-ray emission is not observed when the two stars are closest to one another, implying a strong orbital modulation of the emission or absorption processes.

Final Report Energy Efficiency Plans and Programs Study Committee, February 2009

The Legislative Council created the Energy Efficiency Plans and Programs Study Committee for the 2008 Legislative Interim pursuant to the passage of S.F. 2386 during the 2008 Legislative Session, which provided, in Section 8: The Legislative Council is requested to establish an interim study committee to examine the existence and effectiveness of energy efficiency plans and programs implemented by gas and electric public utilities, with an emphasis on results achieved by current plans and programs from the demand, or customer, perspective, and to make recommendations for additional requirements applicable to energy efficiency plans and programs that would improve such results. In conducting the study and developing recommendations, the Committee shall consider testimony from the Iowa Utilities Board, rate and nonrate-regulated gas and electric utilities, the Consumer Advocate, state agencies involved with energy efficiency program administration, environmental groups and associations, and consumers.