Mitochondrial DNA Content in Human Omental Adipose Tissue

Background: Impairment of mitochondrial function plays an important role in obesity and the development of insulin resistance. The aim of this project was to investigate the mitochondrial DNA copy number in human omental adipose tissue with respect to obesity. Methods: The mitochondrial DNA (mtDNA) content per single adipocyte derived from abdominal omental adipose tissue was determined by quantitative RT-PCR in a group of 75 patients, consisting of obese and morbidly obese subjects, as well as non-obese controls. Additionally, basal metabolic rate and fat oxidation rate were recorded and expressed as total values or per kilogram fat mass. Results: MtDNA content is associated with obesity. Higher body mass index (BMI) resulted in a significantly elevated mtDNA count (ratio = 1.56; p = 0.0331) comparing non-obese (BMI < 30) to obese volunteers (BMI ≥ 30). The mtDNA count per cell was not correlated with age or gender. Diabetic patients showed a trend toward reduced mtDNA content. A seasonal change in mtDNA copy number could not be identified. In addition, a substudy investigating the basal metabolic rate and the fasting fat oxidation did not reveal any associations to the mtDNA count. Conclusions: The mtDNA content per cell of omental adipose tissue did not correlate with various clinical parameters but tended to be reduced in patients with diabetes, which may partly explain the impairment of mitochondrial function observed in insulin resistance. Furthermore, the mtDNA content was significantly increased in patients suffering from obesity (BMI above 30). This might reflect a compensatory response to the development of obesity, which is associated with impairment of mitochondrial functio

Mechanisms of Hepatocellular Toxicity Associated with Dronedarone—A Comparison to Amiodarone

Dronedarone is a new antiarrhythmic drug with an amiodarone-like benzofuran structure. Shortly after its introduction, dronedarone became implicated in causing severe liver injury. Amiodarone is a well-known mitochondrial toxicant. The aim of our study was to investigate mechanisms of hepatotoxicity of dronedarone in vitro and to compare them with amiodarone. We used isolated rat liver mitochondria, primary human hepatocytes, and the human hepatoma cell line HepG2, which were exposed acutely or up to 24h. After exposure of primary hepatocytes or HepG2 cells for 24h, dronedarone and amiodarone caused cytotoxicity and apoptosis starting at 20 and 50µM, respectively. The cellular ATP content started to decrease at 20µM for both drugs, suggesting mitochondrial toxicity. Inhibition of the respiratory chain required concentrations of ~10µM and was caused by an impairment of complexes I and II for both drugs. In parallel, mitochondrial accumulation of reactive oxygen species (ROS) was observed. In isolated rat liver mitochondria, acute treatment with dronedarone decreased the mitochondrial membrane potential, inhibited complex I, and uncoupled the respiratory chain. Furthermore, in acutely treated rat liver mitochondria and in HepG2 cells exposed for 24h, dronedarone started to inhibit mitochondrial β-oxidation at 10µM and amiodarone at 20µM. Similar to amiodarone, dronedarone is an uncoupler and an inhibitor of the mitochondrial respiratory chain and of β-oxidation both acutely and after exposure for 24h. Inhibition of mitochondrial function leads to accumulation of ROS and fatty acids, eventually leading to apoptosis and/or necrosis of hepatocytes. Mitochondrial toxicity may be an explanation for hepatotoxicity of dronedarone in viv

Photoassociation and coherent transient dynamics in the interaction of ultracold rubidium atoms with shaped femtosecond pulses - I. Experiment

We experimentally investigate various processes present in the photoassociative interaction of an ultracold atomic sample with shaped femtosecond laser pulses. We demonstrate the photoassociation of pairs of rubidium atoms into electronically excited, bound molecular states using spectrally cut femtosecond laser pulses tuned below the rubidium D1 or D2 asymptote. Time-resolved pump-probe spectra reveal coherent oscillations of the molecular formation rate, which are due to coherent transient dynamics in the electronic excitation. The oscillation frequency corresponds to the detun-ing of the spectral cut position to the asymptotic transition frequency of the rubidium D1 or D2 lines, respectively. Measurements of the molecular photoassociation signal as a function of the pulse energy reveal a non-linear dependence and indicate a non-perturbative excitation process. Chirping the association laser pulse allowed us to change the phase of the coherent transients. Furthermore, a signature for molecules in the electronic ground state is found, which is attributed to molecule formation by femtosecond photoassociation followed by spontaneous decay. In a subsequent article [A. Merli et al., submitted] quantum mechanical calculations are presented, which compare well with the experimental data and reveal further details about the observed coherent transient dynamics

Coherent control with shaped femtosecond laser pulses applied to ultracold molecules

We report on coherent control of excitation processes of translationally ultracold rubidium dimers in a magneto-optical trap by using shaped femtosecond laser pulses. Evolution strategies are applied in a feedback loop in order to optimize the photoexcitation of the Rb2 molecules, which subsequently undergo ionization or fragmentation. A superior performance of the resulting pulses compared to unshaped pulses of the same pulse energy is obtained by distributing the energy among specific spectral components. The demonstration of coherent control to ultracold ensembles opens a path to actively influence fundamental photo-induced processes in molecular quantum gases

Standby and Off-Mode Energy Losses In New Appliances Measured in Shops

Selina project website at http://selina-project.eu PDF available online at http://selina-project.eu/files/SELINA_book.pdfInternational audienceThis document provides an overview of the most important results of the Intelligent Energy Europe (IEE) Project SELINA - Standby and Off-Mode Energy Losses In New Appliances Measured in Shops. Standby power is a general term commonly used to describe the low power modes in which many electrical and electronic products are, when not performing their main function. For more than a decade, it has been recognized that the energy consumption in low power modes for electrical and electronic products is an important issue because it represent permanent loads (sometimes up to 24 hours per day) of a huge number of products. With the 1 W standby initiative of the International Energy Agency (IEA), several low power mode measurement campaigns have been led on a regular basis in a number of countries outside and inside Europe Union (EU). Based on these results and on the Energy-using Products Study Lot 6, the EU has prepared new regulation to limit the standby and off-mode power consumption of non-networked household electronic and electrical equipment, which is being applied since January 2010. The IEE project SELINA carried out a large scale monitoring campaign in shops in order to characterise the low power modes of new appliances being sold in the EU market. In order to ensure consistency of the collected data, a common measurement methodology was developed and the same high resolution measurement equipment was used by all partners. This document analyzes the results of more than 6000 different equipments measured in the 12 EU countries involved in the project. Standby and off-mode values by product categories were analysed and compared with data from other regions of the World. The measurements were also benchmarked against the new 2010/2013 EU standby and off mode regulation thresholds and the impact of the EU regulation is discussed. It was found that 18.5% of the equipments, whose off-mode power was measured, do not respect the EU regulation threshold of 1 W. When the measurements are compared to the 2013 threshold of 0.5 W, this percentage raises up to 41.5%. Regarding standby mode input power, 31% of the measured products did not comply with EU regulation limit for the 2010 threshold. When the standby measured values are compared to the 2013 limit, the number of products over the EU regulation target increases to 66.4%. When comparing the 2009 and 2010 measurements, only a slight decrease of the share of appliances exceeding the EU regulation limits was observed. In parallel with the measurement campaign, an awareness study of the retailers was carried out. This survey helps to understand the customers' buying motivations and the influence of retailers' advice in their choices. The results of the survey show that, despite of retailer's consciousness about the energy consumption and energy labels of the products, other types of sales arguments like the appliance price or functionalities are more frequently used to sell a product. This could be due to lack of visible information in shops related to the equipment energy consumption. Furthermore, the results show that retailers try to adapt their advice to the customers' needs (price and product functionalities). The retailers admitted that publishing more information regarding the energy consumption of products and some kind of cost saving calculator/reference would make the clients to opt for more efficient equipments. Based on the survey results and on the analysis of different existing policies targeting electrical and electronic products in Europe, examples of policies to improve the low power modes situation of the EU market are reviewed. The survey on measures enhancing the market transformation towards more energy-efficient electrical appliances showed a wide range of actions and policy tools in the SELINA partner countries. In national workshops, which mainly took place in the late summer/early autumn 2010, these measures were presented and discussed with all relevant national stakeholders. In most countries, information campaigns (esp. brochures, leaflets, websites, and national labels) are the dominating measure type. In some countries, however, financial subsidies for very energy-efficient appliances, often paid by an energy utility and not by the government, play an important role, too (e.g. in the Czech Republic or Switzerland). In general, the impact of a financial programme is easier to quantify than the single impact of an information campaign, which often serves as an accompanying measure for regulations (labels, minimum efficiency standards) or fiscal and financial measures. International cooperation with key institutions outside the EU, involved in similar efforts, such as the IEA Implementing Agreement 4E (Efficient Electrical End-use Equipment) with an Annex on Standby, the Energy Star/EPA in USA, the Australia Standby Initiative and the Swiss Federal Office of Energy, were used to promote synergies in the definition of common approaches to characterize the market and to define realistic and cost-effective performance targets which can be achieved in a short time frame. Special care is required when promoting low standby consumption products (without consideration of other attributes) to ensure that there are no perverse effects such as the inadvertent promotion of products with low active mode efficiency and high energy consumption. It is desirable to follow a vertical approach to standby, where low power modes are combined with active modes to give total energy consumption. This approach is particularly preferable for products where the total energy consumption is significant. The definition of usage patterns under such a vertical approach is necessarily product specific and this could vary by region or country. The new technologies offer many opportunities for energy savings potential but there are also some threats which need to be recognized and understood. There is a strong need to ensure that energy saving paradigms and strategies become a core consideration in future product designs. It is recognized that equipments connected to networks are of growing importance. It is recommended that increased efforts to compile data and measurements, of networked products, from a variety of sources in order to obtain better information on networked product characteristics, needs to be made. An online database was created so that everyone can access the input power values, in the different equipment low power modes, of the more than 6000 equipments measured. A Standby Calculator Tool was also developed and can be accessed through the project website. It can be used to calculate the consumed energy, the annual cost and the equivalent CO2 emissions. In order to compare the results in an easy way, a diagram that shows the energy consumption of the different models is presented. Furthermore, the values for the most efficient device are also showed, in order to have an additional comparison. One of the main objectives of this project was to identify effective market transformation policies initiatives targeted at all the key stakeholders involved in the manufacture, distribution, sales, purchasing and operation of appliances with standby and off-mode losses. As a result of the future policy actions that may appear after the end of the project, considering loads in networked mode, it is expected to achieve very large cost-effective savings of electricity (80 TWh projected by 2020) and carbon emissions (30 MTons of CO2 by 2020)

Floral and insect-induced volatile formation in Arabidopsis lyrata ssp. petraea, a perennial, outcrossing relative of A. thaliana

Volatile organic compounds have been reported to serve some important roles in plant communication with other organisms, but little is known about the biological functions of most of these substances. To gain insight into this problem, we have compared differences in floral and vegetative volatiles between two closely related plant species with different life histories. The self-pollinating annual, Arabidopsis thaliana, and its relative, the outcrossing perennial, Arabidopsis lyrata, have markedly divergent life cycles and breeding systems. We show that these differences are in part reflected in the formation of distinct volatile mixtures in flowers and foliage. Volatiles emitted from flowers of a German A. lyrata ssp. petraea population are dominated by benzenoid compounds in contrast to the previously described sesquiterpene-dominated emissions of A. thaliana flowers. Flowers of A. lyrata ssp. petraea release benzenoid volatiles in a diurnal rhythm with highest emission rates at midday coinciding with observed visitations of pollinating insects. Insect feeding on leaves of A. lyrata ssp. petraea causes a variable release of the volatiles methyl salicylate, C11- and C16-homoterpenes, nerolidol, plus the sesquiterpene (E)-β-caryophyllene, which in A. thaliana is emitted exclusively from flowers. An insect-induced gene (AlCarS) with high sequence similarity to the florally expressed (E)-β-caryophyllene synthase (AtTPS21) from A. thaliana was identified from individuals of a German A. lyrata ssp. petraea population. Recombinant AlCarS converts the sesquiterpene precursor, farnesyl diphosphate, into (E)-β-caryophyllene with α-humulene and α-copaene as minor products indicating its close functional relationship to the A. thaliana AtTPS21. Differential regulation of these genes in flowers and foliage is consistent with the different functions of volatiles in the two Arabidopsis species

Mechanisms of hepatocellular toxicity associated with dronedarone -a comparison to amiodarone

Dronedarone is a new antiarrhythmic drug with an amiodarone-like benzofuran structure. Shortly after its introduction, dronedarone became implicated in causing severe liver injury. Amiodarone is a well-known mitochondrial toxicant. The aim of our study was to investigate mechanisms of hepatotoxicity of dronedarone in vitro and to compare them with amiodarone. We used isolated rat liver mitochondria, primary human hepatocytes, and the human hepatoma cell line HepG2, which were exposed acutely or up to 24h. After exposure of primary hepatocytes or HepG2 cells for 24h, dronedarone and amiodarone caused cytotoxicity and apoptosis starting at 20 and 50µM, respectively. The cellular ATP content started to decrease at 20µM for both drugs, suggesting mitochondrial toxicity. Inhibition of the respiratory chain required concentrations of ~10µM and was caused by an impairment of complexes I and II for both drugs. In parallel, mitochondrial accumulation of reactive oxygen species (ROS) was observed. In isolated rat liver mitochondria, acute treatment with dronedarone decreased the mitochondrial membrane potential, inhibited complex I, and uncoupled the respiratory chain. Furthermore, in acutely treated rat liver mitochondria and in HepG2 cells exposed for 24h, dronedarone started to inhibit mitochondrial β-oxidation at 10µM and amiodarone at 20µM. Similar to amiodarone, dronedarone is an uncoupler and an inhibitor of the mitochondrial respiratory chain and of β-oxidation both acutely and after exposure for 24h. Inhibition of mitochondrial function leads to accumulation of ROS and fatty acids, eventually leading to apoptosis and/or necrosis of hepatocytes. Mitochondrial toxicity may be an explanation for hepatotoxicity of dronedarone in vivo

Simultaneous real-time magnetic resonance imaging (MRI) and nose-space analysis by proton-transfer-reaction mass-spectrometry during eating

In order to better understand the performance of food products during the actual process of eating, it is important to develop techniques that allow exploring foods in-vivo and in real-time during consumption. Here we present first results on the simultaneous anal. of the eating process, combining two techniques. This includes real-time magnetic resonance imaging (MRI) to visualize the mastication, breakdown and swallowing and online nose-space anal. by proton-transfer-reaction mass-spectrometry (PTR-MS) to monitor the in-mouth aroma release

Hepatocellular toxicity of benzbromarone : Effects on mitochondrial function and structure

Benzbromarone is an uricosuric structurally related to amiodarone and a known mitochondrial toxicant. The aim of the current study was to improve our understanding in the molecular mechanisms of benzbromarone-associated hepatic mitochondrial toxicity. In HepG2 cells and primary human hepatocytes, ATP levels started to decrease in the presence of 25-50μM benzbromarone for 24-48h, whereas cytotoxicity was observed only at 100μM. In HepG2 cells, benzbromarone decreased the mitochondrial membrane potential starting at 50μM following incubation for 24h. Additionally, in HepG2 cells, 50μM benzbromarone for 24h induced mitochondrial uncoupling,and decreased mitochondrial ATP turnover and maximal respiration. This was accompanied by an increased lactate concentration in the cell culture supernatant, reflecting increased glycolysis as a compensatory mechanism to maintain cellular ATP. Investigation of the electron transport chain revealed a decreased activity of all relevant enzyme complexes. Furthermore, treatment with benzbromarone was associated with increased cellular ROS production, which could be located specifically to mitochondria. In HepG2 cells and in isolated mouse liver mitochondria, benzbromarone also reduced palmitic acid metabolism due to an inhibition of the long-chain acyl CoA synthetase. In HepG2 cells, benzbromarone disrupted the mitochondrial network, leading to mitochondrial fragmentation and a decreased mitochondrial volume per cell. Cell death occurred by both apoptosis and necrosis. The study demonstrates that benzbromarone not only affects the function of mitochondria in HepG2 cells and human hepatocytes, but is also associated with profound changes in mitochondrial structure which may be associated with apoptosis